Cannabis Grow

The cost of a vertical farm can vary significantly depending on various factors such as the scale of the operation, the technology used, the location, and the specific requirements of the farm. Vertical farming systems involve the use of stacked layers or racks to maximize growing space and efficiency in an indoor environment. Here are some cost considerations:

1. Infrastructure: The cost of constructing or retrofitting a building for vertical farming can vary widely depending on the size and condition of the space. This includes expenses such as renovation, insulation, HVAC systems, lighting, plumbing, and electrical installations. Costs can range from tens of thousands to millions of dollars.
2. Equipment: The cost of equipment will depend on the complexity and scale of the vertical farm. This includes vertical farming systems (racks, shelves, or towers), lighting systems (LED or other artificial lighting), irrigation systems, climate control systems, nutrient delivery systems, automation and monitoring systems, and other specialized equipment. Costs for equipment can range from several thousand dollars to hundreds of thousands of dollars.
3. Growing medium and plants: The cost of growing media (such as hydroponic substrates) and plants will depend on the size of the farm and the type of crops being grown. Costs can vary based on the quantity and quality of materials and can range from a few hundred to several thousand dollars.
4. Operational costs: This includes ongoing expenses such as utilities (electricity, water), labor, seeds or seedlings, plant nutrients, pest control, maintenance and repairs, packaging materials, marketing, and administrative costs. Operational costs can vary significantly depending on the scale of the operation and the specific requirements of the crops being grown.
5. Research and development: Investing in research and development for optimizing production techniques, crop selection, and automation can be an additional cost for vertical farming projects.
6. Location and real estate: The cost of land or leasing a suitable location can vary significantly depending on the region and proximity to urban areas. Urban locations or repurposing existing structures may have higher real estate costs.

Given the wide range of variables, it is challenging to provide an exact cost for a vertical farm. Small-scale vertical farms can be established with a limited budget, while large-scale commercial operations can require significant investments. It is important to conduct a detailed feasibility study and cost analysis based on your specific project plans and local market conditions to get a more accurate estimation of the costs involved. Consulting with industry experts and professionals can also provide valuable insights into the cost considerations for vertical farming.

When reported by adolescents, parental involvement in the adolescent’s school life and having a mother that yells at you were significant. Lack of parental involvement in school has been shown previously to be associated with adolescent behavior problems, and yelling is a well known family stressor and supports the finding reported here . Other significant variables were identical between the two models. That is, having a lot of close friends , and peers that model gateway drug use. The discrepancy between adolescent and parent reports is an innovative finding, and suggests that adolescents may provide a more accurate estimate of parenting practices than do parents. Other studies have shown that discrepancies in perceptions between adolescents and their parents may be negatively related to adolescent adjustment, including increased levels of conflict and stress within the family resulting in problem behaviors . Although this study’s objective was not to test how discrepancies predict problem behaviors in adolescents, adolescent perceptions should be considered with or preferentially over that of parent’s estimates of their parenting practices. To this end, Barnes and Farrell suggest that reliance on one respondent in the family represents a common methodological shortfall in many studies, especially when there is not perfect agreement between adolescent and parental perspectives. Findings reported here suggest that in addition to nonconcordance between parents and adolescents, there is a difference in the predictive value of these reports. In terms of impact on future studies, it should be noted that the true parenting behaviors in this study remain unknown. That is, both parent and adolescent reports are subject to error and may include biases. Pelegrina et al. state that adolescents assess certain family characteristics more negatively than their parents,plant grow trays whereas the parents’ self-reports tend to exaggerate certain dimensions, such as acceptance and discipline.

Future studies of the influence of parenting behaviors should incorporate more state of the art objective observational procedures to advance the current state of the science and determine the true parents’ parenting practices. To the extent that such procedures and innovations are incorporated, scientific understanding of parental influence on children will be clarified. The findings from this study should be interpreted in the context of the sample’s limitations. The study sample, though entirely Latino, was not population-based and only represented data from mothers. Whereas these findings may not be generalizable to the Latino population at large, they do speak to the need for the development of more refined measures of parenting practices. Nevertheless, the use of an entirely Latino sample of parents and adolescent dyads represents an important feature of this study, making it a valuable addition to extant literature. Adolescent gateway drug use continues to be a serious problem, contributing to immediate and long-term health consequences and costs to society . Decades of research on uptake of these substances have identified significant individual and social-level risk factors. However, ecological influences have only recently been explored. Recent advancements in software programs that use geographic information systems technology provide the necessary tools to conduct innovative exploratory analyses of ecological influences on gateway drug use. Recent reports regarding adolescent tobacco acquisition suggest that drug products are usually provided by three common sources: a stranger who buys them, family or friends who buy or give them, or a retailer who sells them . Some studies indicate it is easy for adolescents to buy both alcohol and tobacco . Indeed, the California Department of Public Health and Tobacco Control reports that one of the simplest ways for adolescents to buy tobacco is in their local neighborhood store. Data from the American Lung Association indicate that 33% to 50% of San Diego County retailers sell to adolescents . At least three issues should be considered with respect to retailer impact on substance use. First, adolescents are sensitive to cost, including the cost of time spent traveling to purchase products in other neighborhoods . They may also have unreliable transportation and limited spending money.

Frequent use or use of multiple substances may require more disposable income than would be true for youth who use drugs infrequently or only use one substance, e.g., alcohol. Youth who use drugs frequently or many different drugs may have less disposable income to invest and would be more sensitive to the distance from home to a retail business from which alcohol or tobacco could be purchased. Second, substances for first time use are usually not purchased by the adolescent experimenter, and instead may be provided at partiesor group gatherings. Users under these conditions may be less influenced by retailer proximity to their home. Third, retailer presence may provide a critical link to facilitate social processes in a given neighborhood. For example, modeling is a known risk factor for substance use, and seeing other adolescents purchase and use alcohol and tobacco may prompt consumption . The effects of retailer dispersion may be due to increased availability to substances, but it may also relate to increased opportunities for modeling, imitation by substance use, which can then be reinforced by peers. In their introduction of a community systems approach, Treno & Holder identify a limitation with group/individual-level prevention efforts. Mainly, such approaches are effective when the conditions that give rise to undesirable behavior lie solely within the target group, or individual, e.g., lack of knowledge. Indeed, education and awareness prevention efforts have historically been very popular . Nevertheless, efforts that focus entirely at such levels fail to demonstrate long-term results in circumstances where behavioral determinants extend beyond the individual, e.g., policies, alcohol and tobacco access, peer modeling, etc. Uptake and consumption of substances during adolescence is the result of many influences outside the purview of the individual. Despite the rational for environmental approaches, and the compelling evidence of environmental correlates associated with risky substance use practices, proven interventions are still limited in number. Indeed, structural environmental factors rarely makes it past the stage of a theoretical construct to inclusion in analytical models . This is in part due to the relevant infancy-stage of development . Notwithstanding this infancy, various theoretical models have emerged that attempt to address these environmental influences.

The Behavioral Ecological Model is based on the notion that behavioral determinants reside in the environment. Operational measures of Intra personal factors are difficult to validate and therefore excluded from the model that also explicitly assumes that ignoring such individual-level variables does not compromise prediction or control of behavior, thereby placing behavioral causes in the environment . In light of reports describing gender differences with respect to tobacco acquisition,custom grow rooms and the recent reports about the relationship between retailer presence and high risk behaviors, surprisingly little work has been done to highlight differences on this dimension between boys and girls. The purpose of this exploratory study based on the BEM and previous work by Pokorny et al. was to compare gender differences on the relationship between gateway drug use and variables representing both structural and social environments. Alcohol, tobacco and marijuana use variables were selected from a cross-sectional interview of Latino adolescents along the California/Mexico border in San Diego County. Demographic and peer modeling variables were also selected from the interview. A measure of alcohol and tobacco retailer dispersion was calculated from retailer location data obtained through the San Diego County Department of Environmental Health Food & Housing Division . Gateway drug use was regressed using least squares regression on 8 independent variables representing both structural and social environmental influences .The sample of 226 Latino adolescents in this study were students ages 13 to 19, attending high school in south San Diego County, who tested positive for latent tuberculosis infection , volunteered to participate in a medication adherence trial, and planned to receive treatment of their infection in the United States . Data were collected between 2004 and 2005. Participation in this study was limited to adolescents with a residential address in the US. After obtaining informed consent, trained bilingual staff completed a baseline interview in the participant’s home. Age, gender, and acculturation were selected to represent demographic characteristics. Acculturation was measured using the Bidimensional Acculturation Scale for Hispanics . The acculturation scale consists of 24 questions regarding language use , linguistic proficiency , and electronic media use . Each question had four possible responses: very poorly, poorly, well, or very well. The questions were separated into 2 domains, Hispanic and non-Hispanic , with 12 items in each. For each cultural domain, an average of the 12 items was calculated, obtaining a mean range of scores between 1 and 4. Scores on both domains were used to determine the level of acculturation. Acculturation categories were computed using a 2.5 cutoff score to indicate low or high level of adherence to each cultural domain. Individuals scoring higher than 2.5 in both domains were considered bicultural . The participant residential address was geocoded in ArcView 9.2.

Geocoding refers to the process of creating a point along a roadway segment that defines the location of any given address. A quarter-mile street network buffer was then created around each participant’s residential location or point. This buffer was intended to reflect the “walking neighborhood,” or those locations where the participant could easily walk to access various nearby alcohol and tobacco retailers. Currently no standard exists to define a buffer size that appropriately reflects “neighborhood;” however, given the typically limited travel choices of adolescents, the area within a 5-minute walk of his/her home can reasonably be considered a highly accessible area. The quarter mile distance was developed assuming a walking speed of 3.4 miles/hour . One previous study used a circular buffer of 0.5 miles . Buffers created using distances along the street network, such as that employed in the current study, exclude areas of the urban environment that are not accessible via roadways, and are generally considered to more accurately reflect those locations that are truly accessible. US Census Bureau data were obtained from San Diego Geographic Information Source , and used to identify neighborhood characteristics. Items were selected using an adaptation of an approach employed by Sampson, Raudenbush, & Earls and mostly represent indicators of neighborhood poverty . The values used in this study were: 1) percentage of families living below the poverty level, 2) percentage of unemployment, 3) percentage of adults with a high school diploma, 4) percentage of owner occupied homes, 5) percentage of the population under 18 years of age, 6) percentage of homes headed by a single mother, and 7) percentage of Hispanics. The neighborhood characteristic variables from SanGIS were available by Census Block Groups , a census geography that reflects aggregations of several Census Blocks. Since the participant’s neighborhood buffers were irregular and did not fall exactly on the boundaries of the CBGs, it was necessary to estimate Census variable values within each participant’s buffer using a method referred to as “apportioning”. This procedure involves calculating the proportion of each CBG that overlaps with a neighborhood buffer and then using that percentage to factor each respective Census variable. For example, if a participant’s neighborhood buffer included 25% of one CBG, 55% of another, and 20% of a third CBG, then these percentages were used to weight the census values associated with each CBG to develop a unique value more closely aligned with the boundaries of the neighborhood buffer. This is a recognized approach to adjusting Census data so that it more accurately reflects a unique, non-census geography.This study analyzed retailers from the 2004 database, and was limited to convenience stores. Retailers that did not sell alcohol and tobacco were removed. The retailer address was geocoded using ArcView 9.2 and then used to create a measure of retailer dispersion: distance to nearest retailer from each participant’s residential location. Distance to the nearest retailer was calculated using the Network Analyst function in ArcView, which is capable of finding and then measuring the distance of the shortest roadway path between a given participant’s residential point and the nearest retailer point. This variable demonstrated a non-normal distribution and required transformations to reach normality.

What is vertical farming?A vertical farm is an innovative type of indoor agriculture that utilizes vertical space to grow crops in stacked layers or shelves. It is designed to maximize production while minimizing the use of land and resources. Here’s a general overview of how a vertical farm works:

1. Structure and Design: A vertical farm is typically housed in a controlled environment facility such as a warehouse or a specially constructed building. The structure incorporates multiple levels or shelves to create a vertical growing space.
2. Lighting: Artificial lighting systems, such as LED lights, are used to provide the necessary light spectrum for plant growth. The lights are positioned at optimal distances and angles to ensure uniform light distribution across all levels.
3. Hydroponics or Aeroponics: Most vertical farms use hydroponic or aeroponic systems to grow plants without soil. In hydroponics, plants are grown in nutrient-rich water solutions, while in aeroponics, plants are grown in mist or air with nutrient-dense solutions. Both methods provide plants with the necessary nutrients directly to their roots.
4. Climate Control: Vertical farms rely on precise control of temperature, humidity, and airflow to create ideal growing conditions for the plants. This allows year-round cultivation and the ability to grow crops that are not native to the local climate.
5. Irrigation and Nutrient Delivery: The water and nutrient solutions required for plant growth are delivered directly to the plants through a network of irrigation systems. The solutions are carefully monitored and adjusted to maintain optimal nutrient levels for each crop.
6. Monitoring and Automation: Vertical farms often employ advanced monitoring systems to track various environmental factors such as light levels, temperature, humidity, and nutrient concentration. Automation systems control and adjust these factors based on predetermined parameters, ensuring the optimal conditions for plant growth.
7. Plant Growth and Harvesting: Seeds or seedlings are planted in trays or containers and placed in the growing system. As the plants grow, they are periodically moved to higher shelves to utilize the available vertical space efficiently. Harvesting is done manually, typically on a rotating schedule, as different crops reach their maturity.

Benefits of Vertical Farming:

• Increased crop yields: Vertical farming allows for more efficient use of space, enabling higher crop yields per square foot compared to traditional farming.
• Reduced resource usage: Vertical farms typically use less water and fertilizers compared to conventional agriculture.
• Year-round production: The controlled environment in vertical farms allows for continuous cultivation regardless of external weather conditions.
• Locally grown produce: Vertical farms can be located in urban areas, bringing fresh produce closer to consumers, reducing transportation costs, and lowering carbon emissions.

Overall, vertical farming companies presents an innovative approach to sustainable agriculture, offering the potential to address food security, reduce environmental impact, and create more resilient and efficient food production systems.

The Disposal Act allows for individuals to dispose of legally possessed controlled substances via take-back events, mail-in programs, and collection facilities. Improving public awareness and availability of these methods of disposal will offer added protection for the marine environment against flushed pol lutants. However, illicit drugs cannot be legally disposed of using these methods, and the U.S.Because illicit drugs thrown out as household refuse pose a threat to humans and animals that may find them, and domestic incineration of illicit drugs is potentially hazardous, flushing is the only remaining disposal option. To reduce the amount of illicit drugs that are flushed into POTWs, and ultimately into the marine environment, a safe and legal method for disposing of illicit drugs must be developed. Drug possession prohibition laws severely complicate efforts to dispose of illicit drugs.Individuals looking to dispose of illicit drugs will be unwilling to transport or mail them out of fear of criminal prosecution. Additionally, illicit drugs that are found or intercepted pose a high risk of accidental overdose. For these reasons, developing a mechanism for individuals to dispose of small amounts of illicit drugs will prove to be challenging, perhaps prohibitively so. Individuals looking to dispose of large quantities of illicit drugs, however, may warrant more contemplation. Relaxed enforcement of possession laws may be considered in limited circumstances to allow individuals to forfeit illicit drugs through prescribed mechanisms. Drug rehabilitation facilities that collect illicit drugs from their residents also have no legal disposal mechanism,vertical racking system and likely resort to flushing. Regulations should be drafted to provide a process by which these facilities can destroy illicit drugs onsite or can transfer them into DEA custody for destruction. Keeping these drugs out of human hands and out of the marine environment through safe and legal confiscation and destruction is an important cause that is worthy of innovative regulatory reform. Pharmaceutical Extended Producer Responsibility programs should also be implemented throughout California. Alameda County devised the first mandatory drug take-back program in the state by enacting the Safe Drug Disposal Ordinance.

The ordinance requires pharmaceutical manufactur ers who sell or distribute certain prescription and over-the-counter medications in Alameda County to develop, fund, and implement a Product Stewardship Program that facilitates the collection, transportation, and disposal of unwanted pharmaceuticals.Trade associations representing pharmaceutical manufacturers challenged the ordinance, alleging violation of the Dormant Commerce Clause.107 The Dormant Commerce Clause places an implied limitation on a state’s power to enact laws that burden interstate commerce.108 The Ninth Circuit Court of Appeals validated the ordinance, holding that the ordinance did not discriminate against or directly regulate interstate commerce, and that the burden on interstate commerce did not clearly exceed the local benefits of the ordinance. The United States Supreme Court declined to hear the case on appeal, allowing the ordinance to stand and opening the door for similar legislation in other California counties.Similar EPR laws have been passed in Marin County, the City and County of San Francisco,San Mateo County,and Santa Clara County.An EPR ordinance has also been proposed in Los Angeles County.Another way to reduce pharmaceutical flushing is to abandon the U.S. Food and Drug Administration Flush List and to adopt a universal no-pharmaceutical-flushing policy. The FDA Flush List recommends disposal by flushing for pharmaceuticals that present particular concern for abuse and overdose. While this policy is meant to keep humans and pets from ingesting potentially dangerous unused drugs, it favors the introduction of these pharmaceuticals into the marine environment. Because we currently lack sufficient safeguards to prevent flushed pollutants from harming marine organisms and ecosystems, these pharmaceuticals should instead be disposed of through take-back events or transfer to a DEA-authorized collector. Adopting a universal no-pharmaceutical-flushing policy would encourage the use of these alternative disposal methods. Because many of the pharmaceuticals on the FDA Flush List present an especially high risk of overdose to children and others to whom they were not prescribed, the adoption of a universal no-pharmaceutical-flushing policy could be met with potentially insurmountable political opposition.

The development of safe disposal alternatives that are more accessible and convenient than current methods would make the adoption of such a policy more feasible. Innovation of wastewater treatment technology targeted at listed pharmaceuticals and development of marine-safe versions of listed pharmaceuticals would also help to reduce the impact that these flushed pollutants have on the marine environment. In order to evaluate the scope and severity of this issue, research is desperately needed to determine the amounts of flushed pollutants entering the marine environment and the effects these pollutants have on marine organisms and ecosystems. Further research is required to determine acceptable levels of flushed pollutants in treated wastewater effluent discharged into the marine environment to eliminate or minimize these effects, and to determine whether existing technologies are sufficient and economically viable to attain discharge levels deemed acceptable. Imposing comprehensive monitoring requirements and stringent effluent limitations specific to flushed pollutants in POTW effluent will encourage the development of more efficient technological processes for removing pharmaceuticals, illicit drugs, and caffeine from wastewater. Establishing similar requirements and limitations for discharges from healthcare facilities such as hospitals, pharmacies, rehabilitation centers, and long-term care facilities may also put pressure on pharmaceutical companies to engineer medications that are benign to the marine environment and may even prompt government agencies to develop safe and legal disposal alternatives to flushing illicit drugs. Public education is one of the strongest tools for reducing the effects that flushed pollutants have on marine organisms and ecosystems. Household flushing contributes a significant percentage of pharmaceuticals, illicit drugs, and caffeine entering POTWs, yet the general public knows very little about wastewater treatment and oceanic discharge. Campaigns to dispense information about safe and legal disposal methods for unwanted pharmaceuticals and to raise awareness of the potential effects that flushed pollutants may have on marine organisms and ecosystems could help to reduce household flushing of unwanted pharmaceuticals. Despite having a comprehensive tobacco control policy, cigarette smoking continues to be the leading cause of preventable morbidity and mortality in China and other developing countries,indoor grow facility as it already is in developed countries today, and accounts for 5 million deaths globally each year.

When cigarettes are smoked, a host of harmful chemicals contribute to the deleterious effects. Mounting scientific evidence proves the association between chronic smoking and lung cancer, chronic obstructive pulmonary disease, , vascular disease, stroke, and peptic ulcer disease, as well as a wide range of other adverse health effects. Understanding the mechanism of nicotine dependence and developing better therapies to help with smoking cessation is an urgent need. Emerging technologies, such as neuroimaging and genomics, have contributed to new insights into the neurophar macology of tobacco addiction. There is considerable literature from functional neuroimaging studies assessing the effects of chronic cigarette smoking on brain structure and function. However, while several studies have examined gray matter differences between smokers and non-smokers, much is less known about the white matter structural changes in brain in chronic cigarette smokers. Using magnetic resonance imaging to examine the brain structure and function in chronic cigarette smoker provides a better understanding about the adverse effects of chronic cigarette smoking on brain. Diffusion tensor imaging is a sensitive method to measure micro-structural changes by detecting self-diffusion of water molecules caused by Brownian motion and providing parameters of the diffusion tensor, the most commonly used parameter is fractional anisotropy. FA is a commonly used measure for examining white matter spatial organization and integrity. Increased FA indicates a non-spherical tensor with preferential orientation in a particular direction, while a decreased FA indicates more isotropic diffusion which has been found to becharacteristic of disrupted or damaged whiter matter. It has been widely used to identify and quantify white matter abnormalities in psychiatric and neurological diseases, such as schizophrenia showed significantly higher levels of FA in the corpus callosum than nonsmokers; the low Fagerstro¨m scores group exhibited significantly higher levels of FA in the body of the corpus callosum than the high Fagerstro¨m group and the nonsmokers. Jacobsen et al reported that prenatal and adolescent exposure to tobacco smoke showed higher FA in anterior cortical white matter; adolescent smoking also showed higher FA in internal capsule.

Recently, Xiaochu Zhang et al examined a relatively large sample of smokers and found that the most highly dependent smokers exhibited lower prefrontal FA, which was negatively correlated with Fagerstro¨m Test of Nicotine Dependence. In the present study, we examined white matter changes in a relatively large sample of nicotine dependent smokers and non smokers matched for a number of demographic variables using DTI.Eighty-eight subjects , 19–39 years of age, were recruited from the local community using advertisements. They were initially screened during a semi-structured telephone interview to assess smoking, medical, psychiatric, medication, and substance use history. Smokers who had smoked 10 cigarettes per day or more during the previous year and had no period of smoking abstinence longer than 3 months in the past year, and met DSM-IV criteria for nicotine dependence were eligible for this study. All smokers self reported no smoking for the 12 hours before scanning. Nicotine patches were provided as needed. Nonsmoking history was defined as having smoked no more than five cigarettes lifetime. Participants were excluded if they were a minority other than Han Chinese or had: a diagnosis of mental retardation, current or past alcohol or drug abuse/dependence, a current or past central nervous system disease or condition, a medical condition or disease with likely significant central nervous system effects, history of head injury with skull fracture or loss of consciousness greater than 10 min, a physical problem that would render study measures difficult or impossible, any current or previous psychiatric disorder, a family history of a psychotic disorder, current or previous use of electroconvulsive therapy or psychotropic medications, or a positive pregnancy test. A licensed psychiatrist conducted all clinical interviews. The protocol was approved by the university ethics committee and the studies were carried out in accordance with the Declaration of Helsinki. Subjects were fully informed about the measurement and MRI scanning in the study. Written informed consent was given by all study participants. None of the participants reported daily consumption of alcohol, and none reported experiencing social consequences secondary to alcohol use, or any history with difficulty ceasing alcohol intake. All non-smokers in this sample reported no history of smoking behavior in the past.Between-group tests were performed on diffusion tensor images of FA using a parametric two sample t-test on a voxel-by-voxel basis using SPM5 software. A prior white matter mask from WFU_PickAtlas was used to restrict the search volume for analysis. Clusters of 100 voxels or more, surviving an uncorrected threshold of p,0.001, were considered significant. For visualization of the regions showing significantly different FA values between the two groups, significant clusters were superimposed onto SPM5’s spatially normalized template brain. Fiber tracts corresponding to the clusters were identified with reference to the Johns Hopkins University DTI-based White Matter Atlas analyses was performed. MarsBar 0.41 was used to extract ROIs containing all the voxels classified as white matter from spatially normalized and smoothed FA images. Then, mean FA values of the ROI were calculated using log_roi_batch v2.0 . Finally, the aver age FA values of individual clusters were calculated for each subject. A two-sample t-test was used to compare these FA values of the clusters between smokers and non-smoking controls. We used P,0.05 as a statistical threshold to search for significant differences. Correlational analysis of FA values with smoking-related factors including age of smoking onset, number of cigarettes smoked per day, years of smoking and smoking cravings were examined using bivariate correlational analysis . The T1-weighted images were segmented by using VBM5.1 procedures into white matter, gray matter, and CSF . Then, the white matter volumes were compared between groups by univariate GLM using total brain volume as covariate.The present study provides evidence of micro-structural white matter modifications in chronic smokers as measured by whole brain analysis of FA using DTI. Specifically, increased FA was found in white matter of the bilateral fronto-parietal cortices in cigarette smokers relative to healthy non-smoking comparison subjects. In contrast to the findings here with chronic cigarette smokers, previous studies with other drug dependent subjects revealed decreased FA in white matter of the brain. In patients with heroin dependence, reduced FA was observed in the bilateral frontal subgyral cortices, right precentral, and left cingulategyrus.

The estimates of the mean %ABV of beer, wine, and spirits for each state and the District of Columbia for selected years are presented in Table 3. The mean %ABV of each beverage type are seen to vary by state in each year, reflecting the variation in preferences and mean %ABV for each beverage sub-type across states and time. All states and the District of Columbia showed an increase in the mean %ABV of beer between 2003 and 2016, and most states followed the national trend. The states with the least amount of change over the 2003-2016 period were North Dakota, Virginia, and Iowa with percent increases of 1.2%, 1.1%, and 0.9%, respectively, while New Mexico, Montana, and Maine experienced the greatest percent increases of 4.9%, 4.4%, and 4.3%, respectively. For wine, all states showed an increase in mean %ABV and followed the national trend. The states with the greatest increases between 2003-2016 were Idaho, Virginia, and Tennessee with increases of 6.8%, 6.8%, and 6.7%, respectively. The states with the lowest percent change were Illinois, North Carolina, and Mississippi with increases of 3.1%, 3.0%, and 2.9%, respectively. For spirits, 45 states and the District of Columbia showed increases in the mean %ABV of spirits, and of these the vast majority followed the national trend. Ohio, Rhode Island, and Nebraska had the largest percent increases at 10.5%, 7.9%,and 6.6%, respectively, while West Virginia, Mississippi, and Alabama had the largest decreases in %ABV for spirits of 0.4%, 0.5%, and 1.8%, respectively. State mean %ABVs and market shares for beverage sub-types. The change in the mean %ABV of beer, wine, and spirits was driven by changes in beverage sub-type mean %ABVs and preferences, and these %ABVs and preferences varied by state. To describe these state-level beverage sub-type %ABV and preference changes in relation to state-level changes in mean beverage-specific %ABV,horticulture solutions we present data for the states with the largest change in mean %ABV for each beverage type.

The increase in %ABV of beer for New Mexico, which had the largest percent increase of 4.9%, is attributable to a decline in the market shares of beer with relatively low mean %ABV and an increase of relatively higher mean %ABV beer sub-types. Between 2006 and 2016 the market shares of light beer declined from 51.5% to 37.6%. The market shares of the super premium, micro/specialty, and FMBs sub-type category increased from 6.8% in 2006 to 11.9% in 2010, and between 2011 and 2016 the market shares of craft beer increased from 8.2% to 14.9%. Similar to the national trends in the mean %ABV of wine, state-level trends were driven by the increase in the mean %ABV and the market shares of table wine. Idaho, which had the largest percent change in mean %ABV of wine of 6.8%, had the largest market share of table wine for most years between 2003 and 2016, where market shares of table wine were 97.3% in 2003 and 97.4% in 2016. Comparable to national trends in the mean %ABV of spirits, state level trends were driven by declines in the market shares of low %ABV spirit sub-types and increases in high %ABV spirit sub-types. Between 2003 and 2016, Ohio had the largest increase in mean spirits %ABV of 10.5%. Unlike the national trend, it showed a marked increase between 2012 and 2014 after which it leveled off. The increase in %ABV between 2012 and 2014 was driven by a decline in the market shares of prepared cocktails from 9.3% in 2012 to 0.2% in 2014 and a concomitant increase in the market shares of cordials and liqueurs, straight whiskey, tequila, and brandy & cognac. The new beverage-specific %ABV-variant PCC estimates for selected years for each state are presented in Table 3. The estimates varied by state while trends for each beverage type were consistent across states. The total PCC estimates for each state with comparisons to AEDS estimates for 2003 and 2016 are presented in Table 4. The estimates varied by state in each year, representing the range in total PCC by state. Table 4 also shows the percent change in total PCC for each state for both our new estimates and the AEDS estimates. The ranking by percent change varies by the new and AEDS estimates. North Dakota has the largest percent change in total PCC according to both estimates, however, the new estimates rank Vermont second followed by Idaho while the AEDS estimate rank Idaho second followed by Vermont.

The vast majority of states showed an increase in total PCC, although 2 more states, Nebraska and Illinois, showed a decline according to AEDS estimates than did according to our new estimates. For all beverage types, our mean %ABV estimates increased nationally and for all but five states. These increases were driven by an increase in national and state preferences for beverages with a higher and increasing %ABV and a decrease in preferences for lower %ABV beverages. The estimates of PCC from wine and spirits utilizing variable %ABV conversion factors were lower than AEDS estimates, while consumption from beer was higher. While our total PCC estimates were also lower than AEDS estimates, the trends in PCC showed a more dramatic increase in pure alcohol volume than those using ABV-invariant methods. Researchers have used PCC estimates to try to understand the observed increases in alcohol-related morbidity and mortality in the U.S. over the first part of the 21st century. For example, White et al noted an increase of 1.7% in PCC and concluded that it did not appear to be related to the 47% increase in the rate of alcohol-related ED visits from 2006 to 2014 . Using our ABV variant method, PCC between 2006 and 2014 increased by 3.6%, over double the increase using the ABV invariant method. This difference and the absolute increase using the ABV variant method may not alone explain the increase in the rate of alcohol-related ED visits. However, because the change in PCC was likely underestimated, it suggests PCC should not be dismissed and may be one of many factors driving the increase in alcohol-related emergency room visits. This example also highlights the importance of the rate of change in PCC trends,grow shelving and is consistent with findings from an Australian study that similarly showed the value of including time-varying ABV values to ensure precision in PCC estimates so change over time can be accurately measured . It is important to note that cohort and lag effects may also be drivers of the disparity between changes in alcohol-related morbidity and mortality and changes in PCC.

Cohort effects may be related in that previous generations may have been drinking at high levels that resulted in death from alcohol-related diseases so that their alcohol consumption would not be included in current PCC estimates . Lag effects may contribute because the time from changes in PCC to the time to first effect for some alcohol-attributable diseases, such as alcohol-related cancers, is at least 10 years . These effects could result in temporally distinct yet still related changes between PCC and changes in alcohol-related morbidities. There are many reasons why the precision of PCC estimates matters. First, the Tax Cuts and Jobs Act of 2017 reduced excise taxes on all alcoholic beverages. A large body of evidence shows that decreases in alcohol taxes can result in increases in alcohol consumption , which can give rise to alcohol-related morbidity and mortality . If there is a further and continued increase in alcohol consumption by the U.S. population over age 15, then further increases in alcohol-related problems may be forthcoming, such as traffic accidents and suicides . Second, the recent legalization of recreational cannabis in many states is of concern in an environment of increasing alcohol use because of the negative impact of simultaneous cannabis and alcohol use, such as drunk driving, social consequences, and harms to self . Third, recent national surveys report a decline in both any alcohol use and binge drinking among youth , suggesting that the noted increase in PCC is due to more alcohol use and binge drinking among middle-aged and older adults. Indeed, recent surveys have observed an increase in self-reported past-month binge drinking and AUD among adults aged 50 and older , and an increase in alcohol-related emergency department visits . This is cause for concern because older adults are more likely to have various co-morbidities and to use medication that contraindicates the use of alcohol. Finally, the national surveys and meta-analysis that showed an increase in binge drinking generally may be particularly concerning if the alcohol content of the beverages being consumed is higher than previously assumed as this may increase the likelihood of negative alcohol-related consequences. This work has limitations that should be considered when interpreting our results. The estimate for PCC from wine may have been underestimated from 2012 to 2016 since we carried forward the %ABV value for 30% of total sales volume from 2011 to 2016 instead of calculating from actual wine %ABV values. This change in methodology was due to changes in the availability of data, which also highlights the challenge of this methodology to identify adequate and reliable sources of information. Relatedly, how we calculated the mean %ABV of wine by identifying the leading brands of wine based on sales in Pennsylvania only is a limitation because it does not represent sales nationally. Since only general brands and not individual brands are reported nationally it is not possible to determine if using leading individual brand sales of wine in Pennsylvania would result in an over or underestimate of the mean %ABV of wine and thus its impact on PCC wine estimates.

Regarding the %ABV of all alcoholic beverages, the %ABV value taken from producer reports or websites may not accurately reflect the actual amount of alcohol. This is less likely for spirits which are taxed based on alcohol content at the federal level, but may still be relevant for beer and wine which are not routinely tested by independent authorities, except in regard to labelling where considerable error is allowed. Regarding other components of the calculation of PCC estimates, population estimates may also represent another source of error as certain under counted groups, often rural and/or racial/ethnic minorities, and those not included in the population such as foreign tourists and undocumented immigrants, may comprise a greater proportion of the population in recent years . The alcohol sales data may also have error due to unaccounted for changes in reporting practices over time, variation by state, and the time delay between actual consumption and the publication of state tax records . Moreover, alcohol sales data will not include unrecorded consumption from illicit production, importation, and sales. Fortunately, unrecorded consumption is likely minimal due to substantial decreases in illicit alcohol production in the U.S. since the 1970s . Similarly, cross-state sales are also present but not likely to have a significant impact on consumption estimates . However, these factors are a reality and may introduce inaccuracies into our PCC estimates . Finally, the likely errors in each component of the PCC calculation, that is, the alcohol sales figures, the %ABV values, and population estimates, would result in errors in the PCC estimates. Since these error values are unknown, however, statistical tests of differences between ABV-variant and ABV-invariant PCC estimates are not feasible. It is noteworthy that the population estimates and alcohol sales data are also components of the AEDS methodology such that the same errors are included in our PCC estimates. Further, the errors in the estimates of components of the PCC calculation beyond the %ABV values represent other possibilities for improving the precision of PCC estimates, such that refinements in alcohol sales figures and population estimates could improve PCC calculations. These refinements, however, would necessitate changes in the reporting and collection of these data, which would likely be more cumbersome than including data on annual changes in %ABV values of beer, wine, and spirits. The inclusion of time-varying %ABV in the calculation of PCC estimates showed increasing %ABVs for all beverage types, preferences for beverages with higher and increasing %ABV, and a greater increase in PCC estimates compared to those using time invariant %ABV values.

CA3 also gives rise to the very large Schaffer–Commissural projection to pyramidal neurons in field CA1, where further integration likely occurs. CA1 directly and through intermediaries innervates the deep layers of entorhinal cortex . It is widely held that through this circuitry the hippocampus converts a sequence of inputs from cortex into representations that include semantic, spatial, and temporal components . Multiple studies suggest that transmission of this code back to cortex is essential for the construction and retrieval of episodic memory, a fundamental ingredient of orderly thought . Consistent with this role, each of the above hippo campal connections undergoes stable potentiation of synaptic trans mission, long-term potentiation , following brief periods of afferent stimulation including activity patterns exhibited during learning. Much has been learned about the synaptic events that induce, express, and rapidly consolidate the potentiated state, particularly for the CA3–CA1, S–C connection: enduring changes occur post synaptically and involve reorganization of the spine cytoskeleton, enlargement of the postsynaptic density, and an increase in membrane neurotransmitter receptors . Appreciation of how hippocampus executes its memory encoding operations will depend on the extent to which other connections in the circuit use this or other forms of plasticity. Recent work suggests that pronounced pathway-specific differences are in fact present. Specifically, the lateral perforant path afferents from lateral entorhinal cortex to the DG exhibit a form of potentiation that depends on postsynaptic induction but is expressed presynaptically as an increase in evoked transmitter release . The retrograde messenger required by this arrangement proved to be the endocannabinoid 2-arachidonoylglycerol which is synthesized in dendritic spines and diffuses to CB1 receptors on axon terminals. The 2-AG system is present at many types of synapses where its direct retrograde signaling has been shown to transiently depress release ; nevertheless,4 x 8 grow tray it serves the very different purpose of promoting potentiation of transmission in the LPP.

Recent studies demonstrated that presynaptic signaling through ERK1/2 to the vesicular protein Munc18-1 is critical for CB1R-mediated depression of release . Here, we show that CB1R agonists readily activate this signaling cascade at S–C synapses but not in the LPP. Instead, at LPP terminals the CB1R/2-AG system is biased toward a second cascade involving β1 integrins and presynaptic actin regulatory signaling. The finding that a specialized form of synaptic potentiation is used to encode semantic information processed by hippo campus calls for substantial revisions to current hypotheses about how the structure contributes to the formation of memory. It also provides a new perspective for understanding the abnormal encoding of episodes produced by cannabinoid drugs.Animals used for extracellular field recordings were 5- to 8- week-old male rats and mice. The mice included Munc18-1 heterozygote knockouts and background strain matched wild types for comparison, and conditional β1-integrin KOs created by crossing mice with floxed β1-integrin exon 3 with mice expressing Cre recombinase under control of the CaMKIIα promoter ; in the progeny the expression of Cre by excitatory hippocampal and cortical neurons leads to excision of β1 exon 3 and disruption of β1 protein expression beginning at 3 weeks of age. The present studies used β1 KOs at 8 weeks of age. The preparation of hippocampal slices and their maintenance in an interface recording chamber has been described in detail elsewhere . Animals were killed by decapitation under deep isofluorane anesthesia and the brain was quickly submerged into oxygenated, ice-cold, high-magnesium artificial cerebral spinal fluid containing : 124 NaCl, 3 KCl, 1.25 KH2PO4, 5 MgSO4, 26 NaHCO3, and 10 dextrose. For rats, slices from the middle third of the hippo campal septo temporal axis were sectioned at a thickness of 330–400 μm using a McIlwain tissue chopper; for mice 375 μm thick sections were prepared on the horizontal plane using a Leica Vibrating Slicer . In both cases, slices were collected into oxygenated, high-magnesium ACSF and then transferred onto an interface recording chamber and continuously perfused with preheated oxygenated ACSF containing : 124 NaCl, 3 KCl, 1.25 KH2PO4, 1.5 MgSO4, 26 NaHCO3, 2.5 CaCl2, and 10 dextrose at a rate of 60–70 ml/h. Experiments were initiated about 1.5 h after slices were placed on the recording chamber.

Field excitatory postsynaptic potentials were recorded by positioning a glass recording electrode and bipolar stimulating electrode in 2 hippocampal pathways . For studies of the LPP innervation of the DG, recording and stimulating electrodes were both positioned in the outer molecular layer , adjacent to the hippocampal fissure. All evoked responses were initially tested with paired pulse stimuli to confirm specificity of potentials and thus electrode placement: LPP responses show paired-pulse facilitation whereas the adjacent medial perforant path shows paired-pulse depression . For studies of S–C innervation of field CA1 stratum radiatum, recording and stimulating electrodes were positioned in CA1b and CA1c, respectively, at comparable distance from the pyramidal cell layer. Test pulses were delivered at 0.05 Hz and baseline stimulation intensity was adjusted to 50–60% of the maximum spike-free fEPSP. Stable baseline recordings were collected for at least 20 min prior to pharmaco logical manipulation or induction of LTP. For the LPP, LPT was induced using 1 of 2 paradigms: two 100 Hz trains, lasting 1 s and separated by 1 min with stimulus duration and intensity increased to 100% and 50% above baseline levels, respectively, and one 100 Hz train, lasting 1 s, no current changes . Stimulus strength was returned to baseline levels after induction. LTP in field CA1 was induced using one 100 Hz trains, lasting 1 s. The level of potentiation was assessed using 0.05 Hz pulses delivered for ≥1 h after inducing stimulation. In all instances, initial slopes and amplitudes were measured from digitized fEPSPs and normalized to mean responses over the last 20 min of the baseline period. Assessments of the level of potentiation were made for the period from 50 to 60 min after delivery of the inducing 100 Hz stimulation. For analysis of pharmacological treatment effects on synaptic responses, statistical tests considered slice mean responses over the last 5 min of the recording period unless otherwise specified.The present studies provide a first detailed description of the mechanisms underlying a novel form of LTP in a primary cortical input to hippocampus. Given that this projection conveys semantic information to hippocampus , the findings are of basic importance to the development of neurobiologically based theories of episodic memory. The substrates for lppLTP include a repurposing of elements utilized in conventional,vertical racking postsynaptic potentiation, as described for the intensively studied S–C projection to CA1, supplemented with novel features.

Both forms of potentiation are induced post synaptically via NMDARs and increased calcium levels , and both require activation of β1 integrins and their downstream effector ROCK . Integrins are a primary membrane regulator of the actincytoskeleton and their prominent role in both types of plasticity suggests that activity-induced structural changes constitute a shared endpoint. Potentiation of S–C synapses in field CA1 entails integrin-driven assembly of stable actin networks in dendritic spines and an associated shift in spine/synapse morphology . Morphometric studies have yet to be performed for lppLTP but results obtained with the toxin latrunculin A, which selectively blocks actin filament assembly, confirm that in this system the cytoskeletal reorganization is located presynaptically . Thus, integrin regulation of the cytoskeleton, via signaling common to cell adhe sion junctions throughout the body, underlies both forms of potentiation but in the case of lppLTP these processes are active on the presynaptic side. This specialized feature of the LPP results in a new form of LTP. Earlier work showed that LTP induction in the LPP requires stimulation of mGluR5 receptors, something that was not the case for field CA1 or the medial perforant path . The mGluR5 receptor forms a postsynaptic signalosome with the scaffolding protein Homer and the 2-AG synthesizing enzyme diacylglycerol lipase-α . Activation of this unit results in de novo 2-AG production and retrograde signaling to presynaptic CB1Rs, 2 events shown to be essential for lppLTP . The present results establish that this dependency is not due to canonical CB1R signaling, which produces depression of transmitter release at sites throughout the brain. Instead, the critical contribution of CB1Rs to lppLTP involves activation of the integrin-associated kinase FAK and its downstream effector ROCK with high-frequency afferent activity. We found that the CB1R inverse agonist AM251 prevented such activation, whereas the CB1R agonist WIN mimicked it and also lowered the threshold for induction of lppLTP. Conversely, the release depression function of the CB1R was poorly developed in the LPP and not involved in the potentiation effect. ECB-mediated release suppression is reportedly sensitive to locally synthe sized pregnenolone and involves phosphory lation of the vesicular protein Munc18-1 . These effects were evident in S–C projections to CA1 but not in the LPP. Specifically, treatment with CB1R agonist WIN increased phosphorylation of Munc18-1 and caused a Munc18-1 dependent, pregnenolone-sensitive depression of synaptic responses in field CA1. In contrast, neither pregnenolone nor reductions in Munc18- 1 expression affected lppLTP. We propose that a shift in the bias of CB1R signaling away from the Munc18-1 pathway and toward facilitation of the ROCK/FAK, integrin signaling cascade constitutes a projection system-specific specialization that enables the thus far singular form of LTP found in the LPP . Ligands for CB1R, including the ECBs, synthetic cannabinoids such as WIN and phytocannabinoids such as Δ9 -tetrahydrocannabinol, all bind different residues on the receptor. This has been suggested to give rise to ligand-specific conformational changes in CB1R leading to activation of different downstream signaling pathways . Moreover, the functional selectivity of a given ligand can be cell-type-specific . In line with these observations, we found cell-type-specific differences in CB1R-mediated responses to a given ligand and differences in CB1R response to different ligands for a given cell-type . The evidence for projection-specific differences in CB1R signaling gives rise to the prediction that modulation of synaptic transmission by ECBs during behaviorally relevant patterns of synaptic activity, a topic that has received surprisingly little attention, will differ between the S–C and LPP systems. Tests confirmed that stimulation in the low-frequency gamma range, selected to simulate the activity in fields CA3 and CA1 during exploration , engages CB1Rs to depress synaptic responses generated by the S–C, but not LPP, projections. Thus, the projection-specific bias in CB1R function is likely to differentially influence throughput across the nodes of the primary hippocampal network. An interesting issue for future research concerns the extent to which the contribution of ECBs to synaptic function is frequency-tuned and differs across hippocampal rhythms associated with various behaviors. Prior work showed that blocking or enhancing the production of 2-AG produces corresponding effects on both the magnitude of lppLTP and the encoding of olfactory cues carried to hippocampus by the LPP system . The present experiments demonstrate that olfactory discrimination learning elicits evidence for potentiation in the form of increased presynaptic pROCK within the LPP. Questions thus arise about the functional significance of using a specialized form of plasticity to encode the semantic information carried by the LPP. One possibility is that the specialization helps to maintain cue identity through downstream hippocampal processing. The novel lppLTP effect changes the frequency facilitation char acteristics of the LPP, as evidenced by paired-pulse measurements, something that would be expected to alter the spiking response of granule cells to patterned input. This would serve to differentiate the DG outputs produced by learned versus unlearned cues and help maintain cue identity through down stream processing. It would also further distinguish the response of granule cells to input arriving over the LPP from those elicited by the subjacent medial perforant path . Related to this, insertion of a 2-AG step in the mechanisms for encoding opens the way for modulation of lppLTP by afferents arising from sites other than entorhinal cor tex. Cholinergic inputs from the medial septum and diagonal bands are of particular interest in this regard because enhancing constitutive transmission in this projection elevates 2-AG levels and related CB1R signaling in terminals. We used this effect to confirm that the Munc18-1 release suppression system is present in the LPP although not engaged by WIN or afferent stimulation. The studies also demonstrated that increasing cholinergic transmission has a strong positive effect on the production lppLTP, particularly when release suppression machinery is blocked with pregnenolone. It is, therefore, possible that particular patterns of firing by septal afferents or levels of pregnenolone synthesis promote the presynaptic LTP in the LPP while depressing the postsynaptic variant found in the medial perforant path.

We recognize few generalizations can be made with a sample of 19 adolescents; however, an a priori power analysis indicated a sample of 18 participants would be sufficient to conclude significant differences. Our experimental peer influence manipulation, while novel, has limitations, such as we did not measure whether or how attractive participants believed the photographs of the “peer” in manipulation to be. Additionally, we were not able to time how long participants viewed the data and photograph on the screen, though we did monitor participants from our periphery to ensure they saw the monitor before the experimenter approached them to proceed. We are unable to draw conclusions about whether an opposite-sex peer is more influential than a same-sex peer because we did not have a comparison condition in our study. However, our study is the first to successfully introduce an opposite-sex peer influence manipulation in an adolescent sample.While we find our result pertaining to ventral striatum activation enticing, we hesitate to draw broad conclusions, as the variation in self-reported resistance to peer influence is slight. We suggest future research enroll a larger sample to test the differences, and perhaps focus on collecting self-esteem and risk preference information to determine whether these indices moderate or predict experimentally manipulated and self-reported susceptibility to peer influence. The present study validated the Resistance to Peer Influence questionnaire by using an experimentally manipulated peer influence task that asked adolescents about their real-world social behaviors. While other studies have manipulated peer influence in adolescence, we successfully did so in an ecologically valid manner—by collecting information from adolescents regarding their likelihood to engage in risky social behaviors typical of teenagers. While overall self-reported peer influence was not directly associated with experimentally manipulated peer influence, we found variation within question types,equipment for growing weed such that specific types of peer influence were more predictive of changes in specific behaviors .

We propose that adolescents demonstrated greater variability within these types of questions because they are not susceptible to all forms of risk taking, and do not partake in all types of risks. We conclude that adolescents who are more susceptible to peer influence are more considerate of their peers’ perspectives and have a greater desire to be accepted socially—leading to an increased likelihood to engage in behaviors adolescents believe their peers endorse. Interacting with peers is critical for social development, and how one chooses to respond to peer feedback may have significant implications for adolescents, particularly because of the heightened experimentation with drugs of abuse and peer influence during this developmental window. Sensitivity to peer feedback, peer influence, and substance use do not occur independently during adolescence; but surprisingly, these phenomena are often assessed independently of one another. In the last decade or so, research using brain imaging has revealed the neural substrates that might underlie these characteristic adolescent behaviors. One region in particular, the ventral striatum, has been linked to risk taking and susceptibility to peer influence . This dissertation makes a novel contribution to the literature in that it associates ventral striatum response to social violations of expectations with self-reported real-world social behaviors in adolescents. This dissertation implemented multiple methodologies, including self-report, novel experimental designs, and fMRI to examine how adolescents respond to peer feedback, and whether their response is associated with their real-world social behaviors.

Results indicate that adolescents prefer to learn they are accurate about their expectations that pertain to their friendship, over and above learning something better than expected from a friend . This suggests a social violation of expectations from a friend is not necessarily a welcomed experience for an adolescent, perhaps because adolescents encounter an abundance of social uncertainty in their daily lives and are on alert for violations in their social encounters in an effort to adjust their behavior to fit in with their peers. However, a positive violation of expectations from an unknown other may be a welcomed experience by comparison because adolescents would have fewer relationship priors by which to set their expectations. Thus, for unknown peers, we suggest positive violations of expectations may be rewarding to an adolescent, while for well-known peers, non-violations of expectations are more rewarding by comparison. It is then likely that learning they are accurate about their social expectations within their friendship is somewhat of a “relief” signal , whereby adolescents do not need to make the cognitive effort to update their expectations about a relationship that is important to them. It is unknown whether there are developmental differences in meeting or exceeding expectations within a close friendship. We suggest future studies examine differences in meeting/positively violating expectations in an adolescent and adult sample between close friends and unknown-peers to elucidate these supposed differences, as this information may have implications for further identifying a sensitive period for social learning. This study also revealed increased activation in the ventral striatum for positive social violations of expectations, and increased activation in the insula and subgenual anterior cingulate cortex for negative social violations of expectations, though not for non-social violations of expectations. Taken together with self-reported happiness, these results suggest that during adolescence, learning a friend said something better than expected about the friendship is rewarding, while learning a friend said something worse than expected about the friendship is disconcerting by comparison.

This study presents novel fMRI and self-report results comparing valence of social statements, and suggests that adolescents are sensitive to social feedback from a friend. In addition to the neurobiological and self-reported happiness results, this study revealed that adolescents were fastest when their expectations were increasingly positively exceeded. This result could have implications for understanding adolescent behavior in an affective context, where experiencing a negative social violation of expectations from a friend may give a teenager reason to pause and update his expectations; a social positive violation of expectations from a friend may accelerate decision-making in a social context. Future research should consider assessing the differences between positive social violations of expectations, and meeting social expectations within a close friendship in adolescents—while both may be rewarding, the violation magnitude of the former may be more inherently confusing or conflicting, and result in more impulsive behavior. Ventral striatum response to violations of expectations from a friend was found to be associated with real-world socially acceptable substance use, as reported by adolescents . Categorically defining substances by which are “socially acceptable” compared to those that are less socially acceptable or are perceived to have greater consequences by comparison may elucidate distinct differences in the association of recruited brain regions or behavioral differences. Most research has associated ventral striatum response to general substance use ,grow tables 4×8 including drugs not frequently used by adolescents. Because adolescents report using alcohol, tobacco, and cannabis more so than other substances , this association suggests that the rewarding experience of using these substances transcends the neurochemical rewarding effects of them and perhaps permeates the rewarding experience of social interactions. In addition to the results presented in Chapter 3, this also suggests that substance use would not be as rewarding to adolescents if it was independent of social factors, and that the interaction of using these substances that are socially acceptable exacerbates the reward response. The aforementioned theory is supported by the results reported in Chapter 4, such that the adolescents who reported using socially acceptable substances reported being susceptible to peer influence and demonstrated susceptibility to experimentally manipulated peer influence, indicating they cared about being accepted by their peers, using substances perhaps as a means to be accepted by their peers and experience a greater sensation of reward.

The experimental peer influence task was validated by the self-report resistance to peer influence measure, contributing to the literature in suggesting likelihood to use socially acceptable substances increases the more adolescents demonstrate a desire to fit in. Thus, adolescents who avoid using these types of substances may not care as much about peer acceptance and social status amongst their peers—perhaps finding reward either in prosocial or academic activities; while adolescents who use substances that are less socially acceptable by comparison may find more reward in using substances than the contextual factors associated with them —suggesting environmental and historical factors may contribute to these individual differences . This suggests that using tobacco, alcohol, and cannabis occurs in adolescence due to the socially rewarding experience that is associated with them. While novel, the social violations of expectations task used in Study 1 precludes us from identifying whether ventral striatal response to social or non-social reward may be more closely associated with self reported substance use and susceptibility to peer influence—as it is a social task. While our data suggest ventral striatum activation to social violations is associated with the aforementioned variables, future studies should consider implementing a social and non-social design to compare whether ventral striatum activation to rewarding social feedback is more closely associated with likelihood to use substances and succumb to peer influence. Taken together, this research suggests ventral striatal response to social feedback from a friend is associated with self-reported real world socially rewarding behaviors. Future research should consider developing a model to examine adolescent responses to socially rewarding experiences as a predictor of behaviors that occur in social contexts, such as using socially acceptable substances and succumbing to peer influence. This association trifecta provides essential insight into adolescent risk taking, suggesting that beyond the chemical properties of reward, social feedback may exacerbate the experience of reward in adolescence, such that adolescents who care to be accepted by their peers and are attuned to peer feedback are more likely to engage in socially accepting behaviors. This research has important implications for examining real world behaviors through a violations of expectations framework. Results from all three studies indicate there may be distinct types of adolescents—those who are already using socially acceptable substances and require a greater violation of expectations to experience reward; and those who are likely to use socially acceptable substances, are susceptible to peer influence, and require a decreased violation of expectations to experience reward by comparison. Using this basic social learning construct may function as an aid in predicting which adolescents may fit into either group, and whether the adolescents who are susceptible to peer influence eventually become more resistant to it, and require a greater social violation of expectations in order to experience the sensation of reward in a social context.People with HIV are twice as likely to engage in heavy alcohol use and two to three times more likely to meet criteria for an alcohol use disorder in their lifetime than the general population . Heavy alcohol use not only promotes the transmission of HIV through sexual risk-taking behavior and non-adherence to antiretroviral therapy , but also directly exacerbates HIV disease burden by compromising the efficacy of ART and increasing systemic inflammation . In addition to increased risk for physical illness , there is substantial evidence indicating that comorbid HIV and heavy alcohol use is more detrimental to brain structure and results in higher rates of neurocognitive impairment than either condition alone . The impact of comorbid HIV and heavy alcohol use on the central nervous system is especially important to consider in the context of aging. The population of older adults with HIV is rapidly growing; approximately 48% of PWH in the U.S. are aged 50 and older and the prevalence of PWH over the age of 65 increased by 56% from 2012 to 2016 . Trajectories of neurocognitive and brain aging appear to be steeper in PWH , possibly due to chronic inflammation and immune dysfunction, long-term use of ART, frailty, and cardiometabolic comorbidities . In addition to HIV, rates of alcohol use and misuse are also rising in older adults . The neurocognitive and physical consequences of heavy alcohol use are more severe among older than younger adults, and several studies also report accelerated neurocognitive and brain aging in adults with AUD . While mechanisms underlying these effects are poorly understood, older adults may be more vulnerable to alcohol-related neurotoxicity due to a reduced capacity to metabolize alcohol, lower total-fluid volume, and diminished physiologic reserve to withstand biological stressors . Altogether, these studies support a hypothesis that PWH may be particularly susceptible to the combined deleterious effects of aging and heavy alcohol use. For example, in a recent longitudinal report, Pfefferbaum et al. reported that PWH with comorbid alcohol dependence exhibited faster declines in brain volumes in the midposterior cingulate and pallidum above and beyond either condition alone.

Functional Magnetic Resonance Imaging research has identified the striatum as a key hub in PE learning , along with the insula and anterior cingulate cortex . These regions also exhibit significant neurodevelopment during adolescence . Indeed, the first study to have examined PE in adolescents found that teenagers exhibit a similar, albeit stronger striatal response for positive PE compared to adults , and a more recent study found adolescents learn faster from reward PE than adults , suggesting that key PE learning systems are similar though perhaps more sensitive during adolescence. In the current study, we adopted a violations of expectations framework, which is reflective of both the PE calculation as well as the social context in which it occurs. Within this framework, we sought to determine whether adolescents show exaggerated behavioral responses to VoEs, and to extend this question to examine whether they demonstrate unique neural responses when they receive expected and unexpected social feedback from a friend. In adults, social learning tasks with relationship partners and conspecifics implicate a similar neural network as that involved in PE, suggesting that PE computations are conserved across domains. Adolescents spend much of their time with friends but it is unknown whether specific peer feedback , valence, and value from known peers influences behavior and recruitment of still-maturing neural regions. Although several studies have examined adolescent neural reactivity to unexpected peer feedback and peer evaluation ,trimming cannabis few have done so within the context of a close friend, whose opinion may yield more realistic behavioral and neural responses.

The goal of this study was to identify the neural mechanisms associated with learning social information from a friend using a novel social PE task in adolescents. Exploring this phenomenon in adolescents is important compared to other developmental age groups because adolescents often rely on their friends’ opinions to form perceptions of themselves , and learn many social skills necessary for development during this time from their friends. Because building up social expectations is challenging in a laboratory setting, we leveraged real-life social expectations between friends and manipulated them in the laboratory. We hypothesized that adolescents would: 1) demonstrate decreased reaction time when expectations were met compared to when they were violated ; 2) report feeling happier learning their friend reported something better than they expected compared to something worse than what they expected ; 3) activate brain regions previously associated with PE, such as the ventral striatum when they learned something better than expected from their friend; and 4) activate regions associated with socioemotional processing, such as the subgenual anterior cingulate cortex when they learned something worse than expected from their friend. Participants completed a Social Violations of Expectations task while undergoing a brain scan. In this task, we presented target participants with statements that were purportedly based on the friends’ responses to the Friendship Questionnaire. The responses were presented as if they represented the friend’s true response, but in fact they were manipulated. To create positive violations of expectations, we changed the friend’s responses to be greater than the target’s expectation . To meet the expectations of the participant, we modified the friend’s response to match the target’s prediction.

To create negative violations of expectations, we modified the friend’s response to be worse than the target’s expectation . Because the dyads were close friends, participants tended to have relatively positive expectations of their friends’ responses, which limited our ability to change valence and VoE value of the friend’s “responses”. Thus, during the session, each participant was presented with an average of 14.96 positive violations, 7.04 items where expectations were met, and 17.88 negative violations. The task was programmed in E-Prime 2.0 and was presented through an LCD Optoma projector connected via fiber optic cables. Participants were presented with all 40 statements from the Friendship Questionnaire and were asked to press a button on a 4-button button box with their right index finger to proceed to the next question/trial. The trial began with the presentation of the question, followed by the target’s expectation, a 2000-6000ms jittered interstimulus-interval , their friend’s “response,” a jittered ISI, and a request to press a button to proceed to the next trial followed by a 4000-8000ms jittered inter-trial-interval . Participants were allotted a maximum of 5000 ms to press the button before a jittered fixation cross appeared on the screen, and the subsequent trial began . Following the scan, participants completed a questionnaire that contained each statement from the Friendship Questionnaire, along with their predictions and their friend’s “responses.” For example, participants were reminded of the statement, “My friend thinks I’m nice” and were shown that they expected their friend to report 6, while their friend “reported” 10. They were asked to report how seeing this made them feel on a scale of 1 to 10 . The present study was a within-subjects, event related design. Our independent variable was the violation of expectation, operationalized by modifying the friend’s initial response to be better than, equal to, or worse than the target’s expectation. Our dependent variables were 1) behavioral response, 2) self-reported response, and 3) neural activation when targets experienced a violation of expectations. Behavioral response was measured by indexing reaction time to press a button on a response box to move on to the next trial. Self-reported responses were collected via survey following completion of the task. Neural activation was examined using a priori regions of interest .

Behavioral Analyses IBM SPSS Statistics Software, version 23.0 was used to analyze RT and self-report responses to social violations of expectations. The data were analyzed three ways: 1) effects of expected versus unexpected information; 2) effects of valence ; and 3) parametric effects of incremental differences between the expectations and the associated outcomes—which was represented by violations that ranged between 9 values less than their expectation and 9 values greater than their expectation . fMRI Analyses Images were collected using a 3-Tesla Siemens Trio MRI machine equipped with 16- channels at the Staglin Center for Cognitive Neuroscience at UCLA. Two structural MRI images were collected at the start of the scan: a T1-weighted magnetization-prepared rapid-acquisition gradient echo image , 2000 ms; echo time , 2100 ms; matrix, 256 x 256; and field of view, 250 mm) and a T2- weighted matched bandwidth high-resolution scan,vertical cannabis which was prescribed to the functional images. One functional run was collected and consisted of a maximum of 440 and an average of 382 T2*-weighted echo-planar images . The first three TRs of the run were automatically discarded. Data preprocessing and analyses were conducted using the FMRIB Software Library version 5.0 . Images were corrected for motion using MCFLIRT and denoised using multivariate exploratory linear optimized decomposition into independent components analysis. Data were smoothed using a 5-mm full width-half-maximum Gaussian kernel and filtered with a nonlinear high-pass filter . A three-step registration process was used to align individual participant data into standard Montreal Neurological Institute space. EPI images were first registered to the matched band width image, then to the MPRAGE image, and finally to MNI space. Two subjects’ data required truncating of the last 115 volumes due to excess motion in the latter half of the scan. Data were analyzed using a subtraction method to model violations of expectations, the difference between the outcome and the expectation .Six motion parameters were included as covariates in the model for each run for each of the participants. Statistical analyses were performed on each participant’s data using a general linear model to observe neural activation associated with change in expectations. Each participant’s data were modeled using a three-column regressor that contained the onset of each event , its duration, and a standard weight of 1 . Neuroimaging analyses were performed three ways to examine neural response to the following: 1) social versus non-social trials); 2) violations versus nonviolations of expectations; and 3) valence of information . To compare neural activation to violations versus nonviolations of expectations, we averaged all VoE values different from 0 and tested them against VoE0 . To compare neural activation by valence , violations between VoE-9 and VoE-1 were grouped and averaged as negative trials, non-violations were grouped and averaged to represent when expectations were not violated , and VoE+1 to VoE+9 were grouped and averaged as positive trials; respectively. Analyses were conducted using FMRI expert analysis tool , first at a lower level to represent one level of a condition within an individual subject, then at a second level using a fixed-effects model to represent all levels of a condition for one subject. Finally, data were analyzed at a group level analysis using FMRIB’s Local Analysis of Mixed Effects with automatic outlier detection to group all participants together and compare contrasts of interest. Structural ROI masks containing a cluster radius of 6 voxels were created for the amygdala, dorsal anterior cingulate cortex , insula, subgenual anterior cingulate cortex , and ventral striatum based on probability maps from Neurosynth . These masks were added as the Pre-threshold Masks for each respective ROI and were clustered at the voxel level with a Z threshold of 2.3 and probability threshold of p = .05. To compare the RT between trial types to information type , a two-way repeated measures analysis of variance was performed.

This analysis did not reveal a main effect of trial type or information, or an interaction . To determine whether there were differences between valences in the violations, we ran a two-way repeated measures ANOVA comparing trial type to valence of the violations . The results revealed no main effect of valence or interaction between trial type and valence 1 . Thus, we sought to determine whether there were parametric differences between VoE values. Because not all participants had the same number of valence and value trials, a cross classification analysis was performed by indexing each variable of interest by each individual trial. This analysis enabled us to account for the variation that naturally occurred within each participant’s responses, as well as between participants. A regression was performed on the reorganized cross-classified data to account for 1) each trial for each participant; and 2) each VoE value associated with each trial.The goal of this study was to characterize the neural correlates of social violations of expectations in adolescents based on feedback from a close friend. Behaviorally, we found that adolescents’ reaction times decreased linearly as social expectations transitioned from negative to increasingly positive violations. Self-reported happiness increased linearly for social information, as social expectations transitioned from negative to increasingly positive violations. Correlational analyses indicated participants who reported closer friendships were happier to learn they were accurate in their expectations about their friendship, while participants who were not as close were happier when their expectations were positively violated. Neurobiologically, participants demonstrated greater recruitment of the VS for social positive compared to social negative violations; and greater recruitment of the subACC and insula for social negative compared to social positive violations. These results are in accordance with previous literature, such that increased reaction time to negative social expectations may have reflected greater cognitive interference on these trials , especially when the stimuli are emotional in nature . This may have been true specifically for increasingly negative social violations compared to positive social violations, as positive social violations may not have been as surprising to participants who were close friends. Thus, we speculate that participants’ self reported closeness may have contributed to this result, whereby participants were more surprised to receive negative social feedback from their friend.Interestingly, we found participants who reported being closer friends reported feeling happier when expectations were not violated compared to when they were violated, and were increasingly happier as social expectations were increasingly positively violated. Reminding participants of their predictions and their friends’ responses may have felt threatening whereby participants knew their friend could have reported something worse than they expected. In turn, this may have amplified the happiness they reported when expectations were met, perhaps indicating they were relieved and were pleased to experience reciprocity or something better than what they expected. We posit that experiencing a violation of any kind is conflicting and emotionally arousing for an adolescent, as they are hyper-sensitive to peer feedback, and learning they are incorrect about their friendship may be disconcerting compared to learning they are correct.