Hemp Growing

This is more challenging with a subset of the Taxol P450s that are predicted to have multiple transmembrane domains with an uncharacterized ER-binding mechanism. Modifying this interaction without disrupting the internal loop structures and catalytic activity of the protein could prove quite difficult. Another aspect of P450 function is often determined by peripheral protein-protein interactions in the native host. Many highly modified plant natural products are synthesized by a collection of enzymes in complex along the ER membrane called metabolons, with the intermediate substrates shuttled from one reaction center to the next. These highly optimized systems often involve non-catalytic “scaffold” proteins that act as a foundation for the binding and assembly of numerous enzymes. Examining the expression and localization dynamics of Taxol-associated P450s revealed a deficiency in ER localization when tested in their native form in yeast. Expression was seen for all the P450s investigated, but they localize to the cytosol. As mentioned earlier, functionality for the vast majority of P450s from plants are dependent on proper ER-anchoring and redox coupling with additional ER-bound enzymes. We sought to modify the localization of Taxol P450s in yeast by substituting the native ER-anchor region for a sequence previously shown to result in proper ER localization in yeast. Structure modeling and transmembrane domain prediction was carried out for six of the Taxol P450s using the PHYRE2 platform. In general, the first transmembrane domain of a P450 acts as the ER-anchor region. We therefore selected the first amino acid after the predicted transmembrane domain for each P450s as a truncation point. The functional ER-anchor sequence was used to replace the truncated region along with the same linker sequence 264 used for the fluorescent reporter protein fusions.

The linker sequence was added with the aim of improving ER localization by introducing flexibility at the fusion site. Unfortunately,rolling hydro tables even with the modified anchor region the P450s fail to properly localize to the ER . Another potentiality for improving the localization and function of multiple P450s is engineering protein scaffolds that promote assembly at the ER membrane. Membrane steroid binding proteins are a class of protein that are commonly involved with biosynthetic pathways in plants. Furthermore, these are often required for functional biosynthesis, exemplified by the lignin biosynthetic pathway involved in secondary cell wall formation. Biosynthesis of the lignin polymer is highly regulated, multi-branched, and includes several P450s requiring a MSBP for complex assembly. By identifying transmembrane domain anchors and MSBPs with a high affinity for interaction, it may be possible to generate pseudo-metabolons when engineering plant natural product biosynthetic pathways into yeast, specifically those that require numerous ER bound enzymes. To test the potential of this application, we selected a MSBP to test in yeast with a previously characterized fusion protein confirmed for functional ER localization . Fluorescent reporters were used to observe the expression and localization of both MSBP and ER-CslG simultaneously to examine co-localization patterns . ER-CslG:eGFP showed proper ER localization patterns in most of the cells observed , while MSBP:mCherry showed varied patterns of localization . It is important to note that there are potential unknown interactions between MSBP and the mCherry fusion protein. In the cells that showed high levels of co-localization though, robust accumulation of both MSBP and ER-CslG can be seen along the ER envelope of the nucleus . The pattern observed seems to represent a nucleation reaction, with co-localization initiation leading to the accumulation of both MSBP and CslG at high concentrations.

This observation exemplifies a prospective method to promote the accumulation and optimum localization of plant derived P450s, as well as providing a secondary scaffold for the “assembly” of multiple P450s simultaneously. While more optimizations would be needed to integrate numerous enzymes into this engineering scheme, the potential of forming pseudo-metabolons could be a favorable approach when engineering bio-synthetic pathways of plant natural products like Taxol in yeast. They are commonly found in plants from the nightshade family, genus Solanum, including tomato, eggplant, and potato. Yeast provides a relatively unexplored opportunity for the bio-production of steroidal alkaloids in a heterologous host. As yeast does not natively produce cholesterol, the primary substrate for steroidal alkaloids, very limited efforts have been made to explore this molecular space for bio-production. Interrupting ergosterol production and shunting zymosterol to cholesterol can be achieved by genetically exchanging ERG5 and ERG6 with DHCR7 and DHCR24267 . Additionally, the substitution of cholesterol for ergosterol in the cell membrane results in limited disruption on yeast growth and development, making this a plausible system to explore. This “humanized” yeast system has been used in studies of mammalian cell-surface receptors and transporters in the past but harnessing this chassis for the bio-production of plant natural products has untapped economic potential268 . Further modifications could be made to optimize cholesterol overproduction and bio-availability, to ultimately produce a S. cerevisiae strain engineered specifically for the biosynthesis of cholesterol derivatives with diverse structures and applications. To explore the potential of yeast as a platform for steroidal alkaloids production, we engineered a cholesterol producing strain using CEN.PK as our parent line. DHCR7 and DHCR24 from humans were selected based on previous work on cholesterol biosynthesis.

Sequential gene substitution of the native ERG5 and ERG6 genes was carried out via homologous recombination. pADH1-DHCR7 was used to replace ERG5 and its native promoter with pADH1-DCHR24 replacing ERG6 and its native promoter, gene substitutions were performed at the native loci. One deficiency of “humanized” yeast is the capacity for acid transport, as cholesterol substitution disrupts endogenous acid transporters. This was observed when performing counter selection for the URA auxotrophic marker used in cloning, which utilizes plating on 5-FOA . This acidic medium, in conjunction with the 5-FOA counter selection , caused a drastic lag in growth for the final strain with colonies appearing more than ten days after plating. Multiple colonies that cleared PCR and sequencing screens were then selected for GCMS analysis of cholesterol production against an analytical standard. Interestingly, two strains were confirmed for cholesterol production but have varied product profiles. Chl24-20 was the top producing strain in this initial screen, with cholesterol being one of two major products in the GCMS analysis. While Chl75-10 did produce cholesterol, it was a minor product, with two other major peaks present . These were not structurally identified but based on MS spectrum analysis are hypothesized to be structurally similar to cholesterol with variation in the number of C-C double bonds. Chl24-20 was selected as our production strain for downstream analysis. While final cell densities of experimental strains and the control strain were equivalent at 72 hours, there was an observable lag in growth for the experimental strains during the first 36 hours of production. This is most likely due to sub-optimum cholesterol production along with peripheral effects of sterol substitution in the developing membranes of dividing yeast. After confirmation of cholesterol production in Chl24-20 with an analytical standard, we used GCMS analysis of Chl24-20 culture extract and a series of five dilutions of cholesterol standard in ethyl acetate, which is the same final solvent used for extraction . These data were then used to generate a standard curve for cholesterol to quantify production in Chl24-20,vertical horticulture which was calculated to be ~128.4nM with our extraction method . Numerous steroidal alkaloids have implications in human health and research including cyclopamine, α-tomatine, and α-solanine. The interest in α-tomatine is due to its function as an antimicrobial that protects the plant against fungi as well as herbivores270. Its broad-range mechanism of action, which involves disruption of cellular membranes as well as inhibition of acetylcholinesterase, makes it a great candidate for further development of antibiotics. α-solanine, from potato, has a similar membrane disruption effect, but is different in its capacity to interact with mitochondrial membranes. It acts as a poison by disrupting the mitochondrial membrane potential leading to a flood of calcium ions into the cytoplasm causing cell damage/death. Cyclopamine is of particular interest due to its interaction with Hedgehog signaling, which is involved with an array of developmental processes including embryonic development and tumorigenesis. Much like Taxol, it has profound implications for its capacity to inhibit tumor growth as a treatment for a variety of cancers, though the mechanism of action is quite different. Cyclopamine is a steroidal alkaloid derived from cholesterol that does not require glycosylation, making it a great target to test the potential of our steroidal alkaloid yeast platform. Verazine is an intermediate in cyclopamine production that has a well characterized pathway requiring three P450s and an aminotransferase. The conversion of verazine to cyclopamine then only requires two additional reactions that are currently being charactered . What is exciting about this pathway is the potential to generate novel glycosylated steroidal alkaloids with the introduction of GTs from either saponin, tomatine, or solanine biosynthesis for the glycosylation of the 3C position .

Recent advances in engineering nucleotide sugar pathways into yeast, coupled with the promiscuous nature of plant derived GTs, provides an opportunity for the biosynthesis of glycosylated steroidal alkaloids. Solanaceous plants produce a variety of these molecules, with diverse physiological applications and effects and therefore have an abundance of genetic material that can be implemented in yeast. The potential to produce novel glycosylated molecules is especially promising, for example glycosylated cyclopamine derivatives, with the introduction of GTs that glycosylate similar structures such as saponins. These new molecules have a greater degree of structural diversity and may provide enhanced, altered, or even novel properties. This specifically demonstrates the utility of synthetic yeast biology as a tool to produce “new-to-nature” molecules not possible with classic organic chemistry or extraction from plants. While further optimizing the production of free cholesterol, we can begin to introduce key nucleotide sugar pathways that produce the substrate for GT reactions, allowing for pathways requiring glycosylation to be investigated. Engineering a yeast platform specifically for the bio-production of glycosylated steroidal alkaloids would be an excellent resource for future studies on these complex and derivatized molecules.While much of the work discussed is varied in its approach or function, its core follows the reductionist theme of synthetic biology, aiming to rebuild living systems for specific applications in biotechnology. Whether engineering a fungus or a plant, the concepts applied remain the same. The amazing diversity of biological systems present on earth are a canvas for synthetic biologists, providing an almost infinite source of genetic information that can be reengineered and reshaped to solve challenging problems. In my opinion, synthetic biology is still in its infancy, but as we collectively increase our knowledge and understanding of the core tenets of life, we will see the true power of synthetic biology emerge. Even with these limits on our current understanding, we are transforming the old industrial economic model into a bio-based economic model. Opportunities for ambitious and clever engineers are abundant, and I predict an exponential increase in the development of novel synthetic systems in the coming decade. So much untapped potential makes this an exciting era for biotechnology, with the prospect for application of bio-based solutions across all sectors. Eventually, the integration of biological systems with digital systems will exponentially expand the possibilities, as electrical and biological process can be intertwined to generate platforms we have yet to imagine, all made possible with synthetic biology. Observing patterns in retail prices is fund a mental for understanding the economics of any agricultural consumer product. The study of cannabis retail prices, like the study of other economic aspects of the cannabis industry, is fraught with difficulty, in part because cannabis remains a Schedule I narcotic under U.S. federal law. Consumer price indexes, tax records, commercial retail scanner data, industry association reports and other sources of data typically available for agricultural products such as wine, almonds and cut flowers are unavailable for cannabis. Cannabis retailers have limited access to banking services; most cannabis retail transactions are conducted in cash; and cannabis businesses are under standably reluctant to share their financial data. There is a need for better information about all aspects of the cannabis industry, including prices and price patterns. In this article, we aim to contribute to the scant literature on cannabis retail prices by describing the basic patterns of price ranges at retailers in California over a 21-month time span during which the industry under went a series of significant regulatory changes. Several times between October 2016 and July 2018, researchers at the UC Agricultural Issues Center gathered cannabis retail prices published on Weedmaps, a leading online cannabis retail platform.

As such, it may be that in the absence of legally available chemical controls growers were choosing allowable, biologically derived products or alternative strategies such as natural enemy augmentation and sanitation. Our survey population was perhaps biased toward non-chemical pest management — the organizations we contacted for participant recruitment included some that were formed to share and promote sustainability practices. Or, it may be that respondents were reluctant to report using synthetic chemicals or products not licensed for cannabis plants. The only other published data on water application rates for cannabis cultivation in California we are aware of is from Bauer et al. , who used estimates for Humboldt County of 6 gallons per day per plant for outdoor cultivation over the growing season . Grower reported estimates of cannabis water use in this survey were similar to this rate in the peak growing season , but was otherwise lower. Due to the small sample size, we cannot say that groundwater is the primary water source for most cannabis growers in California or that few use surface water diversions. However, Dillis et al. found similar results on groundwater being a major water source for cannabis growers, at least in northwest California. If the irrigation practices reported in our survey represent patterns in California cannabis cultivation, best management practices would be helpful in limiting impacts to freshwater organisms and ecosystems. For example, where groundwater pumping has timely and proximate impacts to surface waters, limiting dry season groundwater extraction by storing groundwater or surface water in the wet season may be beneficial ,indoor grow rack though this will likely require increases in storage capacity. The recently adopted Cannabis Cultivation Policy requires a mandatory dry season forbearance period for surface water diversions, though not for groundwater pumping. Our survey results indicate that the practical constraints on adding storage may be a significant barrier for compliance with mandatory forbearance periods for many growers.

More in-depth research with growers and workers is needed to explore the characteristics of the cannabis labor force and the trajectory of the cannabis labor market, especially in light of legalization. Several growers commented on experiencing labor shortages, a notable finding given that recent market analyses of the cannabis industry suggest that labor compliance costs are the most significant of all of the direct regulatory costs for growers . Higher rates of licensing compliance among medium and large farms is not surprising given the likelihood that they are better able to pay permitting costs. Yet, that the majority of respondents indicated they had not applied for a license to grow cannabis, with over half noting some income from cannabis sales, indicates potentially significant effects if these growers remain excluded from the legalization process. More research is needed to understand the socioeconomic impacts of legalization, which likely extend beyond those accounted for in the state’s economic impact analysis, which primarily focuses on economic contributions that a legalized market will bring to the state . Bodwitch et al. report that surveyed growers characterized legalization as a process that has excluded small farmers, altered local economies and given rise to illicit markets. The environmental impacts of cannabis production have received attention because of expansion into remote areas near sensitive natural habitats. The negative impacts are likely not because cannabis production is inherently detrimental to the environment, but rather due to siting decisions and cultivation practices. In the absence of regulation and best management practices based on research, it is no surprise that there have been instances of negative impacts on the environment. At the same time, many growers appear to have adopted an environmentally proactive approach to production and created networks to share and promote best management practices.

Although widely used in discussions regarding alternative marijuana policy regimes, decriminalization is a policy that to date has gone largely undefined in the international policy arena. The term literally implies a reduction in the criminal status of marijuana possession offences; however, numerous countries and sub-jurisdictions that are recognized as having decriminalized marijuana in fact merely reduce the penalties associated with possession of specified amounts. Hence, the term marijuana depenalization has evolved in the scientific literature as a more accurate term reflecting the diversity in policies that exist across countries . Decriminalization, nonetheless, remains a common term used in policy discussions and debates. The ubiquitous use of the term decriminalization does more than obscure meaningful policy differences that exist across countries; it has led to the development and interpretation of policy research that is myopically focused on evaluating the impact of a single dichotomous indicator that is inconsistently defined within and across countries . Thus, it is not surprising that the literature does not provide a clear, consistent conclusion regarding the impact of decriminalization on marijuana use, its harmful consequences, and arrests when these different studies are in fact evaluating different policies. Although all developed countries today prohibit in some fashion the possession, use, cultivation, distribution and/or sale of marijuana and marijuana products, the countries differ tremendously in the types of behaviours that are allowed, the resources devoted to enforcing the laws, the penalties that are imposed on those who break these laws, and their citizens’ knowledge of these policies. Variations in laws, how they are enforced, and the penalties imposed together determine the policy and the public’s understanding of the policy . Hence, those interested in evaluating the impact of specific policies like marijuana decriminalization need to consider more than just the law and a simple binary label for its penalty structure. They must also consider how and to what degree specific policies get enforced in relevant jurisdictions.

This paper provides a framework for understanding what decriminalization means within the broader context of depenalization. To illustrate these concepts, it provides a detailed discussion of a range of depenalization policies observed in developed countries, highlighting for each country a distinct issue that influences how the policy is implemented and its potential impact. Those interested in analyzing or evaluating the impact of these policies can then use this information to better frame analyses so that policies can be evaluated and compared in a more meaningful way. The paper then demonstrates the problem of using a simple dichotomous indicator, such as “decriminalization”, to differentiate policies within a single country using the United States as the example. It shows that presumed differences in knowledge and enforcement of these laws, factors that should be related to a policy of decriminalization, are not consistent with the current labels that have been given to specific states. Decriminalization and depenalization are both terms that represent a range of policies targeting marijuana users in countries where the supply of marijuana for the purpose of recreational use is statutorily prohibited.Hence, these policies do not relate to how the suppliers of marijuana get treated in specific countries. They only differentiate how those caught in possession get treated.Just as apples are a type of fruit, decriminalization is a specific type of depenalization policy. In this paper, depenalization refers to any policy that reduces the penalties associated with possession or use of marijuana. For example,indoor farming equipment policies that retain the criminal status of possession offences but remove or reduce the amount of incarceration imposed as a penalty would be examples of depenalization policies. Decriminalization, on the other hand, refers specifically to depenalization policies that change the criminal status of possession offences from that of a crime to that of a non-criminal offence. Because penalties are usually graduated with the level of crime, a change in the criminal status of an offence will also imply a reduction in the level and type of penalties imposed with that offence, which is why decriminalization policies may be viewed as a special form of depenalization policies. A country that is interested in reducing the criminal justice burden associated with marijuana possession offences could do so in one of at least two ways: retain the criminal status of the offence, but remove any jail time imposed for these offences , or eliminate the criminal status of the offence, which will also eliminate the jail time imposed with this offence .The first method results in an incremental reduction in the burden for the criminal justice system mainly due to reduced incarceration costs, as court resources may still be required to adjudicate cases depending on the legal structure of the jurisdiction. The second method also generates savings due to incarceration, but may produce larger savings if the resources involved in enforcing and processing civil offences are less intensive than those used to enforce and process criminal offences. If this is not the case, then the non-incarceration savings associated with a change in the criminal status of marijuana would simply reflect a redistribution of these costs from the criminal justice system to another government agency.

Fundamentally, the primary difference between these two methods has to do with the outcome for users. Although the specific penalties imposed on users in each of these cases could be structured identically , depenalization retains the criminal status of the offence while decriminalization does not. The importance of a criminal charge depends on the jurisdiction. In some jurisdictions, criminal charges can influence an individual’s ability to obtain and/or retain work, student loans, and public assistance; hence decriminalization can substantially reduce the personal cost associated with getting charged with possession offences. In other, more rehabilitative jurisdictions, criminal charges do not impose these sort of additional personal burdens.There are a variety of different depenalization models that have been adopted in developed countries. Even within specific countries, important variations to the model can exist. Many countries have adopted a policy of “partial depenalization,” in which the penalties for individual users vary on the basis of the quantity of marijuana that they possess and their number of prior offences. For example, first-time offenders who are caught in possession of small amounts of marijuana might receive civil penalties while those caught in possession of larger quantities or are repeat offenders may face criminal charges. Variants of this policy are seen in Australia, Germany and the United States. Other countries have adopted a policy of “full decriminalization,” where the simple possession or use of any amount of marijuana is not a crime regardless of the number of prior offences. These offences remain illegal but have civil sanctions, typically involving mandatory treatment and a fine. Examples of European countries that have adopted policies of full decriminalization include Italy, which initially adopted its policy in 1975 and reinstated it after a brief period of re-criminalization from 1990-1993, Spain, which adopted its policy in 1983, and Portugal, which only recently adopted its policy in 2001.The Netherlands represents the single biggest outlier to marijuana policy models experimented with thus far, as it is the only country that has allowed a small, regulated market to develop. Even in this case, however, the market is severely limited and stiff penalties remain for individuals caught in possession of large quantities of the drug.Since 1986, the goal of Australia’s national drug strategy has been to “minimize the harmful effects of drugs on Australian society” . Efforts to achieve this goal include the provision of education, a significant expansion of treatment and the collection of national data on drug use and drug-related harms . In the Australian Federal system, states and territories are responsible for enacting legislation and implementing drug policies while the Federal government can influence national policy by tying funding for drug programs to compliance with broadly agreed national goals. Consequently, although harm minimization has been the national drug policy goal, there has been no uniform approach to marijuana and several Australian states and territories have experimented with their own marijuana policies . Since the mid- 1980s, five Australian territories have replaced the criminal penalties associated with minor marijuana offences with administrative fines . South Australia was the first to adopt the Cannabis Expiation Notice system in 1987, eight years after the South Australian Royal Commission into the Non-Medical Use of Drugs recommended that marijuana use not be treated as a criminal offence . In 1992 and 1996, the Australian Capital Territory and Northern Territory, respectively, adopted similar systems. Western Australia has just recently made the change in 2003. Other states in Australia have retained the criminal status of these minor marijuana offences, although diversion to education and treatment are now the most common outcome for first offenders in all states.

Gender identity was collapsed into a 3- level categorical variable; transgender and non-binary were recoded to “self-described.” Additionally, I controlled for sexual orientation as a binary variable: lesbian, gay, bi-sexual, or queer and heterosexual. Lastly, there were three variables measuring employment included in the analysis. Employment status was treated as a dichotomized variable with full-time scored as one and part time scored as zero. Employment tenure in cannabis was also treated as a dichotomous variable to in order to gauge seniority in the industry, pre-legalization of recreational cannabis. Employment tenure in the cannabis industry less than two years was scored as zero, and employment tenure longer than two years was scored as one. Respondents chose one of four options, “less than 6 months” , “6 months to 1 year” , “1 year to 2 years” , and “more than 2 years” . Survey data were analyzed using the statistical program, STATA version 16. Univariate analysis was initially conducted to identify observations with missing data and assess demographic information of the sample. Bivariate analyses, using chi-square, were conducted to investigate the relationships between the three dimensions of sexual harassment and independent variables. Significance was assessed at an alpha level equal to 0.05. Multivariable linear regressions were used to assess relationships with frequency of harassment for the 3 sub-scales and the independent variables. Significance for the logistic regression models was also assessed at an alpha level equal to 0.05. Interviews were transcribed by and coded using Dedoose version 8.3.17.

All interviews were coded twice in order to develop and solidify the codebook. Interviews were analyzed using a deductive approach and thematic content analysis to identify salient responses to organizational risk factors of sexual harassment. Table 3 captures frequency, distribution and Cronbach alpha scores for sexual hostility reported by participants. The most frequent item reported was listening to verbal remarks of a sexual nature at an average frequency of 1.47,horticulture solutions representing an occurrence of once to one or more times a month. Respondents least frequently experienced sexual hostility in the form of persistent and unwanted invitations for discussions of a sexual nature. The average frequency for this item was 1.09. In other words, amongst the study sample, workers experienced harassment in this form on average once in the last 12 months. Unwanted sexual attention was, overall, the least common dimension of sexual harassment experienced by respondents, as demonstrated in table 1. The most frequent item reported in this particular category was uninvited touching, experienced less than once by the entire study sample . The item least reported was being witness to obscene images in the workplace . For bivariate and multivariate analysis, items two and three were removed from the dimension of unwanted sexual attention as they had the lowest response rates, and the highest Cronbach alphas, 0.31 and 0.39, respectively. Although the surveys served as the primary source of data for this study, in-depth interviews were conducted in order to provide more descriptive and clarifying insights into the context of sexual harassment that occurs in dispensaries. I was particularly interested in learning from workers how organizational factors may exacerbate experiences of harassment or serve as protective factors. This information was not collected through the survey as it was more exploratory in nature and hearing from workers directly would offer the most accurate insight. Themes of organizational risk factors were drawn from the data by closely examining examples of harassment described by workers.

Their responses often did not focus on the details of the incident itself but its antecedents and consequences. Additional themes captured from the interviews included apathy towards experiences of harassment and a desire for union led training focused on worker’s rights and de-escalation tactics. Although being a victim of harassment was not a requirement for participating in the interviews, all workers described varying levels of experience with sexual harassment in their work environment. Experiences ranged from personally being a target of harassment, witnessing their co-workers being harassed or learning about instances through co-workers. Among the interviewees, two identified as men, and the rest as women . The age of interviewees ranged from 27 to 32 years of age. All interviewees, except one, had previous experience in illegal dispensaries as well as non-union represented shops. This is important to note as respondents often used their past work experiences as a point of reference for describing their current workplace as well as recent experiences with harassment and their company’s responses. The names of workers have been altered in order to protect the anonymity and confidentiality of respondents. Similar to the survey results, interviewees most often cited customers as the primary sources of sexual harassment in their workplace followed by co-workers and the occasional manger. Perpetrators were also often described as men and experiences with harassment ranged from verbal being the most common form experienced to explicit exposure and physical groping in the workplace. Verbal harassment experienced by workers was often in the context of customers repeatedly flirting with them or being “overly nice,” to the point where it made them uncomfortable during an interaction. Many of these experiences were shaped by their organization’s approach to sexual harassment as organizations are responsible for protective measures that influence a worker’s capacity to confront perpetrators in their work environment.This exploratory study sought to shed light on the issue of sexual harassment in retail store fronts of the cannabis industry as a newly legalized and emerging industry. Findings from this studied aligned with previous research documenting the high prevalence of sexual harassment in other retail and service sector industries .

Of the 117 study participants, 63, 68, and 46% reported experiencing at least one instance of sexist hostility, sexual hostility and unwanted sexual attention, respectively, in their place of work during the past 12 months. Although conducting a comparative analysis between the between prevalence of sexual harassment in cannabis dispensaries and other retail and service industries goes beyond the scope of this study, past literature on harassment in retail provides a reference point for responding to hypothesis one. For example, a study investigating sexual harassment in the restaurant industry found 50% of women and 47% of men experienced scary or unwanted sexual behavior while at work . While the two studies may vary in their methodologies and exact study population, they reach the same conclusion. Sexual harassment is an occupational hazard of retail and service sector industries. Therefore, a cursory comparison suggests harassment in the cannabis industry is equal, if not more prevalent than in other comparable industries. Studies regarding hazards of the retail and service sector industries also point towards customer sexual harassment as the specific context of harassment in retail fronts . The combined results of the multivariate analyses revealing gender identity to be a significant predictor of harassment, and the majority of perpetrators reported to be customers in this study highlights the harassment of women identifying bud tenders from customers as the specific workplace issue needing to be addressed. Furthermore, although only the bivariate analysis for sexual hostility revealed gender identity to be significantly associated with experiencing specific sub-scales of sexual harassment , results from the multivariate analysis,grow benches confirmed hypothesis 2a; gender identity is a significant predictor of all three sub-scales of harassment. Women were more likely to experience a greater frequency of harassment than the men in the workplace. This finding aligns with the literature on sexual harassment in the workplace, confirming women as the primary targets and victims of sexual harassment . These findings were also triangulated through interviews as sexual harassment was always discussed in the context of a female bud tender targeted by customers, co-workers and mangers alike. Only models one and two of the multivariate analyses alluded to hypothesis 2b regarding the racial and the ethnic differences in the likelihood to experience harassment. Model one predicting all form of sexual harassment and model 2 predicting sexist hostility indicated Black respondents experienced a greater frequency of harassment than White respondents. However, this finding was not supported by interview data as workers never revealed the race of the victims targeted for sexual harassment. This may be because they were not explicitly prompted to do so or because they did not believe the race of the victim to be a risk factor. For this particular thesis, the findings on race and ethnicity are inconclusive, however, future studies may seek to investigate how the actions taken to address sexual harassment may vary by the racial and ethnic background of the victim. We know from previous studies investigating sexual harassment that it is often enacted concurrently with racial harassment as a manifestation of power and dominance against minority groups .

Hypothesis 2c was confirmed through both bivariate and multivariate analysis, suggesting LGBQ individuals face substantially greater risks of experiencing sexual harassment in terms of both prevalence and frequency compared to heterosexual individuals. This finding is supported by past literature indicating sexual minorities are more likely to experience sexual harassment than their heterosexual counterparts throughout their lifetime . Although workplace protections for LGBQ individuals have increased in recent decades, this study, alongside others documenting discrimination, harassment and assault of the LGBQ community in work environments , demonstrates the continued need and obligation of employers to prevent the victimization of LGBQ workers. It should be noted that the interviews also did not reveal a connection between sexual orientation and sexual harassment as the primary goal of the interviews was to investigate organizational risk factors. Because previous studies have identified a relationship between workplace policies and the actions workers take to address sexual harassment , I investigated the possible linkage between a worker’s awareness of their employer’s policies to protect them from harassment and the likelihood to report such experiences. My prediction in hypothesis 3a of a negative relationship between the number of policies recalled and the likelihood to experience harassment was not supported by either bivariate or multivariate analysis. Quantitative analysis suggested there was no significant relationship between the number of policies recalled and the likelihood to experience harassment nor the frequency of harassment. However, qualitative results showed workers did feel workplace policies directly affected their likelihood to experience harassment while working. Specific policies described were policies on banning customers and how different stores decided to check the identification of customers which could leave workers in vulnerable positions if left alone with a customer. The conflicting results may be explained by a distinction between policies intended to shape retribution of harassment and policies that indirectly create opportunities for harassment to take place. The latter is more difficult to capture through surveys as the investigator has to have a preconceived notion of what to ask, thus highlighting the benefits of conducting mixed methods studies, particularly in new and understudied environments. In response to research question four, results from the qualitative interviews specifically highlighted tip systems and working in isolation as organizational risk factors for experiencing harassment. Tips in particular have previously been cited in occupational research as a risk factor for harassment as they incentivize workers to sexualize themselves and tolerate abuse from customers for their income . Responses by managers was a common theme discussed by workers as managers have the direct ability to ban customers based on inappropriate behavior and were often the first point-of-contact for workers to report an experience of harassment. The risk of continued harassment is exasperated by apathetic management teams who were described as prioritizing customer satisfaction over workers’ safety. Workers also illustrated the unique history of cannabis as a heavily sexualized industry whose legacy continues to permeate the industry today and negatively impact worker’s experience with sexual harassment. According to interviews, workers believed that customers either could not or refused to distinguish legally operating dispensaries from trap shops where women were explicitly used as props to sell product. The lack of distinction encourages the entitlement customers feel towards exploiting cannabis workers without repercussions. Interview results presented a paradox within the cannabis industry in which legalization introduced new protections to workers while simultaneously ushering in the corporate model of the “customer is always right,” which previous studies highlight as a detriment to the ability of workers to protect themselves from threatening customers . Furthermore, regarding research question five, data indicated workers were most interested in sexual harassment-based training for all workers, managers and supervisors as well establishing and publicizing clear policies on harassment. Findings from the survey were triangulated by interview results.

The project is led by Bonnie Halpern-Felsher, a professor of pediatrics at Stanford University and Mariaelena Gonzalez, assistant professor in public health at UC Merced. According to NCPC Director and UC Merced Associate Professor Anna Song, the researchers intend to provide data to counties that will allow them to make informed decisions about policy. Song notes that the counties in the study area are very different from, say, the Bay Area or Southern California, so state-level data isn’t adequate for formulation of local tobacco and cannabis policy. Song reports that the center’s work will fill gaps in knowledge about cannabis intake behavior; epidemio logical data is spotty, she says, because many people won’t admit to engaging in behavior that has historically been illegal and continues to be federally illegal. The researchers are also keen to understand the interconnections between tobacco and cannabis — emerging data indicates that perceptions of tobacco risk are related to perceptions of cannabis, and the relationship between the two may affect individuals’ future tobacco use. “These are the things we are trying to disentangle,” Song says. The center was founded with a $3.8 million grant from the Tobacco Related Disease Research Program, a state initiative administered by the UC Office of the President,rolling grow tables which dispenses funds derived from the Tobacco Tax Increase Initiative, a proposition approved by California voters in 2016.Cannabis institutes at three UC campuses in Southern California — UC San Diego, UC Irvine and UC Los Angeles — conduct research on the health effects and medical uses of cannabis and its derivatives. But they differ greatly in their approach. The UC Irvine program brings together medicine and law. The UCLA program has set itself the ambitious interdisciplinary task of exploring how cannabis affects society along the medical, legal, economic and social dimensions.

The UC Center for Medicinal Cannabis Research at UC San Diego, the oldest of the three institutes, was established when California Senate Bill 847 enabled UC to establish a program to “enhance understanding of the efficacy and adverse effects of marijuana as a pharma cological agent.” Today, the center’s cannabis research covers a broad range of clinical conditions such as neuropathic pain, autism, bipolar disorder and early psychosis — as well as public safety issues surrounding the use of cannabis and cannabinoids. A notable current CMCR study, authorized by the 2015 Medical Marijuana Regulation and Safety Act, seeks to better understand the effect on driving of THC. CMCR Director Igor Grant describes the study as “one of the first in the United States that looks in great detail into different dosages of THC and their ef fect on driving.” Each research day begins with study participants — already experienced with cannabis — entering driving simulators to undergo driving as sessments. Participants then consume THC in specified doses and continue over the course of the day to undergo driving assessments. Meanwhile, their bodily fluids are drawn over the course of several hours. The study seeks to determine how multiple dosing strengths of cannabis affect driving and for what duration driving impairment continues after cannabis use. The research also seeks to determine if saliva or breath tests can substitute for blood samples in determining cannabis intoxication and if sobriety tests administered with iPads can supplement standard field sobriety tests. The study is led by Thomas Marcotte, a professor of psychiatry at the UCSD School of Medicine. Another notable CMCR study, tentatively set to begin at the end of the summer, concerns autism. The research, which includes both a clinical trial and a basic science component, investigates the effect of CBD on severe autism spectrum disorder, a condition that affects one in every 68 U.S. children.

In the clinical trial — overseen by Doris Trauner, a professor of neurosciences and pediatrics at UCSD — researchers will ad minister oral doses of CBD or a placebo to 30 children who have been diagnosed with moderate to severe autism. CBD interacts with the endocannabinoid system, a network in the human body that regulates various physiological and cognitive processes. Researchers will attempt to determine whether CBD is safe for the study population to use, whether it addresses their symptoms, whether it alters neurotransmitters or improves brain connectivity, and if so, how. In the basic science component of the study, re searchers will use cells from the skin and blood of participants and, in Grant’s words, “re-engineer these cells to be neurons — to create little brain organoids, if you will.” This feat of re-engineering will allow researchers to observe how the cells function and, if CBD has benefited the subjects of the clinical trial, to investigate the associated mechanism of action. The study will be conducted with funding from the Wholistic Research and Education Foundation. Grant notes that Proposition 64 allocates $2 million annually to the CMCR. The center intends to use the funding partly to support its core facility and partly to fund small-scale pilot studies that might be conducted at the center itself, at other UC campuses or at campuses of other universities in California.Amuch newer entrant into medical cannabis re search is UC Irvine’s Center for the Study of Cannabis . As an interdisciplinary venture involving UC Irvine’s School of Medicine and School of Law, the center includes basic medical science, clinical science and jurisprudence in its purview. Daniele Piomelli, di rector of the center — as well as a professor of anatomy and neurobiology at the UC Irvine School of Medicine — calls cannabis “a quintessential multidisciplinary problem.” Because much existing cannabis law was written when medical knowledge about cannabis was scarce, he says, new knowledge to underpin new legislation is urgently needed. Piomelli further argues that because cannabis en compasses, for example, commercial and agricultural dimensions, researchers across disciplines must engage with each other to find realistic solutions to cannabis-related problems. “If medicine and science and law don’t talk to one another,” he says, “we’ll never have sensible legislation.”

In that spirit, the center has two directors — Piomelli representing the medical side of the interdisciplinary undertaking and Robert Solomon, a clinical professor of law at UC Irvine School of Law, representing the legal side. About 30 faculty members across law and medicine are involved in the center’s work. The centerpiece of the CSC’s work so far is an ongoing preclinical study called Impact of Cannabinoids Across the Lifespan. Piomelli, who directs the study while a team of UC Irvine principal investigators conducts the bulk of the research, characterizes it as a broad research project with many components, from which a stream of independent discoveries and publications is expected over the next 3 or 4 years. Piomelli reports that the study’s main purpose is to study THC’s effect on adolescents — and particularly on the adolescent brain. The human brain routinely produces neurotransmitters known as endocannabinoids — molecules, similar to cannabis derivatives, that are important in learning, memory and experiencing emotion. The key questions that the study addresses are these: Does exposure to THC, in a persistent way, change the brain’s endocannabinoid system? If so, what changes at the cellular and molecular level explain the alterations? Does exposure to THC during adolescence carry lasting implications for learning and emotion? The study has received a $9 million Center of Excellence Grant from the National Institute on Drug Abuse.Another new entrant into cannabis research is the UCLA Cannabis Research Initiative, founded in 2017 with a broad remit — “to understand how cannabis affects bodies, brains and society.” The initiative, encompassing an interdisciplinary team of 40 faculty members from 15 university departments, aims to function as an education, research and service organization that leads public discussions of cannabis, policy and health. The initiative got its start in the months before Proposition 64 was approved by voters. According to Jeffrey Chen, the initiative’s director, leadership at the Semel Institute for Neuroscience and Human Behavior anticipated that legalization would soon create the world’s largest market for recreational cannabis — and that California and particularly Los Angeles would “play an outsize role in establishing normative behaviors” around cannabis. Los Angeles, in Chen’s view,growing rack has become the world’s cannabis capital overnight. He and his colleagues hypothesize that, given the city’s status as a major tourist destination and an exporter of culture, “what happens in Los Angeles is very likely to be transmitted around the world.” So far, Chen says, the initiative’s research remains mainly oriented toward health-related issues. One study — soon to start, and led by Kate Wolitzky-Taylor, an assistant clinical professor in UCLA’s Department of Psychiatry and Bio-behavioral Sciences — seeks to develop and evaluate a behavioral treatment for young adults who exhibit cannabis use disorder and who use cannabis to cope with anxiety, depression and the like.

Cannabis, according to the researchers, is the most commonly used drug among young adults, and it can be harmful when its use qualifies as a “maladaptive way” of contending with negative experiences. Wolitzky-Taylor reports that the research project is a randomized clinical trial focusing on participants’ reactions to the anxiety and depression that might lead them to use cannabis. The treatment, she says, will draw on strategies such as “mindfulness, cognitive reappraisal skills, problem solving and … gradual exposure to distressing but objectively safe stimuli.” The treatment was developed in an iterative manner — an early version has already been tested with a small group of patients and further refinements may be made after the clinical trial is complete. The research is funded by a 3-year, $450,000 grant from the National Institute on Drug Abuse. Individuals with cannabis use disorder, if they are 18 to 25 years old, are encouraged to email the project’s coordinator, Nick Pistolesi , regarding participation in the study. A second example of the initiative’s work is de cidedly nonmedical. Brett Hollenbeck, an assistant professor of marketing at the UCLA Anderson School of Management, analyzed — along with Kosuke Uetake of Yale University — a large dataset of cannabis transactions in the state of Washington to learn about firm and consumer behavior in legal cannabis markets . Their goal was to provide policymakers, including in California, information useful for optimal development of cannabis taxation and regulation — optimal in the sense of maximizing tax revenues, safeguarding public health and discouraging a black market for cannabis. Washington created a legal framework for growing and selling cannabis in 2012. Legal sales began there in 2014. Since then, every cannabis transaction in the state has been recorded in an administrative dataset. The re searchers used the data to model consumer demand for cannabis products and measure price elasticity. Their analysis, covering the period from November 2014 to September 2017, indicates that Washington’s strict cap on cannabis retailers — some 550 are allowed in the entire state — has permitted retailers to command high prices and behave like local monopolies. The researchers report that when prices for regulated cannabis rise in Washington, consumers often switch to cheaper cannabis alternatives available from regulated retailers, rather than seeking out black market cannabis. Indeed, the researchers argue that Washington’s 37% sales tax rate for cannabis, though it appears high, does not drive down tax revenue, and in fact the state could generate higher revenue by raising the tax rate to 40% or higher. Further, the researchers calculate that Washington could substantially increase its revenue if it acted as the state’s sole cannabis retailer, as it did for alcohol sales until 2012, and could do so without causing an increase in cannabis prices.UC Riverside, though it has established no dedicated cannabis program, will soon host cannabis research for the first time. Nicholas DiPatrizio — a UC Riverside assistant professor in the School of Medicine’s Division of Biomedical Sciences who is newly equipped with a DEA Schedule I license — is set to begin re search investigating the effects of long-term cannabis use on metabolic diseases, including type 2 diabetes. DiPatrizio’s lab, using technologies such as tandem mass spectrometry, will study how cannabis use affects glucose homeostasis in wild-type mice — and will also investigate whether long-term cannabis use is sometimes associated with positive health outcomes such as increases in high density lipoproteins . DiPatrizio’s research has received more than $700,000 in funding from the Tobacco-Related Disease Research Program, the same entity that provides funding for the UC Nicotine and Cannabis Policy Center at UC Merced.

Principal neurons in the hippocampus and cerebellum use endocannabinoids to carry out a signalling process that is analogous in mechanism, but opposite in sign, to DSI, called depolarization-induced suppression of excitation. Like DSI, DSE is induced by neuronal depolarization, it consists of a transient depression in neurotransmitter release, and it requires a retrograde endocannabinoid messenger. But unlike DSI, DSE targets glutamatergic rather than GABA axon terminals, and results therefore in reduced excitatory input to the affected cell108 . Do DSI and DSE occur simultaneously in a single neuron and, if so, how are they coordinated? In cerebellar Purkinje cells, the two opposing phenomena can be elicited by similar stimulation protocols and so are likely to coexist. Although they might be topographically segregated along the longitudinal axis of the neuron, the significance of their coexistence is not known. On the other hand, in the hippocampus, the induction of DSE requires longer periods of depolarization than does DSI, and its magnitude is smaller. This could be explained by the lower sensitivity of glutamatergic terminals to endocannabinoid activation, which would indicate that a switch from DSI to DSE might occur when endocannabinoid concentrations at hippocampal synapses attain a certain threshold value. Again, the role of such a switch, if any, is undefined.Inhibition of glutamatergic neurotransmission by cannabinoid agonists has been documented in a variety of brain structures besides the hippocampus and cerebellum. These include the prefrontal cortex, amygdala, nucleus accumbens,trimming cannabis striatum and substantia nigra pars reticulata. Whether such effects reflect the existence of regional DSE-like phenomena is an important question that remains to be addressed.The ability of cannabinoid agonists to inhibit the release of neurotransmitters in the CNS is not restricted to glutamate and GABA.

A particularly convincing case has been made for acetylcholine, the release of which is reduced by cannabinoids both in vitro and in vivo, and is enhanced by inactivation of CB1 receptors. Acetylcholine release in the neocortex and hippocampus facilitates learning and memory, so disruption of this facilitatory process might contribute to the detrimental effects of cannabinoid drugs on cognition. Cannabinoids also reduce the release of the biogenic amines noradrenaline and serotonin136, and the neuropeptide CCK-8 . Analogous, but as yet unknown, actions on peptide release in the hypothalamus might underlie the central involvement of the endocannabinoid system in the secretion of stress hormones and regulation of appetite .High-frequency stimulation of cortical fibres that innervate the striatum leads to a form of persistent synaptic plasticity called long-term depression. Like its hippocampal counterpart, striatal LTD is induced when Ca2+ enters the somatodendritic compartment of projection neurons, and is expressed as a decrease in glutamate release from axon terminals of corticostriatal fibres. These analogies with DSI are suggestive of an endocannabinoiddependent process, an idea that has been confirmed experimentally. Striatal LTD is absent in CB1 -deficient mice and is blocked by the CB1 antagonist rimonabant; moreover, it is induced in a CB1 -dependent manner by anandamide or AM404 . A similar form of endocannabinoid-dependent LTD can be produced by low-frequency stimulation of cortical fibres that innervate the nucleus accumbens. Despite differences in induction protocols in vitro __ one is produced by high-frequency,the other by low-frequency, stimulation __ striatal and accumbal LTD could serve complementary functions. For example, they might both contribute to habit formation, a type of striatumdependent learning that underlies the development of motor skills and is implicated in the pathogenesis of drug addiction. Notably, cannabinoid drugs provoke in rats a relapse to drug-seeking behaviour after prolonged periods of abstinence, whereas CB1 antagonists attenuate the relapse induced by drug-associated cues.

These findings have provided the rationale for current clinical trials of rimonabant as a treatment for alcohol and tobacco addiction .In the hippocampal CA1 field, stimulation protocols that cause long-term potentiation at excitatory synapses onto pyramidal neurons simultaneously produce LTD at adjacent inhibitory synapses. Like striatal LTD, I-LTD might be endocannabinoid-mediated, but its molecular mechanism seems to be remarkably different. According to a current model, glutamate released from excitatory terminals activates metabotropic receptors on dendritesof pyramidal neurons, which in turn stimulates 2-AG formation through the DGL pathway. The newly formed endocannabinoid can then depress GABA release by engaging CB1 receptors on inhibitory nerve endings. How this long-lasting disinhibitory process interacts with other forms of endocannabinoiddependent plasticity and contributes to the overall effects of cannabinoids on hippocampus-dependent learning will surely be the object of future discussion and experiments.We have learned that the brain contains multiple endocannabinoid lipids, and that neurons produce them using membrane constituents as starting material. We have also discovered that these lipids behave differently from traditional transmitters. Rather than being secreted from vesicle stores, they are released in a non-synaptic manner and combine with cannabinoid receptors located near their sites of synthesis. Despite this progress, many crucial pieces of the endocannabinoid puzzle are still missing. For example, we need to map the neuronal circuits that produce anandamide and 2-AG, and this requires in turn the molecular characterization of the synthetic enzymes involved. We also need to understand how classical neurotransmitters and drugs of abuse interact with these circuits, and to explore the functional consequences of such interactions. Last, but not least, we must continue to develop selective pharmacological tools that target not only the different cannabinoid receptor subtypes, but also the mechanisms of endocannabinoid synthesis and deactivation. Although these tasks are far from trivial, what is already known about the endocannabinoid system indicates that they are well worth pursuing.

The use of cannabis by older adults increased sharply over the past two decades in the United States 1 with the legalization for medical and recreational purposes in many states. While there is limited evidence that cannabis may be helpful for specific conditions,older adults are increasingly using cannabis to treat a wide range of symptoms and conditions, including recreationally,and their perceived risk of regular cannabis use is decreasing.However, older adults, due to the physiological changes related to aging, medication use, and increased comorbidity, are at high risk for adverse effects of any psychoactive substance, including cannabis.Cannabis is associated with a range of acute adverse effects that can require emergency care and detrimental for older adults, who are already the most frequent utilizers of the emergency department .Cannabis can slow reaction time and impair attention,leading to injuries including falls. Cannabis use is also associated with increased risk for psychosis, delirium, paranoia, and other acute psychiatric symptoms.The use of cannabis can cause acute physiological changes that can exacerbate cardiovascular and pulmonary diseases.Additionally, there are potential drug interactions that can lead to adverse effects and cannabinoid hyperemesis syndrome is related to cannabis use.Many of these complications have resulted in the need for acute clinical care in EDs.Cannabis-related ED visits have increased in the US, with one study finding a 12.1% average annual increase from 2006 to 2014 in cannabis-associated ED visits.This included a sharp increase among adults aged ≥65 who, while having lower overall rates of cannabis associated ED visits compared to younger adults, had the largest one-year increase from 2017 to 2018 compared to all other age groups.A study focused on adults aged ≥50 found that cannabis use increased the likelihood of ED visits due to injury.Despite the increase in cannabis use and its potential for adverse effects requiring emergency care in this age group, there has been little research focusing on cannabis-related ED visits among older adults. In 1996, California became the first state in the country to legalize medical cannabis and in 2016 passed Proposition 64, which legalized the use, sale, and cultivation of recreational cannabis.We aim to help fill this knowledge gap by examining trends in the rates of cannabis-related ED visits among older adults aged ≥65 and to examine trends among subgroups of older adults in the state of California.This was a retrospective cohort study of adults aged ≥65 using visit-level data from 2005 through 2019 from all non-federal acute care hospitals across the state of California using non-public data from the California Department of Healthcare Access and Information . All licensed hospitals in California are subject to mandatory reporting of utilization data in a standardized format to HCAI. The number of hospitals with EDs ranged from 316 to 335 facilities during the study period. Data presented in this study represent unique ED encounters from hospitals providing emergency medical services licensed by the State of California,gardening rack which were available in two separate non-public HCAI research data sources: Patient Discharge Data and Emergency Department and Ambulatory Surgery Data . ED encounters resulting in admission to the same hospital are combined with the inpatient record and only reported in the PDD; all other ED encounters are reported in the EDAS. For this study, same-hospital ED admissions from the PDD were combined with ED encounters from the EDAS to construct a complete ED utilization database for analysis including all non-duplicative ED encounters reported to HCAI.

Detailed descriptions of these data sources can be found elsewhere.This study followed the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline for cross-sectional studies. For each calendar year, we determined the number and rate per 100,000 ED visits for overall cannabis-related ED visits among adults aged ≥65 and estimated trends between 2005–2019. We stratified individual trends of cannabis-related ED visits per 100,000 ED visits by age groups , race/ethnicity , sex , and payer/insurance . The Charlson comorbidity index score was calculated with the enhanced coding algorithm provided by Quan et al25 for both ICD-9 and ICD-10 coding and stratified by the following scores: 0, 1, 2, and ≥3. Finally, cannabis diagnoses were divided into three categories: 1. cannabis abuse and unspecified use, 2. cannabis dependence, and 3. poisoning by cannabis, lysergide, and psychodysleptics . Linear trend p-values were calculated for the overall trend and across subgroups. Statistical significance was defined as a p-value <0.05 All statistical analyses were conducted with IBM SPSS Statistics . This study was approved by UCSD’s Human Research Protections Program. Cannabis-related ED visits significantly increased in California among adults aged ≥65 from a total of 366 visits in 2005, a rate of 20.7 per 100,000 ED visits to 12,167 visits in 2019; a rate of 395.0 per 100,000 ED visits , which is an absolute increase of 374.3 and a 1808.2% relative increase. Table 1 presents cannabis related ED visit trends stratified by patient characteristics. There were significant increases for all subgroups. By age group, adults aged 65–74 had the highest rate in 2019 while also having the largest increase in absolute increase compared to adults aged 75–84 and those aged ≥85. Adults aged 75–84, meanwhile had the largest relative percent change with a 2208.3% increase. By race/ethnicity, older Black adults had the highest rate in 2019 and the largest absolute increase compared to older adults of other races/ethnicities. Older males had a higher ED visit rate in 2019 compared to older females although older females had a larger relative percent increase . Older adults without health insurance had the highest rate in 2019 and the largest absolute and relative increases compared to those with health insurance. Older adults with a higher Charlson comorbidity index score also had the highest rate in 2019 and the largest absolute increase compared to those with lower comorbidity scores; however, those with the lowest comorbidity score had the highest relative increase . Finally, the “cannabis abuse and unspecified use” category comprised nearly all cannabis-related ED visits each year with 369.4 per 100,000 ED visits in 2019 with the largest absolute and relative increases compared to the other categories.Cannabis-related ED visits increased sharply in California among older adults over a 15- year period. While there was a significant increase in cannabis-related ED use among all subgroups of older adults, we identified key subgroups with higher rates and larger increases in cannabis-related ED visits . We found that adults aged 65–74, older males, and those with more comorbidities had higher ED visit rates in 2019, while those with marked relative increases included adults aged 75–84, older females, older adults without health insurance, and those with the lowest comorbidity. Older Black adults had the highest rate of ED visits among all subgroups examined during the study period, consistent with a previous study that showed that among older adults who used cannabis, being Black was associated with an increased likelihood of ED visits.

Such tests of complete SOFC systems are both expensive and complex; therefore, novel modeling practices were developed to avoid costly testing. The balance of plant typically includes thermal insulation, pipework, pumps, heat exchangers, heat utilization plant, fuel processors, control system, start-up heater and power conditioning. Arguably, the BOP is the dominant part of the system. The Engen-2500 system includes a host of BOP components that are commonly used to sustain the SOFC operation. More specifically, these BOP components consist of an external reformer, an oxidizer, a heat exchanger, a condenser with a water drain, a desulfurizer, an evaporator, a pump, two blowers, and three valves. For a visual illustration of the Engen-2500 system setup, refer to Figure 22, “Reproduced design schematic for the Engen-2500 system,” in section 4, Experimental Setup and Results. It is important to note that the Engen-2500 was originally designed for CHP applications and therefore the system is currently designed to produce high-quality waste heat so that the end-user can recycle the heat for additional purposes like building heating. Furthermore, only the external reformer, thermal oxidizer, heat exchangers, and blower components were included in the Engen-2500 system model. The additional BoP components such as the valves, pump, desulfurizer, evaporator, condenser, and water drain were not included in the system model in order to significantly reduce computational time and because these components do not have a significant impact on the overall thermodynamics and performance of the system. Its primary purpose is to chemically convert a readily available fuel such as a hydrocarbon fuel into a hydrogen-rich fluid that can be oxidized at the fuel cell’s anode. It also serves to convert fuel or oxidant not consumed at the fuel cell’s anode and cathode into useful energy. A fuel processing subsystem consists of a series of catalytic chemical reactors that convert hydrocarbon fuel into a low impurity, high-hydrogen content gas.

Some of these chemical processes release heat , while others require heat to be supplied . For high-temperature fuel cells,drying weed the required heat may be supplied by the fuel cell itself. The size and complexity of an external fuel processor depend on the type of fuel reformed, whether impurities or poisons need to be removed, and how much reformate needs to be produced. SolidPower’s Engen-2500 system uses an annular external reformer located in the HotBox section of the system and encompasses the oxidizer component. Placing the external reformer in contact with the oxidizer suggests that the heat produced from the combustion of fuel and air within the oxidizer is transferred via conduction across the walls of the oxidizer and to the reformer. The heat transferred from the oxidizer to the reformer functions as the heat input required for the endothermic steam-methane reformation reaction to occur. Reforming hydrocarbon fuel to hydrogen-rich fuel in the Engen-2500 system is accomplished by two subsequent reactions: steam-methane reformation and water-gas shift . Realistically, while fuel cells stacks cannot use all of the fuel in the anode compartment, fuel cell systems are unable to make use of all the fuel provided. Therefore, the remaining fuel that leaves the anode is sent to the thermal oxidizer – where it is usually mixed with cathode off gas – and undergoes combustion to produce heat and clean the anode off-gas emissions. The oxidizer releases the remaining fuel energy of the anode off-gas as heat and reduces the composition of methane and carbon monoxide to satisfactory levels. The Engen-2500 system has three gas streams that enter the oxidizer: extra natural gas, anode off-gas, and ambient air. A valve controls the addition of natural gas to the oxidizer when additional heating is necessary. As mentioned previously, the external reformer encompasses the thermal oxidizer and therefore the heat produced from the thermal oxidizer is used for the endothermic reformation process occurring within the external reformer component. Therefore, the valve controller controlling the input of extra natural gas to the burner must consider the instantaneous degree of heat being provided to the external reformer so that the system maintains a desired external to internal reforming ratio. The anode off-gas has very little heating value because the majority of its composition is steam and carbon dioxide.

Mixing of these three streams is determined by solving the conservation of mass equations to find the molar flow rate and mixed species concentrations. In any fuel cell system, there are process streams that must be heated. The challenge imposed on the system designer is to use the heat available from one stream to heat another in the most efficient way. The gas or liquid to be heated passes through pipework that is heated by the gas or liquid to be cooled. The pipework is generally referred to as a heat exchanger and is a mechanical device that conveys thermal energy or heat from a hot-fluid stream on one side of a barrier to a cold-fluid stream on the other side without allowing the fluids to directly mix. There are many types of heat exchangers such as shell and tube, plate, fin, tubular, regenerative, phase change, and printed circuit exchangers that all use different geometries and physical means of energy transfer. The key features to consider for selecting a heat exchanger are the surface area available for heat transfer, the types of fluids/solids exchanging heat, inlet temperatures and flow rates, and geometric configuration. The heat exchanger design implemented by SolidPower for their Engen-2500 system is assumed to be a typical cross-flow plate and fin heat exchanger. Entering on the hot side is the thermal oxidizer exhaust stream mixed with the cathode outlet exhaust. The combination of these streams carry high quality heat that preheats the ambient air before it enters the cathode. The ambient air is blown through the cold side of the heat exchanger via a blower. The high operating temperatures of SOFC systems melt most common metals, therefore, high temperature heat exchangers are typically manufactured from high temperature stainless steel or ceramic materials, for which the planar configuration is most common. Incorporating a heat exchanger into the model involved discretizing each plate into a specified number of control volumes, referred to as nodes, along the length of the air flow. This gives detailed temperature profiles, and avoids pinch-point limitations of a bulk counter-flow heat exchanger model. Heat exchanger size varies with the number of plates, allowing dimensional constants to remain fixed. This modeling technique gives an approximation of the surface area required to meet the needs of each particular design and scale.

The following energy balance equations are applied to each control volume. The most general function of a condenser is to change the physical state of gas to its liquid state by cooling it. The condenser can be used to capture the latent heat of condensation. In a fuel cell system, a condenser is important for both recapturing heat and recovering liquid water to achieve neutral system water balance. Neutral water balance is achieved when all of the water that is consumed by the system components is produced by other components internal to the system. In other words, no additional water needs to be suppled from an external source. The Engen-2500 system utilizes a condenser at the tail-end of the SOFC system cycle after the mixing of the cathode outlet exhaust and thermal oxidizer exhaust streams flow across the hot side of the heat exchanger. The hot side exhaust is comprised of mostly carbon dioxide and steam, with extremely small concentrations of methane, carbon monoxide, and hydrogen. The high concentration of steam present in the hot side exhaust is mixed with additional ambient tap water via a valve to help reduce the temperature and condense the high steam concentration to liquid water in the condenser. A water drain is included to capture all the liquid water that leaves the condenser. The remaining gases pass through and are emitted into the atmosphere as exhaust. Two blowers are included in the Engen-2500 system to take ambient air and direct it into the system components. One blower provides ambient air to the oxidizer for combustion of the anode off-gas and extra natural gas to produce enough heat for the endothermic external reformer. A second blower provides ambient air to the heat exchanger so that the air can be preheated before entering the cathode of the SOFC stack. Blowers operate much like a compressor, but with a much lower pressure ratio. Both blowers have their own controllers to provide the necessary pressure rise to its specific component. For the blower that directs air to the oxidizer component,vertical growing systems this blower’s controller attempts to regulate the heat produced by the oxidizer such that it maintains a desired external to internal reforming ratio designated by SolidPower. Considering the blower that directs air to the heat exchanger, this blower’s controller simply regulates the air flow required by the SOFC stack to maintain a constant cathode outlet temperature. A simplified thermodynamic analysis was used to analyze the blowers operation. The dynamics of the blowers are assumed sufficiently quick to minimally affect the remainder of the system due to low rotational inertia of the blowers. The blowers are treated as compressors with an isentropic efficiency factor and are provided enough power to generate the necessary pressure gain. The calculation of the necessary power for the blower is performed by applying an energy conservation analysis to the control volume with the following expression accounting for energy lost to inefficiencies and cooling. Sulfur in any form is harmful to the SOFC stack. It poisons the nickel-containing anode and reduces the stack performance. The Sulphur level must generally be below 0.1 ppm to avoid a performance loss. Natural gas and petroleum liquids naturally contain organic sulfur compounds that normally must be removed before any further fuel processing can be carried out. Even if sulfur levels in fuels are extremely low, 0.2 ppm, some deactivation of steam reforming catalysts can occur. The most common desulfurization techniques use conventional sorbents such as activated carbon, alumina and/or zeolites at low capacity.

Another common technique is to use zinc oxide and/or copper oxide at high capacity with hydrogen and an operating temperature >200°C. The latter reactively adsorbs sulfur and is regenerable. Although the specific type of desulfurizer is not explicitly known, it is acceptable to assume the desulfurizer is removing enough sulfur for continuous, unhindered operation of the SOFC system. Fluid systems generally involve a method of increasing the pressure, velocity, and/or elevation of a fluid. This can be accomplished by supplying mechanical energy to the fluid via a pump, fan, or a compressor. Pumps require mechanical work in the form of shaft work produced by an electric motor, which is transferred to the fluid as mechanical energy. There exists only one pump in the Engen-2500 system, the purpose of which is to pump recycled liquid water from the water drain to the evaporator before it enters the external reformer. Throttling valves are any kind of flow-restricting devices that cause a significant pressure drop in the fluid without involving any work. There are three valves included in the Engen-2500 system, the purposes of which are all the same: vary the pressure change of the fluid to increase or decrease thereby influencing the mass flow rate. Two separate valves vary the mass flow rate of methane going to the external reformer and the thermal oxidizer, independently. A SOFC system controller controls one valve to vary the mass flow rate of methane entering the external reformer such that the system maintains a steam-to-carbon ratio greater than two after taking into account the mass flow rate of steam. Fuel flow delay to the fuel cell can be a primary fuel cell transient limitation. In fuel cell systems, the most significant fuel flow delay is due to fuel flow control valves and pressure transients in the fuel processing system. Another system controller controls a second valve that adjusts the mass flow rate of methane entering the thermal oxidizer such that enough methane is being supplied along with air and anode off-gas to produce enough heat through combustion that maintains a designated external to internal reforming ratio. A third system controller simply controls a third valve to adjust the addition of tap water entering the SOFC system in order to maintain a neutral system water balance. To begin the verification process, the most influential piece of information is verifying that the model performance curve matches that of the experimental results.

In an attempt to achieve net zero emissions, tech companies have strongly considered fuel cell technology as a greener and more efficient alternative to energy conversion than the traditional combustion methods of power plants. Over the past several years, the data center industry has experimented with centralized fuel cells through simulation and pilot installations. There are a few reasons to consider fuel cells for data center power production, the first of which is its reliability when connected to the natural gas grid. Reliability of individual fuel cells themselves is mediocre at best; however, when connected to the natural gas grid their reliability improves dramatically since fuel cells can operate indefinitely as long as they are provided sufficient fuel and air. In addition, because data centers will require multiple fuel cell systems, adding a few redundant ones can easily account for any individual fuel cell failures. The reliability of fuel cells is heavily influenced by the reliability of the gas grid, which is known to be high, exhibiting greater than five nines reliability, much higher than three nines for the electric grid. The second benefit is that gas distribution within a data center is much cheaper than the high voltage switch gear, transformers, and copper cables required to connect to the electric grid. If fuel cells are placed closer to the power consumption units , then data centers can easily eliminate the power distribution system, including the backup power generation system. This is highly favorable because the electrical infrastructure accounts for over 25% of the capital cost for state-of-the-art data centers. The third benefit is that fuel cells are environmentally friendly. Although initial phases of introducing fuel cells into the data center would require that they operate on natural gas, even with this source of fuel, fuel cell emissions are much cleaner and far more efficient than those from traditional combustion methods. Carbon dioxide emissions have the potential to be reduced to 49%,heavy duty propagation trays nitrogen oxides by 91%, carbon monoxide by 68%, and volatile organic compounds by 93% when compared with a combustion cogeneration plant.

With respect to architecture, there are several designs for incorporating fuel cells into data centers: at the utility power level, rack level, or server level. The utility power level combines groups of fuel cells to achieve a power rating on the order of megawatts to replace the traditional electric utility power input, therefore disconnecting the data center from the electric grid, or operating in parallel with the grid. The rack level design uses fuel cells with a power rating on the order of kilowatts to power one or a few nearby server racks, eliminating the entire power distribution network within the data center and replacing it with a fuel distribution network . The server level design integrates small fuel cells on the order of watts into the servers, which is similar to the rack level design but eliminates the short distance power cabling needed from the rack level fuel cells to the servers – helping to minimize DC transmission losses. Reliability can be maximized using the server level design because fuel cell failures would only affect a single server; however, it is worth noting that smaller fuel cells may not be as energy efficient and cost effective as their larger counterparts. Microsoft has envisioned a new concept for their data centers, aptly labelled as the ‘stark’ design. They proposed a direct generation method that places fuel cells at the server rack level, inches from the servers. The close proximity allows for the direct use of DC power without the large capital cost, potential for failures, and efficiency penalties associated with AC-DC inversion equipment. As a result, power distribution units, backup power generation equipment, high voltage transformers, expensive switch gear, and AC-DC power supplies in the servers can be completely removed from the data centers. Previous analysis and experiments have shown that low cost, low greenhouse gas, high reliability , and high efficiency can be achieved by using mid-sized fuel cells at the rack level, directly supplying DC power to the servers, and effectively replacing the power distribution system in a data center with a gas distribution network. Data centers are facilities that contain information technology devices used for data processing, storage, and communications in addition to the infrastructure equipment required to operate them as reliably as possible.

The infrastructure equipment typically consists of specialized power conversion and backup equipment and environmental control equipment . Within the data centers, the volume storage servers and cooling system infrastructure are by far the largest consumers of electricity; together they account for over 70% of current energy demand. As servers become more powerful, more power is needed to run and cool them. Therefore, the biggest consumer of square footage in data centers is not by servers but by the power infrastructure. From an outside perspective, Microsoft’s data center in Tukwila, Washington looks like a nondescript sprawl of beige boxlike buildings arranged to be inconspicuous like remote warehouses. Like most data centers, the Microsoft Tukwila facility comprises a sprawling array of servers, load balancers, routers, fire walls, tape-backup libraries and database machines, all resting on a raised floor of removable white tiles, beneath which run neatly arranged bundles of power cabling. To keep the servers cool, Tukwila has a system of what are known as hot and cold aisles where cold air seeps from perforated tiles in front and is sucked through the servers by fans, ultimately expelled into the space between the backs of the racks and ventilated out and away. Tukwila can be thought of as less a building than a giant machine built for computing. Ranging from small computer server rooms to mammoth server farms, data centers now house more than several millions of computer servers. Even more startling is that in 2013 alone, roughly 3 million server rooms used enough electricity to power all households in New York City for 2 years – equivalent to the annual output of 34 large coal-fired power plants. According to a McKensey Quarterly report, the annual CO2 emissions of data centers will reach approximately 1.54 metric gigatonnes by 2020, which could make IT companies among the biggest greenhouse gas emitters. This would be equivalent to the amount of electricity generated by 50 large coal-fired power plants – each with 500 megawatts of capacity – emitting nearly 150 million metric tons of CO2 emissions per year. There continues to be several persisting issues slowing the progress of energy efficiency in data centers: comatose servers, peak provisioning, limited deployment of virtualization technology, failure to power down unused servers, and shortsighted procurement practices.

Fortunately, Microsoft has taken these issues seriously and has worked with vendors to reduce power use when processors are idle. Dileep Bhandarkar, a distinguished engineer at Microsoft who oversaw the company’s server hardware architecture in 2011, says, “It used to be [that] an idle server would be [at] 50% of the power . We’ve pushed that down to about 30%”. Despite this achievement in reducing power consumption of idle servers, many servers remain “comatose” and no longer needed. If half the savings potential from energy efficient best practices are realized, then America’s data center industry could slash their electricity consumption by as much as 40%. In the last decade, there have been dramatic advances in data center design. Previous methods of using outside air directly to cool servers has been replaced by computer room air conditioning systems, evaporative cooling methods have replaced absorption chillers, and power over subscription is used to better utilize power capacity. The data center industry measures their building system efficiency using the power utilization effectiveness measurement. The PUE measurement must consider all the equipment necessary to maintain the daily operation of the data center after receiving power from the utility grid. A diagram of the major components considered in a PUE calculation is shown in Figure 5. A PUE of 2.0 means that for every watt of IT power consumed, an additional watt is required to cool, distribute power to the IT equipment, and operate the data center. A PUE closer to 1.0 means nearly all of the energy is used for computing – the ideal case. Industry-wide,vertical cannabis the PUE ratio between overall facility power consumption and the power used by servers has improved from a 2.0 to a best practice of 1.11. Despite this significant achievement, the fundamental data center power infrastructure, consisting of transformers, power distribution units, uninterruptible power supply systems, and backup generators has changed very little. The power distribution chain starting from the utility grid to the server racks is illustrated in Figure 6. This power system remains necessary to deal with the high-voltage AC power utility grid and its relatively low reliability of three nines . In an attempt to reduce the PUE measurement of Microsoft’s data centers, Microsoft has decided to pursue alternative means of generating power in order to reduce the power infrastructure required to maintain high reliability. According to the United States Environmental Protection Agency , adapting distributed generation methods in data center design could achieve great energy savings, significant environmental benefits, and high power reliability. Therefore, Microsoft has chosen to focus their research on a novel and promising distributed generation technology: high temperature fuel cell systems . They have proposed to place the HT-FCs at the rack level, significantly close to the servers. This new design layout limits the failure domain to just a few dozen servers instead of the entire data center like what would typically occur if the electric grid were to experience failure. Placing the HT-FCs at the rack level would allow Microsoft to eliminate the backup generators, high-voltage transformers, expensive switch gear, transfer switches and AC-DC conversion systems within a data center.

Currently, less than half of the interior square footage within a data center is dedicated to the electrical infrastructure; therefore eliminating this can significantly shrink the physical space requirements. Additionally, shifting the UPS and battery backup functions from the data center into the server cabinet can reduce the power losses from the multiple AC-DC conversions that occur between the utility power grid and the data center equipment . Currently, over 85% of the world’s energy needs are met and will continue to be met in the coming decades through the consumption of fossil fuels . These fossil fuels have become a very reliable fuel resource that is used to produce power through combustion processes , which transforms the fuel’s chemical energy into other forms of energy for everyday use . The relative ease and low cost of producing power through combustion-based processes has made developed and developing countries extremely reliant on the availability and access to the limited fossil fuels on the planet. Yet, the benefits of combustion-based energy generation do not exist without the consequences of harmful criteria pollutant and greenhouse gases emissions. Combustion emissions continue to remain the major source of urban air pollution leading to respiratory health problems and the primary source of greenhouse gas emissions contributing to global warming. Nevertheless, energy conversion and combustion emissions continue to increase simultaneously as the world’s population increases because combustion-based power production is quick and easy to set up compared to alternative methods of energy conversion.As the inadvertent effects of climate change become a very grim reality in this lifetime, great strides have been made for reducing the pollution emitted by combustion sources thanks to scientific and public awareness of federal and state governments. The first major step toward climate change legislation was made when dense visible smog in many of the nation’s cities and industrial centers circa the 1960’s prompted the United States Environmental Protection Agency to pass the Clean Air Act in 1970 at the height of the national environmental movement. With this legislation, the states were now required to adopt enforceable plans to achieve and maintain air quality meeting the air quality standards for the six common “criteria pollutants”. Following with the federal mandate, California implemented the most progressive power generation legislation in 2001 with the introduction of the California Public Utilities Commission , Self-Generation Incentive Program . The SGIP provided incentives to support existing, new, and emerging distributed energy resources, such as wind turbines, recycling waste heat, microturbines, gas turbines, fuel cells, and advanced energy storage systems.

Uncertainty in when, how and where water is being used, however, threatens the security of water rights — particularly when water is substantially over allocated relative to natural supplies. During the 2012–2016 drought, for example, the SWRCB issued notices of curtailment to water rights holders to protect endangered fish species within priority watersheds. Less controversial targeted cutbacks to individuals might have been sufficient if the agency had more accurate information on how water rights were being exercised. As the 2012–2016 drought progressed, flaws in the state’s accounting system for tracking water rights be came more apparent. This study, together with other policy reports , articulated the need for water accounting reforms, raised public awareness and helped to mobilize support for new legislation in 2015 , which significantly increased water-use monitoring and reporting requirements for water rights holders. The new regulations also extended reporting requirements to senior water rights holders , which are among the largest individual water users in the state.The legalization of recreational cannabis in 2016 with passage of State Proposition 64 prompted state agencies to develop new policies to regulate the production, distribution and use of the plant. For example, California Senate Bill 837 directed the SWRCB to establish a new regulatory program to address potential water quality and quantity issues related to cannabis cultivation. The subsequently enacted California Water Code Section 13149 in 2016 obliged the SWRCB,hydroponic drain table in consultation with the California Department of Fish and Wildlife, to develop both interim and long-term principles and guidelines for water diversion and water quality in cannabis cultivation.

As a result, in 2017, the SWRCB adopted the Cannabis Cultivation Policy: Principles and Guidelines for Cannabis Cultivation . The Cannabis Cultivation Policy’s goal is to provide a framework to regulate the diversion of water and waste discharge associated with cannabis cultivation such that it does not negatively affect fresh water habitats and water quality. A key element of the Cannabis Cultivation Policy is the establishment of environmental flow thresholds, below which diversions for cannabis irrigation are prohibited . During the dry season , no surface water diversions are permitted for cannabis cultivation. Diversions from surface water sources to off-stream storage are allowed between Nov. 1 and March 31. However, water may only be extracted from streams when flow exceeds the amount needed to maintain adult salmon passage and spawning and winter rearing conditions for juvenile salmon. Environmental flow requirements for the winter diversion season were determined by an approach known as the Tessmann Method , which uses proportions of historical mean annual and mean monthly natural flows to set protective thresholds. Because flows are not measured continuously in most streams in California , including at most points of diversion, the Cannabis Cultivation Policy instead relies on using the predictions of natural flows from the models described above. Predicted natural mean monthly and annual flows are used by the SWRCB at compliance gauge points to calculate the Tessmann thresholds. Cannabis cultivators seeking a Cannabis Small Irrigation Use Registration permit from the SWRCB are assigned a compliance gauge near their operation and can legally divert water only when flows recorded at the gauge meet or exceed the Tessmann thresholds during the diversion season . The motivation for developing natural stream flow models and data rests on the premise that rivers and streams can be managed to preserve features of natural stream flow patterns critical to biological systems while still providing benefits to human society . For any stream of interest, balancing the needs of humans and nature requires an understanding of its natural flows, whether observed conditions are modified relative to natural patterns and what degree of modification harms its health. As noted in the examples above, this work has both direct and indirect implications for policy and decision-making.

A database of natural stream flows developed by machine-learning models was used to help define cannabis policy to set minimum flow targets — a direct application of the technique. However, this work also influenced policy and decision-making in more subtle ways, including building awareness of shortcomings in the state’s water rights accounting system. This form of engagement with government agencies and the broader public helps define the agenda early in the pol icy-making process , although quantifying the degree to which our research contributed to policy outcomes such as SB 88 is difficult. The future impact of our work on environmental flow management remains unclear, but early engagement with state and federal agencies through the Environmental Flows Work group suggests that our flow modeling tools and data will have an important role in future policy development. Recognizing there are likely other applications for our modeling tools, we have been working to make the data available to the public. Model predictions have now been generated for every stream in California, including values of mean monthly, maximum and minimum monthly flows and confidence intervals for California’s 139,912 stream segments in the National Hydrography Database . A more dynamic spatial mapping tool has been developed to explore the data in individual rivers, watersheds or regions. An online interactive visualization tool is also available that allows a user to select one or several stream gauges and generate the corresponding hydrograph of observed and expected monthly flows . An immediate next step for this project is to expand the natural flows dataset to include predictions of additional stream flow attributes that are relevant to environmental water management. This will support the Environmental Flows Work group’s goal of defining ecological flow criteria in all rivers and streams of the state and can help inform a variety of programs including, for example, water transactions and stream flow enhancement programs.

Other direct applications of the natural flows data may be in hydropower project relicensing, which requires consideration of environmental flow needs. In addition, under the Sustainable Groundwater Management Act , groundwater sustainability agencies are required to avoid undesirable rsults including depletions of interconnected surface water that have significant and unreasonable adverse impacts on beneficial uses of the surface water. Because environmental flow criteria have not been established for most streams in California, GSAs are rightfully confused as to the standards they are expected to meet. Statewide environmental flow criteria may help to define management targets required for SGMA implementation. Looking to the future, society will continue to face challenges in balancing environmental protections with the demands of a growing population. Tools that make use of long-term monitoring data and modern computing power, such as the models described here, can help inform policy and management intended to achieve this balance.Future high-performance computing systems are1 driven toward heterogeneity of compute and memory resources in response to the expected halt of traditional technology scaling, combined with continuous demands for increased performance and the wide landscape of HPC applications. In the long term, many HPC systems are expected to feature a variety of graphical processing units , partially programmable accelerators, fixed-function accelerators, reconfigurable accelerators such as field-programmable gate arrays, and new classes of memory that blur the line between memory and storage technology. If we preserve our current method of allocating resources to applications in units of statically configured nodes where every node is identical, then future systems risk substantially underutilizing expensive resources. This is because not every application will be able to profitably use specialized hardware resources as the value of a given accelerator can be very application-dependent. The potential for waste of resources when a given application does not use them grows with the number of new heterogeneous technologies and accelerators that might be co-integrated into future nodes. This observation, combined with the desire to increase utilization even of “traditional” resources, has led to research on systems that can pool and compose resources of different types in a fine-grain manner to match application requirements. This capability is referred to as resource disaggregation. In datacenters, resource disaggregation has increased the utilization of GPUs and memory. Such approaches usually employ a full-system solution where resources can be pooled from across the system. While this approach maximizes the flexibility and range of resource disaggregation,rolling benches hydroponcis it also increases the overhead to implement resource disaggregation, for instance by requiring long-range communication that stresses bandwidth and increases latency. As a result, some work focuses on intra-rack disaggregation. While resource disaggregation is regarded as a promising approach in HPC in addition to datacenters, there is currently no solid understanding of what range or flexibility of disaggregation HPC applications require and what is the expected improvement of resource utilization through this approach.

Without any data-driven analysis of the workload, we risk over designing resource disaggregation that will make it not only unnecessarily expensive but also may overly penalize application performance due to high latencies and limited communication bandwidth. To that end, we study and quantify what level of resource disaggregation is sufficient for typical HPC workloads and what the efficiency increase opportunity is if HPC embraces this approach, to guide future research into specific technological solutions. We perform a detailed, data-driven analysis in an exemplar open-science, high-ranked, production HPC system with a diverse scientific workload and complement our analysis with profiling key machine learning applications. For our system analysis, we sample key system-wide and per-job metrics that indicate how efficiently resources are used, sampled every second for a duration of three weeks on NERSC’s Cori. Cori is a top 20, open-science HPC system that supports thousands of projects, multiple thousands of users, and executes a diverse set of HPC workloads from fusion energy, material science, climate research, physics, computer science, and many other science domains. Because Cori has no GPUs, we also study machine learning applications executing on NVIDIA GPUs. For these applications, we examine a range of scales, training, and inference while analyzing utilization of key resources.Based on our analysis, we find that for a system configuration similar to Cori, intra-rack disag gregation suffices the vast majority of the time even after reducing overall resources. In particular, in a rack configuration similar to Cori but with ideal intra-rack resource disaggregation where network interface controllers and memory resources can be allocated to jobs in a fine-grain manner but only within racks, we show that a central processing unit has 99.5% probability to find all resources it requires inside its rack. Focusing on jobs, with 20% fewer memory modules and NIC bandwidth per rack, a job has an 11% probability to have to span more racks than its minimum possible in Cori. In addition, in our sampling time range and at worst across Haswell and KNL nodes, we could reduce 69.01% memory bandwidth, 5.36% memory capac ity, and 43.35% NIC bandwidth in Cori while still satisfying the worst-case average rack utilization. This quantifies how many resources intra-rack disaggregation can reduce at best.Future HPC systems are expected to have a variety of compute and memory resources as a means to reduce cost and preserve performance scaling. The onset of this trend is evident in recent HPC systems that feature partially programmable compute accelerators, with GPUs quickly gaining traction. For instance, approximately a third of the computational throughput of today’s top 500 HPC systems is attributed to accelerators. At the same time, recent literature proposes fixed function accelerators such as for artificial intelligence. Consequently, past work has examined how job scheduling should consider heterogeneous re source requests, how the operating system and runtime should adapt, how to write applications for heterogeneous systems, how to partition data-parallel applications onto heterogeneous compute resources, how to consider the different fault tolerances of heterogeneous resources, how to fairly compare the performance of different heteroge neous systems, and what the impact of heterogeneous resources is to application performance.Resource disaggregation refers to the ability of a system to pool and compose resources in a fine grain manner and thus be capable of allocating exactly the resources an application requests. This is in contrast to many systems today where nodes are allocated to applications as a unit with identical fixed-sized resources; any resources inside nodes that the application does not use have no choice but to idle. Following the trend for hardware specialization and the desire to better utilize resources as systems scale up, resource disaggregation across the system or a group of racks has been actively researched and deployed in commercial hyperscale datacenters in Google, Facebook, and others. In addition, many studies focus on disaggregation of GPUs and memory capacity. Resource disaggregation is slowly coming into focus for HPC in addition to the existing hyper scale datacenter deployments.

Several social behavioral theories have placed perceived risks as a precursor to risky behavior,with lower risk perceptions leading to increased substance use.For example, young people who perceive long-term tobacco use as low risk are nearly four times more likely to start smoking than peers with high risk perceptions.Perception of harm for marijuana use has been decreasing in the United States, even among young people .The proportion of high school seniors reporting that regular marijuana use poses little to no health risks more than doubled between 2004 and 2014, from 20% to 45%.468 Youth at low risk for drug use report greater intentions to use marijuana if full legalization of medical and/or retail marijuana occurred.469 Data from Colorado show that risk perceptions among 18-25 year olds decreased from 2006 to 2014, with 18.5% of young adults perceiving “great risk” from once-per-month marijuana used in 2006 to 8.4% in 2014; among 26 years and above from 32.8% in 2006 to 19.8% in 2014 . 406 While use among youth has not increased since legalization of recreational use in 2013, perception of “great risk” from monthly marijuana use declined from 30% in 2006 to 17% in 2014, and past 30-day use was 12.6%, well above the national average of 7.2% . By 2014, almost 100% of the 10th and 12th grade current users reported no perceived harm. The 10th grade students reported no risk at 95%, 8th grade students reported no risk at 90%, and 6th graders reported no risk at 75%.407 Given the association between reduced risk perceptions and substance use, it is likely that as social norms on marijuana use increase and access becomes more widespread,hydroponic table use among youth will also increase in Colorado and Washington. US youth perceive marijuana to be either harmless or less risky than tobacco or alcohol.

Data from California, which legalized medical use in 1996 show that teens perceive marijuana and blunts as more socially acceptable and less risky than cigarettes. Exposure to positive messages on therapeutic benefits of marijuana use was associated with a 6% greater odds of marijuana use while peer use was associated with 27% greater odds of use.Similarly young adults in Colorado acknowledged the harmful effects of tobacco use, including secondhand exposure, while exposure to marijuana smoke was perceived as benign.The trend in marijuana legalization may contribute to shifts toward reduces risk perceptions and more permissive norms among young people in the US.Indeed, a 2014 Canadian study with adults found that social normalization of cannabis is driven and reinforced by its perceived widespread use, low incidence of harm from use, and positive social norms surrounding medical use. Canadians were also skeptical of the media’s “exaggerated” portrayal of the harms and risks of cannabis use, although some users did acknowledge health risks, particularly for smoked marijuana. Health risks commonly cited in the public discourse, including respiratory problems, mental health problems, cognitive and memory deficits, were not salient to cannabis users who perceived use was associated with a low incidence of cannabis related harm. Some participants in the study perceived risks of cannabis to be modest compared to tobacco and alcohol.Marijuana use in the United States has been rising since 2002 in both young and older adult populations, while days of use among past year users has also increased. Hall and Pacula’s initial comparisons of young adults in the United States found few differences between use in decriminalization versus prohibition states. Williams and Bretteville-Jensen used the 2001 National Drug Strategy Household Survey to assess the impact of marijuana decriminalization policy on marijuana smoking prevalence in Australia and found that decriminalization is associated with earlier youth marijuana use,and short-term increases in the population prevalence of useLiving in a medical marijuana state was associated with an increased likelihood of initiating marijuana use among young adults, although states with medical marijuana laws had higher rates of use before legalization.

No clear increases have been found since legalization of medical marijuana, especially in youth. Marijuana prevalence among young adults in Colorado went from 21% in 2006 to 31% in 2014 and among adults from 5% in 2006 to 12% in 2014.406 In 2014, 14% of adults were regular marijuana users , with 33% reporting daily use.In Washington young adult use went from 11% in 2011 to 15% in 2013, and older adult use from 4% in 2011 to 8% in 2013.Eighteen percent of young adults in Oregon and 21% in Alaska reported past 30-day marijuana use in 2014, prior to state implementation of retail marijuana laws. In Uruguay, marijuana use has been increasing since 2001, with 23% reporting ever use, 9.3% reporting past year use, and 6.5% reporting current use in 2014 . Of note, since Oregon, Alaska, and Uruguay had not fully implemented marijuana regulatory frameworks these data provide very little information about the direct impact of legalization laws on risk perceptions and use. While previous research argued that marijuana prevalence is unrelated to legalization because higher use rates were generally found prior to legalization,392 data from Denver and Seattle suggest that youth perceptions of risk have decreased and adult use has increased since implementation of retail marijuana laws.480 Moreover, while prevalence was indeed higher than the national average in the four US states that legalized recreational marijuana, liberalizing marijuana laws in 2013 and 2014 has led to dramatic increases in young adult prevalence in Colorado and Washington after the retail market opened. Notably, in Oregon, marijuana use among those 26 years and older nearly doubled between 2006–2007 and 2012-2013 , while national use has increased only slightly .Noncombustible forms of marijuana are increasing in popularity.Even though the use of noncombustible products might be increasing, their overall share is still very low among youth and adults compared to combustible product use in the four US states and Uruguay. Among current marijuana users in Colorado, young adults were more likely to report smoking marijuana than vaporizing and consuming edibles .Cross-sectional data show similar findings among high school seniors with 74% in Washington and 88% in Alaska reporting combustible product use as the preferred mode of consumption.

Similar findings were noted in Oregon in 2015, with nearly 90% of adults and youth reporting combustible marijuana use .In Washington, in 2014 high school seniors were less likely to report oral ingestion , vaporization , or other modes of administration than combustible product use.In Oregon, adults were less likely to report edible use , vaporization , while 25% reported using multiple routes of administration.Multiple administrative routes was most frequent among heavy marijuana users than less frequent users. Among frequent cannabis users in Montevideo,greenhouse tables use of joints and pipes were two of the most widely reported modes of administration in the past 12-months. Other modes of administration that were less popular include: edibles , vaporization , drinks , tinctures , and creams .368 Thus, while consuming edibles and vaporizing marijuana may be less dangerous in terms of cancer, heart disease, and lung disease than using smoked products, smoking remains the dominate mode for consuming marijuana. In addition, it is unknown what the health impacts of these forms of administration are on cardiovascular health or brain function.Marijuana commercialization was associated with a significant increase in annual hospitalizations from 803 to 2,413 in Colorado following the opening of the commercial retail market in 2013. In addition, emergency room visits increased from 739 per 100,000 to 956 per 100,000 ED visits .There was also an increase in emergency room visits for burns, cyclic vomiting syndrome, and marijuana intoxication. At the University of Denver’s burn center, 31 people were treated for marijuana related burns as a result of unexperienced users experimenting with chemical extraction using butane.Some of the increase in hospital utilization could be explained by an increase in new users experimenting with alternative ways to use and produce marijuana.The prevalence of cyclic vomiting syndrome increased after legalization of for-profit medical dispensaries in Colorado in 2010.Since 2012, when retail marijuana laws were implemented, cyclic vomiting syndrome has doubled from 41 per 113, 262 ED visits in to 87 per 125, 095 after medical marijuana was legalized. Legalization of retail marijuana in Colorado was associated with a 44% increase in marijuana-related auto fatalities, from 55 in 2013 to 79 in 2014. In Washington, auto fatalities that involved drivers with active THC in their blood increased by 122.2% from 2010 to 2014 .The interpretation of marijuana-related traffic fatalities is difficult because, unlike alcohol, there is no scientific consensus on what defines “THC impairment,” and THC can be found in the blood or urine several days after use.Legalization may also have resulted in ascertainment bias in that police in Colorado were testing more frequently for THC levels in drivers than prior to legalization. Rather an increase in drivers who tested positive for THC may better explain an increase in marijuana use generally rather than marijuana-impaired drivers specifically. The available epidemiological data on risk perceptions and use patterns from the four US states are limited in their ability to provide a comprehensive overview of the effects of state implementation of marijuana laws because legalization has only been in place for a relatively short period of time. The best that public health authorities can do is provide evidence from the tobacco control experience to have at least an understanding of what potentially the impact of these laws could be on marijuana risk perceptions, use, social norms, and harms associated with use. These shortcomings in the available literature indicate the importance of collecting adequate baseline data before enacting policy change .

Identifing proximal measures of harm with which to measure impacts of legalization would also facilitate evaluating the effects of marijuana policy change.In many ways the state of the marijuana market is similar to where tobacco was at the turn of the 20th Century, before corporatization of the market, with industrialized product design and production and mass marketing.The result was the rise of a sophisticated and politically powerful tobacco industry that led to the death and suffering of hundreds of millions of people worldwide. It took nearly a century to begin to bring the tobacco industry under control as a result of the combined forces of national and international public health advocacy and policy making, as exemplified by the WHO Framework Convention on Tobacco Control.The four US states that have legalized retail marijuana to date have used regulatory regimes largely modeled on alcohol policy regimes. There has not yet been a legalized nationwide market available for entry of major corporations. It is likely that large corporations, including the tobacco industry,with the product engineering and marketing power to quickly transform the market, could capitalize on the opportunities that such a market represents. In part because of relatively low use and the fact that marijuana and tobacco are often used together, the specific health dangers of marijuana are not yet fully defined. We do know that marijuana smoke is toxicologically similar to tobacco smoke and had been identified as a human carcinogen by the California Environmental Protection Agency72 since 2009. There is also evidence of risk of heart and lung disease as well as psychological issues. Other forms, such as edibles, oils, and vaporized marijuana have other risk profiles that are not yet well defined. The question from a policy making perspective is whether to apply the precautionary principle and develop policies to minimize use based on the existing evidence base or wait, likely 20 to 30 years, until the specific risks of marijuana and secondhand exposure have been quantified as precisely as they have been for tobacco today. There is evidence to support the conclusion that without adequate public health controls a newly legalized marijuana market will transform into one modelled on the tobacco market. There are enough similarities between tobacco and marijuana products that the evidence and experience from successful tobacco control programs could form the basis for a public health approach to legalizing marijuana. principles defined in the WHO Framework Convention on Tobacco Control486 could form the basis for a public health approach to legalizing marijuana, which would seek to minimize industry influence in the policy process and to minimize consumption of marijuana products and the associated health risks of a new legal marijuana market.