A New Proposal for Collection and Generation of Information on Financial Institutions' Risk: the case of derivatives

This article aims at providing a new alternative for the collection of information on risks taken by financial institutions, which enables the calculation of risk tools usually used in risk management, such as VaR and stress tests. This approach should help risk managers, off-site supervision and academics in assessing the potential risks in financial institutions principally due to derivatives positions. The basic idea, for linear financial instruments, like the traditionally used by the management risk systems, is to reduce positions in risk factors and then mapping by vertices. For the nonlinear financial instruments all of the positions in different types of options – European, Americans, exotic, etc.– are represented as plain vanilla European options or replicated by portfolios of plain vanilla European options. The methodology was applied to Brazil, within the worst scenarios during the period from 1994 to 2004, and the paper demonstrates that the proposed approach captured the risks satisfactorily in the analyzed portfolios, including the risk existent in the strategies involving options, given an accepted error margin. This approach could be useful for regulators, risk managers; financial institutions and risk management modeling as it can be used as an input in general risk management models.

Interpreting frequency responses to dose-conserved pulsatile input signals in simple cell signaling motifs.

This is the final version of the article. Available from PLoS via the DOI in this record.Many hormones are released in pulsatile patterns. This pattern can be modified, for instance by changing pulse frequency, to encode relevant physiological information. Often other properties of the pulse pattern will also change with frequency. How do signaling pathways of cells targeted by these hormones respond to different input patterns? In this study, we examine how a given dose of hormone can induce different outputs from the target system, depending on how this dose is distributed in time. We use simple mathematical models of feedforward signaling motifs to understand how the properties of the target system give rise to preferences in input pulse pattern. We frame these problems in terms of frequency responses to pulsatile inputs, where the amplitude or duration of the pulses is varied along with frequency to conserve input dose. We find that the form of the nonlinearity in the steady state input-output function of the system predicts the optimal input pattern. It does so by selecting an optimal input signal amplitude. Our results predict the behavior of common signaling motifs such as receptor binding with dimerization, and protein phosphorylation. The findings have implications for experiments aimed at studying the frequency response to pulsatile inputs, as well as for understanding how pulsatile patterns drive biological responses via feedforward signaling pathways.This work was partially supported by the National Science Foundation grant DMS-1220063 to R. Bertram and J. Tabak (http://www.nsf.gov) and by the large-scale action REGATE (REgulation of the GonAdoTropE axis) to F. Clement and A. Vidal (https://www.rocq.inria.fr/sisyphe/reglo/regate.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Dissemination and implementation science training needs: Insights from practitioners and researchers

INTRODUCTION: Dissemination and implementation research training has great potential to improve the impact and reach of health-related research; however, research training needs from the end user perspective are unknown. This paper identifies and prioritizes dissemination and implementation research training needs. METHODS: A diverse sample of researchers, practitioners, and policymakers was invited to participate in Concept Mapping in 2014–2015. Phase 1 (Brainstorming) gathered participants' responses to the prompt: To improve the impact of research evidence in practice and policy settings, a skill in which researchers need more training is… The resulting statement list was edited and included subsequent phases. Phase 2 (Sorting) asked participants to sort each statement into conceptual piles. In Phase 3 (Rating), participants rated the difficulty and importance of incorporating each statement into a training curriculum. A multidisciplinary team synthesized and interpreted the results in 2015–2016. RESULTS: During Brainstorming, 60 researchers and 60 practitioners/policymakers contributed 274 unique statements. Twenty-nine researchers and 16 practitioners completed sorting and rating. Nine concept clusters were identified: Communicating Research Findings, Improve Practice Partnerships, Make Research More Relevant, Strengthen Communication Skills, Develop Research Methods and Measures, Consider and Enhance Fit, Build Capacity for Research, and Understand Multilevel Context. Though researchers and practitioners had high agreement about importance (r =0.93) and difficulty (r =0.80), ratings differed for several clusters (e.g., Build Capacity for Research). CONCLUSIONS: Including researcher and practitioner perspectives in competency development for dissemination and implementation research identifies skills and capacities needed to conduct and communicate contextualized, meaningful, and relevant research

A role for Vps1p, actin, and the Myo2p motor in peroxisome abundance and inheritance in Saccharomyces cerevisiae

In vivo time-lapse microscopy reveals that the number of peroxisomes in Saccharomyces cerevisiae cells is fairly constant and that a subset of the organelles are targeted and segregated to the bud in a highly ordered, vectorial process. The dynamin-like protein Vps1p controls the number of peroxisomes, since in a vps1Δ mutant only one or two giant peroxisomes remain. Analogous to the function of other dynamin-related proteins, Vps1p may be involved in a membrane fission event that is required for the regulation of peroxisome abundance. We found that efficient segregation of peroxisomes from mother to bud is dependent on the actin cytoskeleton, and active movement of peroxisomes along actin filaments is driven by the class V myosin motor protein, Myo2p: (a) peroxisomal dynamics always paralleled the polarity of the actin cytoskeleton, (b) double labeling of peroxisomes and actin cables revealed a close association between both, (c) depolymerization of the actin cytoskeleton abolished all peroxisomal movements, and (d) in cells containing thermosensitive alleles of MYO2, all peroxisome movement immediately stopped at the nonpermissive temperature. In addition, time-lapse videos showing peroxisome movement in wild-type and vps1Δ cells suggest the existence of various levels of control involved in the partitioning of peroxisomes

Mathematical Modelling of Endocrine Systems

This is the final (in press) version. Available from Elsevier via the DOI in this recordHormone rhythms are ubiquitous and essential to sustain normal physiological functions. Combined mathematical modelling and experimental approaches have shown that these rhythms result from regulatory processes occurring at multiple levels of organisation and require continuous dynamic equilibration, particularly in response to stimuli. We review how such an interdisciplinary approach has been successfully applied to unravel complex regulatory mechanisms in the metabolic, stress, and reproductive axes. We discuss how this strategy is likely to be instrumental for making progress in emerging areas such as chronobiology and network physiology. Ultimately, we envisage that the insight provided by mathematical models could lead to novel experimental tools able to continuously adapt parameters to gradual physiological changes and the design of clinical interventions to restore normal endocrine function.Medical Research Council (MRC)Engineering and Physical Sciences Research Council (EPSRC)Wellcome Trus

Candidemia on presentation to the hospital: development and validation of a risk score

Introduction: Candidemia results in substantial morbidity and mortality, especially if initial antifungal therapy is delayed or is inappropriate; however, candidemia is difficult to diagnose because of its nonspecific presentation. Methods: To develop a risk score for identifying hospitalized patients with candidemia, we performed a retrospective analysis of a large database of 176 acute-care hospitals in the United States. We studied 64,019 patients with bloodstream infection (BSI) on presentation from 2000 through 2005 (derivation cohort) and 24,685 from 2006 to 2007 (validation cohort). We used recursive partitioning (RPART) to identify the best discriminators for Candida as the cause of BSI. We compared three sets of models (equal-weight, unequal-weight, vs full model with additional variables from logistic regression model) for sensitivity analysis. Results: The RPART identified 6 variables as the best discriminators: age 0.10, indicating predicted and observed candidemia rates did not differ significant across the 7 risk stratus). The full model with 16 risk factors had slightly higher AUROCs (0.74 versus 0.73 for derivation versus validation); however, 7 variables were no longer significant in the recalibrated model for the validation cohort, indicating that the additional items did not materially enhance the model. Conclusions: A simple equal-weight risk score differentiated patients' risk for candidemia in a graded fashion upon hospital presentation

Morbidity and cost burden of methicillin-resistant Staphylococcus aureus in early onset ventilator-associated pneumonia

INTRODUCTION: To gain a better understanding of the clinical and economic outcomes associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in patients with early onset ventilator-associated pneumonia (VAP), we retrospectively analyzed a multihospital US database to identify patients with VAP over a 24 month period (2002–2003). METHOD: Data recorded included physiologic, laboratory, culture, and other clinical variables from 59 institutions. VAP was defined as new positive respiratory culture after at least 24 hours of mechanical ventilation (MV) and the presence of primary or secondary ICD-9-CM diagnosis codes of pneumonia. Outcomes measures included in-hospital morbidity and mortality for the population overall and after onset of VAP (duration of MV, intensive care unit [ICU] stay, in-hospital stay, and case mix and severity-adjusted operating cost). The overall cost was calculated at the hospital level using the Center for Medicare and Medicaid Services Cost/Charge Index for each calendar year. RESULTS: A total of 499 patients were identified as having VAP. S. aureus was the leading organism (31% of isolates). Patients with MRSA were significantly older than patients with methicillin-sensitive Staphylococcus aureus (MSSA; median age 74 versus 67 years, P < 0.05) and more likely to be medical patients. Compared with MSSA patients, MRSA patients on average consumed excess resources of 4.4 (95% confidence interval 0.6–8.2) overall MV days, 3.8 (-0.5 to +8.0) days of inpatient length of stay (LOS), 5.3 (1.0–9.7) ICU days, and US$7731 (-US$8393 to +US$23,856) total cost after controlling for case mix and other factors. Furthermore, MRSA patients needed excess resources after the onset of VAP (4.5 [95$8000 per case after controlling for case mix and severity

Crystallization and preliminary structural analysis of the giant haemoglobin from Glossoscolex paulistus at 3.2 Å

Diffraction data to 3.2 Å from crystals of the 3.6 MDa erythrocruorin from a Brazilian earthworm represent the highest resolution reported to date for similar complexes. An unambiguous molecular replacement solution shows the particle to belong to the type I class