Bioinformatics resources for cancer research with an emphasis on gene function and structure prediction tools

The immensely popular fields of cancer research and bioinformatics overlap in many different areas, e.g. large data repositories that allow for users to analyze data from many experiments (data handling, databases), pattern mining, microarray data analysis, and interpretation of proteomics data. There are many newly available resources in these areas that may be unfamiliar to most cancer researchers wanting to incorporate bioinformatics tools and analyses into their work, and also to bioinformaticians looking for real data to develop and test algorithms. This review reveals the interdependence of cancer research and bioinformatics, and highlight the most appropriate and useful resources available to cancer researchers. These include not only public databases, but general and specific bioinformatics tools which can be useful to the cancer researcher. The primary foci are function and structure prediction tools of protein genes. The result is a useful reference to cancer researchers and bioinformaticians studying cancer alike

Explaining the uptake of paediatric guidelines in a Kenyan tertiary hospital--mixed methods research.

BACKGROUND: Evidence-based standards for management of the seriously sick child have existed for decades, yet their translation in clinical practice is a challenge. The context and organization of institutions are known determinants of successful translation, however, research using adequate methodologies to explain the dynamic nature of these determinants in the quality-of-care improvement process is rarely performed. METHODS: We conducted mixed methods research in a tertiary hospital in a low-income country to explore the uptake of locally adapted paediatric guidelines. The quantitative component was an uncontrolled before and after intervention study that included an exploration of the intervention dose-effect relationship. The qualitative component was an ethnographic research based on the theoretical perspective of participatory action research. Interpretive integration was employed to derive meta-inferences that provided a more complete picture of the overall study results that reflect the complexity and the multifaceted ontology of the phenomenon studied. RESULTS: The improvement in health workers' performance in relation to the intensity of the intervention was not linear and was characterized by improved and occasionally declining performance. Possible root causes of this performance variability included challenges in keeping knowledge and clinical skills updated, inadequate commitment of the staff to continued improvement, limited exposure to positive professional role models, poor teamwork, failure to maintain professional integrity and mal-adaptation to institutional pressures. CONCLUSION: Implementation of best-practices is a complex process that is largely unpredictable, attributed to the complexity of contextual factors operating predominantly at professional and organizational levels. There is no simple solution to implementation of best-practices. Tackling root causes of inadequate knowledge translation in this tertiary care setting will require long-term planning, with emphasis on promotion of professional ethics and values and establishing an organizational framework that enhances positive aspects of professionalism. This study has significant implications for the quality of training in medical institutions and the development of hospital leadership

Gender difference in mortality among pulmonary tuberculosis HIV co-infected adults aged 15-49 years in Kenya

Setting: Kenya, 2012–2015 Objective: To explore whether there is a gender difference in all-cause mortality among smear positive pulmonary tuberculosis (PTB)/ HIV co-infected patients treated for tuberculosis (TB) between 2012 and 2015 in Kenya. Design: Retrospective cohort of 9,026 smear-positive patients aged 15–49 years. All-cause mortality during TB treatment was the outcome of interest. Time to start of antiretroviral therapy (ART) initiation was considered as a proxy for CD4 cell count. Those who took long to start of ART were assumed to have high CD4 cell count. Results: Of the 9,026 observations analysed, 4,567(51%) and 4,459(49%) were women and men, respectively. Overall, out of the 9,026 patients, 8,154 (90%) had their treatment outcome as cured, the mean age in years (SD) was 33.3(7.5) and the mean body mass index (SD) was 18.2(3.4). Men were older (30% men’ vs 17% women in those ≥40 years, p = \u3c0.001) and had a lower BMI \u3c18.5 (55.3% men vs 50.6% women, p = \u3c0.001). Men tested later for HIV: 29% (1,317/4,567) of women HIV tested more than 3 months prior to TB treatment, as compared to 20% (912/4,459) men (p\u3c0.001). Mortality was higher in men 11% (471/4,459) compared to women 9% (401/4,567, p = 0.004). There was a 17% reduction in the risk of death among women (adjusted HR 0.83; 95% CI 0.72–0.96; p = 0.013). Survival varied by age-groups, with women having significantly better survival than men, in the age-groups 40 years and over (log-rank p = 0.006). Conclusion: Women with sputum positive PTB/HIV co-infection have a significantly lower risk of all-cause mortality during TB treatment compared to men. Men were older, had lower BMI and tested later for HIV than women

Numerical study for the c-dependence of fractal dimension in two-dimensional quantum gravity

We numerically investigate the fractal structure of two-dimensional quantum gravity coupled to matter central charge c for $-2 \leq c \leq 1$. We reformulate Q-state Potts model into the model which can be identified as a weighted percolation cluster model and can make continuous change of Q, which relates c, on the dynamically triangulated lattice. The c-dependence of the critical coupling is measured from the percolation probability and susceptibility. The c-dependence of the string susceptibility of the quantum surface is evaluated and has very good agreement with the theoretical predictions. The c-dependence of the fractal dimension based on the finite size scaling hypothesis is measured and has excellent agreement with one of the theoretical predictions previously proposed except for the region near $c\approx 1$.Comment: 41 pages, 16 figure

Evaluation of Clinical and Immunological Markers for predicting Virological Failure in a HIV/AIDS treatment cohort in Busia, Kenya

In resource-limited settings where viral load (VL) monitoring is scarce or unavailable, clinicians must use immunological and clinical criteria to define HIV virological treatment failure. This study examined the performance of World Health Organization (WHO) clinical and immunological failure criteria in predicting virological failure in HIV patients receiving antiretroviral therapy (ART)

Biallelic mutations in <i>KDSR </i>disrupt ceramide synthesis and result in a spectrum of keratinization disorders associated with thrombocytopenia

Mutations in ceramide biosynthesis pathways have been implicated in a few Mendelian disorders of keratinization, although ceramides are known to have key roles in several biological processes in skin and other tissues. Using whole-exome sequencing in four probands with undiagnosed skin hyperkeratosis/ichthyosis, we identified compound heterozygosity for mutations in KDSR, encoding an enzyme in the de novo synthesis pathway of ceramides. Two individuals had hyperkeratosis confined to palms, soles, and anogenital skin, whereas the other two had more severe, generalized harlequin ichthyosis-like skin. Thrombocytopenia was present in all patients. The mutations in KDSR were associated with reduced ceramide levels in skin and impaired platelet function. KDSR enzymatic activity was variably reduced in all patients, resulting in defective acylceramide synthesis. Mutations in KDSR have recently been reported in inherited recessive forms of progressive symmetric erythrokeratoderma, but our study shows that biallelic mutations in KDSR are implicated in an extended spectrum of disorders of keratinization in which thrombocytopenia is also part of the phenotype. Mutations in KDSR cause defective ceramide biosynthesis, underscoring the importance of ceramide and sphingosine synthesis pathways in skin and platelet biology

Parallel Tempering: Theory, Applications, and New Perspectives

We review the history of the parallel tempering simulation method. From its origins in data analysis, the parallel tempering method has become a standard workhorse of physiochemical simulations. We discuss the theory behind the method and its various generalizations. We mention a selected set of the many applications that have become possible with the introduction of parallel tempering and we suggest several promising avenues for future research.Comment: 21 pages, 4 figure