Black race as a predictor of poor health outcomes among a national cohort of HIV/AIDS patients admitted to US hospitals: a cohort study

BACKGROUND: In general, the Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) population has begun to experience the benefits of highly active antiretroviral therapy (HAART); unfortunately, these benefits have not extended equally to Blacks in the United States, possibly due to differences in patient comorbidities and demographics. These differences include rates of hepatitis B and C infection, substance use, and socioeconomic status. To investigate the impact of these factors, we compared hospital mortality and length of stay (LOS) between Blacks and Whites with HIV/AIDS while adjusting for differences in these key characteristics. METHODS: The 1996-2006 National Hospital Discharge Surveys were used to identify HIV/AIDS patients admitted to US hospitals. Survey weights were incorporated to provide national estimates. Patients < 18 years of age, those who left against medical advice, those with an unknown discharge disposition and those with a LOS < 1 day were excluded. Patients were stratified into subgroups by race (Black or White). Two multivariable logistic regression models were constructed with race as the independent variable and outcomes (mortality and LOS > 10 days) as the dependent variables. Factors that were significantly different between Blacks and Whites at baseline via bivariable statistical tests were included as covariates. RESULTS: In the general US population, there are approximately 5 times fewer Blacks than Whites. In the present study, 1.5 million HIV/AIDS hospital discharges were identified and Blacks were 6 times more likely to be hospitalized than Whites. Notably, Blacks had higher rates of substance use (30% vs. 24%; P < 0.001), opportunistic infections (27% vs. 26%; P < 0.001) and cocaine use (13% vs. 5%; P < 0.001). Conversely, fewer Blacks were co-infected with hepatitis C virus (8% vs. 12%; P < 0.001). Hepatitis B virus was relatively infrequent (3% for both groups). Crude mortality rates were similar for both cohorts (5%); however, a greater proportion of Blacks had a LOS > 10 days (21% vs. 19%; P < 0.001). Black race, in the presence of comorbidities, was correlated with a higher odds of LOS > 10 days (OR, 95% CI = 1.20 [1.10-1.30]), but was not significantly correlated with a higher odds of mortality (OR, 95% CI = 1.07 [0.93-1.25]). CONCLUSION: Black race is a predictor of LOS > 10 days, but not mortality, among HIV/AIDS patients admitted to US hospitals. It is possible that racial disparities in hospital outcomes may be closing with time

H2r: Identification of evolutionary important residues by means of an entropy based analysis of multiple sequence alignments

BACKGROUND: A multiple sequence alignment (MSA) generated for a protein can be used to characterise residues by means of a statistical analysis of single columns. In addition to the examination of individual positions, the investigation of co-variation of amino acid frequencies offers insights into function and evolution of the protein and residues. RESULTS: We introduce conn(k), a novel parameter for the characterisation of individual residues. For each residue k, conn(k) is the number of most extreme signals of co-evolution. These signals were deduced from a normalised mutual information (MI) value U(k, l) computed for all pairs of residues k, l. We demonstrate that conn(k) is a more robust indicator than an individual MI-value for the prediction of residues most plausibly important for the evolution of a protein. This proposition was inferred by means of statistical methods. It was further confirmed by the analysis of several proteins. A server, which computes conn(k)-values is available at http://www-bioinf.uni-regensburg.de. CONCLUSION: The algorithms H2r, which analyses MSAs and computes conn(k)-values, characterises a specific class of residues. In contrast to strictly conserved ones, these residues possess some flexibility in the composition of side chains. However, their allocation is sensibly balanced with several other positions, as indicated by conn(k)

Calibrating ADL-IADL scales to improve measurement accuracy and to extend the disability construct into the preclinical range: a systematic review

<p>Abstract</p> <p>Background</p> <p>Interest in measuring functional status among nondisabled older adults has increased in recent years. This is, in part, due to the notion that adults identified as 'high risk' for functional decline portray a state that is potentially easier to reverse than overt disability. Assessing relatively healthy older adults with traditional self-report measures (activities of daily living) has proven difficult because these instruments were initially developed for institutionalised older adults. Perhaps less evident, are problems associated with change scores and the potential for 'construct under-representation', which reflects the exclusion of important features of the construct (e.g., disability). Furthermore, establishing a formal hierarchy of functional status tells more than the typical simple summation of functional loss, and may have predictive value to the clinician monitoring older adults: if the sequence task difficulty is accelerated or out of order it may indicate the need for interventions.</p> <p>Methods</p> <p>This review identified studies that employed item response theory (IRT) to examine or revise functional status scales. IRT can be used to transform the ordinal nature of functional status scales to interval level data, which serves to increase diagnostic precision and sensitivity to clinical change. Furthermore, IRT can be used to rank items unequivocally along a hierarchy based on difficulty. It should be noted that this review is not concerned with contrasting IRT with more traditional classical test theory methodology.</p> <p>Results</p> <p>A systematic search of four databases (PubMed, Embase, CINAHL, and PsychInfo) resulted in the review of 2,192 manuscripts. Of these manuscripts, twelve met our inclusion/exclusion requirements and thus were targeted for further inspection.</p> <p>Conclusions</p> <p>Manuscripts presented in this review appear to summarise gerontology's best efforts to improve construct validity and content validity (i.e., ceiling effects) for scales measuring the early stages of activity restriction in community-dwelling older adults. Several scales in this review were exceptional at reducing ceiling effects, reducing gaps in coverage along the construct, as well as establishing a formal hierarchy of functional decline. These instrument modifications make it plausible to detect minor changes in difficulty for IADL items positioned at the edge of the disability continuum, which can be used to signal the onset of progressive type disability in older adults.</p

Revealing hidden species distribution with pheromones: the case of Synanthedon vespiformis (Lepidoptera: Sesiidae) in Sweden

Synanthedon vespiformis L. (Lepidoptera: Sesiidae) is considered a rare insect in Sweden, discovered in 1860, with only a few observations recorded until a sex pheromone attractant became available recently. This study details a national survey conducted using pheromones as a sampling method for this species. Through pheromone trapping we captured 439 specimens in Southern Sweden at 77 sites, almost tripling the number of previously reported records for this species. The results suggest that S. vespiformis is truly a rare species with a genuinely scattered distribution, but can be locally abundant. Habitat analyses were conducted in order to test the relationship between habitat quality and the number of individuals caught. In Sweden, S. vespiformis is thought to be associated with oak hosts, but our attempts to predict its occurrence by the abundance of oaks yielded no significant relationships. We therefore suggest that sampling bias and limited knowledge on distribution may have led to the assumption that this species is primarily reliant on oaks in the northern part of its range, whereas it may in fact be polyphagous, similar to S. vespiformis found as an agricultural pest in Central and Southern Europe. We conclude that pheromones can massively enhance sampling potential for this and other rare lepidopteran species. Large-scale pheromone-based surveys provide a snapshot of true presences and absences across a considerable part of a species national distribution range, and thus for the first time provide a viable means of systematically assessing changes in distribution over time with high spatiotemporal resolution

Cooperative Transition between Open and Closed Conformations in Potassium Channels

Potassium (K+) ion channels switch between open and closed conformations. The nature of this important transition was revealed by comparing the X-ray crystal structures of the MthK channel from Methanobacterium thermoautotrophicum, obtained in its open conformation, and the KcsA channel from Streptomyces lividans, obtained in its closed conformation. We analyzed the dynamic characteristics and energetics of these homotetrameric structures in order to study the role of the intersubunit cooperativity in this transition. For this, elastic models and in silico alanine-scanning mutagenesis were used, respectively. Reassuringly, the calculations manifested motion from the open (closed) towards the closed (open) conformation. The calculations also revealed a network of dynamically and energetically coupled residues. Interestingly, the network suggests coupling between the selectivity filter and the gate, which are located at the two ends of the channel pore. Coupling between these two regions was not observed in calculations that were conducted with the monomer, which emphasizes the importance of the intersubunit interactions within the tetrameric structure for the cooperative gating behavior of the channel

Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials

INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the over 400 publications using ADNI data during 2014 and 2015. METHODS: We used standard searches to find publications using ADNI data. RESULTS: (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses. Models of prion-like spreading of Aβ pathology along WM tracts predict known patterns of cortical Aβ deposition and declines in glucose metabolism; (7) New AD risk and protective gene loci have been identified using biologically informed approaches; (8) Cognitively normal and mild cognitive impairment (MCI) subjects are heterogeneous and include groups typified not only by "classic" AD pathology but also by normal biomarkers, accelerated decline, and suspected non-Alzheimer's pathology; (9) Selection of subjects at risk of imminent decline on the basis of one or more pathologies improves the power of clinical trials; (10) Sensitivity of cognitive outcome measures to early changes in cognition has been improved and surrogate outcome measures using longitudinal structural magnetic resonance imaging may further reduce clinical trial cost and duration; (11) Advances in machine learning techniques such as neural networks have improved diagnostic and prognostic accuracy especially in challenges involving MCI subjects; and (12) Network connectivity measures and genetic variants show promise in multimodal classification and some classifiers using single modalities are rivaling multimodal classifiers. DISCUSSION: Taken together, these studies fundamentally deepen our understanding of AD progression and its underlying genetic basis, which in turn informs and improves clinical trial desig

Integration of Evolutionary Features for the Identification of Functionally Important Residues in Major Facilitator Superfamily Transporters

The identification of functionally important residues is an important challenge for understanding the molecular mechanisms of proteins. Membrane protein transporters operate two-state allosteric conformational changes using functionally important cooperative residues that mediate long-range communication from the substrate binding site to the translocation pathway. In this study, we identified functionally important cooperative residues of membrane protein transporters by integrating sequence conservation and co-evolutionary information. A newly derived evolutionary feature, the co-evolutionary coupling number, was introduced to measure the connectivity of co-evolving residue pairs and was integrated with the sequence conservation score. We tested this method on three Major Facilitator Superfamily (MFS) transporters, LacY, GlpT, and EmrD. MFS transporters are an important family of membrane protein transporters, which utilize diverse substrates, catalyze different modes of transport using unique combinations of functional residues, and have enough characterized functional residues to validate the performance of our method. We found that the conserved cores of evolutionarily coupled residues are involved in specific substrate recognition and translocation of MFS transporters. Furthermore, a subset of the residues forms an interaction network connecting functional sites in the protein structure. We also confirmed that our method is effective on other membrane protein transporters. Our results provide insight into the location of functional residues important for the molecular mechanisms of membrane protein transporters

Measuring the quality of life of visually impaired children: First stage psychometric evaluation of the Novel VQoL_CYP Instrument

Purpose: To report piloting and initial validation of the VQoL_CYP, a novel age-appropriate vision-related quality of life (VQoL) instrument for self-reporting by children with visual impairment (VI). Methods: Participants were a random patient sample of children with VI aged 10–15 years. 69 patients, drawn from patient databases at Great Ormond Street Hospital and Moorfields Eye Hospital, United Kingdom, participated in piloting of the draft 47-item VQoL instrument, which enabled preliminary item reduction. Subsequent administration of the instrument, alongside functional vision (FV) and generic health-related quality of life (HRQoL) self-report measures, to 101 children with VI comprising a nationally representative sample enabled further item reduction and evaluation of psychometric properties using Rasch analysis. Construct validity was assessed through Pearson correlation coefficients. Results: Item reduction through piloting (8 items removed for skewness and individual item response pattern) and validation (1 item removed for skewness and 3 for misfit in Rasch) produced a 35-item scale, with fit values within acceptable limits, no notable differential item functioning, good measurement precision, ordered response categories and acceptable targeting in Rasch. The VQoL_CYP showed good construct validity, correlating strongly with HRQoL scores, moderately with FV scores but not with acuity. Conclusions: Robust child-appropriate self-report VQoL measures for children with VI are necessary for understanding the broader impacts of living with a visual disability, distinguishing these from limited functioning per se. Future planned use in larger patient samples will allow further psychometric development of the VQoL_CYP as an adjunct to objective outcomes assessment

Using qualitative and quantitative methods to choose a habitat quality metric for air pollution policy evaluation

Atmospheric nitrogen (N) deposition has had detrimental effects on species composition in a range of sensitive habitats, although N deposition can also increase agricultural productivity and carbon storage, and favours a few species considered of importance for conservation. Conservation targets are multiple, and increasingly incorporate services derived from nature as well as concepts of intrinsic value. Priorities vary. How then should changes in a set of species caused by drivers such as N deposition be assessed? We used a novel combination of qualitative semi-structured interviews and quantitative ranking to elucidate the views of conservation professionals specialising in grasslands, heathlands and mires. Although conservation management goals are varied, terrestrial habitat quality is mainly assessed by these specialists on the basis of plant species, since these are readily observed. The presence and abundance of plant species that are scarce, or have important functional roles, emerged as important criteria for judging overall habitat quality. However, species defined as ‘positive indicator-species’ (not particularly scarce, but distinctive for the habitat) were considered particularly important. Scarce species are by definition not always found, and the presence of functionally important species is not a sufficient indicator of site quality. Habitat quality as assessed by the key informants was rank-correlated with the number of positive indicator-species present at a site for seven of the nine habitat classes assessed. Other metrics such as species-richness or a metric of scarcity were inconsistently or not correlated with the specialists’ assessments. We recommend that metrics of habitat quality used to assess N pollution impacts are based on the occurrence of, or habitat-suitability for, distinctive species. Metrics of this type are likely to be widely applicable for assessing habitat change in response to different drivers. The novel combined qualitative and quantitative approach taken to elucidate the priorities of conservation professionals could be usefully applied in other contexts

An Automated Statistical Technique for Counting Distinct Multiple Sclerosis Lesions

Background and purposeLesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with clinical outcome. Lesion count, which encapsulates the natural history of lesion formation and is thought to provide complementary information, is difficult to assess in patients with confluent (ie, spatially overlapping) lesions. We introduce a statistical technique for cross-sectionally counting pathologically distinct lesions.Materials and methodsMR imaging was used to assess the probability of a lesion at each location. The texture of this map was quantified using a novel technique, and clusters resembling the center of a lesion were counted. Validity compared with a criterion standard count was demonstrated in 60 subjects observed longitudinally, and reliability was determined using 14 scans of a clinically stable subject acquired at 7 sites.ResultsThe proposed count and the criterion standard count were highly correlated (r = 0.97, P &lt; .001) and not significantly different (t59 = -.83, P = .41), and the variability of the proposed count across repeat scans was equivalent to that of lesion load. After accounting for lesion load and age, lesion count was negatively associated (t58 = -2.73, P &lt; .01) with the Expanded Disability Status Scale. Average lesion size had a higher association with the Expanded Disability Status Scale (r = 0.35, P &lt; .01) than lesion load (r = 0.10, P = .44) or lesion count (r = -.12, P = .36) alone.ConclusionsThis study introduces a novel technique for counting pathologically distinct lesions using cross-sectional data and demonstrates its ability to recover obscured longitudinal information. The proposed count allows more accurate estimation of lesion size, which correlated more closely with disability scores than either lesion load or lesion count alone