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Higher education institutions continually increase the demands on college instructors. Yet, all too often, many college instructors have had little to no preparation for teaching in higher education. What is needed is a comprehensive and clear list of characteristics expected of effective college teachers, both in-person and online, comprised by those who are focused on studying the subject matter deeply. To assess the characteristics deemed essential for college instructors to possess, a nationwide, modified Delphi technique was employed, eliciting opinions from an established panel of experts. At the conclusion of a three-round Delphi study, 46 of the 55 original items submitted by the panelists reached consensus of agreement. The 46 items were then categorized to establish six overarching themes associated with effective college teaching. The categorized themes and characteristics determined in the study of effective college teachers should be used as a comprehensive and clear list to provide college faculty with expectations of effective teaching. Additional research is needed to convert the items found in this study into an effective college teaching instrument. Such an instrument should be validated for use across academia as a starting point for the development, training, and support of future and current college teachers.

Abstract This paper describes the design and performance of a compact detector, BDX-MINI, that incorporates all features of a concept that optimized the detection of light dark matter in the MeV-GeV mass range produced by electrons in a beam dump. It represents a reduced version of the future BDX experiment expected to run at JLAB. BDX-MINI was exposed to penetrating particles produced by a 2.176 GeV electron beam incident on the beam dump of Hall A at Jefferson Lab. The detector consists of 30.5 kg of PbWO $$_4$$ 4 crystals with sufficient material following the beam dump to eliminate all known particles except neutrinos. The crystals are read out using silicon photomultipliers. Completely surrounding the detector are a passive layer of tungsten and two active scintillator veto systems, which are also read out using silicon photomultipliers. The design was validated and the performance of the robust detector was shown to be stable during a six month period during which the detector was operated with minimal access.

Abstract Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we have developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are highest in liver tissue, which is also a hub for lipid production. While the loss of GSH does not cause liver failure, it decreases lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we find that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver’s balance of redox buffering and triglyceride production.

We assigned the side-chain resonances of the Crimean–Congo hemorrhagic fever virus (CCHFV) glycoprotein n (Gn) cytosolic domain that is 69 amino acids long to complete the backbone resonances previously published by Estrada et al. (2011). The process was facilitated by three factors. First, sample preparation using cell-free protein synthesis (CFPS) was completed in less than 2 d and allowed for correct zinc finger formation by adding zinc ions to the reaction. Second, access to NMR platforms with standardized pulse sequences allowed for data acquisition in 18 d. Third, data analysis using the online platform NMRtist allowed sequential resonance assignments to be made in a day, and assignments were verified and finalized in less than a week. Our work thus provides an example of how NMR assignments, including side chains, of small and well-behaved proteins can be approached in a rapid routine, at protein concentrations of 150 µM.

This paper presents the development and execution of a specialised university training program designed to support Peer Support Advisors (PSAs) within The Living Room: a low barrier peer-led mental health service. The primary objective was to investigate the training program's impact on the knowledge and attitudes of PSAs. Two questionnaires were administered: a pre-training questionnaire to establish participants' initial attitudes and knowledge levels, and a post-training questionnaire to assess any changes following completion of the program. Additionally, a feedback questionnaire was used to gather qualitative insights on the training experience. The integration of qualitative narrative accounts with quantitative data facilitated a thorough understanding of the program's effects. The results revealed a consistent enhancement in confidence and understanding among PSAs post-training, indicating significant improvements in their knowledge and attitudes relevant to their roles. The study highlights the effectiveness of this training approach in bolstering PSA skills and capabilities. The Living Room's PSA training program exemplifies the positive impact of such initiatives on students' ability to provide effective peer support. Key insights include the importance of inclusivity, awareness of available services, and practical application of acquired skills in diverse student contexts. The utilisation of pre/post assessments and feedback surveys offers a robust framework for evaluating training efficacy and overall participant satisfaction. These findings emphasise the value of investing in comprehensive training programs to empower peers and cultivate a supportive university community. --- The Living Room peer support training: Leading the way in unlocking mental health benefits for university students in peer-led service models in higher education by Amanda L. Cole & Dawn Reid is licensed under CC BY 4.0

Abstract Cannabidiol (CBD) is widely used in sports for recovery, pain management, and sleep improvement, yet its effects on muscle are not well understood. This study aimed to determine the transcriptional response of murine skeletal muscle myotubes to broad‐spectrum CBD and synthetic CBD (sCBD). Differentiated C2C12 myotubes were treated with 10 μM CBD, sCBD, or vehicle control (DMSO) for 24 h before RNA extraction. Poly‐A tail‐enriched mRNA libraries were constructed and sequenced using 2 × 50 bp paired‐end sequencing. CBD and sCBD treatment induced 4489 and 1979 differentially expressed genes (DEGs; p

Background Nearly half of the global population has some form of oral health-related disease primarily associated with caries or tooth decay, periodontal disease, tooth loss or oral cancer. Oral and face pains are a primary motivator for healthcare consultation. While not specifically included in global estimates, orofacial pain associated with oral diseases and orofacial pain disorders pose significant global public health and financial burdens. Thus, it is paramount to act on opportunities to improve the practice of medicine in dentistry.Examined Literature and Conceptual Advancement This article centers on areas for improvement in the fields of oral health and dentistry in defining, evaluating, and treating musculoskeletal orofacial pains, a category of pain disorders within orofacial pain leading to physical pain and both mental and physical disability. We discuss how features of dentistry, current modes of specialist training, and cultural norms have inadvertently created barriers to improvements in care quality and may even promote harms to patient groups with musculoskeletal pain. We provide critical insights and solutions in patient safety and quality improvement efforts from other areas of medicine, such as in emergency or acute care settings.Practical Implications Because musculoskeletal orofacial pains are a wide-spread, common, and costly constellation of oral health disorders, they represent a keystone treatment area for the fields of dentistry and oral health to bridge with existing patient safety and quality improvement efforts. We conclude by providing several recommendations from lessons learned in patient safety and quality improvement applied to musculoskeletal pain care. Collectively, these lessons stand to: (1) promote sharing of information, (2) encourage collaboration and transdisciplinary problem solving as a medical community, and (3) improve diagnostic accuracy and optimal delivery of the highest quality treatment as safely as possible for both patients and providers.

Spontaneous intracerebral hemorrhage (sICH) is associated with significant morbidity and mortality, with subsequent hematoma expansion (HE) linked to worse neurologic outcomes. Accurate, real-time predictions of the risk of HE could enable tailoring management—including blood pressure control or surgery—based on individual patient risk. Although multiple radiographic markers of HE have been proposed based on standard imaging, their clinical utility remains limited by a reliance on subjective interpretation of often ambiguous findings and a poor overall predictive power. Radiomics refers to the quantitative analysis of medical images that can be combined with machine-learning algorithms to identify predictive features for a chosen clinical outcome with a granularity beyond human limitations. Emerging data have supported the potential utility of radiomics in the prediction of HE after sICH. In this review, we discuss the current clinical management of sICH, the impact of HE and standard imaging predictors, and finally, the current data and potential future role of radiomics in HE prediction and management of patients with sICH.

The Study Demands and Resources Scale (SDRS) has shown promise as a valid and reliable measure for measuring students’ specific study demands and -resources. However, there is no evidence as to its psychometric properties outside of the original context in which it was developed. This study aimed to assess the psychometric properties of the SDRS in a cross-national student population through examining its longitudinal factorial validity, internal consistency, and temporal invariance as well as criterion validity through its association with study engagement and task performance over time. Results showed that a Bifactor Exploratory Structural Equation Model (ESEM) with one general factor (overall study characteristics) and five specific factors (workload, growth opportunities, lecturer support, peer support, information availability) fitted the data, showed strong measurement invariance over time, and was reliable at different time points. The study further established criterion validity for the overall study characteristics factor through its concurrent and predictive associations with study engagement and task performance. However, the specific factors’ concurrent and predictive capacity could only partially be established when controlling for the general study characteristics factor. These findings suggest that study characteristics should be measured as a dynamic interaction between study demands and resources, rather than a hierarchical model.

PurposeSomatic molecular profiling of pediatric brain tumors aids with the diagnosis and treatment of patients with a variety of high- and low-grade central nervous system neoplasms. Here, we report follow-up targeted germline evaluation for patients with possible germline variants following tumor only testing in the initial year in which somatic molecular testing was implemented at a single institution.Patients and MethodsSomatic testing was completed for all tumors of the central nervous system (CNS) undergoing diagnostic workup at Seattle Children’s Hospital during the study period of November 2015 to November 2016. Sequencing was performed in a College of American Pathologists-accredited, Clinical Laboratory Improvements Amendments-certified laboratory using UW-OncoPlex™ assay (version 5), a DNA-based targeted next generation sequencing panel validated to detect genetic alterations in 262 cancer-related genes. We tracked subsequent clinical evaluation and testing on a subgroup of this cohort found to have potential germline variants of interest.ResultsMolecular sequencing of 88 patients’ tumors identified 31 patients with variants that warranted consideration of germline testing. To date, 19 (61%) patients have been tested. Testing confirmed germline variants for ten patients (31% of those identified for testing), one with two germline variants (NF1 and mosaic TP53). Eight (26%) patients died before germline testing was sent. One patient (13%) has not yet had testing.ConclusionClinically validated molecular profiling of pediatric brain tumors identifies patients who warrant further germline evaluation. Despite this, only a subset of these patients underwent the indicated confirmatory sequencing. Further work is needed to identify barriers and facilitators to this testing, including the role of genetic counseling and consideration of upfront paired somatic-germline testing.

ObjectiveThis study examined the effects of a peer-led integrated nutrition education intervention with maternal social support using Care Groups on infant growth among South Sudanese refugees in Uganda.MethodsA community-based cluster-randomized trial (RCT) was conducted among 390 pregnant women (third trimester). Two intervention study arms were Mothers-only(n = 131) and Parents-combined (n = 142) with a Control (n = 117). WHO infant growth standards defined length-for-age z-scores (LAZ) for stunting, weight-for-age z-scores (WAZ) for underweight and weight-for-length z-scores (WLZ) for wasting. The Medical Outcomes Study (MOS) social support index was a proxy measure for social support. A split-plot ANOVA tested the interaction effects of social support, intervention, and time on infant growth after adjusting for covariates. Further, pairwise comparisons explained mean differences in infant growth among the study arms.ResultsThe mean infant birth weight was 3.1 ± 0.5 kg. Over the study period, infant stunting was most prevalent in the Control (≥ 14%) compared to Mothers-only (< 9.5%) and Parents-combined (< 7.4%) arms. There were significant interaction effects of the Care Group intervention and social support by time on infant mean LAZ (F (6, 560) = 28.91, p < 0.001), WAZ (F (5.8, 539.4) = 12.70, p = < 0.001) and WLZ (F (5.3, 492.5) = 3.38, p = 0.004). Simple main effects by the end of the study showed that the intervention improved infant mean LAZ (Mothers-only vs. Control (mean difference, MD) = 2.05, p < 0.001; Parents-combined vs. Control, MD = 2.00, p < 0.001) and WAZ (Mothers-only vs. Control, MD = 1.27, p < 0.001; Parents-combined vs. Control, MD = 1.28, p < 0.001).ConclusionMaternal social support with an integrated nutrition education intervention significantly improved infant stunting and underweight. Nutrition-sensitive approaches focused on reducing child undernutrition among post-emergency refugees may benefit from using Care Groups in programs.Trial registrationClinicaltrials.gov, NCT05584969.

Noninvasive imaging is central to preclinical, in vivo models of pancreatic ductal adenocarcinoma (PDAC). While bioluminescent imaging (BLI) is a gold standard, its signal is dependent on the metabolic activity of tumor cells. In contrast, dual energy X-ray absorptiometry (DEXA) is a direct measure of body composition. Thus, we aimed to assess its potential for longitudinal quantification of tumor burden versus BLI. We utilized the KCKO murine model of PDAC and subjected tumor-bearing (n = 20) and non-tumor control (NTC) (n = 10) animals to weekly BLI and DEXA measurements for up to 10 weeks. While BLI detected tumors at 1-week, it failed to detect tumor growth, displayed a decreasing trend overtime (slope = -9.0x108; p = 0.0028), and terminal signal did not correlate with ex vivo tumor mass (r = 0.01853; p = 0.6286). In contrast, DEXA did not detect elevated changes in abdominal cavity lean mass until week 2 post inoculation and tumors were not visible until week 3, but successfully quantified a tumor growth trend (slope = 0.7322; p

Abstract Introduction The adverse effects of corticosteroids are dose‐dependent, and guidance is to use the lowest effective dose in most disease states. The study facility recently reported a steroid stewardship program that reduced steroid dosing in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients by 50%. The purpose of this post‐hoc analysis was to evaluate the effect of this intervention on glycemic control in hospitalized AECOPD before and after cohorts. Methods This was a retrospective post‐hoc review of hospitalized patients in a before and after study design (n = 27 in each group). The primary endpoint was the proportion of glucose readings >180 mg/dL. Baseline characteristics, mean glucose levels, and corrective insulin were also collected. Continuous variables were compared with a Student's t‐test (or Mann–Whitney U where appropriate) and nominal variables with a chi‐square test in R Studio. Results There was a significantly higher proportion of glucose >180 mg/dL readings in the pre‐intervention cohort: 38% vs. 25% (p = 0.007). The mean glucose levels were numerically lower post‐intervention but did not reach statistical significance (160 mg/dL vs. 145 mg/dL, p = 0.27) both in diabetics (192 mg/dL vs. 181 mg/dl, p = 0.69) and non‐diabetics (142 mg/dL vs. 125 mg/dL, p = 0.08). The use of correctional insulin was similar: a median of 25 units vs. 24.5 units (p = 0.92). Conclusion A stewardship program focused on steroid reduction in AECOPD significantly lowered the proportion of hyperglycemic readings but did not significantly affect mean glucose and corrective insulin usage while hospitalized.

Seven new species of very small Gulella Pfeiffer, 1856 are described from two regions in the interior of south-eastern South Africa within the Maputaland-Pondoland-Albany biodiversity hotspot. In addition, the status of Gulella darglensis benthodon van Bruggen, 1980 is revised and raised to species level. All species are very small-shelled and are narrow-range endemics. Six species, G. judithmastersae sp. nov., G. kevincolei sp. nov., G. hlathikhulu sp. nov., G. nkandla sp. nov., G. mystica sp. nov. and G. libertas sp. nov. are each known from only one locality. The first two as well as G. benthodon and G. mcmasteri sp. nov. are found only in the Amathole Mountains, where poaching, illegal harvesting of plant products and uncontrolled access of cattle take place, including in protected areas. The other four species each occur at one locality in north-central KwaZulu-Natal. The localities of three of the last-mentioned species are in protected areas although they are isolated and surrounded by a heavily transformed cultural landscape rendering enforcement of conservation legislation a challenge. Six species occur in nature reserves, highlighting the importance of small pockets of protected habitat for the conservation of terrestrial snails.

Constitutional mismatch repair deficiency (CMMRD) is a cancer predisposition syndrome associated with the development of hypermutant pediatric high-grade glioma, and confers a poor prognosis. While therapeutic histone deacetylase (HDAC) inhibition of diffuse intrinsic pontine glioma (DIPG) has been reported; here, we use a clinically relevant biopsy-derived hypermutant DIPG model (PBT-24FH) and a CRISPR-Cas9 induced genetic model to evaluate the efficacy of HDAC inhibition against hypermutant DIPG. We screened PBT-24FH cells for sensitivity to a panel of HDAC inhibitors (HDACis) in vitro, identifying two HDACis associated with low nanomolar IC50s, quisinostat (27 nM) and romidepsin (2 nM). In vivo, quisinostat proved more efficacious, inducing near-complete tumor regression in a PBT-24FH flank model. RNA sequencing revealed significant quisinostat-driven changes in gene expression, including upregulation of neural and pro-inflammatory genes. To validate the observed potency of quisinostat in vivo against additional hypermutant DIPG models, we tested quisinostat in genetically-induced mismatch repair (MMR)-deficient DIPG flank tumors, demonstrating that loss of MMR function increases sensitivity to quisinostat in vivo. Here, we establish the preclinical efficacy of quisinostat against hypermutant DIPG, supporting further investigation of epigenetic targeting of hypermutant pediatric cancers with the potential for clinical translation. These findings support further investigation of HDAC inhibitors against pontine high-grade gliomas, beyond only those with histone mutations, as well as against other hypermutant central nervous system tumors.

Abstract Background Although treatment options and algorithms for rheumatoid arthritis (RA) have improved remarkably in recent decades, there continues to be no definitive cure or pharmacologic intervention with reliable long-term efficacy. For this reason, the combination of medications and healthy lifestyle modifications are essential for controlling joint disease, and extra-articular manifestations of RA, such as interstitial lung disease (ILD) and other lung pathologies, which greatly impact morbidity and mortality. Generally, exercise has been deemed beneficial in RA patients, and both patients and clinicians are motivated to incorporate effective non-pharmacologic interventions. However, there are limited evidence-based and specific exercise regimens available to support engagement in such activities for RA patients. Here, we provided the continuous opportunity for exercise to mice and implemented automated recording and quantification of wheel running behavior. This allowed us to describe the associated effects on the progression of inflammatory-erosive arthritis and ILD in the tumor necrosis factor transgenic (TNF-Tg) mouse model of RA. Methods Wild-type (WT; males, n=9; females, n=9) and TNF-Tg (males, n=12; females, n=14) mice were singly housed with free access to a running wheel starting at 2 months until 5 to 5.5 months of age. Measures of running included distance, rate, length, and number of run bouts, which were derived from continuously recorded data streams collected automatically and in real-time. In vivo lung, ankle, and knee micro-computed tomography (micro-CT), along with terminal micro-CT and histology were performed to examine the association of running behaviors and disease progression relative to sedentary controls. Results TNF-Tg males and females exhibited significantly reduced running distance, rate, length, and number of run bouts compared to WT counterparts by 5 months of age (p

The soil-dwelling larval stage of crane flies, commonly known as leatherjackets, are classified as agricultural pests in Europe, and pests of turf in North America and Canada. They cause significant damage and yield loss in many cropping systems through their feeding on plant roots and stems at ground level. The effective chemical control for these pests, chlorpyrifos (available since 1965), was prohibited across Europe in 2019. This has left severely restricted control options for growers. Unlike Northern Ireland and Great Britain, no leatherjacket surveys or routine identifications have been conducted across Ireland. Therefore, the leatherjacket species of agronomic importance has not been confirmed. Since lifecycles, feeding behaviour and damage periods differ between species, identifying the most common species is a vital first step in any pest management strategy. Here we report key findings from a 2-yr structured survey of Irish crops, conducted in 2019 and 2021, where 135 sites were sampled. Both grassland and cereal crops were inspected. Soil cores and soil samples were collected and larval abundance determined. The European crane fly, Tipula paludosa Meigen, accounted for approximately 70% of larvae collected and identified (n = 337). In 2019, 40% of grasslands exceeded the threshold of 1 million larvae/ha, while only 3.3% of cereal fields were over the threshold of 600,000 larvae/ha. These results indicate that agricultural grasslands in Ireland have the potential to be significantly impacted by leatherjacket damage, although this may vary temporally and geographically across the island. Without effective control options, yield losses will be highly probable.

Recent research has focused on identifying neural markers associated with risk for anxiety, including the error-related negativity (ERN). An elevated ERN amplitude has been observed in anxious individuals from middle childhood onward and has been shown to predict risk for future increases in anxiety development. The ERN is sensitive to environmental influences during development, including interpersonal stressors. Of note, one particular type of interpersonal stressor, relational victimization, has been related to increases in anxiety in adolescents. We tested whether relational victimization predicts increases in the ERN and social anxiety symptoms across two years in a sample of 152 child and adolescent females (ages 8 – 15). Results indicated that children and adolescents’ baseline ERN was positively related to the ERN two years later. Furthermore, greater relational victimization at baseline predicted greater increases in the ERN two years later, controlling for baseline ERN. Moreover, relational victimization at baseline predicted increases in social anxiety, and this relationship was mediated by increases in the ERN. These results suggest that relational victimization impacts the developmental trajectory of the neural response to errors and thereby impacts increases in social anxiety among children and adolescents.

Abstract Microstructure profiling was utilized to estimate vertical mixing (via vertical turbulent buoyancy flux) during a tidal pulse in the interior Merrimack River plume in calm winds. Multiple stratified shear mixing regimes appear and evolve with time. Initially the plume acts as a nearfield jet, with mixing in the plume (plume layer mixing) and over the plume‐ambient interface (nearfield interfacial mixing). As the plume grows, interfacial mixing is suppressed offshore of the nearfield as currents slow, diminishing turbulent exchange between plume and shelf. At the end of ebb, ambient tidal currents reverse direction below plume, initiating another mode of internal, interfacial mixing (coined here as tidal interfacial mixing), allowing exchange between plume and ambient waters offshore. This work highlights previously unreported tidally modulated mixing within the near and midfield of a river plume.

Strengths, Opportunities, Aspirations, and Results (SOAR) is a strengths-based framework for strategic thinking, planning, conversations, and leading that focuses on strengths, opportunities, aspirations, and results. The SOAR framework leverages and integrates Appreciative Inquiry (AI) to create a transformation process through generative questions and positive framing. While SOAR has been used by practitioners since 2000 as a framework for generating positive organizational change, its use in empirical research has been limited by the absence of reliable and valid measures. We report on the reliability, construct validity, and measurement invariance of the SOAR Scale, a 12-item self-report survey organized into four first-order factors (Strengths, Opportunities, Aspirations, and Results). Data from a sample of 285 U.S. professionals were analyzed in Mplus using confirmatory factor analysis and exploratory structural equation modeling. The Four-Factor first-order exploratory structure equation modeling (ESEM) had the best model fit. Measurement invariance tests found the scalar invariance of the SOAR Scale across gender and education groups. Implications are discussed for using the SOAR Scale to build resilience at the individual, the team, and the organizational levels.

Abstract Background Heme oxygenase-1 (HMOX1) catalyzes the metabolism of heme into carbon monoxide, ferrous iron, and biliverdin. Through biliverdin reductase, biliverdin becomes bilirubin. HMOX1-deficiency is a rare autosomal recessive disorder with hallmark features of direct antibody negative hemolytic anemia with normal bilirubin, hyperinflammation and features similar to macrophage activation syndrome. Clinical findings have included asplenia, nephritis, hepatitis, and vasculitis. Pulmonary features and evaluation of the immune response have been limited. Case presentation We present a young boy who presented with chronic respiratory failure due to nonspecific interstitial pneumonia following a chronic history of infection-triggered recurrent hyperinflammatory flares. Episodes included hemolysis without hyperbilirubinemia, immunodeficiency, hepatomegaly with mild transaminitis, asplenia, leukocytosis, thrombocytosis, joint pain and features of macrophage activation with negative autoimmune serologies. Lung biopsy revealed cholesterol granulomas. He was found post-mortem by whole exome sequencing to have a compound heterozygous paternal frame shift a paternal frame shift HMOX1 c.264_269delCTGG (p.L89Sfs*24) and maternal splice donor HMOX1 (c.636 + 2 T > A) consistent with HMOX1 deficiency. Western blot analysis confirmed lack of HMOX1 protein upon oxidant stimulation of the patient cells. Conclusions Here, we describe a phenotype expansion for HMOX1-deficiency to include not only asplenia and hepatomegaly, but also interstitial lung disease with cholesterol granulomas and inflammatory flares with hemophagocytosis present in the bone marrow.

Abstract Terrestrial organic carbon (OC) plays an important role in the carbon cycle, but questions remain regarding the controls and timescale(s) over which atmospheric CO2 remains sequestered as particulate OC (POC). Motivated by observations that terrestrial POC is physically stored within soils and other shallow sedimentary deposits, we examined the role that sediment storage plays in the terrestrial OC cycle. Specifically, we tested the hypothesis that sediment storage impacts the age of terrestrial POC. We focused on the Efri Haukadalsá River catchment in Iceland as it lacks ancient sedimentary bedrock that would otherwise bias radiocarbon‐based determinations of POC storage duration by supplying pre‐aged “petrogenic” POC. Our radiocarbon measurements of riverine suspended sediments and deposits implicated millennial‐scale storage times. Comparison between the sample types (suspended and deposits) suggested an age offset between transported (suspended sediments) and stored (deposits) POC at the time of sampling, which is predicted by theory for the sediment age distribution in floodplains. We also observed that POC in suspended sediments is younger than the predicted mean storage duration generated from independent geomorphological data, which suggested an additional role for OC cycling. Consistent with this, we observed interparticle heterogeneity in the composition of POC by imaging our samples at the microscale using X‐ray absorption spectroscopy. Specifically, we found that particles within individual samples differed in their sulfur oxidation state, which is indicative of multiple origins and/or diagenetic histories. Altogether, our results support recent coupled sediment storage and OC cycling models and indicate that the physical drivers of sediment storage are important factors controlling the cadence of carbon cycling.

A majority of ventures are started by entrepreneurial teams rather than individuals. More than half of team-based new venture failures are believed to be due to problems with the entrepreneurial team. Collaboration among entrepreneurial team members is important for increasing the likelihood of successful venture outcomes. We investigated collaboration in professionals working in teams using survey methodology. Results found a framework for collaborative dialogue, SOAR (strengths, opportunities, aspirations, and results), mediates the relationship between emotional intelligence and team collaboration. We discuss practical recommendations to increase the strength of the relationship between emotional intelligence and collaboration to increase entrepreneurial team performance. For example, behavioral coaches are recommended to use dialogical exercises to help team members develop emotional intelligence competencies of awareness and regulation of emtions in self and others. Entrepreneurs are recommended to create teams that build on member strengths and aspirations, and identify opportunities for achieving measurable positive results.

BackgroundHospitalizations for acute myocardial infarctions (AMIs) are associated with changes in statin adherence. It is unclear to what extent adherence changes, which patients are likely to change, and how post‐discharge follow‐up is associated with statin adherence change. Methods and ResultsThis retrospective study used Medicare data for all fee‐for‐service beneficiaries 66 years and older with an AMI hospitalization in 2008–2010 and statin use before their index AMI. Multivariable multinomial logistic regression models (odds ratio [OR] and 99% confidence interval [CI]) were applied to assess associations between both patient characteristics and follow‐up with a primary care provider and/or cardiologist with the outcome of statin adherence change (increase or decrease) from the 6‐month pre‐ to 6‐month post‐AMI periods. Of 113 296 patients, 64.0% had no change in adherence, while 19.7% had increased and 16.3% had decreased adherence after AMI hospitalization. Black and Hispanic patients were more likely to have either increased or decreased adherence than white patients. Patients who required coronary artery bypass graft surgery (OR, 1.34; 99% CI, 1.21–1.49) or percutaneous transluminal coronary angioplasty/stent procedure (OR, 1.25; 99% CI, 1.17–1.32) during their index hospitalization were more likely to have increased adherence. Follow‐up with a primary care provider was only mildly associated with increased adherence (OR, 1.08; 99% CI, 1.00–1.16), while follow‐up with a cardiologist (OR, 1.15; 99% CI, 1.05–1.25) or both provider types (OR, 1.21; 99% CI, 1.12–1.30) had stronger associations with increased adherence. ConclusionsPost‐AMI changes in statin adherence varied by patient characteristics, and improved adherence was associated with post‐discharge follow‐up care, particularly with a cardiologist or both a primary care provider and a cardiologist.

Thiazolidinedione (TZD) insulin sensitizers have the potential to effectively treat a number of human diseases, however the currently available agents have dose-limiting side effects that are mediated via activation of the transcription factor PPARγ. We have recently shown PPARγ-independent actions of TZD insulin sensitizers, but the molecular target of these molecules remained to be identified. Here we use a photo-catalyzable drug analog probe and mass spectrometry-based proteomics to identify a previously uncharacterized mitochondrial complex that specifically recognizes TZDs. These studies identify two well-conserved proteins previously known as brain protein 44 (BRP44) and BRP44 Like (BRP44L), which recently have been renamed Mpc2 and Mpc1 to signify their function as a mitochondrial pyruvate carrier complex. Knockdown of Mpc1 or Mpc2 in Drosophila melanogaster or pre-incubation with UK5099, an inhibitor of pyruvate transport, blocks the crosslinking of mitochondrial membranes by the TZD probe. Knockdown of these proteins in Drosophila also led to increased hemolymph glucose and blocked drug action. In isolated brown adipose tissue (BAT) cells, MSDC-0602, a PPARγ-sparing TZD, altered the incorporation of (13)C-labeled carbon from glucose into acetyl CoA. These results identify Mpc1 and Mpc2 as components of the mitochondrial target of TZDs (mTOT) and suggest that understanding the modulation of this complex, which appears to regulate pyruvate entry into the mitochondria, may provide a viable target for insulin sensitizing pharmacology.

Alzheimer's disease (AD), the most common cause of dementia in the elderly, has two pathological hallmarks: Aβ plaques and aggregation of hyperphosphorylated tau (p-tau). Aβ is a cleavage product of Amyloid Precursor Protein (APP). Presenilin 1 (PS1) and presenilin 2 (PS2) are the catalytic subunit of γ-secretase, which cleaves APP and mediates Aβ production. Genetic mutations in APP, PSEN1 or PSEN2 can lead to early onset of familial AD (FAD). Although mutations in the tau encoding gene MAPT leads to a subtype of frontotemporal dementia and these mutations have been used to model AD tauopathy, no MAPT mutations have been found to be associated with AD.To model AD pathophysiology in mice without the gross overexpression of mutant transgenes, we created a humanized AD mouse model by crossing the APP and PSEN1 FAD knock-in mice with the htau mice which express wildtype human MAPT genomic DNA on mouse MAPT null background (APP/PS1/htau). The APP/PS1/htau mice displayed mild, age-dependent, Aβ plaques and tau hyperphosphorylation, thus successfully recapitulating the late-onset AD pathological hallmarks. Selected biochemical analyses, including p-tau western blot, γ-secretase activity assay, and Aβ ELISA, were performed to study the interaction between Aβ and p-tau. Subsequent behavioral studies revealed that the APP/PS1/htau mice showed reduced mobility in old ages and exaggerated fear response. Genetic analysis suggested that the fear phenotype is due to a synergic interaction between Aβ and p-tau, and it can be completely abolished by tau deletion.The APP/PS1/htau model represents a valuable and disease-relevant late-onset pre-clinical AD animal model because it incorporates human AD genetics without mutant protein overexpression. Analysis of the mice revealed both cooperative and independent effects of Aβ and p-tau.

This study aims to explore the perceptions held by law students who work collaboratively with social work students. Findings from the focus group data indicate that law students’ perceptions of social work may be influenced by stereotypes. Implications for students preparing to enter into forensic social work practice are considered.

Heparan sulfate (HS) is an important regulator of the assembly and activity of various angiogenic signalling complexes. However, the significance of precisely defined HS structures in regulating cytokine-dependent angiogenic cellular functions and signalling through receptors regulating angiogenic responses remains unclear. Understanding such structure-activity relationships is important for the rational design of HS fragments that inhibit HS-dependent angiogenic signalling complexes.We synthesized a series of HS oligosaccharides ranging from 7 to 12 saccharide residues that contained a repeating disaccharide unit consisting of iduronate 2-O-sulfate linked to glucosamine with or without N-sulfate. The ability of oligosaccharides to compete with HS for FGF2 and VEGF165 binding significantly increased with oligosaccharide length and sulfation. Correspondingly, the inhibitory potential of oligosaccharides against FGF2- and VEGF165-induced endothelial cell responses was greater in longer oligosaccharide species that were comprised of disaccharides bearing both 2-O- and N-sulfation (2SNS). FGF2- and VEGF165-induced endothelial cell migration were inhibited by longer 2SNS oligosaccharide species with 2SNS dodecasaccharide activity being comparable to that of receptor tyrosine kinase inhibitors targeting FGFR or VEGFR-2. Moreover, the 2SNS dodecasaccharide ablated FGF2- or VEGF165-induced phosphorylation of FAK and assembly of F-actin in peripheral lamellipodia-like structures. In contrast, FGF2-induced endothelial cell proliferation was only moderately inhibited by longer 2SNS oligosaccharides. Inhibition of FGF2- and VEGF165-dependent endothelial tube formation strongly correlated with oligosaccharide length and sulfation with 10-mer and 12-mer 2SNS oligosaccharides being the most potent species. FGF2- and VEGF165-induced activation of MAPK pathway was inhibited by biologically active oligosaccharides correlating with the specific phosphorylation events in FRS2 and VEGFR-2, respectively.These results demonstrate structure-function relationships for synthetic HS saccharides that suppress endothelial cell migration, tube formation and signalling induced by key angiogenic cytokines.