Wrangling Weirdness: Lessons Learned from Academic Law Library Collections

Academic law libraries face some challenges that are consistent with larger trends in higher education. However, there are unique aspects that shape the way collections are selected, evaluated, managed, and promoted. Most electronic resources designed for legal research do not generate COUNTER compliant usage data. Many subscription resources and services that libraries provide access to are primarily geared towards non-academic customers, such as law firms and corporations. Patrons increasingly need and request research products that rely on data collection, personalization, and non-IP access controls, which complicates law librarians’ professional commitment to things like preserving patron privacy and providing walk-in access. Law library technical services departments are perpetually negotiating these and other challenges to ensure the needs of law faculty and students are met as seamlessly as possible. Some of these methods and strategies might be applicable to other types of libraries navigating unfamiliar issues

Expression of Ifnlr1 on intestinal epithelial cells is critical to the antiviral effects of IFN-lambda against norovirus and reovirus

Lambda interferon (IFN-λ) has potent antiviral effects against multiple enteric viral pathogens, including norovirus and rotavirus, in both preventing and curing infection. Because the intestine includes a diverse array of cell types, however, the cell(s) upon which IFN-λ acts to exert its antiviral effects is unclear. Here, we sought to identify IFN-λ-responsive cells by generation of mice with lineage-specific deletion of the receptor for IFN-λ, Ifnlr1. We found that expression of IFNLR1 on intestinal epithelial cells (IECs) in the small intestine and colon is required for enteric IFN-λ antiviral activity. IEC Ifnlr1 expression also determines the efficacy of IFN-λ in resolving persistent murine norovirus (MNoV) infection and regulates fecal shedding and viral titers in tissue. Thus, the expression of Ifnlr1 by IECs is necessary for the response to both endogenous and exogenous IFN-λ. We further demonstrate that IEC Ifnlr1 expression is required for the sterilizing innate immune effects of IFN-λ by extending these findings in Rag1-deficient mice. Finally, we assessed whether our findings pertained to multiple viral pathogens by infecting mice specifically lacking IEC Ifnlr1 expression with reovirus. These mice phenocopied Ifnlr1-null animals, exhibiting increased intestinal tissue titers and enhanced reovirus fecal shedding. Thus, IECs are the critical cell type responding to IFN-λ to control multiple enteric viruses. This is the first genetic evidence that supports an essential role for IECs in IFN-λ-mediated control of enteric viral infection, and these findings provide insight into the mechanism of IFN-λ-mediated antiviral activity. IMPORTANCE Human noroviruses (HNoVs) are the leading cause of epidemic gastroenteritis worldwide. Type III interferons (IFN-λ) control enteric viral infections in the gut and have been shown to cure mouse norovirus, a small-animal model for HNoVs. Using a genetic approach with conditional knockout mice, we identified IECs as the dominant IFN-λ-responsive cells in control of enteric virus infection in vivo. Upon murine norovirus or reovirus infection, Ifnlr1 depletion in IECs largely recapitulated the phenotype seen in Ifnlr1(−/−) mice of higher intestinal tissue viral titers and increased viral shedding in the stool. Moreover, IFN-λ-mediated sterilizing immunity against murine norovirus requires the capacity of IECs to respond to IFN-λ. These findings clarify the mechanism of action of this cytokine and emphasize the therapeutic potential of IFN-λ for treating mucosal viral infections

Impact of Cardiorespiratory Fitness on Markers of Cardiovascular Disease in Professional Firefighters

Higher cardiorespiratory fitness (CRF) levels (V̇O2max) are associated with lower oxidative stress and inflammatory markers in addition to lower cardiovascular disease (CVD) risk; however, there are a lack of data examining this relationship among firefighters. CVD is the leading cause of mortality among firefighters and correlates with low CRF. PURPOSE: To examine differences in markers of CVD risk between firefighters classified as having either high or low levels of CRF. METHODS: Forty-six professional firefighters performed a maximal graded exercise test (GXT; Bruce Protocol), where V̇O2max was estimated from the Foster equation using time to exhaustion. Fasted blood samples were also taken to assess traditional and non-traditional biomarkers of CVD risk: HDL, LDL, glucose, cholesterol, triglycerides, advanced oxidation protein products (AOPP), homeostatic model assessment for insulin resistance (HOMA-IR) and C-reactive protein (CRP). Body fat percentage (BF%) was determined via Dual-Energy X-Ray Absorptiometry (DEXA),V̇O2max values were categorized based on American College of Sports Medicine (ACSM) guidelines to establish a high fitness group (n=19; V̇O2max = 44.7 ± 5.2 ml·kg-1·min-1; age = 35.94 ± 9.73 yrs; height = 178.86 ± 7.28 cm; waist circumference = 35.5 ± 2.73 cm; BF% = 19.9 ± 2.66) and a low fitness group (n=27; V̇O2max = 28.2 ± 4.9ml·kg-1·min-1; age = 38.5 ± 9.33 yrs; height = 179.21 ± 8.48 cm; waist circumference = 40.06 ± 4.29 cm; BF% = 27.2 ± 5.07). Non-parametric Mann-Whitney U tests were used to assess differences in CVD risk markers between the high and low fitness groups. Effect sizes were calculated as Cohen’s d (i.e., small [0.2-0.5], medium [0.5-0.8], large [\u3e 0.8]). RESULTS: Participants classified as high fitness had significantly (p \u3c 0.05) higher V̇O2max and HDL concentrations coupled with significantly lower BF%, cholesterol, triglycerides, LDL, insulin, HOMA-IR, CRP, and AOPP. Half of the observed differences demonstrated a medium effect size (LDL, insulin, HOMA-IR, CRP, and AOPP), while large effect sizes were noted for V̇O2max, BF%, cholesterol, triglycerides, HDL, LDL/HDL risk ratio. CONCLUSION: The high fitness group exhibited lower CVD risk levels and higher HDL levels compared to the low fitness group. Considering the results, firefighters are encouraged to maintain high CRF as well as lower BF% in an effort to reduce the risk of CVD and on-duty cardiac events

Relationship Between Body Composition, Body Fat Distribution, and Blood Lipids Among Law Enforcement Officers: Part 2

Law enforcement officers (LEOs) have a high-stress occupation, which is prone to cardiovascular disease (CVD). Data suggest a 1.7-fold higher CVD prevalence versus the general public, in addition to 40.5% of LEOs being classified as obese. Emerging evidence suggests that lipid-related atherosclerotic risk may be better captured by including advanced blood lipid panels (i.e., cholesterol particle type and size). However, there needs to be more research regarding the relationship between body composition, body fat distribution, and advanced blood lipid panels concerning CVD risk in LEOs. PURPOSE: To determine if body composition and fat distribution measures correlate with predictive advanced lipid markers in LEOs. METHODS: Forty-three LEOs (male: n=40; Female: n=3; age = 41.7±9.6 yrs; weight = 91.9±15.4 kg; height = 179.8±8.7 cm; VO2max: 37.0±6.1 ml/kg/min) from a local police department were evaluated. Fasting blood samples were collected to assess biomarkers of CVD risk: number of low-density lipoprotein particles (LDL-p), small LDL-p, LDL size (LDL-s), number of high-density lipoprotein particles (HDL-p), large HDL-p, HDL size (HDL-s), number of very low-density lipoprotein particles (VLDL-p), and VLDL size (VLDL-s). Dual-energy x-ray absorptiometry was used to measure body composition. Bivariate Pearson correlation matrix and ordinary least squares (OLS) regression analyses were used to examine the relationship between body composition and fat distribution. RESULTS: The Bivariate Pearson correlation matrix revealed higher body weight, lean mass, visceral adipose tissue, and gynoid adiposity correlated with several advanced lipid biomarkers. The OLS regression analysis revealed Body weight to be positively predictive (p\u3c0.05) of LDL-p and small LDL-p but inversely predictive (p\u3c0.05) of LDL-s, large HDL-p, and HDL-s; Lean mass to be positively predictive of LDL-p, small LDL-p, but inversely predictive of LDL-s, HDL-p, large HDL-p, and HDL-s; Visceral adipose tissue to be positively predictive of small LDL-p and large VLDL-p, but inversely predictive of LDL-s, large HDL-p, and HDL-s; and gynoid fat distribution to be positively predictive of HDL-p, large HDL-p, and HDL-s. CONCLUSION: Changes in body composition seen in LEOs with increased weight and fat distribution showed correlations with advanced blood lipid markers, which can be predictive of high CVD risk and other potential medical conditions. These data provide insight into the association of body composition and fat distribution with markers of CVD risk (i.e., advanced blood lipids)

Predictors of Cardiometabolic Disease Risk Factors in Professional Firefighters

The leading cause of mortality (~50% of deaths) among on-duty firefighters is sudden cardiac death. Firefighters with adequate cardiorespiratory fitness levels (among other muscular fitness metrics) and lower body fat percentage (BF%) are likely to better combat on-duty cardiac events and cardiovascular disease (CVD) risk. Individuals with higher VO2max values may be at lower risk noted by lower oxidative stress and inflammatory biomarkers, which may be more ideal predictors of CVD risk compared to traditional biomarkers (i.e., blood glucose and lipids) among the fire community; however, more research is needed to elucidate. PURPOSE: This study examined the relationship between fitness metrics, body fat percentage, and traditional and non-traditional biomarkers among professional firefighters. METHODS: Ninety-eight professional, male firefighters (age = 36.26 ± 9.08 yrs; height = 179.53 ± 7.06 cm; waist circumference = 37.99 ± 4.13 cm; BF% = 24.39 ± 5.21; years of experience = 11.81 ± 8.00 yrs) from a local fire department were studied VO2max was estimated from total treadmill exercise time using the Foster equation.. Fitness metrics including muscular strength, endurance, and power variables were also measured. Fasted blood samples were analyzed for concentrations of lipids, glucose, insulin resistance (HOMA-IR), advanced oxidation protein products (AOPP), and ultra-sensitive C-reactive protein (CRP). To assess the relationship between fitness metrics and AOPP, CRP, and HOMA-IR, ordinary least square regression analyses were used. RESULTS: VO2max values were inversely (p \u3c 0.05) related to AOPP, HOMA-IR, and CRP. Waist circumference was positively correlated to AOPP concentrations and HOMA-IR, while increased BF% was significantly related to increased CRP concentrations. CONCLUSION: High VO2max values were significantly related to lower AOPP, CRP, and HOMA-IR. Additionally, high waist circumference and BF% values were related to increases in oxidative stress, inflammation, and insulin resistance. Firefighters are encouraged to maintain high cardiorespiratory fitness (VO2max) and lower BF% to reduce CVD and, ultimately, on-duty sudden cardiac death risk

Relationship Between Body Composition, Body Fat Distribution, and Blood Lipids Among Law Enforcement Officers: Part 1

Law enforcement officers (LEOs) have a high-stress occupation which is prone to cardiovascular disease (CVD). In fact, data suggest that LEOs have a 1.7-fold higher CVD prevalence versus the general public, in addition to 40.5% of LEOs being classified as obese. However, research is lacking regarding the relationship between body composition, body fat distribution, and blood lipid panels as it pertains to CVD risk in LEOs. PURPOSE: To determine if body composition and fat distribution measures correlate with predictive lipid markers in LEOs. METHODS: Forty-three LEOs (age = 41.7±9.6 yrs; weight = 91.9±15.4 kg; height = 179.8±8.7 cm; VO2max: 37.0±6.16 ml/kg/min) from a local police department were evaluated. Fasting blood samples were collected to assess biomarkers of CVD risk: low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and triglycerides (TG). Dual-energy x-ray absorptiometry was used to measure body composition and body fat distribution. Bivariate Pearson correlation matrix was used to determine correlations (p\u3c0.05* and p\u3c0.01**). To further assess the relationship between body composition, fat distribution measures, and blood lipids, ordinary least square (OLS) regression analyses were used. RESULTS: Lower body weight correlated with greater HDL concentrations (r=-0.432**). Higher fat mass correlated with greater TG concentrations (r=0.338*), while greater lean mass was inversely correlated with HDL concentrations (r=-0.496**). Android and gynoid adiposity were positively correlated with greater TG (r=0.359*) and HDL (r=0.320*) concentrations, respectively. Lastly, higher visceral adipose tissue was correlated with greater TG concentrations (r=0.430**). The OLS regression analysis revealed (p\u3c0.05) 1) weight was inversely predictive of HDL, 2) Fat mass was positively predictive of TG, 3) lean mass was inversely predictive of HDL, 4) android adiposity was positively predictive of TG, 5) gynoid adiposity was positively predictive of HDL, and 6) visceral adipose tissue was positively predictive of TG. CONCLUSION: Measures of body composition seen in LEOs with increased body fat showed positive correlations with blood lipid markers (TG and HDL), which can be predictive of high CVD risk and other potential medical conditions. These data provide insight into the association of body composition and fat distribution with markers of CVD risk

Descriptive Analysis of a Baseline Concussion Battery Among U.S. Service Academy Members: Results from the Concussion Assessment, Research, and Education (CARE) Consortium

Introduction The prevalence and possible long-term consequences of concussion remain an increasing concern to the U.S. military, particularly as it pertains to maintaining a medically ready force. Baseline testing is being used both in the civilian and military domains to assess concussion injury and recovery. Accurate interpretation of these baseline assessments requires one to consider other influencing factors not related to concussion. To date, there is limited understanding, especially within the military, of what factors influence normative test performance. Given the significant physical and mental demands placed on service academy members (SAM), and their relatively high risk for concussion, it is important to describe demographics and normative profile of SAMs. Furthermore, the absence of available baseline normative data on female and non-varsity SAMs makes interpretation of post-injury assessments challenging. Understanding how individuals perform at baseline, given their unique individual characteristics (e.g., concussion history, sex, competition level), will inform post-concussion assessment and management. Thus, the primary aim of this manuscript is to characterize the SAM population and determine normative values on a concussion baseline testing battery. Materials and Methods All data were collected as part of the Concussion Assessment, Research and Education (CARE) Consortium. The baseline test battery included a post-concussion symptom checklist (Sport Concussion Assessment Tool (SCAT), psychological health screening inventory (Brief Symptom Inventory (BSI-18) and neurocognitive evaluation (ImPACT), Balance Error Scoring System (BESS), and Standardized Assessment of Concussion (SAC). Linear regression models were used to examine differences across sexes, competition levels, and varsity contact levels while controlling for academy, freshman status, race, and previous concussion. Zero inflated negative binomial models estimated symptom scores due to the high frequency of zero scores. Results Significant, but small, sex effects were observed on the ImPACT visual memory task. While, females performed worse than males (p < 0.0001, pη2 = 0.01), these differences were small and not larger than the effects of the covariates. A similar pattern was observed for competition level on the SAC. There was a small, but significant difference across competition level. SAMs participating in varsity athletics did significantly worse on the SAC compared to SAMs participating in club or intramural athletics (all p’s < 0.001, η2 = 0.01). When examining symptom reporting, males were more than two times as likely to report zero symptoms on the SCAT or BSI-18. Intramural SAMs had the highest number of symptoms and severity compared to varsity SAMs (p < 0.0001, Cohen’s d < 0.2). Contact level was not associated with SCAT or BSI-18 symptoms among varsity SAMs. Notably, the significant differences across competition level on SCAT and BSI-18 were sub-clinical and had small effect sizes. Conclusion The current analyses provide the first baseline concussion battery normative data among SAMs. While statistically significant differences may be observed on baseline tests, the effect sizes for competition and contact levels are very small, indicating that differences are likely not clinically meaningful at baseline. Identifying baseline differences and significant covariates is important for future concussion-related analyses to inform concussion evaluations for all athlete levels

Psychedelics Promote Structural and Functional Neural Plasticity.

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both&nbsp;structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in&nbsp;vitro and in&nbsp;vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders

Conversion of the LIMA1 tumour suppressor into an oncogenic LMO-like protein by API2-MALT1 in MALT lymphoma.

MALT1 is the only known paracaspase and is a critical mediator of B- and T-cell receptor signalling. The function of the MALT1 gene is subverted by oncogenic chimeric fusions arising from the recurrent t(11;18)(q21;q21) aberration, which is the most frequent translocation in mucosa-associated lymphoid tissue (MALT) lymphoma. API2-MALT1-positive MALT lymphomas manifest antibiotic resistance and aggressive clinical behaviour with poor clinical outcome. However, the mechanisms underlying API2-MALT1-induced MALT lymphomagenesis are not fully understood. Here we show that API2-MALT1 induces paracaspase-mediated cleavage of the tumour suppressor protein LIMA1. LIMA1 binding by API2-MALT1 is API2 dependent and proteolytic cleavage is dependent on MALT1 paracaspase activity. Intriguingly, API2-MALT1-mediated proteolysis generates a LIM domain-only (LMO)-containing fragment with oncogenic properties in vitro and in vivo. Importantly, primary MALT lymphomas harbouring the API2-MALT1 fusion uniquely demonstrate LIMA1 cleavage fragments. Our studies reveal a novel paracaspase-mediated oncogenic gain-of-function mechanism in the pathogenesis of MALT lymphoma.This work was supported in part by NIH grants R01 DE119249 and R01 CA136905 (K.S.J.E-J.), R01 CA140806 (M.S.L.) and the Department of Pathology at the University of Michigan.This is the accepted manuscript. The final version is available from Nature at http://www.nature.com/ncomms/2015/150108/ncomms6908/full/ncomms6908.html