Turning points: the personal and professional circumstances that lead academics to become middle managers

In the current higher education climate, there is a growing perception that the pressures associated with being an academic middle manager outweigh the perceived rewards of the position. This article investigates the personal and professional circumstances that lead academics to become middle managers by drawing on data from life history interviews undertaken with 17 male and female department heads from a range of disciplines, in a post-1992 UK university. The data suggests that experiencing conflict between personal and professional identities, manifested through different socialization experiences over time, can lead to a ‘turning point’ and a decision that affects a person’s career trajectory. Although the results of this study cannot be generalized, the findings may help other individuals and institutions move towards a firmer understanding of the academic who becomes head of department—in relation to theory, practice and research

Interactions between sediment microbial ecology and physical dynamics drive heterogeneity in contextually similar depositional systems

This study focuses on the interactions between sediment stability and biological and physical variables that influence the erodibility across different habitats. Sampling at short‐term temporal scales illustrated the persistence of the microphytobenthos (MPB) biomass even during periods of frequent, high physical disturbance. The role of MPB in biological stabilization along the changing sedimentary habitat was also assessed. Key biological and physical properties, such as the MPB biomass, composition, and extracellular polymeric substances, were used to predict the sediment stability (erosion threshold) of muddy and sandy habitats within close proximity to one another over multiple days, and within emersion periods. The effects of dewatering, MPB growth, and productivity were examined as well as the resilience and recovery of the MPB community after disturbance from tidal currents and waves. Canonical analysis of principal components (CAP) ordinations were used to visualize and assess the trends observed in biophysical properties between the sites, and marginal and sequential distance‐based linear models were used to identify the key properties influencing erodibility. While the particle size of the bed was important for differences between sites in the CAP analysis, it contributed less to the variability in sediment erodibility than key biological parameters. Among the biological predictors, MPB diversity explained very little variation in marginal tests but was a significant predictor in sequential tests when MPB biomass was also considered. MPB diversity and biomass were both key predictors of sediment stability, contributing 9% and 10%, respectively, to the final model compared to 2% explained by grain size

Sex differences and drug dose influence the role of the alpha 7 nicotinic acetylcholine receptor in the mouse dextran sodium sulfate-induced colitis model

Introduction: alpha 7 nicotinic acetylcholine receptors (nAChRs) play an important role in vagus nerve-based cholinergic anti-inflammatory effects. This study was designed to assess the role of alpha 7 nAChRs in dextran sodium sulfate (DSS)-induced colitis in male and female mouse. We first compared disease activity and pathogenesis of colitis in alpha 7 knockout and wild-type mice. We then evaluated the effect of several alpha 7 direct and indirect agonists on the severity of disease in the DSS-induced colitis. Methods: Male and female adult mice were administered 2.5% DSS solution freely in the drinking water for 7 consecutive days and the colitis severity (disease activity index) was evaluated as well as colon length, colon histology, and levels of tumor necrosis factor-alpha colonic levels. Results: Male, but not female, alpha 7 knockout mice displayed a significantly increased colitis severity and higher tumor necrosis factor-alpha levels as compared with their littermate wild-type mice. Moreover, pretreatment with selective alpha 7 ligands PHA-543613, choline, and PNU-120596 decreased colitis severity in male but not female mice. The anti-colitis effects of these alpha 7 compounds dissipated when administered at higher doses. Conclusions: Our results suggest the presence of a alpha 7-dependent anti-colitis endogenous tone in male mice. Finally, our results show for the first time that female mice are less sensitive to the anticolitis activity of alpha 7 agonists. Ovarian hormones may play a key role in the sex difference effect of alpha 7 nAChRs modulation of colitis in the mouse. Implications: Our collective results suggest that targeting alpha 7 nAChRs could represent a viable therapeutic approach for intestinal inflammation diseases such as ulcerative colitis with the consideration of sex differences.United States Department of Health & Human Services National Institutes of Health (NIH) - USA - DA-019377 - DK046367United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Drug Abuse (NIDA) European Commission - R01DA03697

Diacylglycerol lipase beta inhibition reverses nociceptive behaviour in mouse models of inflammatory and neuropathic pain

Background and PurposeInhibition of diacylglycerol lipase (DGL) prevents LPS-induced pro-inflammatory responses in mouse peritoneal macrophages. Thus, the present study tested whether DGL inhibition reverses allodynic responses of mice in the LPS model of inflammatory pain, as well as in neuropathic pain models. Experimental ApproachInitial experiments examined the cellular expression of DGL and inflammatory mediators within the LPS-injected paw pad. DAGL- (-/-) mice or wild-type mice treated with the DGL inhibitor KT109 were assessed in the LPS model of inflammatory pain. Additional studies examined the locus of action for KT109-induced antinociception, its efficacy in chronic constrictive injury (CCI) of sciatic nerve and chemotherapy-induced neuropathic pain (CINP) models. Key ResultsIntraplantar LPS evoked mechanical allodynia that was associated with increased expression of DGL, which was co-localized with increased TNF- and prostaglandins in paws. DAGL- (-/-) mice or KT109-treated wild-type mice displayed reductions in LPS-induced allodynia. Repeated KT109 administration prevented the expression of LPS-induced allodynia, without evidence of tolerance. Intraplantar injection of KT109 into the LPS-treated paw, but not the contralateral paw, reversed the allodynic responses. However, i.c.v. or i.t. administration of KT109 did not alter LPS-induced allodynia. Finally, KT109 also reversed allodynia in the CCI and CINP models and lacked discernible side effects (e.g. gross motor deficits, anxiogenic behaviour or gastric ulcers). Conclusions and ImplicationsThese findings suggest that local inhibition of DGL at the site of inflammation represents a novel avenue to treat pathological pain, with no apparent untoward side effects.United States Department of Health & Human Services - DA009789 - DA017259 - DA032933 - DA033934-01A1 DA035864 - DA038493-01A1National Institutes of Health (NIH) - USANIH-NINDS Center core grant - 5P30NS047463United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA - P30NS047463NIH National Institute of Neurological Disorders & Stroke (NINDS)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA - R01DA032933 - K99DA035864 - P01DA017259 - P01DA009789 - F32DA038493 - R00DA035864 - P30DA033934NIH National Institute on Drug Abuse (NIDA)European Commissio

A randomised multicentre phase II trial of capecitabine vs S-1 as first-line treatment in elderly patients with metastatic or recurrent unresectable gastric cancer

This randomised multicentre phase II study was conducted to investigate the activity and safety of two oral fluoropyrimidines, capecitabine or S-1, in elderly patients with advanced gastric cancer (AGC). Elderly (⩾65 years) chemo-naive patients with AGC were randomly assigned to receive capecitabine 1250 mg m−2 two times daily on days 1–14 every 3 weeks or S-1 40–60 mg two times daily according to body surface area on days 1–28 every 6 weeks. Ninety-six patients were enrolled and 91 patients were randomised to capecitabine (N=46) or S-1 (N=45). Overall response rate, the primary end point, was 27.2% (95% CI, 14.1–40.4, 12 of 44 assessable patients) with capecitabine and 28.9% (95% CI, 15.6–42.1, 13 of 45) with S-1. Median times to progression and overall survival in the capecitabine arm (4.7 and 9.5 months, respectively) were similar to those in the S-1 arm (4.2 and 8.2 months, respectively). The incidence of grade 3–4 granulocytopenia was 6.8% with capecitabine and 4.8% with S-1. Grade 3–4 nonhaematologic toxicities were: asthenia (9.1% with capecitabine vs 7.1% with S-1), anorexia (6.8 vs 9.5%), diarrhoea (2.3 vs 0%), and hand–foot syndrome (6.8 vs 0%). Both capecitabine and S-1 monotherapies were active and tolerable as first-line treatment for elderly patients with AGC

Detecting depression in patients with coronary heart disease: a diagnostic evaluation of the PHQ-9 and HADS-D in Primary Care, findings from the UPBEAT-UK Study

People with coronary heart disease (CHD) are at heightened risk of depression, and this co-occurrence of conditions is associated with poorer outcomes including raised mortality. This study compares the diagnostic accuracy of two depression case finding instruments in CHD patients relative to a diagnostic standard, the revised Clinical Interview Schedule (CIS-R)

Leveraging Rural Energy Investment for Parasitic Disease Control: Schistosome Ova Inactivation and Energy Co-Benefits of Anaerobic Digesters in Rural China

Cooking and heating remain the most energy intensive activities among the world's poor, and thus improved access to clean energies for these tasks has been highlighted as a key requirement of attaining the major objectives of the UN Millennium Development Goals. A move towards clean energy technologies such as biogas systems (which produce methane from human and animal waste) has the potential to provide immediate benefits for the control of neglected tropical diseases. Here, an assessment of the parasitic disease and energy benefits of biogas systems in Sichuan Province, China, is presented, highlighting how the public health sector can leverage the proliferation of rural energy projects for infectious disease control. ova) counted at the influent of two biogas systems were removed in the systems when adjusted for system residence time, an approximate 1-log removal attributable to sedimentation. Combined, these inactivation/removal processes underscore the promise of biogas infrastructure for reducing parasite contamination resulting from nightsoil use. When interviewed an average of 4 years after construction, villagers attributed large changes in fuel usage to the installation of biogas systems. Household coal usage decreased by 68%, wood by 74%, and crop waste by 6%. With reported energy savings valued at roughly 600 CNY per year, 2–3 years were required to recoup the capital costs of biogas systems. In villages without subsidies, no new biogas systems were implemented.Sustainable strategies that integrate rural energy needs and sanitation offer tremendous promise for long-term control of parasitic diseases, while simultaneously reducing energy costs and improving quality of life. Government policies can enhance the financial viability of such strategies by introducing fiscal incentives for joint sanitation/sustainable energy projects, along with their associated public outreach and education programs

Nitrosative and Oxidative Stresses Contribute to Post-Ischemic Liver Injury Following Severe Hemorrhagic Shock: The Role of Hypoxemic Resuscitation

Purpose: Hemorrhagic shock and resuscitation is frequently associated with liver ischemia-reperfusion injury. The aim of the study was to investigate whether hypoxemic resuscitation attenuates liver injury. Methods: Anesthetized, mechanically ventilated New Zealand white rabbits were exsanguinated to a mean arterial pressure of 30 mmHg for 60 minutes. Resuscitation under normoxemia (Normox-Res group, n = 16, PaO2 = 95–105 mmHg) or hypoxemia (Hypox-Res group, n = 15, PaO 2 = 35–40 mmHg) followed, modifying the FiO 2. Animals not subjected to shock constituted the sham group (n = 11, PaO 2 = 95–105 mmHg). Indices of the inflammatory, oxidative and nitrosative response were measured and histopathological and immunohistochemical studies of the liver were performed. Results: Normox-Res group animals exhibited increased serum alanine aminotransferase, tumor necrosis factor- alpha, interleukin (IL)-1b and IL-6 levels compared with Hypox-Res and sham groups. Reactive oxygen species generation, malondialdehyde formation and myeloperoxidase activity were all elevated in Normox-Res rabbits compared with Hypox-Res and sham groups. Similarly, endothelial NO synthase and inducible NO synthase mRNA expression was up-regulated and nitrotyrosine immunostaining increased in animals resuscitated normoxemically, indicating a more intense nitrosative stress. Hypox-Res animals demonstrated a less prominent histopathologic injury which was similar to sham animals. Conclusions: Hypoxemic resuscitation prevents liver reperfusion injury through attenuation of the inflammatory respons