End-stage Renal Disease and Economic Incentives: The International Study of Health Care Organization and Financing

End-stage renal disease (ESRD), or kidney failure, is a debilitating, costly, and increasingly common medical condition. Little is known about how different financing approaches affect ESRD outcomes and delivery of care. This paper presents results from a comparative review of 12 countries with alternative models of incentives and benefits, collected under the International Study of Health Care Organization and Financing, a substudy within the Dialysis Outcomes and Practice Patterns Study. Variation in spending per ESRD patient is relatively small and is correlated with overall per capita health care spending. Between-country variations in spending are reduced using an input price parity index constructed for this study. Remaining differences in costs and outcomes do not seem strongly linked to differences in incentives embedded in national programs.

Identification and functional characterization of the distinct plant pectin esterases PAE8 and PAE9 and their deletion mutants

MAIN CONCLUSION: PAE8 and PAE9 have pectin acetylesterase activity and together remove one-third of the cell wall acetate associated with pectin formation in Arabidopsis leaves. Inpae8andpae9mutants, substantial amounts of acetate accumulate in cell walls. In addition, the inflorescence stem height is decreased. Pectic polysaccharides constitute a significant part of the primary cell walls in dicotyledonous angiosperms. This diverse group of polysaccharides has been implicated in several physiological processes including cell-to-cell adhesion and pathogenesis. Several pectic polysaccharides contain acetyl-moieties directly affecting their physical properties such as gelling capacity, an important trait for the food industry. In order to gain further insight into the biological role of pectin acetylation, a reverse genetics approach was used to investigate the function of genes that are members of the Pectin AcetylEsterase gene family (PAE) in Arabidopsis. Mutations in two members of the PAE family (PAE8 and PAE9) lead to cell walls with an approximately 20 % increase in acetate content. High-molecular-weight fractions enriched in pectic rhamnogalacturonan I (RGI) extracted from the mutants had increased acetate content. In addition, the pae8 mutant displayed increased acetate content also in low-molecular-weight pectic fractions. The pae8/pae9-2 double mutant exhibited an additive effect by increasing wall acetate content by up to 37 %, suggesting that the two genes are not redundant and act on acetyl-substituents of different pectic domains. The pae8 and pae8/pae9-2 mutants exhibit reduced inflorescence growth underscoring the role of pectic acetylation in plant development. When heterologously expressed and purified, both gene products were shown to release acetate from the corresponding mutant pectic fractions in vitro. PAEs play a significant role in modulating the acetylation state of pectic polymers in the wall, highlighting the importance of apoplastic metabolism for the plant cell and plant growth. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00425-014-2139-6) contains supplementary material, which is available to authorized users

Using Sequential Statistical Tests for Efficient Hyperparameter Tuning

Hyperparameter tuning is one of the the most time-consuming parts in machine learning. Despite the existence of modern optimization algorithms that minimize the number of evaluations needed, evaluations of a single setting may still be expensive. Usually a resampling technique is used, where the machine learning method has to be fitted a fixed number of k times on different training datasets. The respective mean performance of the k fits is then used as performance estimator. Many hyperparameter settings could be discarded after less than k resampling iterations if they are clearly inferior to high-performing settings. However, resampling is often performed until the very end, wasting a lot of computational effort. To this end, we propose the Sequential Random Search (SQRS) which extends the regular random search algorithm by a sequential testing procedure aimed at detecting and eliminating inferior parameter configurations early. We compared our SQRS with regular random search using multiple publicly available regression and classification datasets. Our simulation study showed that the SQRS is able to find similarly well-performing parameter settings while requiring noticeably fewer evaluations. Our results underscore the potential for integrating sequential tests into hyperparameter tuning

End-Stage Renal Disease and Economic Incentives: The International Study of Health Care Organization and Financing

End-stage renal disease (ESRD), or kidney failure, is a debilitating, costly, and increasingly common medical condition. Little is known about how different financing approaches affect ESRD outcomes and delivery of care. This paper presents results from a comparative review of 12 countries with alternative models of incentives and benefits, collected under the International Study of Health Care Organization and Financing, a substudy within the Dialysis Outcomes and Practice Patterns Study. Variation in spending per ESRD patient is relatively small and is correlated with overall per capita health care spending. Between-country variations in spending are reduced using an input price parity index constructed for this study. Remaining differences in costs and outcomes do not seem strongly linked to differences in incentives embedded in national programs

Meshless animation of fracturing solids

We present a new meshless animation framework for elastic and plastic materials that fracture. Central to our method is a highly dynamic surface and volume sampling method that supports arbitrary crack initiation, propagation, and termination, while avoiding many of the stability problems of traditional mesh-based techniques. We explicitly model advancing crack fronts and associated fracture surfaces embedded in the simulation volume. When cutting through the material, crack fronts directly affect the coupling between simulation nodes, requiring a dynamic adaptation of the nodal shape functions. We show how local visibility tests and dynamic caching lead to an efficient implementation of these effects based on point collocation. Complex fracture patterns of interacting and branching cracks are handled using a small set of topological operations for splitting, merging, and terminating crack fronts. This allows continuous propagation of cracks with highly detailed fracture surfaces, independent of the spatial resolution of the simulation nodes, and provides effective mechanisms for controlling fracture paths. We demonstrate our method for a wide range of materials, from stiff elastic to highly plastic objects that exhibit brittle and/or ductile fracture. Copyright © 2005 by the Association for Computing Machinery, Inc

Efficient raytracing of deforming point-sampled surfaces

We present efficient data structures and caching schemes to accelerate ray-surface intersections for deforming point-sampled surfaces. By exploiting spatial and temporal coherence of the deformation during the animation, we are able to improve rendering performance by a factor of two to three compared to existing techniques. Starting from a tight bounding sphere hierarchy for the undeformed object, we use a lazy updating scheme to adapt the hierarchy to the deformed surface in each animation step. In addition, we achieve a significant speedup for ray-surface intersections by caching per-ray intersection points. We also present a technique for rendering sharp edges and corners in point-sampled models by introducing a novel surface clipping algorithm. © The Eurographics Association and Blackwell Publishing 2005

“PPI? That sounds like Payment Protection Insurance”: Reflections and learning from a substance use and homelessness study Experts by Experience group

BackgroundPatient and Public Involvement in research is important for citizenship, accountability and transparency, and has the practical benefit of helping to ensure its quality and applicability. Involving members of the public in research is becoming increasingly commonplace, in the UK and internationally. It is essential that public involvement is inclusive of individuals and their diverse life experiences, including challenging experiences that may be associated with stigma and social exclusion. The involvement of people with lived/living experience of substance use and homelessness in research is increasing in response to increased recognition of the importance of inclusion and the benefits conferred to research.Main bodyIn this commentary, we share our own experiences of being part of a Patient and Public Involvement group that was convened during a feasibility study of a peer-delivered harm reduction intervention. We are a diverse group but share experience of the field of substance use/homelessness, as people with lived/living experience, and as researchers and practitioners. We share our reflections and learning, as well as offer recommendations for researchers working in our field. Our group worked together to make a positive and deliberate contribution to the study. This did not happen by chance but required the development of mutual trust and respect, with each member having a commitment to support the group for its two-year duration.Short conclusionIt is important for researchers to appreciate that meaningful Patient and Public Involvement is very valuable but requires a commitment from all involved. Regarding our field of substance use and homelessness specifically, it is essential that people with these experiences have opportunities to contribute to research and can do so in a meaningful way. People with lived/living experience are able to bring to life the rich tapestry of others’ experiences. However, the involvement must be neither tokenistic nor indifferent to the wider challenges common to these experiences.---Plain English SummaryThis article describes the activities and lessons learned from the involvement of an Experts by Experience group in a National Institute for Health Research (NIHR) study. The study was about peer support for people experiencing homelessness and substance use challenges. The Experts by Experience group was made up of research team members, and a range of individuals from across the UK who had experienced homelessness and/or drug use and/or alcohol use, and who were recruited from a range of services who currently worked with people experiencing homelessness and/or substance use. The purpose of the group was to ‘sense check’ the study throughout. The group was a requirement from NIHR who funded the project. These groups are usually known as PPI groups (Patient and Public Involvement), but members of the group felt that ‘Experts by Experience’ was a more accurate term to describe the membership. The lived/living experience members’ knowledge of the topic, and experience of using the types of services and interventions involved in the study, helped to guide the study team. Study team members facilitated Experts by Experience group meetings, but everyone was equal. The group gelled and worked well together to oversee the study. This article describes the benefits of having Experts by Experience members as part of the project from the inception through to the end. Ensuring the group had autonomy enhanced the study and was a powerful and empowering experience for the lived/living experience members

Chronic Illness, Treatment Choice and Workforce Participation

Choices with respect to labor force participation and medical treatment are increasingly intertwined. Technological advances present patients with new choices and may facilitate continued employment for the growing number of chronically ill individuals. We examine joint work/treatment decisions of end stage renal disease patients, a group for whom these tradeoffs are particularly salient. Using a simultaneous equations probit model, we find that treatment choice is a significant predictor of employment status. However, the effect size is considerably smaller than in models that do not consider the joint nature of these choices.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45858/1/10754_2004_Article_5145693.pd

Mucus detachment by host metalloprotease meprin \beta requires shedding of its inactive pro-form, which is abrogated by the pathogenic protease RgpB

The host metalloprotease meprin β is required for mucin 2 (MUC2) cleavage, which drives intestinal mucus detachment and prevents bacterial overgrowth. To gain access to the cleavage site in MUC2, meprin β must be proteolytically shed from epithelial cells. Hence, regulation of meprin β shedding and activation is important for physiological and pathophysiological conditions. Here, we demonstrate that meprin β activation and shedding are mutually exclusive events. Employing ex vivo small intestinal organoid and cell culture experiments, we found that ADAM-mediated shedding is restricted to the inactive pro-form of meprin β and is completely inhibited upon its conversion to the active form at the cell surface. This strict regulation of meprin β activity can be overridden by pathogens, as demonstrated for the bacterial protease Arg-gingipain (RgpB). This secreted cysteine protease potently converts membrane-bound meprin β into its active form, impairing meprin β shedding and its function as a mucus-detaching protease