Screening for childhood anaemia using copper sulphate densitometry

Objective. To evaluate copper sulphate densitometry to screen for childhood anaemia in a primary care setting, with a view to identifying children requiring definitive diagnostic testing and treatment. Design. A cross-sectional screening study. Results of densitometry with a copper sulphate solution of specific gravity (SG) 1.048, corresponding to a haemoglobin (Hb) concentration of 10 g/dl, were compared with laboratory Hb determination. Setting. Outpatient department of Pretoria Academic Hospital (73 children) and a local cr_che (27 children). Subjects. One hundred consecutive children, aged between 6 months and 6 years, with informed written consent by parents. Outcome measure(s). Accuracy of copper sulphate densitometry in screening for Hb concentration below 10 g/dl in terms of sensitivity, specificity, positive and negative predictive values, as well as likelihood ratio. Results. The prevalence of anaemia (Hb < 10 g/dl) was 17% (95% confidence interval (CI) 10.2; 25.8). Copper sulphate densitometry had a sensitivity of 88.2% (95% CI 62.3; 97.9), a specificity of 89.2% (95% CI 79.9; 94.6), a positive predictive value of 62.5% (95% CI 40.8; 80.5) and a negative predictive value of 97.4% (95%CI 90.0; 99.5) in screening for anaemia. The likelihood ratio of a positive screening test was 8.17. Conclusions. Copper sulphate densitometry was accurate in screening for childhood anaemia. (South African Medical Journal: 2002 92(12): 978-981

Immune targets for therapeutic development in depression: towards precision medicine.

Over the past two decades, compelling evidence has emerged indicating that immune mechanisms can contribute to the pathogenesis of major depressive disorder (MDD) and that drugs with primary immune targets can improve depressive symptoms. Patients with MDD are heterogeneous with respect to symptoms, treatment responses and biological correlates. Defining a narrower patient group based on biology could increase the treatment response rates in certain subgroups: a major advance in clinical psychiatry. For example, patients with MDD and elevated pro-inflammatory biomarkers are less likely to respond to conventional antidepressant drugs, but novel immune-based therapeutics could potentially address their unmet clinical needs. This article outlines a framework for developing drugs targeting a novel patient subtype within MDD and reviews the current state of neuroimmune drug development for mood disorders. We discuss evidence for a causal role of immune mechanisms in the pathogenesis of depression, together with targets under investigation in randomized controlled trials, biomarker evidence elucidating the link to neural mechanisms, biological and phenotypic patient selection strategies, and the unmet clinical need among patients with MDD.Johnson and Johnso

The impact of sea surface temperature biases on North American precipitation in a high-resolution climate model

Positive precipitation biases over western North America have remained a pervasive problem in the current generation of coupled global climate models. These biases are substantially reduced, however, in a version of the Geophysical Fluid Dynamics Laboratory Forecast-Oriented Low Ocean Resolution (FLOR) coupled climate model with systematic sea surface temperature (SST) biases artificially corrected through flux adjustment. This study examines how the SST biases in the Atlantic and Pacific Oceans contribute to the North American precipitation biases. Experiments with the FLOR model in which SST biases are removed in the Atlantic and Pacific are carried out to determine the contribution of SST errors in each basin to precipitation statistics over North America. Tropical and North Pacific SST biases have a strong impact on northern North American precipitation, while tropical Atlantic SST biases have a dominant impact on precipitation biases in southern North America, including the western United States. Most notably, negative SST biases in the tropical Atlantic in boreal winter induce an anomalously strong Aleutian low and a southward bias in the North Pacific storm track. In boreal summer, the negative SST biases induce a strengthened North Atlantic subtropical high and Great Plains low-level jet. Each of these impacts contributes to positive annual mean precipitation biases over western North America. Both North Pacific and North Atlantic SST biases induce SST biases in remote basins through dynamical pathways, so a complete attribution of the effects of SST biases on precipitation must account for both the local and remote impacts

Frailty among older adults and its distribution in England

Background: Information on the spatial distribution of the frail population is crucial to inform service planning in health and social care. Objectives: To estimate small-area frailty prevalence among older adults using survey data. To assess whether prevalence differs between urban, rural, coastal and inland areas of England. Design: Using data from the English Longitudinal Study of Ageing (ELSA), ordinal logistic regression was used to predict the probability of frailty, according to age, sex and area deprivation. Probabilities were applied to demographic and economic information in 2020 population projections to estimate the district-level prevalence of frailty. Results: The prevalence of frailty in adults aged 50+ (2020) in England was estimated to be 8.1 [95% CI 7.3–8.8]%. We found substantial geographic variation, with the prevalence of frailty varying by a factor of 4.0 [3.5–4.4] between the most and least frail areas. A higher prevalence of frailty was found for urban than rural areas, and coastal than inland areas. There are widespread geographic inequalities in healthy ageing in England, with older people in urban and coastal areas disproportionately frail relative to those in rural and inland areas. Conclusions: Interventions aimed at reducing inequalities in healthy ageing should be targeted at urban and coastal areas, where the greatest benefit may be achieved

Is late-life dependency increasing or not? A comparison of the Cognitive Function and Ageing Studies (CFAS)

Background: Little is known about how dependency levels have changed between generational cohorts of older people. We estimated years lived in different care states at age 65 in 1991 and 2011 and new projections of future demand for care. Methods: Two population-based studies of older people in defined geographical areas conducted two decades apart (the Cognitive Function and Ageing Studies) provided prevalence estimates of dependency in four states: high (24-hour care); medium (daily care); low (less than daily); independent. Years in each dependency state were calculated by Sullivan’s method. To project future demand, the proportions in each dependency state (by age group and sex) were applied to the 2014 England population projections. Findings: Between 1991 and 2011 there were significant increases in years lived from age 65 with low (men:1·7 years, 95%CI 1·0-2·4; women:2·4 years, 95%CI 1·8-3·1) and high dependency (men:0·9 years, 95%CI 0·2-1·7; women:1·3 years, 95%CI 0·5-2·1). The majority of men’s extra years of life were independent (36%) or with low dependency (36%) whilst for women the majority were spent with low dependency (58%), only 5% being independent. There were substantial reductions in the proportions with medium and high dependency who lived in care homes, although, if these dependency and care home proportions remain constant in the future, further population ageing will require an extra 71,000 care home places by 2025. Interpretation: On average older men now spend 2.4 years and women 3.0 years with substantial care needs (medium or high dependency), and most will live in the community. These findings have considerable implications for older people’s families who provide the majority of unpaid care, but the findings also supply valuable new information for governments and care providers planning the resources and funding required for the care of their future ageing populations

Eccrine porocarcinoma of the head: An important differential diagnosis in the elderly patient

Background: Eccrine porocarcinoma is a rare malignant tumor of the sweat gland, characterized by a broad spectrum of clinicopathologic presentations. Surprisingly, unlike its benign counterpart eccrine poroma, eccrine porocarcinoma is seldom found in areas with a high density of eccrine sweat glands, like the palms or soles. Instead, eccrine porocarcinoma frequently occurs on the lower extremities, trunk and abdomen, but also on the head, resembling various other skin tumors, as illustrated in the patients described herein. Observations: We report 5 cases of eccrine porocarcinoma of the head. All patients were initially diagnosed as having epidermal or melanocytic skin tumors. Only after histopathologic examination were they classified as eccrine porocarcinoma, showing features of epithelial tumors with abortive ductal differentiation. Characteristic clinical, histopathologic and immunohistochemical findings of eccrine porocarcinomas are illustrated. Conclusion: Eccrine porocarcinomas are potentially fatal adnexal malignancies, in which extensive metastatic dissemination may occur. Porocarcinomas are commonly overlooked, or misinterpreted as squamous or basal cell carcinomas as well as other common malignant and even benign skin tumors. Knowledge of the clinical pattern and histologic findings, therefore, is crucial for an early therapeutic intervention, which can reduce the risk of tumor recurrence and serious complications. Copyright (c) 2008 S. Karger AG, Basel

Extensive Chaos in the Nikolaevskii Model

We carry out a systematic study of a novel type of chaos at onset ("soft-mode turbulence") based on numerical integration of the simplest one dimensional model. The chaos is characterized by a smooth interplay of different spatial scales, with defect generation being unimportant. The Lyapunov exponents are calculated for several system sizes for fixed values of the control parameter $\epsilon$. The Lyapunov dimension and the Kolmogorov-Sinai entropy are calculated and both shown to exhibit extensive and microextensive scaling. The distribution functional is shown to satisfy Gaussian statistics at small wavenumbers and small frequency.Comment: 4 pages (including 5 figures) LaTeX file. Submitted to Phys. Rev. Let

Optimization Strategies for Interactive Classification of Interstitial Lung Disease Textures

For computerized analysis of textures in interstitial lung disease, manual annotations of lung tissue are necessary. Since making these annotations is labor intensive, we previously proposed an interactive annotation framework. In this framework, observers iteratively trained a classifier to distinguish the different texture types by correcting its classification errors. In this work, we investigated three ways to extend this approach, in order to decrease the amount of user interaction required to annotate all lung tissue in a computed tomography scan. First, we conducted automatic classification experiments to test how data from previously annotated scans can be used for classification of the scan under consideration. We compared the performance of a classifier trained on data from one observer, a classifier trained on data from multiple observers, a classifier trained on consensus training data, and an ensemble of classifiers, each trained on data from different sources. Experiments were conducted without and with texture selection (ts). In the former case, training data from all eight textures was used. In the latter, only training data from the texture types present in the scan were used, and the observer would have to indicate textures contained in the scan to be analyzed. Second, we simulated interactive annotation to test the effects of (1) asking observers to perform ts before the start of annotation, (2) the use of a classifier trained on data from previously annotated scans at the start of annotation, when the interactive classifier is untrained, and (3) allowing observers to choose which interactive or automatic classification results they wanted to correct. Finally, various strategies for selecting the classification results that were presented to the observer were considered. Classification accuracies for all possible interactive annotation scenarios were compared. Using the best-performing protocol, in which observers select the textures that should be distinguished in the scan and in which they can choose which classification results to use for correction, a median accuracy of 88% was reached. The results obtained using this protocol were significantly better than results obtained with other interactive or automatic classification protocols

Effects of immunomodulatory drugs on depressive symptoms: A mega-analysis of randomized, placebo-controlled clinical trials in inflammatory disorders.

Activation of the innate immune system is commonly associated with depression. Immunomodulatory drugs may have efficacy for depressive symptoms that are co-morbidly associated with inflammatory disorders. We report a large-scale re-analysis by standardized procedures (mega-analysis) of patient-level data combined from 18 randomized clinical trials conducted by Janssen or GlaxoSmithKline for one of nine disorders (N = 10,743 participants). Core depressive symptoms (low mood, anhedonia) were measured by the Short Form Survey (SF-36) or the Hospital Anxiety and Depression Scale (HADS), and participants were stratified into high (N = 1921) versus low-depressive strata based on baseline ratings. Placebo-controlled change from baseline after 4-16 weeks of treatment was estimated by the standardized mean difference (SMD) over all trials and for each subgroup of trials targeting one of 7 mechanisms (IL-6, TNF-α, IL-12/23, CD20, COX2, BLγS, p38/MAPK14). Patients in the high depressive stratum showed modest but significant effects on core depressive symptoms (SMD = 0.29, 95% CI [0.12-0.45]) and related SF-36 measures of mental health and vitality. Anti-IL-6 antibodies (SMD = 0.8, 95% CI [0.20-1.41]) and an anti-IL-12/23 antibody (SMD = 0.48, 95% CI [0.26-0.70]) had larger effects on depressive symptoms than other drug classes. Adjustments for physical health outcome marginally attenuated the average treatment effect on depressive symptoms (SMD = 0.20, 95% CI: 0.06-0.35), but more strongly attenuated effects on mental health and vitality. Effects of anti-IL-12/23 remained significant and anti-IL-6 antibodies became a trend after controlling for physical response to treatment. Novel immune-therapeutics can produce antidepressant effects in depressed patients with primary inflammatory disorders that are not entirely explained by treatment-related changes in physical health.MR