753 research outputs found

    Sharing as Risk Pooling in a Social Dilemma Experiment

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    In rural economies with missing or incomplete markets, idiosyncratic risk is frequently pooled through informal networks. Idiosyncratic shocks, however, are not limited to private goods but can also restrict an individual from partaking in or benefiting from a collective activity. In these situations, a group must decide whether to provide insurance to the affected member. In this paper, we describe results of a laboratory experiment designed to test whether a simple sharing institution can sustain risk pooling in a social dilemma with idiosyncratic risk. We test whether risk can be pooled without a commitment device and, separately, whether effective risk pooling induces greater cooperation in the social dilemma. We find that even in the absence of a commitment device or reputational considerations, subjects voluntarily pool risk thereby reducing variance in individual earnings. In spite of effective risk pooling, however, cooperation in the social dilemma is unaffected

    Comparing Vertical and Horizontal Screening Methods for Pharmacy Resident Candidates Before Interviews

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    Purpose: Prior studies have examined autobiographical screening methods among medical student applicants, and demonstrated halo bias with single-rater scoring; though others have questioned its practical significance. Comparing with traditional vertical screening method, we evaluated a horizontal method for initial screening of Post-Graduate Year-1 (PGY-1) pharmacy practice resident candidate applications prior to interviews. Methods: Our screening rubric for PGY-1 pharmacy residency candidates consisted of eight criteria, each scored using a 5-point Likert scale. During the 2014 residency recruitment season, two single-evaluators (A&B) scored all eight criteria and their scores were summed into total application scores (vertical method). Meanwhile two other evaluators (C&D) each evaluated only two criteria for all applications. The four combined-evaluators (A-D) scores, on two criteria each, were summed together into total application scores (horizontal method). For statistical comparison of single-evaluator and combined-evaluators, inter-component reliabilities were analyzed for each evaluator, while inter-rater consistency was also examined. For practical significance, actual selection differences were reviewed. Results:Forty-six applications were evaluated to determine 24 invitations for on-site interviews. Inter-component reliability differed among evaluatorA, evaluatorB, combined-evaluators A-D (Cronbach’s alpha of 0.74, 0.73, 0.58, respectively; lower better). Among raters, inter-rater consistency was excellent (0.86 by intraclass correlation, p Conclusion: Halo bias was seen with the single-evaluators (vertical method); two interview invitations were negatively impacted. For pharmacy resident screening, a horizontal screening method appears to be rigorous in promoting fairness for applicants. As pharmacy residency applications continue to grow, a fair and time-efficient method of screening seems imperative.   Type: Original Researc

    Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice

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    <p>Abstract</p> <p>Background</p> <p>Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified <it>R</it>-flurbiprofen (tarenflurbil) as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic <it>R</it>-flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice.</p> <p>Results</p> <p>A four-month preventative treatment regimen with <it>R</it>-flurbiprofen (10 mg/kg/day) was administered to young Tg2576 mice prior to robust plaque or Aβ pathology. This treatment regimen improved spatial learning as assessed by the Morris water maze, indicated by an increased spatial bias during the third probe trial and an increased utilization of a place strategy to solve the water maze. These results are consistent with an improvement in hippocampal- and medial temporal lobe-dependent memory function. A modest, though not statistically significant, reduction in formic acid-soluble levels of Aβ was also observed. To determine if R-flurbiprofen could reverse cognitive deficits in Tg2576 mice where plaque pathology was already robust, a two-week therapeutic treatment was given to older Tg2576 mice with the same dose of <it>R</it>-flurbiprofen. This approach resulted in a significant decrease in Aβ plaque burden but no significant improvement in spatial learning.</p> <p>Conclusion</p> <p>We have found that chronic administration of <it>R</it>-flurbiprofen is able to attenuate spatial learning deficits if given prior to plaque deposition in Tg2576 mice. Given its ability to selectively target Aβ42 production and improve cognitive impairments in transgenic APP mice, as well as promising data from a phase 2 human clinical trial, future studies are needed to investigate the utility of <it>R</it>-flurbiprofen as an AD therapeutic and its possible mechanisms of action.</p

    Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football

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    IMPORTANCE: Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE). OBJECTIVE: To determine the neuropathological and clinical features of deceased football players with CTE. DESIGN, SETTING, AND PARTICIPANTS: Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history. EXPOSURES: Participation in American football at any level of play. MAIN OUTCOMES AND MEASURES: Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia. RESULTS: Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre–high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia. CONCLUSIONS AND RELEVANCE: In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.This study received support from NINDS (grants U01 NS086659, R01 NS078337, R56 NS078337, U01 NS093334, and F32 NS096803), the National Institute on Aging (grants K23 AG046377, P30AG13846 and supplement 0572063345-5, R01 AG1649), the US Department of Defense (grant W81XWH-13-2-0064), the US Department of Veterans Affairs (I01 CX001038), the Veterans Affairs Biorepository (CSP 501), the Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (grant B6796-C), the Department of Defense Peer Reviewed Alzheimer’s Research Program (grant 13267017), the National Operating Committee on Standards for Athletic Equipment, the Alzheimer’s Association (grants NIRG-15-362697 and NIRG-305779), the Concussion Legacy Foundation, the Andlinger Family Foundation, the WWE, and the NFL

    A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity

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    Epidemiological studies have documented a reduced prevalence of Alzheimer's disease among users of nonsteroidal anti-inflammatory drugs (NSAIDs). It has been proposed that NSAIDs exert their beneficial effects in part by reducing neurotoxic inflammatory responses in the brain, although this mechanism has not been proved. Here we report that the NSAIDs ibuprofen, indomethacin and sulindac sulphide preferentially decrease the highly amyloidogenic Aβ42 peptide (the 42-residue isoform of the amyloid-β peptide) produced from a variety of cultured cells by as much as 80%. This effect was not seen in all NSAIDs and seems not to be mediated by inhibition of cyclooxygenase (COX) activity, the principal pharmacological target of NSAIDs. Furthermore, short-term administration of ibuprofen to mice that produce mutant β-amyloid precursor protein (APP) lowered their brain levels of Aβ42. In cultured cells, the decrease in Aβ42 secretion was accompanied by an increase in the Aβ(1–38) isoform, indicating that NSAIDs subtly alter γ-secretase activity without significantly perturbing other APP processing pathways or Notch cleavage. Our findings suggest that NSAIDs directly affect amyloid pathology in the brain by reducing Aβ42 peptide levels independently of COX activity and that this Aβ42-lowering activity could be optimized to selectively target the pathogenic Aβ42 species

    Revisiting Soil C and N Sampling: Quantitative Pits vs. Rotary Cores

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    Increasing atmospheric carbon dioxide and its feedbacks with global climate have sparked renewed interest in quantifying ecosystem carbon (C) budgets, including quantifying belowground pools. Belowground nutrient budgets require accurate estimates of soil mass, coarse fragment content, and nutrient concentrations. It has long been thought that the most accurate measurement of soil mass and coarse fragment content has come from excavating quantitative soil pits. However, this methodology is labor intensive and time consuming. We propose that diamond-tipped rotary cores are an acceptable if not superior alternative to quantitative soil pits for the measurement of soil mass, coarse fragment content, C and total nitrogen (N) concentrations. We tested the rotary core methodology against traditional quantitative pits at research sites in California, Nevada, and New York. We found that soil cores had 16% higher estimates of less than 2-mm soil mass than estimates obtained from quantitative pits. Conversely, soil cores had 8% lower estimates of coarse fragment mass compared with quantitative pits. There were no statistical differences in measured C or N concentrations between the two methods. At the individual site level, differences in estimates for the two methods were more pronounced, but there was no consistent tendency for cores to overestimate or underestimate a soil parameter when compared with quantitative pits

    A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory

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    The SNARE-mediated vesicular transport pathway plays major roles in synaptic remodeling associated with formation of long-term memories, but the mechanisms that regulate this pathway during memory acquisition are not fully understood. Here we identify miRNAs that are up-regulated in the rodent hippocampus upon contextual fear-conditioning and identify the vesicular transport and synaptogenesis pathways as the major targets of the fear-induced miRNAs. We demonstrate that miR-153, a member of this group, inhibits the expression of key components of the vesicular transport machinery, and down-regulates Glutamate receptor A1 trafficking and neurotransmitter release. MiR-153 expression is specifically induced during LTP induction in hippocampal slices and its knockdown in the hippocampus of adult mice results in enhanced fear memory. Our results suggest that miR-153, and possibly other fear-induced miRNAs, act as components of a negative feedback loop that blocks neuronal hyperactivity at least partly through the inhibition of the vesicular transport pathway.Brain & Behavior Research Foundation (Young Investigator Award)JPB Foundatio

    Financing Direct Democracy: Revisiting the Research on Campaign Spending and Citizen Initiatives

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    The conventional view in the direct democracy literature is that spending against a measure is more effective than spending in favor of a measure, but the empirical results underlying this conclusion have been questioned by recent research. We argue that the conventional finding is driven by the endogenous nature of campaign spending: initiative proponents spend more when their ballot measure is likely to fail. We address this endogeneity by using an instrumental variables approach to analyze a comprehensive dataset of ballot propositions in California from 1976 to 2004. We find that both support and opposition spending on citizen initiatives have strong, statistically significant, and countervailing effects. We confirm this finding by looking at time series data from early polling on a subset of these measures. Both analyses show that spending in favor of citizen initiatives substantially increases their chances of passage, just as opposition spending decreases this likelihood
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