F_B from moving B mesons

We show results for the B meson decay constant calculated both for B mesons at rest and those with non-zero momentum and using both the temporal and spatial components of the axial vector current. It is an important check of lattice systematic errors that all these determinations of f_B should agree. We also describe how well different smearings for the B meson work at non-zero momentum - the optimal smearing has a narrow smearing for the b quark.Comment: Lattice2001(heavyquark

Identification of zoonotic genotypes of Giardia duodenalis

Giardia duodenalis, originally regarded as a commensal organism, is the etiologic agent of giardiasis, a gastrointestinal disease of humans and animals. Giardiasis causes major public and veterinary health concerns worldwide. Transmission is either direct, through the faecal-oral route, or indirect, through ingestion of contaminated water or food. Genetic characterization of G. duodenalis isolates has revealed the existence of seven groups (assemblages A to G) which differ in their host distribution. Assemblages A and B are found in humans and in many other mammals, but the role of animals in the epidemiology of human infection is still unclear, despite the fact that the zoonotic potential of Giardia was recognised by the WHO some 30 years ago. Here, we performed an extensive genetic characterization of 978 human and 1440 animal isolates, which together comprise 3886 sequences from 4 genetic loci. The data were assembled into a molecular epidemiological database developed by a European network of public and veterinary health Institutions. Genotyping was performed at different levels of resolution (single and multiple loci on the same dataset). The zoonotic potential of both assemblages A and B is evident when studied at the level of assemblages, sub-assemblages, and even at each single locus. However, when genotypes are defined using a multi-locus sequence typing scheme, only 2 multi-locus genotypes (MLG) of assemblage A and none of assemblage B appear to have a zoonotic potential. Surprisingly, mixtures of genotypes in individual isolates were repeatedly observed. Possible explanations are the uptake of genetically different Giardia cysts by a host, or subsequent infection of an already infected host, likely without overt symptoms, with a different Giardia species, which may cause disease. Other explanations for mixed genotypes, particularly for assemblage B, are substantial allelic sequence heterogeneity and/or genetic recombination. Although the zoonotic potential of G. duodenalis is evident, evidence on the contribution and frequency is (still) lacking. This newly developed molecular database has the potential to tackle intricate epidemiological questions concerning protozoan diseases.This study was partially funded by the European MED-VET-NET project contract FOOD-CT-2004-506122, and by the Dutch Food and Consumer Product Safety Authority (VWA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Heritage Requires Citizens’ Knowledge : The COST Place-Making Action and Responsible Research

This chapter reflects on responsible science with an eye toward concrete research practice. To this end, we briefly introduce the RRI paradigm (Responsible Research and Innovation) and then highlight seven EU research projects in the con- text of a transnational COST Action project. This COST Action will investigate how placemaking activities, like public art, civil urban design, and local knowledge pro- duction, reshape and reinvent public space, and improve citizens’ involvement in urban planning and urban design, especially in the context of heritage sites. The chapter introduces heritage case studies that either contrast, differentiate, and add to existing knowledge and practices in placemaking through specific initiatives, or enable the establishment of common ground within a wider constellation of societal actors and both, as we see, contribute in different ways to responsible research. We analyze how the four criteria of RRI, namely anticipation, reflexivity, inclusion, and responsiveness are considered and implemented, and the extent to which digital tools are supportive. Obviously, coproduction of knowledge is not sufficient when we call for responsible science in the narrow sense, hence the development of com- mon ground also appears necessary.Peer reviewe

Thresholds for Arterial Wall Inflammation Quantified by 18F-FDG PET Imaging Implications for Vascular Interventional Studies

AbstractObjectivesThis study assessed 5 frequently applied arterial 18fluorodeoxyglucose (18F-FDG) uptake metrics in healthy control subjects, those with risk factors and patients with cardiovascular disease (CVD), to derive uptake thresholds in each subject group. Additionally, we tested the reproducibility of these measures and produced recommended sample sizes for interventional drug studies.Background18F-FDG positron emission tomography (PET) can identify plaque inflammation as a surrogate endpoint for vascular interventional drug trials. However, an overview of 18F-FDG uptake metrics, threshold values, and reproducibility in healthy compared with diseased subjects is not available.Methods18F-FDG PET/CT of the carotid arteries and ascending aorta was performed in 83 subjects (61 ± 8 years) comprising 3 groups: 25 healthy controls, 23 patients at increased CVD risk, and 35 patients with known CVD. We quantified 18F-FDG uptake across the whole artery, the most-diseased segment, and within all active segments over several pre-defined cutoffs. We report these data with and without background corrections. Finally, we determined measurement reproducibility and recommended sample sizes for future drug studies based on these results.ResultsAll 18F-FDG uptake metrics were significantly different between healthy and diseased subjects for both the carotids and aorta. Thresholds of physiological 18F-FDG uptake were derived from healthy controls using the 90th percentile of their target to background ratio (TBR) value (TBRmax); whole artery TBRmax is 1.84 for the carotids and 2.68 in the aorta. These were exceeded by >52% of risk factor patients and >67% of CVD patients. Reproducibility was excellent in all study groups (intraclass correlation coefficient >0.95). Using carotid TBRmax as a primary endpoint resulted in sample size estimates approximately 20% lower than aorta.ConclusionsWe report thresholds for physiological 18F-FDG uptake in the arterial wall in healthy subjects, which are exceeded by the majority of CVD patients. This remains true, independent of readout vessel, signal quantification method, or the use of background correction. We also confirm the high reproducibility of 18F-FDG PET measures of inflammation. Nevertheless, because of overlap between subject categories and the relatively small population studied, these data have limited generalizability until substantiated in larger, prospective event-driven studies. (Vascular Inflammation in Patients at Risk for Atherosclerotic Disease; NTR5006

The price of tumor control

Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

Comparison Studies of Finite Momentum Correlators on Anisotropic and Isotropic Lattices

We study hadronic two- and three-point correlators relevant for heavy to light pseudoscalar meson semi-leptonic decays, using Symanzik improved glue, D234 light quark and NRQCD heavy quark actions. Detailed comparisons are made between simulations on anisotropic and isotropic lattices involving finite momentum hadrons. We find evidence that having an anisotropy helps in extracting better signals at higher momenta. Initial results for the form factors f_+(q^2) and f_0(q^2) are presented with tree-level matching of the lattice heavy-light currents.Comment: 43 pages with 50 postscript figure

Heritage Requires Citizens’ Knowledge : The COST Place-Making Action and Responsible Research

This chapter reflects on responsible science with an eye toward concrete research practice. To this end, we briefly introduce the RRI paradigm (Responsible Research and Innovation) and then highlight seven EU research projects in the con- text of a transnational COST Action project. This COST Action will investigate how placemaking activities, like public art, civil urban design, and local knowledge pro- duction, reshape and reinvent public space, and improve citizens’ involvement in urban planning and urban design, especially in the context of heritage sites. The chapter introduces heritage case studies that either contrast, differentiate, and add to existing knowledge and practices in placemaking through specific initiatives, or enable the establishment of common ground within a wider constellation of societal actors and both, as we see, contribute in different ways to responsible research. We analyze how the four criteria of RRI, namely anticipation, reflexivity, inclusion, and responsiveness are considered and implemented, and the extent to which digital tools are supportive. Obviously, coproduction of knowledge is not sufficient when we call for responsible science in the narrow sense, hence the development of com- mon ground also appears necessary.Peer reviewe

Demystifying image-based machine learning: a practical guide to automated analysis of field imagery using modern machine learning tools

Image-based machine learning methods are becoming among the most widely-used forms of data analysis across science, technology, engineering, and industry. These methods are powerful because they can rapidly and automatically extract rich contextual and spatial information from images, a process that has historically required a large amount of human labor. A wide range of recent scientific applications have demonstrated the potential of these methods to change how researchers study the ocean. However, despite their promise, machine learning tools are still under-exploited in many domains including species and environmental monitoring, biodiversity surveys, fisheries abundance and size estimation, rare event and species detection, the study of animal behavior, and citizen science. Our objective in this article is to provide an approachable, end-to-end guide to help researchers apply image-based machine learning methods effectively to their own research problems. Using a case study, we describe how to prepare data, train and deploy models, and overcome common issues that can cause models to underperform. Importantly, we discuss how to diagnose problems that can cause poor model performance on new imagery to build robust tools that can vastly accelerate data acquisition in the marine realm. Code to perform analyses is provided at https://github.com/heinsense2/AIO_CaseStudy

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

Freshwater systems and ecosystem services: challenges and chances for crossfertilization of disciplines

Freshwater ecosystems are among the most threatened in the world, while providing numerous essential ecosystem services (ES) to humans. Despite their importance, research on freshwater ecosystem services is limited. Here, we examine how freshwater studies could help to advance ES research and vice versa. We summarize major knowledge gaps and suggest solutions focusing on science and policy in Europe. We found several features that are unique to freshwater ecosystems, but often disregarded in ES assessments. Insufficient transfer of knowledge towards stakeholders is also problematic. Knowledge transfer and implementation seems to be less effective towards South-east Europe. Focusing on the strengths of freshwater research regarding connectivity, across borders, involving multiple actors can help to improve ES research towards a more dynamic, landscape-level approach, which we believe can boost the implementation of the ES concept in freshwater policies. Bridging these gaps can contribute to achieve the ambitious targets of the EU’s Green Deal