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Sleep and circadian timing shifts later during adolescence, conflicting with early school start times, and resulting in circadian misalignment. Although circadian misalignment has been linked to depression, substance use, and altered reward function, a paucity of experimental studies precludes the determination of causality. Here we tested, for the first time, whether experimentally-imposed circadian misalignment alters the neural response to monetary reward and/or response inhibition.
Healthy adolescents (n = 25, ages 13–17) completed two in-lab sleep schedules in counterbalanced order: An ‘aligned’ condition based on typical summer sleep-wake times (0000–0930) and a ‘misaligned’ condition mimicking earlier school year sleep-wake times (2000–0530). Participants completed morning and afternoon functional magnetic resonance imaging scans during each condition, including monetary reward (morning only) and response inhibition (morning and afternoon) tasks. Total sleep time and circadian phase were assessed via actigraphy and salivary melatonin, respectively.
Bilateral ventral striatal (VS) activation during reward outcome was lower during the Misaligned condition after accounting for the prior night's total sleep time. Bilateral VS activation during reward anticipation was lower during the Misaligned condition, including after accounting for covariates, but did not survive correction for multiple comparisons. Right inferior frontal gyrus activation during response inhibition was lower during the Misaligned condition, before and after accounting for total sleep time and vigilant attention, but only during the morning scan.
Our findings provide novel experimental evidence that circadian misalignment analogous to that resulting from school schedules may have measurable impacts on healthy adolescents' reward processing and inhibition of prepotent responses.
ABSTRACT IMPACT: We hope to provide a more nuanced understanding of the type-III IFN system, thereby exploring its therapeutic potential in the realm of infectious diseases. OBJECTIVES/GOALS: The role of IFNLR1 receptor dynamics and plasticity in regulating the type-III IFN response is largely unknown. As a specific, powerful component of innate immunity, understanding how the type-III IFN system is regulated could lead to the development of novel therapeutic targets and strategies to face a multitude of viral illnesses. METHODS/STUDY POPULATION: To facilitate our investigation, we will generate doxycycline-inducible FLAG-tagged IFNLR1-expression plasmids representing all known transcriptional variants. These plasmids will allow us to: 1) Evaluate the effect of IFNLR1 surface abundance on the type-III IFN transcriptional profile and 2) Assess the extent of IFNLR1-FLAG co-localization with several notable intracellular structures using immunofluorescence, before and after stimulation with IFNL3. RESULTS/ANTICIPATED RESULTS: We have successfully generated three IFNLR1-FLAG transcriptional variants and confirmed inducible-expression and function in vitro. We are currently assessing the role of surface abundance, internalization, differential isoform expression, and trafficking. DISCUSSION/SIGNIFICANCE OF FINDINGS: By completing this study, we hope to provide a more nuanced understanding of the type-III IFN system, thereby exploring its therapeutic potential in the realm of infectious diseases.
The term ‘green economy’ re-emerged over a decade ago as a buzzword in notably inconclusive discussions across the globe amongst politicians, civil servants, business, non-governmental organisations (NGOs), community interest groups, the media and academics. By offering the possibility of integrating economic priorities with more ecologically sensitive and socially just forms of overall progress, the concept of a green economy outwardly seems to provide some guidance and direction for achieving long-term sustainability across a range of tiers of governance and different types of economy. We argue that the notion of a green economy remains elusive and is deeply disputed, often poorly understood and unevenly applied. Hence, it is in danger of remaining both unworkable and marginalised. This chapter traces the development of the concept, not only in Europe but beyond, in order to provide context for the deliberations in Europe. The chapter also outlines contemporary debates, and identifies emerging themes in order to argue that the idea of a green economy, as currently practiced, requires urgent rethinking and application. This chapter also furnishes background for the remainder of this edited volume, in which European case studies are presented that grapple with definitional issues and the practical challenges of implementation.
Evidence is limited on how to synthesize and incorporate the views of stakeholders into a multisite pragmatic trial and how much academic teams change study design and protocol in response to stakeholder input. This qualitative study describes how stakeholders contributed to the design, conduct, and dissemination of findings of a multisite pragmatic clinical trial, the COMprehensive Post-Acute Stroke Services (COMPASS) Study. We engaged stakeholders as integral research partners by embedding them in study committees and community resource networks that supported local sites. Data stemmed from formal focus groups and continuous participation in working groups. Guided by Grounded Theory, we extracted themes from focus group and meeting notes. These were discussed as a team and with other stakeholder groups for feasibility. A consensus approach was used. Stakeholder input changed many aspects of the study including: the care model that treated stroke as a chronic condition after hospital discharge, training for hospital-based providers who often lacked awareness of the barriers to recovery that patients face, support for caregivers who were essential for stroke patients’ recovery, and for community-based health and social service providers whose services can support recovery yet often go underutilized. Stakeholders brought value to both pragmatic research and health service delivery. Future studies should test the impact of elements of study implementation informed by stakeholders vs those that are not.
Weed control of paraquat can be erratic and may be attributable to differing species sensitivity and/or environmental factors for which minor guidance is available on commercial labels. Therefore, the objectives of this research were to quantify selectivity of paraquat across select weed species and the influence of environmental factors. Experiments were performed under controlled conditions in the greenhouse and growth chamber. Compared with purple deadnettle (dose necessary to reduce shoot biomass by 50% = 39 g ai ha−1), waterhemp, Palmer amaranth, giant ragweed, and horseweed were 4.9, 3.3, 1.9, and 1.3 times more sensitive to paraquat, respectively. The injury progression rate over 3 d after treatment (DAT) was a more accurate predictor of final efficacy at 14 DAT than the lag phase until symptoms first appeared. For example, at the 17.5 g ha−1 dose, the injury rate of waterhemp and Palmer amaranth was, on average, 3.6 times greater than that of horseweed and purple deadnettle. The influence of various environmental factors on paraquat efficacy was weed specific. Applications made at sunrise improved control of purple deadnettle over applications at solar noon or sunset. Lower light intensities (200 or 600 μmol m−2 s−1) surrounding the time of application improved control of waterhemp and horseweed more than 1,000 μmol m−2 s−1. Day/night temperatures of 27/16 C improved horseweed and purple deadnettle control compared with day/night temperatures of 18/13 C. Though control was positively associated with injury rates in the application time of day and temperature experiments, a negative relationship was observed for waterhemp in the light-intensity experiment. Thus, although there are conditions that enhance paraquat efficacy, the specific target species must also be considered. These results advocate paraquat dose recommendations, currently based on weed height, be expanded to address sensitivity differences among weeds. Moreover, these findings contrast with paraquat labels stating temperatures of 13 C or lower do not reduce paraquat efficacy.
Endogenous cannabinoids assist in regulation of hunger, pain perception, inflammation, and stress responses. Tetrahydrocannabinol (THC), a component of cannabis, activates cannabinoid receptors, producing effects that are often emotionally pleasing and cognitively interesting. THC effects impair complex tasks, such as driving. Addiction develops in 8--10 percent of all cannabis users, and in about 25 percent of daily users. Regular adolescent users are especially vulnerable. Adverse outcomes of cannabis addiction include too much time spent intoxicated, important activities given up, worsening of psychological problems, and failed attempts to stop use. The withdrawal syndrome includes irritability, anxiety, depression, and sleep difficulties. Long-term heavy use of cannabis is associated with academic failure and subtle cognitive impairment. Medical uses of cannabis include relief of nausea, appetite improvement, and lessened neuropathic pain. Medical use may increase cannabis addiction, a risk somewhat similar to that of other, more traditional medications for pain, anxiety, and attention disorders. Because cannabis is now a commercial product, its potency has increased in recent years.
This textbook surveys the current knowledge on substance use disorders (SUD), summarizing scientific evidence from numerous fields. It uses a biopsychosocial framework to integrate the many factors that contribute to addictions, from genetic predispositions, neurological responses caused by drugs, co-occurring psychiatric disorders, personality traits, and developmental conditions to cultural influences. Real-life vignettes and first-person accounts build understanding of the lived experience of addiction. The currently accepted practices for diagnosis and treatment are presented, including the role of 12-step programmes and other mutual-assistance groups. The text also investigates the research methods that form the foundation of evidence-based knowledge. The main body text is augmented by study guideposts such as learning objectives, review exercises, highlighted key terms, and chapter summaries, which enable more efficient comprehension and retention of the book's material.
According to behavioral theory, positive and negative reinforcement, along with stimuli associated with positive or negative incentives, control SUD as well as benign drug use. Cognitive theory adds the influence of the social context and human cognition. Positive reinforcement, often experienced as pleasure, is most effective immediately after a given behavior – such as addictive drug use. Negative reinforcement (relief of an aversive state) also has powerful behavioral control. Addictive drugs temporarily relieve many unpleasant conditions, including the shame and guilt of addiction. Any aversive (punishing) consequences usually appear much later, decreasing their power to suppress behavior. When drugs are easily available and intoxication is tolerated in a society, heavy use is more prevalent, abuse is enabled, and addiction develops in those with fewer risk factors. Eventually, after losses resulting from heavy drug use, further use may be the only available coping tactic and source of reward. Continued drug use brings additional harm, but now has even greater control over behavior because it is the sole source of even temporary relief.