mspire: mass spectrometry proteomics in Ruby

Summary: Mass spectrometry-based proteomics stands to gain from additional analysis of its data, but its large, complex datasets make demands on speed and memory usage requiring special consideration from scripting languages. The software library ‘mspire’—developed in the Ruby programming language—offers quick and memory-efficient readers for standard xml proteomics formats, converters for intermediate file types in typical proteomics spectral-identification work flows (including the Bioworks .srf format), and modules for the calculation of peptide false identification rates

Experience of primary care for people with HIV: a mixed-method analysis

Background Advances in treatment have transformed HIV into a long-term condition (LTC), presenting fresh challenges for health services, HIV specialists and general practitioners (GPs). Aim To explore the experience of people living with HIV (PLHIV) regarding using their GPs. Design and setting A mixed-method analysis using data from two sources: a nationally-representative survey of PLHIV and a qualitative study with London-based PLHIV. Methods Univariate logistic regression for quantitative data and Framework analysis for qualitative data. Results The survey had 4,422 participants; the qualitative study included 52 participants. In both studies, GP registration and HIV status disclosure were high. Similar to general population trends, recent GP use was associated with poor self-rated health status, co-morbidities, older age and lower socioeconomic status. Two-thirds reported a good experience with GPs; a lower proportion felt comfortable asking HIV-related questions. Actual or perceived HIV stigma were consistently associated with poor satisfaction. In the interviews, participants with additional LTCs valued sensitive and consistent support from GPs. Some anticipated, and sometimes experienced, problems relating to HIV status, GPs’ limited experience and time to manage their complex needs. Sometimes they took their own initiatives to facilitate coordination and communication. For PLHIV, a ‘good’ GP offered continuity and took time to know and accept them without judgement. Conclusion We suggest clarification of roles and provision of relevant support to build confidence in GPs and primary care staff to care for PLHIV. As PLHIV population ages, there is a strong need to develop trusting patient/GP relationships and HIV-friendly GP practices

On the Sensitivity and Specificity of Postmortem Upper Respiratory Tract Testing for SARS-CoV-2

Background Postmortem testing can improve our understanding of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) if sufficiently sensitive and specific. Methods We investigated the postmortem sensitivity and specificity of reverse transcriptase polymerase chain reaction (PCR) testing on upper respiratory swabs using a dataset of everyone tested for SARS-CoV-2 before and after death in England, 1 March to 29 October 2020. We analyzed sensitivity in those with a positive test before death by time to postmortem test. We developed a multivariate model and conducted time-to-negativity survival analysis. For specificity, we analyzed those with a negative test in the week before death. Results Postmortem testing within a week after death had a sensitivity of 96.8% if the person had tested positive within a week before death. There was no effect of age, sex, or specimen type on sensitivity, but individuals with coronavirus disease 2019 (COVID-19)–related codes on their death certificate were 5.65 times more likely to test positive after death (95% confidence interval, 2.31–13.9). Specificity was 94.2%, increasing to 97.5% in individuals without COVID-19 on the death certificate. Conclusion Postmortem testing has high sensitivity (96.8%) and specificity (94.2%) if performed within a week after death and could be a useful diagnostic tool

An ALM model for pension funds using integrated chance constraints

We discuss integrated chance constraints in their role of short-term risk constraints in a strategic ALM model for Dutch pension funds. The problem is set up as a multistage recourse model, with special attention for modeling short-term risk prompted by the development of new guidelines by the regulating authority for Dutch pension funds. The paper concludes with a numerical illustration of the importance of such short-term risk constraints

Mortality and causes of death in people diagnosed with HIV in the era of highly active antiretroviral therapy compared with the general population: an analysis of a national observational cohort

BACKGROUND: Deaths in HIV-positive people have decreased since the introduction of highly active antiretroviral therapy (HAART) in 1996. Fewer AIDS-related deaths and an ageing cohort have resulted in an increase in the proportion of HIV patients dying from non-AIDS-related disorders. Here we describe mortality and causes of death in people diagnosed with HIV in the HAART era compared with the general population. METHODS: In this observational analysis, we linked cohort data collected by Public Health England (PHE) for individuals aged 15 years and older, diagnosed with HIV in England and Wales from 1997 to 2012, to the Office for National Statistics (ONS) national mortality register. Cohort inclusion began at diagnosis with follow-up clinical information collected every year from all 220 National Health Service (NHS) HIV outpatient clinics nationwide. To classify causes of death we used a modified Coding Causes of Death in HIV (CoDe) protocol, which uses death certificate data and clinical markers. We applied Kaplan-Meier analysis for survival curves and mortality rate estimation and Cox regression to establish independent predictors of all-cause mortality, adjusting for sex, infection route, age at diagnosis, region of birth, year of diagnosis, late diagnosis, and history of HAART. We used standardised mortality ratios (SMRs) to make comparisons with the general population. FINDINGS: Between 1997 and 2012, 88 994 people were diagnosed with HIV, contributing 448 839 person-years of follow up. By the end of 2012, 5302 (6%) patients had died (all-cause mortality 118 per 10 000 person-years, 95% CI 115–121). In multivariable analysis, late diagnosis was a strong predictor of death (hazard ratio [HR] 3·50, 95% CI 3·13–3·92). People diagnosed more recently had a lower risk of death (2003–07: HR 0·66, 95% CI 0·62–0·70; 2008–12: HR 0·65, 95% CI 0·60–0·71). Cause of death was determinable for 4808 (91%) of 5302 patients; most deaths (2791 [58%] of 4808) were attributable to AIDS-defining illnesses. Cohort mortality was significantly higher than the general population for all causes (SMR 5·7, 95% CI 5·5–5·8), particularly non-AIDS infections (10·8, 9·8–12·0) and liver disease (3·7, 3·3–4·2). All-cause mortality was highest in the year after diagnosis (SMR 24·3, 95% CI 23·4–25·2). INTERPRETATION: Despite the availability of free treatment and care in the UK, AIDS continues to account for the majority of deaths in HIV-positive people, and mortality remains higher in HIV-positive people than in the general population. These findings highlight the importance of prompt diagnosis, care engagement, and optimum management of comorbidities in reducing mortality in people with HIV

Modeling peptide fragmentation with dynamic Bayesian networks for peptide identification

Motivation: Tandem mass spectrometry (MS/MS) is an indispensable technology for identification of proteins from complex mixtures. Proteins are digested to peptides that are then identified by their fragmentation patterns in the mass spectrometer. Thus, at its core, MS/MS protein identification relies on the relative predictability of peptide fragmentation. Unfortunately, peptide fragmentation is complex and not fully understood, and what is understood is not always exploited by peptide identification algorithms

Where do we diagnose HIV infection? Monitoring new diagnoses made in nontraditional settings in England, Wales and Northern Ireland.

OBJECTIVES: The objectives of the study were to describe 10-year trends in HIV diagnosis setting and to explore predictors of being diagnosed outside a sexual health clinic (SHC). METHODS: Analyses of national HIV surveillance data were restricted to adults (aged ≥ 15 years) diagnosed in 2005-2014 in England, Wales and Northern Ireland. Logistic regression identified factors associated with diagnosis outside an SHC (2011-2014). RESULTS: Between 2005 and 2014, 63 599 adults were newly diagnosed with HIV infection; 83% had a diagnosis setting reported. Most people were diagnosed in SHCs (69%) followed by: medical admissions/accident and emergency (A&E; 8.6%), general practice (6.4%), antenatal services (5.5%), out-patient services (3.6%), infectious disease units (2.7%) and other settings (4.0%). The proportion of people diagnosed outside SHCs increased from 2005 to 2014, overall (from 27% to 32%, respectively) and among men who have sex with men (MSM) (from 14% to 21%) and black African men (from 25% to 37%) and women (from 39% to 52%) (all trend P < 0.001). Median CD4 increased across all settings, but was highest in SHCs (384 cells/μL) and lowest in medical admissions/A&E (94 cells/μL). Predictors of being diagnosed outside SHCs included: acquiring HIV through heterosexual contact [adjusted odds ratio (aOR) 1.99; 95% confidence interval (CI) 1.81-2.18] or injecting drug use (aOR: 3.28; 95% CI: 2.56-4.19; reference: MSM), being diagnosed late (< 350 cells/μL) (aOR: 2.55; 95% CI: 2.36-2.74; reference: diagnosed promptly) and being of older age at diagnosis (35-49 years: aOR: 1.60; 95% CI: 1.39-1.83; ≥ 50 years: aOR: 2.48; 95% CI: 2.13-2.88; reference: 15-24 years). CONCLUSIONS: The proportion of HIV diagnoses made outside SHCs has increased over the past decade in line with evolving HIV testing guidelines. However, the rate of late diagnosis remains high, indicating that further expansion of testing is necessary, as many people may have had missed opportunities for earlier diagnosis