Flexible and efficient spatial extremes emulation via variational autoencoders

Many real-world processes have complex tail dependence structures that cannot be characterized using classical Gaussian processes. More flexible spatial extremes models exhibit appealing extremal dependence properties but are often exceedingly prohibitive to fit and simulate from in high dimensions. In this paper, we develop a new spatial extremes model that has flexible and non-stationary dependence properties, and we integrate it in the encoding-decoding structure of a variational autoencoder (XVAE), whose parameters are estimated via variational Bayes combined with deep learning. The XVAE can be used as a spatio-temporal emulator that characterizes the distribution of potential mechanistic model output states and produces outputs that have the same statistical properties as the inputs, especially in the tail. As an aside, our approach also provides a novel way of making fast inference with complex extreme-value processes. Through extensive simulation studies, we show that our XVAE is substantially more time-efficient than traditional Bayesian inference while also outperforming many spatial extremes models with a stationary dependence structure. To further demonstrate the computational power of the XVAE, we analyze a high-resolution satellite-derived dataset of sea surface temperature in the Red Sea, which includes 30 years of daily measurements at 16703 grid cells. We find that the extremal dependence strength is weaker in the interior of Red Sea and it has decreased slightly over time.Comment: 30 pages, 8 figure

Caffeine taste signaling in drosophila larvae

The Drosophila larva has a simple peripheral nervous system with a comparably small number of sensory neurons located externally at the head or internally along the pharynx to assess its chemical environment. It is assumed that larval taste coding occurs mainly via external organs (the dorsal, terminal, and ventral organ). However, the contribution of the internal pharyngeal sensory organs has not been explored. Here we find that larvae require a single pharyngeal gustatory receptor neuron pair called D1, which is located in the dorsal pharyngeal sensilla, in order to avoid caffeine and to associate an odor with caffeine punishment. In contrast, caffeine-driven reduction in feeding in non-choice situations does not require D1. Hence, this work provides data on taste coding via different receptor neurons, depending on the behavioral context. Furthermore, we show that the larval pharyngeal system is involved in bitter tasting. Using ectopic expressions, we show that the caffeine receptor in neuron D1 requires the function of at least four receptor genes: the putative co-receptors Gr33a, Gr66a, the putative caffeine-specific receptor Gr93a, and yet unknown additional molecular component(s). This suggests that larval taste perception is more complex than previously assumed already at the sensory level. Taste information from different sensory organs located outside at the head or inside along the pharynx of the larva is assembled to trigger taste guided behaviors

Mechanisms of T cell organotropism

F.M.M.-B. is supported by the British Heart Foundation, the Medical Research Council of the UK and the Gates Foundation

Energy Level Modulation of HOMO, LUMO, and Band‐Gap in Conjugated Polymers for Organic Photovoltaic Applications

To devise a reliable strategy for achieving specific HOMO and LUMO energy level modulation via alternating donor‐acceptor monomer units, we investigate a series of conjugated polymers (CPs) in which the electron withdrawing power of the acceptor group is varied, while maintaining the same donor group and the same conjugated chain conformation. Through experiment and DFT calculations, good correlation is identified between the withdrawing strength of the acceptor group, the HOMO and LUMO levels, and the degree of orbital localization, which allows reliable design principles for CPs. Increasing the acceptor strength results in an enhanced charge transfer upon combination with a donor monomer and a more pronounced decrease of the LUMO level. Moreover, while HOMO states remain delocalized along the polymer chain, LUMO states are strongly localized at specific bonds within the acceptor group. The degree of LUMO localization increases with increasing polymer length, which results in a further drop of the LUMO level and converges to its final value when the number of repeat units reaches the characteristic conjugation length. Based on these insights we designed PBT8PT, which exhibits 6.78% power conversion efficiency after device optimization via the additive assisted annealing, demonstrating the effectiveness of our predictive design approach. A strong acceptor lowers both the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) levels of conjugated polymers (CPs), ultimately producing a narrowed band‐gap. The energy level difference between the CP and the constituent monomers converge to a constant value, providing an energy level prediction tool. Organic photovoltaic performance is correlated with the CP's energy levels, and a 6.78% power conversion efficiency is achieved.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96311/1/adfm_201201385_sm_suppl.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96311/2/439_ftp.pd

Improving the physician-patient cardiovascular risk dialogue to improve statin adherence

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate the effectiveness of a patient education program developed to facilitate statin adherence.</p> <p>Methods</p> <p>A controlled trial was designed to test the effectiveness of a multifaceted patient education program to facilitate statin adherence. The program included a brief, in-office physician counseling kit followed by patient mailings. The primary end point was adherence to filling statin prescriptions during a 120-day period. Patients new to statins enrolled and completed a survey. Data from a national pharmacy claims database were used to track adherence.</p> <p>Results</p> <p>Patients new to statin therapy exposed to a patient counseling and education program achieved a 12.4 higher average number of statin prescription fill days and were 10% more likely to fill prescriptions for at least 120 days (<it>p </it>= .01).</p> <p>Conclusion</p> <p>Brief in-office counseling on cardiovascular risk followed by patient education mailings can be effective in increasing adherence. Physicians found a one-minute counseling tool and pocket guidelines useful in counseling patients.</p

Observational Health Data Sciences and Informatics (OHDSI): Opportunities for Observational Researchers.

The vision of creating accessible, reliable clinical evidence by accessing the clincial experience of hundreds of millions of patients across the globe is a reality. Observational Health Data Sciences and Informatics (OHDSI) has built on learnings from the Observational Medical Outcomes Partnership to turn methods research and insights into a suite of applications and exploration tools that move the field closer to the ultimate goal of generating evidence about all aspects of healthcare to serve the needs of patients, clinicians and all other decision-makers around the world

The Genome Characteristics and Predicted Function of Methyl-Group Oxidation Pathway in the Obligate Aceticlastic Methanogens, Methanosaeta spp

In this work, we report the complete genome sequence of an obligate aceticlastic methanogen, Methanosaeta harundinacea 6Ac. Genome comparison indicated that the three cultured Methanosaeta spp., M. thermophila, M. concilii and M. harundinacea 6Ac, each carry an entire suite of genes encoding the proteins involved in the methyl-group oxidation pathway, a pathway whose function is not well documented in the obligately aceticlastic methanogens. Phylogenetic analysis showed that the methyl-group oxidation-involving proteins, Fwd, Mtd, Mch, and Mer from Methanosaeta strains cluster with the methylotrophic methanogens, and were not closely related to those from the hydrogenotrophic methanogens. Quantitative PCR detected the expression of all genes for this pathway, albeit ten times lower than the genes for aceticlastic methanogenesis in strain 6Ac. Western blots also revealed the expression of fwd and mch, genes involved in methyl-group oxidation. Moreover, 13C-labeling experiments suggested that the Methanosaeta strains might use the pathway as a methyl oxidation shunt during the aceticlastic metabolism. Because the mch mutants of Methanosarcina barkeri or M. acetivorans failed to grow on acetate, we suggest that Methanosaeta may use methyl-group oxidation pathway to generate reducing equivalents, possibly for biomass synthesis. An fpo operon, which encodes an electron transport complex for the reduction of CoM-CoB heterodisulfide, was found in the three genomes of the Methanosaeta strains. However, an incomplete protein complex lacking the FpoF subunit was predicted, as the gene for this protein was absent. Thus, F420H2 was predicted not to serve as the electron donor. In addition, two gene clusters encoding the two types of heterodisulfide reductase (Hdr), hdrABC, and hdrED, respectively, were found in the three Methanosaeta genomes. Quantitative PCR determined that the expression of hdrED was about ten times higher than hdrABC, suggesting that hdrED plays a major role in aceticlastic methanogenesis

The RISAP-study: a complex intervention in risk communication and shared decision-making in general practice

General practitioners (GPs) and patients find it difficult to talk about risk of future disease, especially when patients have asymptomatic conditions, and treatment options are unlikely to cause immediate perceptible improvements in well-being. Further studies in risk communication training are needed. Aim:1) to systematically develop, describe and evaluate a complex intervention comprising a training programme for GPs in risk communication and shared decision-making, 2) to evaluate the effect of the training programme on real-life consultations between GPs and patients with high cholesterol levels, and 3) to evaluate patients' reactions during and after the consultations. Methods/Design The effect of the complex intervention, based around a training programme, will be evaluated in a cluster-randomised controlled trial with an intervention group and an active control group with 40 GPs and 280 patients in each group. The GPs will receive a questionnaire at baseline and after 6 months about attitudes towards risk communication and cholesterol-reducing medication. After each consultation with a participating high cholesterol-patient, the GPs will complete a questionnaire about decision satisfaction (Provider Decision Process Assessment Instrument). The patients will receive a questionnaire at baseline and after 3 and 6 months. It includes questions about adherence to chosen treatment (Morisky Compliance Scale), self-rated health (SF-12), enablement (Patient Enablement Instrument), and risk communication and decision-making effectiveness (COMRADE Scale). Prescriptions, contacts to the health services, and cholesterol level will be drawn from the registers. In each group, 12 consultations will be observed and tape-recorded. The patients from these 24 consultations will be interviewed immediately after the consultation and re-interviewed after 6 months. Eight purposefully selected GPs from the intervention group will be interviewed in a focus group 6 months after participation in the training programme. The process and context of the RISAP-study will be investigated in detail using an action research approach, in order to analyse adaptation of the intervention model to the specific context. Discussion This study aims at providing GPs and patients with a firm basis for active deliberation about preventive treatment options, with a view to optimising adherence to chosen treatment. Trial registration ClinicalTrials.gov Protocol Registration System NCT0118705

New developments in osteoarthritis. Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options

Joint trauma can lead to a spectrum of acute lesions, including osteochondral fractures, ligament or meniscus tears and damage to the articular cartilage. This is often associated with intraarticular bleeding and causes posttraumatic joint inflammation. Although the acute symptoms resolve and some of the lesions can be surgically repaired, joint injury triggers a chronic remodeling process in cartilage and other joint tissues that ultimately manifests as osteoarthritis in a majority of cases. The objective of the present review is to summarize information on pathogenetic mechanisms involved in the acute and chronic consequences of joint trauma and discuss potential pharmacological interventions. The focus of the review is on the early events that follow joint trauma since therapies for posttraumatic joint inflammation are not available and this represents a unique window of opportunity to limit chronic consequences