Accounting for Skill in Trend, Variability, and Autocorrelation Facilitates Better Multi-Model Projections: Application to the AMOC and Temperature Time Series

We present a novel quasi-Bayesian method to weight multiple dynamical models by their skill at capturing both potentially non-linear trends and first-order autocorrelated variability of the underlying process, and to make weighted probabilistic projections. We validate the method using a suite of one-at-a-time cross-validation experiments involving Atlantic meridional overturning circulation (AMOC), its temperature-based index, as well as Korean summer mean maximum temperature. In these experiments the method tends to exhibit superior skill over a trend-only Bayesian model averaging weighting method in terms of weight assignment and probabilistic forecasts. Specifically, mean credible interval width, and mean absolute error of the projections tend to improve. We apply the method to a problem of projecting summer mean maximum temperature change over Korea by the end of the 21st century using a multi-model ensemble. Compared to the trend-only method, the new method appreciably sharpens the probability distribution function (pdf) and increases future most likely, median, and mean warming in Korea. The method is flexible, with a potential to improve forecasts in geosciences and other fields

A role for eisosomes in maintenance of plasma membrane phosphoinositide levels

The plasma membrane delineates the cell and mediates its communication and material exchange with the environment. Many processes of the plasma membrane occur through interactions of proteins with phosphatidylinositol(4,5)-bisphosphate (PI(4,5)P2), which is highly enriched in this membrane and is a key determinant of its identity. Eisosomes function in lateral organization of the plasma membrane, but the molecular function of their major protein subunits, the BAR domain–containing proteins Pil1 and Lsp1, is poorly understood. Here we show that eisosomes interact with the PI(4,5)P2 phosphatase Inp51/Sjl1, thereby recruiting it to the plasma membrane. Pil1 is essential for plasma membrane localization and function of Inp51 but not for the homologous phosphatidylinositol bisphosphate phosphatases Inp52/Sjl2 and Inp53/Sjl3. Consistent with this, absence of Pil1 increases total and available PI(4,5)P2 levels at the plasma membrane. On the basis of these findings, we propose a model in which the eisosomes function in maintaining PI(4,5)P2 levels by Inp51/Sjl1 recruitment

Top guns may not fire:Best-shot group contests with group-specific public good prizes

We analyze a group contest in which n groups compete to win a group-specific public good prize. Group sizes can be different and any player may value the prize differently within and across groups. Players exert costly efforts simultaneously and independently. Only the highest effort (the best-shot) within each group represents the group effort that determines the winning group. We fully characterize the set of equilibria and show that in any equilibrium at most one player in each group exerts strictly positive effort. There always exists an equilibrium in which only the highest value player in each active group exerts strictly positive effort. However, perverse equilibria may exist in which the highest value players completely free-ride on others by exerting no effort. We provide conditions under which the set of equilibria can be restricted and discuss contest design implications

Atenolol versus losartan in children and young adults with Marfan's syndrome

BACKGROUND : Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS : We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS : From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [+/- SD] age, 11.5 +/- 6.5 years in the atenolol group and 11.0 +/- 6.2 years in the losartan group), who had an aorticroot z score greater than 3.0. The baseline-adjusted rate of change (+/- SE) in the aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139 +/- 0.013 and -0.107 +/- 0.013 standard-deviation units per year, respectively; P = 0.08). Both slopes were significantly less than zero, indicating a decrease in the degree of aortic-root dilatation relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS : Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aorticroot dilatation between the two treatment groups over a 3-year period

A climate sensitivity estimate using Bayesian fusion of instrumental observations and an Earth System model

Current climate model projections are uncertain. This uncertainty is partly driven by the uncertainty in key model parameters such as climate sensitivity (CS), vertical ocean diffusivity (Kv), and strength of anthropogenic sulfate aerosol forcing. These parameters are commonly estimated using ensembles of model runs constrained by observations. Here we obtain a probability density function (pdf) of these parameters using the University of Victoria Earth System Climate Model (UVic ESCM) - an intermediate complexity model with a dynamic three-dimensional ocean. Specifically, we run an ensemble of UVic ESCM runs varying parameters that affect CS, ocean vertical diffusion, and the effects of anthropogenic sulfate aerosols. We use a statistical emulator that interpolates the UVic ESCM output to parameter settings where the model was not evaluated. We adopt a Bayesian approach to constrain the model output with instrumental surface temperature and ocean heat observations. Our approach accounts for the uncertainties in the properties of model-data residuals. We use a Markov chain Monte Carlo method to obtain a posterior pdf of these parameters. The mode of the climate sensitivity estimate is 2.8°C, with the corresponding 95% credible interval ranging from 1.8 to 4.9°C. These results are generally consistent with previous studies. The CS pdf is sensitive to the assumptions about the priors, to the effects of anthropogenic sulfate aerosols, and to the background vertical ocean diffusivity. Our method can be used with more complex climate models

Towards Integrated Ethical and Scientific Analysis of Geoengineering: A Research Agenda

Concerns about the risks of unmitigated greenhouse gas emissions are growing. At the same time, confidence that international policy agreements will succeed in considerably lowering anthropogenic greenhouse gas emissions is declining. Perhaps as a result, various geoengineering solutions are gaining attention and credibility as a way to manage climate change. Serious consideration is currently being given to proposals to cool the planet through solar-radiation management. Here we analyze how the unique and nontrivial risks of geoengineering strategies pose fundamental questions at the interface between science and ethics. To illustrate the importance of integrated ethical and scientific analysis, we define key open questions and outline a coupled scientific-ethical research agenda to analyze solar-radiation management geoengineering proposals. We identify nine key fields of coupled research including whether solar-radiation management can be tested, how quickly learning could occur, normative decisions embedded in how different climate trajectories are valued, and justice issues regarding distribution of the harms and benefits of geoengineering. To ensure that ethical analyses are coupled with scientific analyses of this form of geoengineering, we advocate that funding agencies recognize the essential nature of this coupled research by establishing an Ethical, Legal, and Social Implications program for solar-radiation management

A flexible integrative approach based on random forest improves prediction of transcription factor binding sites

Transcription factor binding sites (TFBSs) are DNA sequences of 6-15 base pairs. Interaction of these TFBSs with transcription factors (TFs) is largely responsible for most spatiotemporal gene expression patterns. Here, we evaluate to what extent sequence-based prediction of TFBSs can be improved by taking into account the positional dependencies of nucleotides (NPDs) and the nucleotide sequence-dependent structure of DNA. We make use of the random forest algorithm to flexibly exploit both types of information. Results in this study show that both the structural method and the NPD method can be valuable for the prediction of TFBSs. Moreover, their predictive values seem to be complementary, even to the widely used position weight matrix (PWM) method. This led us to combine all three methods. Results obtained for five eukaryotic TFs with different DNA-binding domains show that our method improves classification accuracy for all five eukaryotic TFs compared with other approaches. Additionally, we contrast the results of seven smaller prokaryotic sets with high-quality data and show that with the use of high-quality data we can significantly improve prediction performance. Models developed in this study can be of great use for gaining insight into the mechanisms of TF binding

Outcomes in patients with gunshot wounds to the brain.

Introduction:Gunshot wounds to the brain (GSWB) confer high lethality and uncertain recovery. It is unclear which patients benefit from aggressive resuscitation, and furthermore whether patients with GSWB undergoing cardiopulmonary resuscitation (CPR) have potential for survival or organ donation. Therefore, we sought to determine the rates of survival and organ donation, as well as identify factors associated with both outcomes in patients with GSWB undergoing CPR. Methods:We performed a retrospective, multicenter study at 25 US trauma centers including dates between June 1, 2011 and December 31, 2017. Patients were included if they suffered isolated GSWB and required CPR at a referring hospital, in the field, or in the trauma resuscitation room. Patients were excluded for significant torso or extremity injuries, or if pregnant. Binomial regression models were used to determine predictors of survival/organ donation. Results:825 patients met study criteria; the majority were male (87.6%) with a mean age of 36.5 years. Most (67%) underwent CPR in the field and 2.1% (n=17) survived to discharge. Of the non-survivors, 17.5% (n=141) were considered eligible donors, with a donation rate of 58.9% (n=83) in this group. Regression models found several predictors of survival. Hormone replacement was predictive of both survival and organ donation. Conclusion:We found that GSWB requiring CPR during trauma resuscitation was associated with a 2.1% survival rate and overall organ donation rate of 10.3%. Several factors appear to be favorably associated with survival, although predictions are uncertain due to the low number of survivors in this patient population. Hormone replacement was predictive of both survival and organ donation. These results are a starting point for determining appropriate treatment algorithms for this devastating clinical condition. Level of evidence:Level II

Healthcare workers' knowledge towards Zika virus infection in Indonesia: A survey in Aceh

Objective To assess the knowledge on Zika virus infection among healthcare providers (doctors) in Aceh province, Indonesia. Methods A self-administered internet based survey was conducted from 3 May to 3 June 2016 among the members of doctor organizations in Aceh province. A set of validated, pre-tested questionnaire was used to measure knowledge regarding Zika infection and to collect a range of explanatory variables. A two-steps logistic regression analysis was employed to assess the association of participants' demographic, workplace characteristics and other explanatory variables with the knowledge. Results A total of 442 participants included in the final analysis and 35.9% of them (159) had a good knowledge on Zika infection. Multivariate model revealed that type of occupation, type of workplace, availability of access to medical journals and experience made Zika disease as differential diagnose were associated with knowledge on Zika infection. In addition, three significant source of information regarding Zika were online media (60%), medical article or medical news (16.2%) and television (13.2%). Conclusion The knowledge of the doctors in Aceh regarding Zika infection is relatively low. Doctors who have a good knowledge on Zika infection are more confident to established Zika disease as differential diagnosis in their clinical setting. Therefore, such program to increase healthcare providers' knowledge regarding Zika infection is needed to screen potential carriers of Zika infection

The National Women's Health Study: assembly and description of a population-based reproductive cohort

BACKGROUND: Miscarriage is a common event but is remarkably difficult to measure in epidemiological studies. Few large-scale population-based studies have been conducted in the UK. METHODS: This was a population-based two-stage postal survey of reproductive histories of adult women living in the United Kingdom in 2001, sampled from the electronic electoral roll. In Stage 1 a short "screening" questionnaire was sent to over 60,000 randomly selected women in order to identify those aged 55 and under who had ever been pregnant or ever attempted to achieve a pregnancy, from whom a brief reproductive history was requested. Stage 2 involved a more lengthy questionnaire requesting detailed information on every pregnancy (and fertility problems), and questions relating to socio-demographic, behavioural and other factors for the most recent pregnancy in order to examine risk factors for miscarriage. Data on stillbirth, multiple birth and maternal age are compared to national data in order to assess response bias. RESULTS: The response rate was 49% for Stage 1 and 73% for the more targeted Stage 2. A total of 26,050 questionnaires were returned in Stage 1. Of the 17,748 women who were eligible on the grounds of age, 27% reported that they had never been pregnant and had never attempted to conceive a child. The remaining 13,035 women reported a total of 30,661 pregnancies. Comparison of key reproductive indicators (stillbirth and multiple birth rates and maternal age at first birth) with national statistics showed that the data look remarkably similar to the general population. CONCLUSIONS: This study has enabled the assembly of a large population-based dataset of women's reproductive histories which appears unbiased compared to the general UK population and which will enable investigation of hard-to-measure outcomes such as miscarriage and infertility