Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes.

Multi-nucleotide variants (MNVs), defined as two or more nearby variants existing on the same haplotype in an individual, are a clinically and biologically important class of genetic variation. However, existing tools typically do not accurately classify MNVs, and understanding of their mutational origins remains limited. Here, we systematically survey MNVs in 125,748 whole exomes and 15,708 whole genomes from the Genome Aggregation Database (gnomAD). We identify 1,792,248 MNVs across the genome with constituent variants falling within 2 bp distance of one another, including 18,756 variants with a novel combined effect on protein sequence. Finally, we estimate the relative impact of known mutational mechanisms - CpG deamination, replication error by polymerase zeta, and polymerase slippage at repeat junctions - on the generation of MNVs. Our results demonstrate the value of haplotype-aware variant annotation, and refine our understanding of genome-wide mutational mechanisms of MNVs

Do female association preferences predict the likelihood of reproduction?

Sexual selection acting on male traits through female mate choice is commonly inferred from female association preferences in dichotomous mate choice experiments. However, there are surprisingly few empirical demonstrations that such association preferences predict the likelihood of females reproducing with a particular male. This information is essential to confirm association preferences as good predictors of mate choice. We used green swordtails (<i>Xiphophorus helleri</i>) to test whether association preferences predict the likelihood of a female reproducing with a male. Females were tested for a preference for long- or short-sworded males in a standard dichotomous choice experiment and then allowed free access to either their preferred or non-preferred male. If females subsequently failed to produce fry, they were provided a second unfamiliar male with similar sword length to the first male. Females were more likely to reproduce with preferred than non-preferred males, but for those that reproduced, neither the status (preferred/non-preferred) nor the sword length (long/short) of the male had an effect on brood size or relative investment in growth by the female. There was no overall preference based on sword length in this study, but male sword length did affect likelihood of reproduction, with females more likely to reproduce with long- than short-sworded males (independent of preference for such males in earlier choice tests). These results suggest that female association preferences are good indicators of female mate choice but that ornament characteristics of the male are also important

The Critical Role of Supervision in Retaining Staff in Obstetric Services: A Three Country Study

Millennium Development Goal (MDG) 5 commits us to reducing maternal mortality rates by three quarters and MDG 4 commits us to reducing child mortality by two-thirds between 1990 and 2015. In order to reach these goals, greater access to basic emergency obstetric care (EmOC) as well as comprehensive EmOC which includes safe Caesarean section, is needed.. The limited capacity of health systems to meet demand for obstetric services has led several countries to utilize mid-level cadres as a substitute to more extensively trained and more internationally mobile healthcare workers. Although this does provide greater capacity for service delivery, concern about the performance and motivation of these workers is emerging. We propose that poor leadership characterized by inadequate and unstructured supervision underlies much of the dissatisfaction and turnover that has been shown to exist amongst these mid-level healthcare workers and indeed health workers more generally. To investigate this, we conducted a large-scale survey of 1,561 mid-level cadre healthcare workers (health workers trained for shorter periods to perform specific tasks e.g. clinical officers) delivering obstetric care in Malawi, Tanzania, and Mozambique. Participants indicated the primary supervision method used in their facility and we assessed their job satisfaction and intentions to leave their current workplace. In all three countries we found robust evidence indicating that a formal supervision process predicted high levels of job satisfaction and low intentions to leave. We find no evidence that facility level factors modify the link between supervisory methods and key outcomes. We interpret this evidence as strongly supporting the need to strengthen leadership and implement a framework and mechanism for systematic supportive supervision. This will promote better job satisfaction and improve the retention and performance of obstetric care workers, something which has the potential to improve maternal and neonatal outcomes in the countdown to 2015

Not all coping strategies are created equal: a mixed methods study exploring physicians' self reported coping strategies

<p>Abstract</p> <p>Background</p> <p>Physicians experience workplace stress and draw on different coping strategies. The primary goal of this paper is to use interview data to explore physicians' self reported coping strategies. In addition, questionnaire data is utilized to explore the degree to which the coping strategies are used and are associated with feelings of emotional exhaustion, a key symptom of burnout.</p> <p>Methods</p> <p>This mixed methods study explores factors related to physician wellness within a large health region in Western Canada. This paper focuses on the coping strategies that physicians use in response to work-related stress. The qualitative component explores physicians' self reported coping strategies through open ended interviews of 42 physicians representing diverse medical specialties and settings (91% response rate). The major themes extracted from the qualitative interviews were used to construct 12 survey items that were included in the comprehensive quantitative questionnaire. Questionnaires were sent to all eligible physicians in the health region with 1178 completed surveys (40% response rate.) Questionnaire items were used to measure how often physicians draw on the various coping strategies. Feelings of burnout were also measured in the survey by 5 items from the Emotional Exhaustion subscale of the revised Maslach Burnout Inventory.</p> <p>Results</p> <p>Major themes identified from the interviews include coping strategies used at work (e.g., working through stress, talking with co-workers, taking a time out, using humor) and after work (e.g., exercise, quiet time, spending time with family). Analysis of the questionnaire data showed three often used workplace coping strategies were positively correlated with feeling emotionally exhausted (i.e., keeping stress to oneself (r = .23), concentrating on what to do next (r = .16), and going on as if nothing happened (r = .07)). Some less often used workplace coping strategies (e.g., taking a time out) and all those used after work were negatively correlated with frequency of emotional exhaustion.</p> <p>Conclusions</p> <p>Physicians' self reported coping strategies are not all created equal in terms of frequency of use and correlation with feeling emotionally exhausted from one's work. This knowledge may be integrated into practical physician stress reduction interventions.</p

Observation of an Exotic S=+1S=+1 Baryon in Exclusive Photoproduction from the Deuteron

In an exclusive measurement of the reaction $\gamma d \to K^+ K^- p n$, a narrow peak that can be attributed to an exotic baryon with strangeness $S=+1$ is seen in the $K^+n$ invariant mass spectrum. The peak is at $1.542\pm 0.005$ GeV/c$^2$ with a measured width of 0.021 GeV/c$^2$ FWHM, which is largely determined by experimental mass resolution. The statistical significance of the peak is $5.2 \pm 0.6 \sigma$. The mass and width of the observed peak are consistent with recent reports of a narrow $S=+1$ baryon by other experimental groups.Comment: 5 pages, 5 figure

Measurement of Beam-Spin Asymmetries for Deep Inelastic π+\pi^+ Electroproduction

We report the first evidence for a non-zero beam-spin azimuthal asymmetry in the electroproduction of positive pions in the deep-inelastic region. Data have been obtained using a polarized electron beam of 4.3 GeV with the CLAS detector at the Thomas Jefferson National Accelerator Facility (JLab). The amplitude of the $\sin\phi$ modulation increases with the momentum of the pion relative to the virtual photon, $z$, with an average amplitude of $0.038 \pm 0.005 \pm 0.003$ for $0.5 < z < 0.8$ range.Comment: 5 pages, RevTEX4, 3 figures, 2 table

Measurement of the Polarized Structure Function σLT′\sigma_{LT^\prime} for p(e⃗,e′p)πop(\vec{e},e'p)\pi^o in the Δ(1232)\Delta(1232) Resonance Region

The polarized longitudinal-transverse structure function $\sigma_{LT^\prime}$ has been measured in the $\Delta(1232)$ resonance region at $Q^2=0.40$ and 0.65 GeV$^2$. Data for the $p(\vec e,e'p)\pi^o$ reaction were taken at Jefferson Lab with the CEBAF Large Acceptance Spectrometer (CLAS) using longitudinally polarized electrons at an energy of 1.515 GeV. For the first time a complete angular distribution was measured, permitting the separation of different non-resonant amplitudes using a partial wave analysis. Comparison with previous beam asymmetry measurements at MAMI indicate a deviation from the predicted $Q^2$ dependence of $\sigma_{LT^{\prime}}$ using recent phenomenological models.Comment: 5 pages, LaTex, 4 eps figures: to be published in PRC/Rapid Communications. Version 2 has revised Q^2 analysi

Two-Nucleon Momentum Distributions Measured in 3He(e,e'pp)n

We have measured the 3He(e,e'pp)n reaction at 2.2 GeV over a wide kinematic range. The kinetic energy distribution for `fast' nucleons (p > 250 MeV/c) peaks where two nucleons each have 20% or less, and the third nucleon has most of the transferred energy. These fast pp and pn pairs are back-to-back with little momentum along the three-momentum transfer, indicating that they are spectators. Experimental and theoretical evidence indicates that we have measured distorted two-nucleon momentum distributions by striking the third nucleon and detecting the spectator correlated pair.Comment: 6 pages, 5 figures, submitted to PR