Maximum Likelihood Estimator for Hidden Markov Models in continuous time

The paper studies large sample asymptotic properties of the Maximum Likelihood Estimator (MLE) for the parameter of a continuous time Markov chain, observed in white noise. Using the method of weak convergence of likelihoods due to I.Ibragimov and R.Khasminskii, consistency, asymptotic normality and convergence of moments are established for MLE under certain strong ergodicity conditions of the chain.Comment: Warning: due to a flaw in the publishing process, some of the references in the published version of the article are confuse

Defining features of the practice of global health research: an examination of 14 global health research teams

Objectives: This paper strives to develop a pragmatic view of the scope of practice and core characteristics of global health research (GHR) by examining the activities of 14 Canadian-funded global health teams that were in the process of implementing research programs. Methods: Information was collected by a reflective exploration of team proposals and progress reports, a content analysis of the outputs from an all-team meeting and review of the literature. Results: Teams adopted equity-centered, problem-focused, systems-based approaches intended to find upstream determinants that could make people more resilient to social and ecological factors impacting their health. Long-term visions and time frames were needed to develop and solidify fully functional interdisciplinary, multinational, multicultural partnerships. The implementation of research into practice was a motivating factor for all teams, but to do this, they recognized the need for evidence-based advice on how to best do this. Traditional measures of biomedical research excellence were necessary but not sufficient to encompass views of excellence of team-based interdisciplinary research, which includes features like originality, coherence and cumulative contributions to fields of study, acceptance by peers and success in translating research into gains in health status. An innovative and nuanced approached to GHR ethics was needed to deal with some unique ethical issues because the needs for GHR were not adequately addressed by institutional biomedical research ethics boards. Core competencies for GHR researchers were a blend of those needed for health promotion, population health, international development, sustainable development, and systems science. Discussion: Developing acceptable and meaningful ways to evaluate the short-term contributions for GHR and forecast its long-term impacts is a strategic priority needed to defend decisions being made in GHR development. Planning and investing to support the underlying GHR elements and competencies that allow for adaptive, innovative, and supportive research partnerships to achieve ‘health for all’ are more likely to have long-term impacts than building research strategies around specific diseases of interest

Anemia and chronic kidney disease are associated with poor outcomes in heart failure patients

BACKGROUND: Chronic kidney disease (CKD) has been linked to higher heart failure (HF) risk. Anemia is a common consequence of CKD, and recent evidence suggests that anemia is a risk factor for HF. The purpose of this study was to examine among patients with HF, the association between CKD, anemia and inhospital mortality and early readmission. METHODS: We performed a retrospective cohort study in two Swiss university hospitals. Subjects were selected based the presence of ICD-10 HF codes in 1999. We recorded demographic characteristics and risk factors for HF. CKD was defined as a serum creatinine ≥ 124 956;mol/L for women and ≥ 133 μmol/L for men. The main outcome measures were inhospital mortality and thirty-day readmissions. RESULTS: Among 955 eligible patients hospitalized with heart failure, 23.0% had CKD. Twenty percent and 6.1% of individuals with and without CKD, respectively, died at the hospital (p < 0.0001). Overall, after adjustment for other patient factors, creatinine and hemoglobin were associated with an increased risk of death at the hospital, and hemoglobin was related to early readmission. CONCLUSION: Both CKD and anemia are frequent among older patients with heart failure and are predictors of adverse outcomes, independent of other known risk factors for heart failure

Management of congestive heart failure: a gender gap may still exist. Observations from a contemporary cohort

BACKGROUND: Unlike other cardiovascular diseases the incidence and prevalence of congestive heart failure (CHF) continues to increase. While gender differences in coronary artery disease have been well described, to date, there has been a relative paucity of similar data in patients with CHF. We conducted a pilot study to evaluate the profile and management of patients with CHF at a tertiary care centre to determine if a gender difference exists. METHODS: A chart review was performed at a tertiary care centre on consecutive patients admitted with a primary diagnosis of CHF between June 1997 and 1998. Co-morbidity, diagnostic investigations, and management of CHF were recorded. Comparisons between male and female patients were conducted. RESULTS: One hundred and forty five patients were reviewed. There were 80 male (M) and 65 female (F) patients of similar age [71.6 vs. 71.3 (M vs. F), p = NS]. Male patients were more likely to have had a previous myocardial infarction (66% vs. 35%, p < 0.01) and revascularization (41% vs. 20%, p < 0.05), and had worse left ventricular ejection fraction (LVEF) than women, [median LVEF 3 vs. 2 (M vs. F), p < 0.01]. Male patients were more likely to have a non-invasive assessment of left ventricular (LV) function [85% vs. 69%, (M vs. F), p < 0.05]. A logistic regression analysis suggests that amongst those without coronary disease, males were more likely to receive non-invasive testing. There were no differences in the use of prescribed medications, in this cohort. CONCLUSIONS: This pilot study demonstrated that there seem to be important gender differences in the profile and management of patients with CHF. Importantly women were less likely to have an evaluation of LV function. As assessment of LV function has significant implications on patient management, this data justifies the need for larger studies to assess gender differences in CHF profile and treatment

Persistent C-peptide secretion in Type 1 diabetes and its relationship to the genetic architecture of diabetes

Background: The objective of this cross-sectional study was to explore the relationship of detectable C-peptide secretion in type 1 diabetes to clinical features and to the genetic architecture of diabetes. Methods: C-peptide was measured in an untimed serum sample in the SDRNT1BIO cohort of 6076 Scottish people with clinically diagnosed type 1 diabetes or latent autoimmune diabetes of adulthood. Risk scores at loci previously associated with type 1 and type 2 diabetes were calculated from publicly available summary statistics. Results: Prevalence of detectable C-peptide varied from 19% in those with onset before age 15 and duration greater than 15 years to 92% in those with onset after age 35 and duration less than 5 years. Twenty-nine percent of variance in C-peptide levels was accounted for by associations with male gender, late age at onset and short duration. The SNP heritability of residual C-peptide secretion adjusted for gender, age at onset and duration was estimated as 26%. Genotypic risk score for type 1 diabetes was inversely associated with detectable C-peptide secretion: the most strongly associated loci were the HLA and INS gene regions. A risk score for type 1 diabetes based on the HLA DR3 and DQ8-DR4 serotypes was strongly associated with early age at onset and inversely associated with C-peptide persistence. For C-peptide but not age at onset, there were strong associations with risk scores for type 1 and type 2 diabetes that were based on SNPs in the HLA region but not accounted for by HLA serotype. Conclusions: Persistence of C-peptide secretion varies widely in people clinically diagnosed as type 1 diabetes. C-peptide persistence is influenced by variants in the HLA region that are different from those determining risk of early-onset type 1 diabetes. Known risk loci for diabetes account for only a small proportion of the genetic effects on C-peptide persistence

A Novel System of Polymorphic and Diverse NK Cell Receptors in Primates

There are two main classes of natural killer (NK) cell receptors in mammals, the killer cell immunoglobulin-like receptors (KIR) and the structurally unrelated killer cell lectin-like receptors (KLR). While KIR represent the most diverse group of NK receptors in all primates studied to date, including humans, apes, and Old and New World monkeys, KLR represent the functional equivalent in rodents. Here, we report a first digression from this rule in lemurs, where the KLR (CD94/NKG2) rather than KIR constitute the most diverse group of NK cell receptors. We demonstrate that natural selection contributed to such diversification in lemurs and particularly targeted KLR residues interacting with the peptide presented by MHC class I ligands. We further show that lemurs lack a strict ortholog or functional equivalent of MHC-E, the ligands of non-polymorphic KLR in “higher” primates. Our data support the existence of a hitherto unknown system of polymorphic and diverse NK cell receptors in primates and of combinatorial diversity as a novel mechanism to increase NK cell receptor repertoire

Phosphorus–iron interaction in sediments : can an electrode minimize phosphorus release from sediments?

All restoration strategies to mitigate eutrophication depend on the success of phosphorus (P) removal from the water body. Therefore, the inputs from the watershed and from the enriched sediments, that were the sink of most P that has been discharged in the water body, should be controlled. In sediments, iron (hydr)oxides minerals are potent repositories of P and the release of P into the water column may occur upon dissolution of the iron (hydr)oxides mediated by iron reducing bacteria. Several species of these bacteria are also known as electroactive microorganisms and have been recently identified in lake sediments. This capacity of bacteria to transfer electrons to electrodes, producing electricity from the oxidation of organic matter, might play a role on P release in sediments. In the present work it is discussed the relationship between phosphorus and iron cycling as well as the application of an electrode to work as external electron acceptor in sediments, in order to prevent metal bound P dissolution under anoxic conditions.The authors are grateful to two anonymous reviewers of a previous version of the manuscript for the constructive comments and suggestions. The authors also acknowledge the Grant SFRH/BPD/80528/2011 from the Foundation for Science and Technology, Portugal, awarded to Gilberto Martins

Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17

Background Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. Methods We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40.0% (95% uncertainty interval [UI] 39.4-40.7) to 50.3% (50.0-50.5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46.3% (95% UI 46.1-46.5) in 2017, compared with 28.7% (28.5-29.0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88.6% (95% UI 87.2-89.7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664-711) of the 1830 (1797-1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76.1% (95% UI 71.6-80.7) of countries from 2000 to 2017, and in 53.9% (50.6-59.6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.Peer reviewe