Initial validation of the Chinese Quality of Life Questionnaire - Intellectual Disabilities (CQOL-ID): A cultural perspective

Background In the field of intellectual disabilities (ID), the quality of life concept has been developing rapidly in Chinese societies including Hong Kong, mainland China and Taiwan. However, there is a lack of locally validated instruments to measure the quality of life of people with ID. The study reported in this paper attempted to validate the Chinese Quality of Life Questionnaire - Intellectual Disabilities adapted from the Quality of Life Questionnaire developed by Schalock & Keith. Methods People with mild/moderate ID aged 15 years or above were recruited from special schools, skills centres, community service units and residential units in different regions of Hong Kong. A number of procedures were followed including reliability tests, factor analysis, content validity and construct validity. Results A total of 359 participants were recruited for the study. Factor analysis was conducted according to the rotated component matrix method, in which 23 items were extracted from the original 40-item version of the Quality of Life Questionnaire and three domains (renamed satisfaction, competence and daily choice making/interpersonal relations) were observed. The items in each domain were shown to have factor loadings ranging from 0.42 to 0.90. Construct validity tests indicated the positive nature of the relationship between earnings, and that self-determination and social interaction increase with more independent living environments and less segregated work environments achieving higher scores (P<0.000, P<0.01 and P<0.05 respectively). The scale also achieved a good degree of reliability (Cronbach's α=0.79). Conclusions Initial validity tests indicated that the Chinese Quality of Life Questionnaire - Intellectual Disabilities may be a useful instrument for measuring the quality of life of Chinese people with ID. Cultural issues are discussed and recommendations for future research and service development are made. © 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.postprin

Effects of Epistasis and Pleiotropy on Fitness Landscapes

The factors that influence genetic architecture shape the structure of the fitness landscape, and therefore play a large role in the evolutionary dynamics. Here the NK model is used to investigate how epistasis and pleiotropy -- key components of genetic architecture -- affect the structure of the fitness landscape, and how they affect the ability of evolving populations to adapt despite the difficulty of crossing valleys present in rugged landscapes. Populations are seen to make use of epistatic interactions and pleiotropy to attain higher fitness, and are not inhibited by the fact that valleys have to be crossed to reach peaks of higher fitness.Comment: 10 pages, 6 figures. To appear in "Origin of Life and Evolutionary Mechanisms" (P. Pontarotti, ed.). Evolutionary Biology: 16th Meeting 2012, Springer-Verla

Heart rate, startle response, and intrusive trauma memories.

The current study adopted the trauma film paradigm to examine potential moderators affecting heart rate (HR) as an indicator of peritraumatic psychological states and as a predictor of intrusive memories. We replicated previous findings that perifilm HR decreases predicted the development of intrusive images and further showed this effect to be specific to images rather than thoughts, and to detail rather than gist recognition memory. Moreover, a group of individuals showing both an atypical sudden reduction in HR after a startle stimulus and higher trait dissociation was identified. Only among these individuals was lower perifilm HR found to indicate higher state dissociation, fear, and anxiety, along with reduced vividness of intrusions. The current findings emphasize how peritraumatic physiological responses relate to emotional reactions and intrusive memory. The moderating role of individual difference in stress defense style was highlighted

MemBrain: Improving the Accuracy of Predicting Transmembrane Helices

Prediction of transmembrane helices (TMH) in α helical membrane proteins provides valuable information about the protein topology when the high resolution structures are not available. Many predictors have been developed based on either amino acid hydrophobicity scale or pure statistical approaches. While these predictors perform reasonably well in identifying the number of TMHs in a protein, they are generally inaccurate in predicting the ends of TMHs, or TMHs of unusual length. To improve the accuracy of TMH detection, we developed a machine-learning based predictor, MemBrain, which integrates a number of modern bioinformatics approaches including sequence representation by multiple sequence alignment matrix, the optimized evidence-theoretic K-nearest neighbor prediction algorithm, fusion of multiple prediction window sizes, and classification by dynamic threshold. MemBrain demonstrates an overall improvement of about 20% in prediction accuracy, particularly, in predicting the ends of TMHs and TMHs that are shorter than 15 residues. It also has the capability to detect N-terminal signal peptides. The MemBrain predictor is a useful sequence-based analysis tool for functional and structural characterization of helical membrane proteins; it is freely available at http://chou.med.harvard.edu/bioinf/MemBrain/

Laboratory biomarkers associated with COVID-19 severity and management

The heterogeneous disease course of COVID-19 is unpredictable, ranging from mild self-limiting symptoms to cytokine storms, acute respiratory distress syndrome (ARDS), multi-organ failure and death. Identification of high-risk cases will enable appropriate intervention and escalation. This study investigates the routine laboratory tests and cytokines implicated in COVID-19 for their potential application as biomarkers of disease severity, respiratory failure and need of higher-level care. From analysis of 203 samples, CRP, IL-6, IL-10 and LDH were most strongly correlated with the WHO ordinal scale of illness severity, the fraction of inspired oxygen delivery, radiological evidence of ARDS and level of respiratory support (p ≤ 0.001). IL-6 levels of ≥3.27 pg/ml provide a sensitivity of 0.87 and specificity of 0.64 for a requirement of ventilation, and a CRP of ≥37 mg/l of 0.91 and 0.66. Reliable stratification of high-risk cases has significant implications on patient triage, resource management and potentially the initiation of novel therapies in severe patients

A review of critical project management techniques to enhance construction SMEs project performance

Abstract: Performance is linked with implementation of project management techniques. Literature suggests that problems such as inefficiency, poor budgetary issues, improper planning, scheduling and control in projects execution are associated with inadequate implementation of the essential techniques for meeting project deliverables. These shortcomings are prevalent among Small and Medium Enterprises (SMEs) in the developing countries including South Africa. Hence, the primary objective of this paper is to review the critical project management techniques for the improvement of construction project performance especially among SMEs in South Africa. The study is based on previous literature on construction SMEs project performance as well as project management techniques implementation. The literature review centered on both international and South African context. The study revealed that critical path method, work breakdown structure, and earned value management analysis were the most occurring project management techniques from the sampled literature. Findings from this study are envisaged to be beneficial to construction stakeholders in developing relevant project management techniques to improve the performance of SMEs

Combinatorial epigenetic therapy in diffuse large B cell lymphoma pre-clinical models and patients

BACKGROUND: Refractory and/or relapsed diffuse large B cell lymphoma (RR-DLBCL) patients are incurable with conventional chemotherapy due to the aggressiveness and the chemorefractory state of these tumors. DNA hypermethylation and histone deacetylation are two major epigenetic modifications by which aggressive DLBCL maintain their oncogenic state. We have previously reported that DNA methyltransferase inhibitors (DNMTI) affect RR-DLBCL growth and improve chemosensitivity. Here, we hypothesized that the combination of DNMTI with histone deacetylase inhibitor (HDI) would be an active and feasible therapeutic strategy in RR-DLBCL. Thus, we evaluated the anti-lymphoma activity of the HDI vorinostat (VST) in combination with the DNMTI azacitidine (AZA) or decitabine (DAC) in pre-clinical models of RR-DLBCL, and we determined the feasibility of the combination by conducting a phase Ib trial in RR-DLBCL patients. RESULTS: Concurrent combination of DNMTI and HDI resulted in synergistic anti-lymphoma effect toward RR-DLBCL cells in vitro and in vivo, with no significant toxicity increase. In a phase Ib trial, a total of 18 patients with a median of three prior therapies were treated with four different dose levels of AZA and VST. The most common toxicities were hematological, followed by gastrointestinal and metabolic. The clinical benefit was low as only one subject had a partial response and three subjects had stable disease. Interestingly, two of the seven patients that received additional chemotherapy post-study achieved a complete response and three others had a significant clinical benefit. These observations suggested that the combination might have a delayed chemosensitization effect that we were able to confirm by using in vitro and in vivo models. These studies also demonstrated that the addition of VST does not improve the chemosensitizing effect of DAC alone. CONCLUSIONS: Our data supports the strategy of epigenetic priming by employing DNMTI in RR-DLBCL patients in order to overcome resistance and improve their outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-016-0245-y) contains supplementary material, which is available to authorized users

Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles

BACKGROUND: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41. RESULTS: 1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles. CONCLUSIONS: CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection

Modular prediction of protein structural classes from sequences of twilight-zone identity with predicting sequences

<p>Abstract</p> <p>Background</p> <p>Knowledge of structural class is used by numerous methods for identification of structural/functional characteristics of proteins and could be used for the detection of remote homologues, particularly for chains that share twilight-zone similarity. In contrast to existing sequence-based structural class predictors, which target four major classes and which are designed for high identity sequences, we predict seven classes from sequences that share twilight-zone identity with the training sequences.</p> <p>Results</p> <p>The proposed MODular Approach to Structural class prediction (MODAS) method is unique as it allows for selection of any subset of the classes. MODAS is also the first to utilize a novel, custom-built feature-based sequence representation that combines evolutionary profiles and predicted secondary structure. The features quantify information relevant to the definition of the classes including conservation of residues and arrangement and number of helix/strand segments. Our comprehensive design considers 8 feature selection methods and 4 classifiers to develop Support Vector Machine-based classifiers that are tailored for each of the seven classes. Tests on 5 twilight-zone and 1 high-similarity benchmark datasets and comparison with over two dozens of modern competing predictors show that MODAS provides the best overall accuracy that ranges between 80% and 96.7% (83.5% for the twilight-zone datasets), depending on the dataset. This translates into 19% and 8% error rate reduction when compared against the best performing competing method on two largest datasets. The proposed predictor provides accurate predictions at 58% accuracy for membrane proteins class, which is not considered by majority of existing methods, in spite that this class accounts for only 2% of the data. Our predictive model is analyzed to demonstrate how and why the input features are associated with the corresponding classes.</p> <p>Conclusions</p> <p>The improved predictions stem from the novel features that express collocation of the secondary structure segments in the protein sequence and that combine evolutionary and secondary structure information. Our work demonstrates that conservation and arrangement of the secondary structure segments predicted along the protein chain can successfully predict structural classes which are defined based on the spatial arrangement of the secondary structures. A web server is available at <url>http://biomine.ece.ualberta.ca/MODAS/</url>.</p