ROC curve regression analysis: the use of ordinal regression models for diagnostic test assessment.

Diagnostic tests commonly are characterized by their true positive (sensitivity) and true negative (specificity) classification rates, which rely on a single decision threshold to classify a test result as positive. A more complete description of test accuracy is given by the receiver operating characteristic (ROC) curve, a graph of the false positive and true positive rates obtained as the decision threshold is varied. A generalized regression methodology, which uses a class of ordinal regression models to estimate smoothed ROC curves has been described. Data from a multi-institutional study comparing the accuracy of magnetic resonance (MR) imaging with computed tomography (CT) in detecting liver metastases, which are ideally suited for ROC regression analysis, are described. The general regression model is introduced and an estimate for the area under the ROC curve and its standard error using parameters of the ordinal regression model is given. An analysis of the liver data that highlights the utility of the methodology in parsimoniously adjusting comparisons for covariates is presented

Use of an Inner-city Well-baby Clinic

This prospective, longitudinal investigation examined factors that influenced the use of well-baby services among a low-income, minority, high-risk group. The health belief model was used as the theoretical framework. Data were collected from 44 primiparous, black mothers attending an urban maternal child health care clinic by interviews at the first and sixth months after the birth of their infants. Analysis focused on the cues component of the model and explored the kinds of cues that influenced the mothers to bring their babies to the well-baby clinic. One important finding was that for mothers influenced by health information from radio or television, FYI commercials on television were most often reported.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72805/1/j.1525-1446.1987.tb00535.x.pd

Single-molecule real-time sequencing combined with optical mapping yields completely finished fungal genome

Next-generation sequencing (NGS) technologies have increased the scalability, speed, and resolution of genomic sequencing and, thus, have revolutionized genomic studies. However, eukaryotic genome sequencing initiatives typically yield considerably fragmented genome assemblies. Here, we assessed various state-of-the-art sequencing and assembly strategies in order to produce a contiguous and complete eukaryotic genome assembly, focusing on the filamentous fungus Verticillium dahliae. Compared with Illumina-based assemblies of the V. dahliae genome, hybrid assemblies that also include PacBio- generated long reads establish superior contiguity. Intriguingly, provided that sufficient sequence depth is reached, assemblies solely based on PacBio reads outperform hybrid assemblies and even result in fully assembled chromosomes. Furthermore, the addition of optical map data allowed us to produce a gapless and complete V. dahliae genome assembly of the expected eight chromosomes from telomere to telomere. Consequently, we can now study genomic regions that were previously not assembled or poorly assembled, including regions that are populated by repetitive sequences, such as transposons, allowing us to fully appreciate an organism’s biological complexity. Our data show that a combination of PacBio-generated long reads and optical mapping can be used to generate complete and gapless assemblies of fungal genomes. IMPORTANCE Studying whole-genome sequences has become an important aspect of biological research. The advent of nextgeneration sequencing (NGS) technologies has nowadays brought genomic science within reach of most research laboratories, including those that study nonmodel organisms. However, most genome sequencing initiatives typically yield (highly) fragmented genome assemblies. Nevertheless, considerable relevant information related to genome structure and evolution is likely hidden in those nonassembled regions. Here, we investigated a diverse set of strategies to obtain gapless genome assemblies, using the genome of a typical ascomycete fungus as the template. Eventually, we were able to show that a combination of PacBiogenerated long reads and optical mapping yields a gapless telomere-to-telomere genome assembly, allowing in-depth genome sanalyses to facilitate functional studies into an organism’s biology

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

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