Stress, Motivation and Professional Satisfaction among Health Care Workers in HIV/AIDS Care and Treatment Centers in Urban Tanzania: A Cross-Sectional Study.

Shortages of health care workers (HCWs) represents a serious challenge to ensuring effective HIV care in resource-limited settings (RLS). Stress, motivation, and job satisfaction have been linked with HCW retention and are important in addressing HCW shortages. In this cross-sectional study HCW stress, motivation and perceived ability to meet patient needs were assessed in PEPFAR-supported urban HIV care and treatment clinics (CTCs) in Tanzania. A self-administered questionnaire measuring motivation, stress, and perceived ability to and meet patient needs was given to HCWs at 16 CTCs. Scales measuring HCW satisfaction, motivation, and stress were developed using principle components analysis. Hierarchical linear models were used to explore the association of HCW and site characteristics with reported satisfaction, stress, motivation, and ability to meet patients' needs.\ud Seventy-three percent (279) of HCWs completed the questionnaire. Most (73%) HCWs reported minimal/no work-related stress, with 48% reporting good/excellent motivation, but 41% also reporting feeling emotionally drained. Almost all (98%) reported feeling able to help their patients, with 68% reporting work as rewarding. Most reported receipt of training and supervision, with good availability of resources. In the multivariate model, direct clinical providers reported lower motivation than management (p < 0.05) and HCWs at medium-sized sites reported higher motivation than HCWs at larger sites (p < 0.05). HCWs at small and medium sites were more likely to feel able to help patients than those from larger sites (p < 0.05 and p < 0.001 respectively). Despite significant patient loads, HCWs in these PEPFAR-supported CTCs reported high levels of motivation, job satisfaction, ability to meet patients' needs, low levels of stress but significant emotional toll. Understanding the relationship between support systems such as strong supervision and training and these outcomes is critical in designing interventions to improve motivation, reduce stress and increase retention of HCWs

Phosphoproteomic Analyses of Interleukin 2 Signaling Reveal Integrated JAK Kinase-Dependent and -Independent Networks in CD8+ T Cells

SummaryInterleukin-2 (IL-2) is a fundamental cytokine that controls proliferation and differentiation of T cells. Here, we used high-resolution mass spectrometry to generate a comprehensive and detailed map of IL-2 protein phosphorylations in cytotoxic T cells (CTL). The data revealed that Janus kinases (JAKs) couple IL-2 receptors to the coordinated phosphorylation of transcription factors, regulators of chromatin, mRNA translation, GTPases, vesicle trafficking, and the actin and microtubule cytoskeleton. We identified an IL-2-JAK-independent SRC family Tyr-kinase-controlled signaling network that regulates ∼10% of the CTL phosphoproteome, the production of phosphatidylinositol (3,4,5)-trisphosphate (PIP3), and the activity of the serine/threonine kinase AKT. These data reveal a signaling framework wherein IL-2-JAK-controlled pathways coordinate with IL-2-independent networks of kinase activity and provide a resource toward the further understanding of the networks of protein phosphorylation that program CTL fate

21-cm synthesis observations of VIRGOHI 21 - a possible dark galaxy in the Virgo Cluster

Many observations indicate that dark matter dominates the extra-galactic Universe, yet no totally dark structure of galactic proportions has ever been convincingly identified. Previously we have suggested that VIRGOHI 21, a 21-cm source we found in the Virgo Cluster using Jodrell Bank, was a possible dark galaxy because of its broad line-width (~200 km/s) unaccompanied by any visible gravitational source to account for it. We have now imaged VIRGOHI 21 in the neutral-hydrogen line and find what could be a dark, edge-on, spinning disk with the mass and diameter of a typical spiral galaxy. Moreover, VIRGOHI 21 has unquestionably been involved in an interaction with NGC 4254, a luminous spiral with an odd one-armed morphology, but lacking the massive interactor normally linked with such a feature. Numerical models of NGC 4254 call for a close interaction ~10^8 years ago with a perturber of ~10^11 solar masses. This we take as additional evidence for the massive nature of VIRGOHI 21 as there does not appear to be any other viable candidate. We have also used the Hubble Space Telescope to search for stars associated with the HI and find none down to an I band surface brightness limit of 31.1 +/- 0.2 mag/sq. arcsec.Comment: 8 pages, accepted to ApJ, uses emulateapj.cls. Mpeg animation (Fig. 2) available at ftp://ftp.naic.edu/pub/publications/minchin/video2.mp

Regulation of PTEN Inhibition by the Pleckstrin Homology Domain of P-REX2 During Insulin Signaling and Glucose Homeostasis

Insulin activation of phosphoinositide 3-kinase (PI3K) signaling regulates glucose homeostasis through the production of phosphatidylinositol 3,4,5-trisphosphate (PIP3). The dual-specificity phosphatase and tensin homolog deleted on chromosome 10 (PTEN) blocks PI3K signaling by dephosphorylating PIP3, and is inhibited through its interaction with phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 (P-REX2). The mechanism of inhibition and its physiological significance are not known. Here, we report that P-REX2 interacts with PTEN via two interfaces. The pleckstrin homology (PH) domain of P-REX2 inhibits PTEN by interacting with the catalytic region of PTEN, and the inositol polyphosphate 4-phosphatase domain of P-REX2 provides high-affinity binding to the postsynaptic density-95/Discs large/zona occludens-1-binding domain of PTEN. P-REX2 inhibition of PTEN requires C-terminal phosphorylation of PTEN to release the P-REX2 PH domain from its neighboring diffuse B-cell lymphoma homology domain. Consistent with its function as a PTEN inhibitor, deletion of Prex2 in fibroblasts and mice results in increased Pten activity and decreased insulin signaling in liver and adipose tissue. Prex2 deletion also leads to reduced glucose uptake and insulin resistance. In human adipose tissue, P-REX2 protein expression is decreased and PTEN activity is increased in insulin-resistant human subjects. Taken together, these results indicate a functional role for P-REX2 PH-domain-mediated inhibition of PTEN in regulating insulin sensitivity and glucose homeostasis and suggest that loss of P-REX2 expression may cause insulin resistance

Quantitative Analysis of Radiation-Associated Parenchymal Lung Change

We present a novel classification system of the parenchymal features of radiation-induced lung damage (RILD). We developed a deep learning network to automate the delineation of five classes of parenchymal textures. We quantify the volumetric change in classes after radiotherapy in order to allow detailed, quantitative descriptions of the evolution of lung parenchyma up to 24 months after RT, and correlate these with radiotherapy dose and respiratory outcomes. Diagnostic CTs were available pre-RT, and at 3, 6, 12 and 24 months post-RT, for 46 subjects enrolled in a clinical trial of chemoradiotherapy for non-small cell lung cancer. All 230 CT scans were segmented using our network. The five parenchymal classes showed distinct temporal patterns. Moderate correlation was seen between change in tissue class volume and clinical and dosimetric parameters, e.g., the Pearson correlation coefficient was ≤0.49 between V30 and change in Class 2, and was 0.39 between change in Class 1 and decline in FVC. The effect of the local dose on tissue class revealed a strong dose-dependent relationship. Respiratory function measured by spirometry and MRC dyspnoea scores after radiotherapy correlated with the measured radiological RILD. We demonstrate the potential of using our approach to analyse and understand the morphological and functional evolution of RILD in greater detail than previously possible

Functional Redundancy of Class I Phosphoinositide 3-Kinase (PI3K) Isoforms in Signaling Growth Factor-Mediated Human Neutrophil Survival

We have investigated the contribution of individual phosphoinositide 3-kinase (PI3K) Class I isoforms to the regulation of neutrophil survival using (i) a panel of commercially available small molecule isoform-selective PI3K Class I inhibitors, (ii) novel inhibitors, which target single or multiple Class I isoforms (PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ), and (iii) transgenic mice lacking functional PI3K isoforms (p110δKOγKO or p110γKO). Our data suggest that there is considerable functional redundancy amongst Class I PI3Ks (both Class IA and Class IB) with regard to GM-CSF-mediated suppression of neutrophil apoptosis. Hence pharmacological inhibition of any 3 or more PI3K isoforms was required to block the GM-CSF survival response in human neutrophils, with inhibition of individual or any two isoforms having little or no effect. Likewise, isolated blood neutrophils derived from double knockout PI3K p110δKOγKO mice underwent normal time-dependent constitutive apoptosis and displayed identical GM-CSF mediated survival to wild type cells, but were sensitized to pharmacological inhibition of the remaining PI3K isoforms. Surprisingly, the pro-survival neutrophil phenotype observed in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) was resilient to inactivation of the PI3K pathway

Identifying uncertainties in Arctic climate change projections

Wide ranging climate changes are expected in the Arctic by the end of the 21st century, but projections of the size of these changes vary widely across current global climate models. This variation represents a large source of uncertainty in our understanding of the evolution of Arctic climate. Here we systematically quantify and assess the model uncertainty in Arctic climate changes in two CO2 doubling experiments: a multimodel ensemble (CMIP3) and an ensemble constructed using a single model (HadCM3) with multiple parameter perturbations (THC-QUMP). These two ensembles allow us to assess the contribution that both structural and parameter variations across models make to the total uncertainty and to begin to attribute sources of uncertainty in projected changes. We find that parameter uncertainty is an major source of uncertainty in certain aspects of Arctic climate. But also that uncertainties in the mean climate state in the 20th century, most notably in the northward Atlantic ocean heat transport and Arctic sea ice volume, are a significant source of uncertainty for projections of future Arctic change. We suggest that better observational constraints on these quantities will lead to significant improvements in the precision of projections of future Arctic climate change

Recovery-based staff training intervention within mental health rehabilitation units: A two-stage analysis using realistic evaluation principles and framework approach

Background - Long-term change in recovery-based practice in mental health rehabilitation is a research priority. Methods - We used a qualitative case study analysis using a blend of traditional 'framework' analysis and 'realist' realist principles toapproaches to carry-out an evaluation of a recovery-focused staff training intervention within three purposively selected mental health rehabilitation units. We tried to ensure the validity of the data by using triangulation of multiple data sources and were collected using different methods. Results - We found that organisational culture and embedding of a change management programme in routine practice were reported as key influences to sustain any change in practice. The qualitative study generated 10 recommendations on how to achieve long-term change in practice including dealing with pre-existing organisational and cultural problems in NHS units. Conclusions - We would propose that a recovery-focused staff training intervention requires leadership, continuity and integration with existing change management programme for long-term change. The intervention must be embedded into routine practice for sustainability

Meeting the Cool Neighbors. IX. The Luminosity Function of M7-L8 Ultracool Dwarfs in the Field

We present a 20-pc, volume-limited sample of M7-L8 dwarfs created through spectroscopic follow-up of sources selected from the Two Micron All Sky Survey (2MASS) Second Incremental Release Point Source Catalog. In this paper, we present optical spectroscopy of 198 candidate nearby ultracool dwarfs, including 12 late-M and L dwarfs likely to be within 20 pc of the Sun and 94 more distant late-type dwarfs. We have also identified five ultracool dwarfs with spectral signatures of low-gravity. Combining these data with previous results, we define a sample of 99 ultracool dwarfs in 91 systems within 20 pc. These are used to estimate the J- and K-band luminosity functions for dwarfs with optical spectral types between M7 and L8 (10.5<M_J<15, 9.5<M_K<13). We find a space density of 4.9 x 10^-3 pc^-3 for late-M dwarfs (M7-M9.5) and a lower limit of 3.8 x 10^-3 pc^-3 for L dwarfs.Comment: Accepted to A