Intrinsic Properties of the <z>=2.7 Lyman Alpha Forest from Keck Spectra of QSO HS 1946+7658

We present the highest quality Lyman Alpha forest spectra published to date, from the QSO HS 1946+7658. The distribution of H I column densities is a power law of slope -1.5 from Log N = 12.1 - 14. This power law can extend to N = 0, because lines weaker than Log N = 12.1 do not have a large H I optical depth. Low column lines with Log N > 9 could account for all observed He II absorption, but lines with Log N > 12 alone are unlikely to do so. The b distribution between 20 and 60 km/sec is a Gaussian with a mean of 23 km/sec (less than reported in past at this z), and a sigma b of 14 km/sec. We report no evolution in the Lyman alpha forest (except the number of lines), because Lu et al. (1997) found the same N and b distributions at = 3.7. We see lines with 14 80 km/sec that cannot be accounted for by noise or blending effects. We discover that the lower cutoff in the b distribution varies with N, from b = 14 km/sec at Log N = 12.5 to b = 22 km/sec at Log N = 14.0, but otherwise b and N are not correlated. We see no Lyman Alpha line clustering above 50 \kms, in disagreement with previous results from lower signal to noise data, but we do see a 3 sigma clustering signal at 25 - 50 km/sec among lines with Log N > 13.6Comment: (Minor changes including new identifications for two weak lines) 46 pages including 16 Figures, Latex Table 1 Available at http://nately.ucsd.edu/~david . To appear in Ap

Resilience intervention for families of autistic children : reviewing the literature

: Given the rising diagnostic rates of autism, it is imperative to investigate the well-being of families with autistic children. Families of autistic children report more mental health difficulties than families of typically developing children. Resilience is identified as a key protective factor for mental health difficulties in many populations, and research suggests that this construct is effective for coping with mental health difficulties in families of autistic children. However, reviews on resilience interventions for families of autistic children are lacking. Accordingly, this paper aims to report (a) common mental health difficulties that families of autistic children experience, (b) how resilience may reduce mental health difficulties, (c) interventions to enhance resilience in families of autistic children, and (d) discuss implications for practice and future research. Our review identified that mental distress resulting from feelings of uncertainty and helplessness following a diagnosis, in addition to caregiving stressors, is especially common among families of autistic children. Enhancing resilience is suggested to reduce those difficulties by tapping into strengths related to various positive psychological resources such as internal locus of control, positive cognitive appraisal, acceptance and self-efficacy. Interventions such as Dance Movement Psychotherapy and spirituality-based approaches, are deemed especially helpful to families of autistic children. However, research in this area is still underdeveloped, and there is a pressing need to build a more rigorous evidence base. Findings reviewed in the current work can aid families of autistic children, healthcare practitioners, and researchers to support the mental wellbeing of families of autistic children, which in turn would support the wellbeing of autistic children

Learning from errors:Assessing final year medical students' reflection on safety improvement, five year cohort study

Abstract Background Investigation of real incidents has been consistently identified by expert reviews and student surveys as a potentially valuable teaching resource for medical students. The aim of this study was to adapt a published method to measure resident doctors’ reflection on quality improvement and evaluate this as an assessment tool for medical students. Methods The design is a cohort study. Medical students were prepared with a tutorial in team based learning format and an online Managing Incident Review course. The reliability of the modified Mayo Evaluation of Reflection on Improvement tool (mMERIT) was analysed with Generalizability G-theory. Long term sustainability of assessment of incident review with mMERIT was tested over five consecutive years. Results A total of 824 students have completed an incident review using 167 incidents from NHS Tayside’s online reporting system. In order to address the academic practice gap students were supervised by Senior Charge Nurses or Consultants on the wards where the incidents had been reported. Inter-rater reliability was considered sufficiently high to have one assessor for each student report. There was no evidence of a gradient in student marks across the academic year. Marks were significantly higher for students who used Section Questions to structure their reports compared with those who did not. In Year 1 of the study 21 (14%) of 153 mMERIT reports were graded as concern. All 21 of these students achieved the required standard on resubmission. Rates of resubmission were lower (3% to 7%) in subsequent years. Conclusions We have shown that mMERIT has high reliability with one rater. mMERIT can be used by students as part of a suite of feedback to help supplement their self-assessment on their learning needs and develop insightful practice to drive their development of quality, safety and person centred professional practice. Incident review addresses the need for workplace based learning and use of real life examples of mistakes, which has been identified by previous studies of education about patient safety in medical schools

Phosphoenolpyruvate carboxylase dentified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism

Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in thePlasmodium falciparum genome, suggesting that PEPC has a parasite-specific function. To investigate its importance in P. falciparum, we generated a pepc null mutant (D10Δpepc), which was only achievable when malate, a reduction product of oxaloacetate, was added to the growth medium. D10Δpepc had a severe growth defect in vitro, which was partially reversed by addition of malate or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics using 13C-U-D-glucose and 13C-bicarbonate showed that the conversion of glycolytically-derived PEP into malate, fumarate, aspartate and citrate was abolished in D10Δpepc and that pentose phosphate pathway metabolites and glycerol 3-phosphate were present at increased levels. In contrast, metabolism of the carbon skeleton of 13C,15N-U-glutamine was similar in both parasite lines, although the flux was lower in D10Δpepc; it also confirmed the operation of a complete forward TCA cycle in the wild type parasite. Overall, these data confirm the CO2 fixing activity of PEPC and suggest that it provides metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic and mitochondrial redox balance. Moreover, these findings imply that PEPC may be an exploitable target for future drug discovery

Assessing the health and development of ART-conceived young adults: A study of feasibility, parent recall, and acceptability

<p>Abstract</p> <p>Background</p> <p>Assisted reproductive technologies (ART) to treat infertility have been available for nearly three decades. There have been a number of systematic comparisons of the health and development of ART-conceived with spontaneously-conceived (SC) children. Data are equivocal, some finding no differences and others that there are more health and developmental problems in the ART group. It is agreed that perinatal mortality and morbidity are worse after assisted than spontaneous conception and the impact of the hormonally altered intrauterine environment on puberty and later fertility of offspring are unknown. To date however, there has been no investigation of the health and development of ART-conceived young adults, including from the world's few prospective cohorts of ART conceived children. Obtaining these data requires contact to be made with people at least twenty years after discharge from the treating service. Given the ethical difficulties of approaching families to participate in research up to two decades after cessation of treatment, the aim of this exploratory qualitative investigation was to assess the feasibility and acceptability of approaching mothers treated for infertility prior to 1988, and their recall of the health and development of their ART-conceived young adult children.</p> <p>Methods</p> <p>Mothers treated for infertility at the Royal Women's Hospital Reproductive Biology Unit in Melbourne, Australia prior to 1988 were approached by a senior clinician and invited to participate in individual semi-structured interviews which could include their partners and/or young adult children if they wished. Recruitment continued until theoretic saturation had been reached.</p> <p>Results</p> <p>Ten mothers, two of their husbands and five young adults participated in interviews, and the health and development of 15 ART-conceived young adults were described. The experience of conception, pregnancy, birth and the health and development of the children were recalled vividly and in detail. Families were pleased to have been approached and supported the need for systematic data collection. Mode of conception had been disclosed from childhood to all the offspring.</p> <p>Conclusion</p> <p>With careful and sensitive recruitment strategies it is feasible and acceptable to contact women treated for infertility at least two decades ago and their families, to assess the health and development of ART-conceived young adults.</p

Individualism and stock price crash risk

Employing a sample of 26,473 firms across 42 countries from 1990 to 2013, we find that firms located in countries with higher individualism have higher stock price crash risk. Furthermore, individualism can be transmitted by foreign investors from overseas markets to influence local firms’ crash risk, and can exacerbate the impact of firm risk taking and earnings management on crash risk. Moreover, the positive relation between individualism and crash risk is amplified during the global financial crisis and attenuated by enhanced country-level financial information transparency and the adoption of International Financial Reporting Standards

Local Loss and Spatial Homogenization of Plant Diversity Reduce Ecosystem Multifunctionality

Biodiversity is declining in many local communities while also becoming increasingly homogenized across space. Experiments show that local plant species loss reduces ecosystem functioning and services, but the role of spatial homogenization of community composition and the potential interaction between diversity at different scales in maintaining ecosystem functioning remains unclear, especially when many functions are considered (ecosystem multifunctionality). We present an analysis of eight ecosystem functions measured in 65 grasslands worldwide. We find that more diverse grasslands—those with both species-rich local communities (α-diversity) and large compositional differences among localities (β-diversity)—had higher levels of multifunctionality. Moreover, α- and β-diversity synergistically affected multifunctionality, with higher levels of diversity at one scale amplifying the contribution to ecological functions at the other scale. The identity of species influencing ecosystem functioning differed among functions and across local communities, explaining why more diverse grasslands maintained greater functionality when more functions and localities were considered. These results were robust to variation in environmental drivers. Our findings reveal that plant diversity, at both local and landscape scales, contributes to the maintenance of multiple ecosystem services provided by grasslands. Preserving ecosystem functioning therefore requires conservation of biodiversity both within and among ecological communities

Exploiting evolutionary steering to induce collateral drug sensitivity in cancer

Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another drug. These evolutionary trade-offs can be exploited using 'evolutionary steering' to control the tumour population and delay resistance. However, recapitulating cancer evolutionary dynamics experimentally remains challenging. Here, we present an approach for evolutionary steering based on a combination of single-cell barcoding, large populations of 108-109 cells grown without re-plating, longitudinal non-destructive monitoring of cancer clones, and mathematical modelling of tumour evolution. We demonstrate evolutionary steering in a lung cancer model, showing that it shifts the clonal composition of the tumour in our favour, leading to collateral sensitivity and proliferative costs. Genomic profiling revealed some of the mechanisms that drive evolved sensitivity. This approach allows modelling evolutionary steering strategies that can potentially control treatment resistance

Belowground biomass response to nutrient enrichment depends on light limitation across globally distributed grasslands

Anthropogenic activities are increasing nutrient inputs to ecosystems worldwide, with consequences for global carbon and nutrient cycles. Recent meta-analyses show that aboveground primary production is often co-limited by multiple nutrients; however, little is known about how root production responds to changes in nutrient availability. At twenty-nine grassland sites on four continents, we quantified shallow root biomass responses to nitrogen (N), phosphorus (P) and potassium plus micronutrient enrichment and compared below- and aboveground responses. We hypothesized that optimal allocation theory would predict context dependence in root biomass responses to nutrient enrichment, given variation among sites in the resources limiting to plant growth (specifically light versus nutrients). Consistent with the predictions of optimal allocation theory, the proportion of total biomass belowground declined with N or P addition, due to increased biomass aboveground (for N and P) and decreased biomass belowground (N, particularly in sites with low canopy light penetration). Absolute root biomass increased with N addition where light was abundant at the soil surface, but declined in sites where the grassland canopy intercepted a large proportion of incoming light. These results demonstrate that belowground responses to changes in resource supply can differ strongly from aboveground responses, which could significantly modify predictions of future rates of nutrient cycling and carbon sequestration. Our results also highlight how optimal allocation theory developed for individual plants may help predict belowground biomass responses to nutrient enrichment at the ecosystem scale across wide climatic and environmental gradients