Parallel classification and feature selection in microarray data using SPRINT

The statistical language R is favoured by many biostatisticians for processing microarray data. In recent times, the quantity of data that can be obtained in experiments has risen significantly, making previously fast analyses time consuming or even not possible at all with the existing software infrastructure. High performance computing (HPC) systems offer a solution to these problems but at the expense of increased complexity for the end user. The Simple Parallel R Interface is a library for R that aims to reduce the complexity of using HPC systems by providing biostatisticians with drop‐in parallelised replacements of existing R functions. In this paper we describe parallel implementations of two popular techniques: exploratory clustering analyses using the random forest classifier and feature selection through identification of differentially expressed genes using the rank product method

Evaluating Depressive Symptoms in Schizophrenia: A Psychometric Comparison of the Calgary Depression Scale for Schizophrenia and the Hamilton Depression Rating Scale

Background: The aim of this study was to compare two measures of depression in patients with schizophrenia and schizophrenia spectrum disorder, including patients with delusional and schizoaffective disorder, to conclude implications for their application. Sampling and Methods: A total of 278 patients were assessed using the Calgary Depression Scale for Schizophrenia (CDSS) and the Hamilton Depression Rating Scale (HAMD-17). The Positive and Negative Syndrome Scale (PANSS) was also applied. At admission and discharge, a principal component analysis was performed with each depression scale. The two depression rating scales were furthermore compared using correlation and regression analyses. Results: Three factors were revealed for the CDSS and HAMD-17 factor component analysis. A very similar item loading was found for the CDSS at admission and discharge, whereas results of the loadings of the HAMD-17 items were less stable. The first two factors of the CDSS revealed correlations with positive, negative and general psychopathology. In contrast, multiple significant correlations were found for the HAMD-17 factors and the PANSS sub-scores. Multiple regression analyses demonstrated that the HAMD-17 accounted more for the positive and negative symptom domains than the CDSS. Conclusions:The present results suggest that compared to the HAMD-17, the CDSS is a more specific instrument to measure depressive symptoms in schizophrenia and schizophrenia spectrum disorder, especially in acutely ill patients. Copyright (c) 2012 S. Karger AG, Base

A proposed quantitative methodology for the evaluation of the effectiveness of Human Element, Leadership and Management (HELM) training in the UK

In 2006, a review of maritime accidents found that non-technical skills (NTSs) are the single largest contributing factor towards such incidents. NTSs are composed of both interpersonal and cognitive elements. These include things such as situational awareness, teamwork, decision making, leadership, management and communication skills. In a crisis situation, good NTSs allow a deck officer to quickly recognise that a problem exists and then harness the resources that are at their disposal to safely and efficiently bring the situation back under control. This paper has two aims. The first is to develop a methodology which will enable educators to quantitatively assess the impact of Maritime and Coastguard Agency (MCA)-approved Human Element, Leadership and Management (HELM) training on deck officer’s NTSs with a view to identifying further training requirements. The second is to determine whether the HELM training provided to develop the NTSs of trainee deck officers is fit for purpose. To achieve these aims, a three-phase approach was adopted. Initially, a taxonomy for deck officer’s NTSs is established, behavioural markers are identified and the relative importance of each attribute is calculated using the analytical hierarchy process (AHP). Subsequently, a set of scenarios were identified for the assessment of deck officer’s NTSs in a ship bridge simulator environment. A random selection of students that have completed the Chief Mate (CM) programme was performed, and data regarding their NTS-related performance in the scenarios was collected. Finally, the collected data was fed into the evidential reasoning (ER) algorithm, utility values were produced and, having established these values, the effectiveness of the HELM training that the students have received was then evaluated

K70Q Adds High-Level Tenofovir Resistance to “Q151M Complex” HIV Reverse Transcriptase through the Enhanced Discrimination Mechanism

HIV-1 carrying the “Q151M complex” reverse transcriptase (RT) mutations (A62V/V75I/F77L/F116Y/Q151M, or Q151Mc) is resistant to many FDA-approved nucleoside RT inhibitors (NRTIs), but has been considered susceptible to tenofovir disoproxil fumarate (TFV-DF or TDF). We have isolated from a TFV-DF-treated HIV patient a Q151Mc-containing clinical isolate with high phenotypic resistance to TFV-DF. Analysis of the genotypic and phenotypic testing over the course of this patient's therapy lead us to hypothesize that TFV-DF resistance emerged upon appearance of the previously unreported K70Q mutation in the Q151Mc background. Virological analysis showed that HIV with only K70Q was not significantly resistant to TFV-DF. However, addition of K70Q to the Q151Mc background significantly enhanced resistance to several approved NRTIs, and also resulted in high-level (10-fold) resistance to TFV-DF. Biochemical experiments established that the increased resistance to tenofovir is not the result of enhanced excision, as K70Q/Q151Mc RT exhibited diminished, rather than enhanced ATP-based primer unblocking activity. Pre-steady state kinetic analysis of the recombinant enzymes demonstrated that addition of the K70Q mutation selectively decreases the binding of tenofovir-diphosphate (TFV-DP), resulting in reduced incorporation of TFV into the nascent DNA chain. Molecular dynamics simulations suggest that changes in the hydrogen bonding pattern in the polymerase active site of K70Q/Q151Mc RT may contribute to the observed changes in binding and incorporation of TFV-DP. The novel pattern of TFV-resistance may help adjust therapeutic strategies for NRTI-experienced patients with multi-drug resistant (MDR) mutations

Factor analysis of the Zung self-rating depression scale in a large sample of patients with major depressive disorder in primary care

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the symptomatic dimensions of depression in a large sample of patients with major depressive disorder (MDD) in the primary care (PC) setting by means of a factor analysis of the Zung self-rating depression scale (ZSDS).</p> <p>Methods</p> <p>A factor analysis was performed, based on the polychoric correlations matrix, between ZSDS items using promax oblique rotation in 1049 PC patients with a diagnosis of MDD (DSM-IV).</p> <p>Results</p> <p>A clinical interpretable four-factor solution consisting of a <it>core depressive </it>factor (I); a <it>cognitive </it>factor (II); an <it>anxiety </it>factor (III) and a <it>somatic </it>factor (IV) was extracted. These factors accounted for 36.9% of the variance on the ZSDS. The 4-factor structure was validated and high coefficients of congruence were obtained (0.98, 0.95, 0.92 and 0.87 for factors I, II, III and IV, respectively). The model seemed to fit the data well with fit indexes within recommended ranges (GFI = 0.9330, AGFI = 0.9112 and RMR = 0.0843).</p> <p>Conclusion</p> <p>Our findings suggest that depressive symptoms in patients with MDD in the PC setting cluster into four dimensions: <it>core depressive, cognitive, anxiety </it>and <it>somatic</it>, by means of a factor analysis of the ZSDS. Further research is needed to identify possible diagnostic, therapeutic or prognostic implications of the different depressive symptomatic profiles.</p

Comparing the degrees of enumerability and the closed Medvedev degrees

We compare the degrees of enumerability and the closed Medvedev degrees and find that many situations occur. There are nonzero closed degrees that do not bound nonzero degrees of enumerability, there are nonzero degrees of enumerability that do not bound nonzero closed degrees, and there are degrees that are nontrivially both degrees of enumerability and closed degrees. We also show that the compact degrees of enumerability exactly correspond to the cototal enumeration degrees

Host sequence motifs shared by HIV predict response to antiretroviral therapy

<p>Abstract</p> <p>Background</p> <p>The HIV viral genome mutates at a high rate and poses a significant long term health risk even in the presence of combination antiretroviral therapy. Current methods for predicting a patient's response to therapy rely on site-directed mutagenesis experiments and <it>in vitro </it>resistance assays. In this bioinformatics study we treat response to antiretroviral therapy as a two-body problem: response to therapy is considered to be a function of both the host and pathogen proteomes. We set out to identify potential responders based on the presence or absence of host protein and DNA motifs on the HIV proteome.</p> <p>Results</p> <p>An alignment of thousands of HIV-1 sequences attested to extensive variation in nucleotide sequence but also showed conservation of eukaryotic short linear motifs on the protein coding regions. The reduction in viral load of patients in the Stanford HIV Drug Resistance Database exhibited a bimodal distribution after 24 weeks of antiretroviral therapy, with 2,000 copies/ml cutoff. Similarly, patients allocated into responder/non-responder categories based on consistent viral load reduction during a 24 week period showed clear separation. In both cases of phenotype identification, a set of features composed of short linear motifs in the reverse transcriptase region of HIV sequence accurately predicted a patient's response to therapy. Motifs that overlap resistance sites were highly predictive of responder identification in single drug regimens but these features lost importance in defining responders in multi-drug therapies.</p> <p>Conclusion</p> <p>HIV sequence mutates in a way that preferentially preserves peptide sequence motifs that are also found in the human proteome. The presence and absence of such motifs at specific regions of the HIV sequence is highly predictive of response to therapy. Some of these predictive motifs overlap with known HIV-1 resistance sites. These motifs are well established in bioinformatics databases and hence do not require identification via <it>in vitro </it>mutation experiments.</p

A randomized clinical trial comparing hydrocolloid, phenytoin and simple dressings for the treatment of pressure ulcers [ISRCTN33429693]

BACKGROUND: Pressure sores are important and common complications of spinal cord injury. Many preventive and therapeutic approaches have been tried and new trials are evolving. One relatively recent method is application of a hydrocolloid dressing (HD). In this study we compared the therapeutic effects of HD on pressure ulcer healing with two other topical applications, phenytoin cream (PC) and simple dressing (SD). METHODS: Ninety-one stage I and stage II pressure ulcers of 83 paraplegic male victims of the Iran-Iraq war were randomly allocated to three treatment groups. Mean age and weight of the participants were 36.64 ± 6.04 years and 61.12 ± 5.08 kg, respectively. All the patients were managed in long term care units or in their homes for 8 weeks by a team of general practitioners and nurses, and the ulcer status was recorded as "Complete healing", "Partial healing", "Without improvement" and "Worsening". RESULTS: Complete healing of ulcers, regardless of location and stage, was better in the HD group than the PC [23/31(74.19%) vs 12/30(40%); difference: 34.19%, 95% CI = 10.85–57.52, (P < 0.01)] or the SD [23/31(74.19%) vs 8/30(26.66%); difference: 47.53%, 95% CI = 25.45–69.61, (P < 0.005)] groups. Complete healing of stage I ulcers in the HD group [11/13(85%)] was better than in the SD [5/11(45%); difference: 40%, 95% CI = 4.7–75.22, (P < 0.05)] or PC [2/9 (22%); difference: 63%, 95% CI = 29.69–96.3, (P < 0.005)] groups. Complete healing of stage II ulcer in the HD group [12/18 (67%)] was better than in the SD group [3/19(16%); difference: 51%, 95% CI = 23.73–78.26, (P < 0.005)], but not significantly different from the PC group [10/21 (48%); difference: 19%, 95% CI = -11.47–49.47, (P > 0.05)]. We performed a second analysis considering only one ulcer per patient (i.e. 83 ulcers in 83 patients). This "per patient" analysis showed that complete ulcer healing in the HD group was better than in the PC [20/28(71.4%) vs 11/28 (39.3%); difference: 32.1%, 95% CI = 7.4–56.7, (P < 0.01)] or SD [20/28(71.4%) vs 8/27 (29.6%); difference: 41.8%, 95% CI = 17.7–65.8, (P < 0.005)] groups. CONCLUSION: We deduced that HD is the most effective method investigated for treating stage I and II pressure ulcers in young paraplegic men