HIV and respiratory illness in the antiretroviral therapy era

Respiratory illness is a common manifestation of HIV infection. The availability of effective antiretroviral therapy (ART) has changed the pattern of respiratory ill-health experienced by people living with HIV (PLWH). Among populations with good access to ART, opportunistic respiratory infections such as Pneumocystis jirovecii pneumonia (PCP) are becoming less frequent. However, there is evidence to suggest that these populations may be at greater risk of serious non-AIDS illness including chronic respiratory disease. Although there is remaining uncertainty about the extent to which HIV represents an independent risk-factor for respiratory illness in individuals with a suppressed HIV viral load and immune reconstitution, in many settings PLWH have greater exposure to risk factors for respiratory illness (in particular tobacco smoking), which contribute to this burden of disease. As HIV-positive populations age, management of these conditions will therefore become increasingly important. Healthcare services need to manage this growing burden of chronic respiratory illness and provide access to preventative measures including smoking cessation and immunisation against vaccine-preventable respiratory infections in a way that is appropriate to the populations served

The Invisible Thin Red Line

The aim of this paper is to argue that the adoption of an unrestricted principle of bivalence is compatible with a metaphysics that (i) denies that the future is real, (ii) adopts nomological indeterminism, and (iii) exploits a branching structure to provide a semantics for future contingent claims. To this end, we elaborate what we call Flow Fragmentalism, a view inspired by Kit Fine (2005)’s non-standard tense realism, according to which reality is divided up into maximally coherent collections of tensed facts. In this way, we show how to reconcile a genuinely A-theoretic branching-time model with the idea that there is a branch corresponding to the thin red line, that is, the branch that will turn out to be the actual future history of the world

Plasma and cerebrospinal fluid concentrations of linezolid in neurosurgical critically ill patients with proven or suspected central nervous system infections

Linezolid is a valuable treatment option for central nervous system (CNS) infections caused by multidrug-resistant Gram-positive micro-organisms. Data regarding its penetration into the CNS have shown wide variability. The aim of this study was to describe the population pharmacokinetics of linezolid in plasma and cerebrospinal fluid (CSF) in critically ill patients with external CSF drainage and proven or suspected CNS infections. This was an observational pharmacokinetic (PK) study in 11 critically ill patients with proven or suspected CNS infection receiving linezolid. Serial blood and CSF samples were taken and were subject to population PK analysis. The median (interquartile range) of AUC(0-12h) was 47.6 (17.9-58.6) mg h/L in plasma and 21.1(18.8-30.4) mg h/L in CSF, with a median CSF/plasma ratio of 0.77. At pre-dose at steady state, a strong positive correlation was observed between linezolid concentrations in CSF and plasma (Spearman's rho = 0.758; P = 0.011). For a minimum inhibitory concentration (MIC) of 2 mg/L, the median AUC(0-24h)/MIC values in plasma and CSF wer

Estimating the risk of mortality attributable to recent late HIV diagnosis following admission to the intensive care unit: A single-centre observational cohort study

OBJECTIVES: Despite improvements in survival of people with HIV admitted to the intensive care unit (ICU), late diagnosis continues to contribute to in-ICU mortality. We quantify the population attributable fraction (PAF) of in-ICU mortality for recent late diagnosis among people with HIV admitted to a London ICU. METHODS: Index ICU admissions among people with HIV were considered from 2000 to 2019. Recent late diagnosis was a CD4 T-cell count < 350 cells/μL and/or AIDS-defining illness at/within 6 months prior to ICU admission. Univariate comparisons were conducted using Wilcoxon rank-sum/Cochran-Armitage/χ2 /Fisher's exact tests. We used Poisson regression (robust standard errors) to estimate unadjusted/adjusted (age, sex, calendar year of ICU admission) risk ratios (RRs) and regression standardization to estimate the PAF. RESULTS: In all, 207 index admissions were included [median (interquartile range) age: 46 (38-53) years; 72% male]; 58 (28%) had a recent late diagnosis, all of whom had a CD4 count < 350 cells/μL, and 95% had advanced HIV (CD4 count < 200 cells/μL and/or AIDS at admission) as compared with 57% of those who did not have a recent late diagnosis (p < 0.001). In-ICU mortality was 27% (55/207); 38% versus 22% in those who did and did not have a recent late diagnosis, respectively (p = 0.02). Recent late diagnosis was independently associated with increased in-ICU mortality risk (adjusted RR = 1.75) (95% confidence interval: 1.05-2.91), with 17.08% (16.04-18.12%) of deaths being attributable to this. CONCLUSIONS: There is a need for improved public health efforts focused on HIV testing and reporting of late diagnosis to better understand potentially missed opportunities for earlier HIV diagnosis in healthcare services

Asymptotic Behavior of Ext functors for modules of finite complete intersection dimension

Let $R$ be a local ring, and let $M$ and $N$ be finitely generated $R$-modules such that $M$ has finite complete intersection dimension. In this paper we define and study, under certain conditions, a pairing using the modules \Ext_R^i(M,N) which generalizes Buchweitz's notion of the Herbrand diference. We exploit this pairing to examine the number of consecutive vanishing of \Ext_R^i(M,N) needed to ensure that \Ext_R^i(M,N)=0 for all $i\gg 0$. Our results recover and improve on most of the known bounds in the literature, especially when $R$ has dimension at most two

Access to influenza immunisation services by HIV positive patients in the UK.

Influenza is an important cause of morbidity in HIV positive adults, who may be more susceptible and more likely to develop severe disease.(1,2) Annual influenza immunisation is recommended for all HIV positive adults in the UK, supported by British HIV Association (BHIVA) guidelines,(1) with evidence for reasonably good uptake (3). HIV services do not receive specific funding to provide immunisation; and the National Flu Immunisation Programme offers this instead via Primary Care and pharmacies.(4) Whether this meets the needs of people living with HIV has not been evaluated. This article is protected by copyright. All rights reserved

Helping education undergraduates to use appropriate criteria for evaluating accounts of motivation

The aim of the study was to compare students in a control group with those in a treatment group with respect to evaluative comments on psychological accounts of motivation. The treatment group systematically scrutinized the nature and interpretation of evidence that supported different accounts, and the assumptions, logic, coherence and clarity of accounts. Content analysis of 74 scripts (using three categories) showed that the control group students made more assertions than either evidential or evaluative points, whereas the treatment group used evaluative statements as often as they used assertion. The findings provide support for privileging activities that develop understanding of how knowledge might be contested, and suggest a need for further research on pedagogies to serve this end. The idea is considered that such understanding has a pivotal role in the development of critical thinking

Young children's research: children aged 4-8 years finding solutions at home and at school

Children's research capacities have become increasingly recognised by adults, yet children remain excluded from the academy, with reports of their research participation generally located in adults' agenda. Such practice restricts children's freedom to make choices in matters affecting them, underestimates children’s capabilities and denies children particular rights. The present paper reports on one aspect of a small-scale critical ethnographic study adopting a constructivist grounded approach to conceptualise ways in which children's naturalistic behaviours may be perceived as research. The study builds on multi-disciplinary theoretical perspectives, embracing 'new' sociology, psychology, economics, philosophy and early childhood education and care (ECEC). Research questions include: 'What is the nature of ECEC research?' and 'Do children’s enquiries count as research?' Initially, data were collected from the academy: professional researchers (n=14) confirmed 'finding solutions' as a research behaviour and indicated children aged 4-8 years, their practitioners and primary carers as 'theoretical sampling'. Consequently, multi-modal case studies were constructed with children (n=138) and their practitioners (n=17) in three ‘good’ schools, with selected children and their primary carers also participating at home. This paper reports on data emerging from children aged 4-8 years at school (n=17) and at home (n=5). Outcomes indicate that participating children found diverse solutions to diverse problems, some of which they set themselves. Some solutions engaged children in high order thinking, whilst others did not; selecting resources and trialing activities engaged children in 'finding solutions'. Conversely, when children's time, provocations and activities were directed by adults, the quality of their solutions was limited, they focused on pleasing adults and their motivation to propose solutions decreased. In this study, professional researchers recognised 'finding solutions' as research behaviour and children aged 4-8 years naturalistically presented with capacities for finding solutions; however, the children's encounters with adults affected the solutions they found