Problems in the treatment of malabsorption in CF

ABSTRACT. Several factors play a role in the cause of malabsorption in CF. Besides the enzyme deficiency in the secretion of the exocrine pancreas, decreased bile‐salt concentration in the gut may also be an important factor in the fat malabsorption. The contribution to the fat absorption by other lipases, such as lingual lipase and gastric lipase, remains to he proved. The therapeutic measures are only partly effective because of the breakdown of swalled enzymes by gastric acid. Some improvement is reached by using a new acid‐resistant coating for the enzyme supplement. Newly developed and essential for its success is the application of small coated particles to prevent retention in the stomach, and the easy breakdown of the coating in an alkaline solution. The treatment of the bile salt deficiency has not been successful until now. A trial with additional Tween 80, with the option of supplementing the detergent activity which was found to he successful in Crohn disease, was without marked success. Copyrigh

A physical activity intervention to improve the quality of life of patients with a stoma: a feasibility study

Background We hypothesise that a physical activity (PA) intervention will improve the quality of life (QoL) of people with a stoma. A feasibility study of the intervention and trial parameters is necessary to inform a future main trial. Methods Participants received a weekly PA consultation by telephone, video conferencing, or face-to-face for 12 weeks with a PA instructor who prescribed physical activities and supported participants by addressing stoma-related concerns and using behaviour change techniques. A feasibility study of the intervention and trial parameters was conducted in three UK sites using mixed methods. Results The number of eligible patients consenting to the study was 30 out of 174 (17%). Most participants were female (73%); 73% had an ileostomy and 27% a colostomy; mean time since diagnosis was 6 months. A total of 18 (64%) participants completed pre- (baseline) and post-intervention (follow-up) measures. Results show an improvement on all scales measuring QoL and disease-specific fatigue. The median PA consultation rate per participant was eight sessions. Participants reported completing 75% or more of the prescribed PA each week. Eight stoma-related themes were identified from qualitative interviews: fear of hernia, bending down, fatigue, pain, prolapse, surgical wounds, stoma appliance, and stigma. The intervention appeared to address these issues. Conclusion This feasibility study demonstrated that a novel manualised PA intervention for people with a stoma is safe, feasible, and acceptable, and shows promise for improving outcomes. However, difficulties with recruitment will need to be carefully considered to ensure the success of future studies in this area

Delayed crystallization of ultrathin Gd2O3 layers on Si(111) observed by in situ X-ray diffraction

We studied the early stages of Gd2O3 epitaxy on Si(111) in real time by synchrotron-based, high-resolution X-ray diffraction and by reflection high-energy electron diffraction. A comparison between model calculations and the measured X-ray scattering, and the change of reflection high-energy electron diffraction patterns both indicate that the growth begins without forming a three-dimensional crystalline film. The cubic bixbyite structure of Gd2O3 appears only after a few monolayers of deposition

Microsomal epoxide hydrolase gene polymorphism and susceptibility to colon cancer

We examined polymorphisms in exons 3 and 4 of microsomal epoxide hydrolase in 101 patients with colon cancer and compared the results with 203 control samples. The frequency of the exon 3 T to C mutation was higher in cancer patients than in controls (odds ratio 3.8; 95% confidence intervals 1.8–8.0). This sequence alteration changes tyrosine residue 113 to histidine and is associated with lower enzyme activity when expressed in vitro. This suggests that putative slow epoxide hydrolase activity may be a risk factor for colon cancer. This appears to be true for both right- and left-sided tumours, but was more apparent for tumours arising distally (odds ratio 4.1; 95% confidence limits 1.9–9.2). By contrast, there was no difference in prevalence of exon 4 A to G transition mutation in cancer vs controls. This mutation changes histidine residue 139 to arginine and produces increased enzyme activity. There was no association between epoxide hydrolase genotype and abnormalities of p53 or Ki- Ras. © 1999 Cancer Research Campaig

Radiative Transfer for Exoplanet Atmospheres

Remote sensing of the atmospheres of distant worlds motivates a firm understanding of radiative transfer. In this review, we provide a pedagogical cookbook that describes the principal ingredients needed to perform a radiative transfer calculation and predict the spectrum of an exoplanet atmosphere, including solving the radiative transfer equation, calculating opacities (and chemistry), iterating for radiative equilibrium (or not), and adapting the output of the calculations to the astronomical observations. A review of the state of the art is performed, focusing on selected milestone papers. Outstanding issues, including the need to understand aerosols or clouds and elucidating the assumptions and caveats behind inversion methods, are discussed. A checklist is provided to assist referees/reviewers in their scrutiny of works involving radiative transfer. A table summarizing the methodology employed by past studies is provided.Comment: 7 pages, no figures, 1 table. Filled in missing information in references, main text unchange

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

The emergence of synaesthesia in a Neuronal Network Model via changes in perceptual sensitivity and plasticity

Synaesthesia is an unusual perceptual experience in which an inducer stimulus triggers a percept in a different domain in addition to its own. To explore the conditions under which synaesthesia evolves, we studied a neuronal network model that represents two recurrently connected neural systems. The interactions in the network evolve according to learning rules that optimize sensory sensitivity. We demonstrate several scenarios, such as sensory deprivation or heightened plasticity, under which synaesthesia can evolve even though the inputs to the two systems are statistically independent and the initial cross-talk interactions are zero. Sensory deprivation is the known causal mechanism for acquired synaesthesia and increased plasticity is implicated in developmental synaesthesia. The model unifies different causes of synaesthesia within a single theoretical framework and repositions synaesthesia not as some quirk of aberrant connectivity, but rather as a functional brain state that can emerge as a consequence of optimising sensory information processing

The BridgeDb framework: standardized access to gene, protein and metabolite identifier mapping services

BACKGROUND: Many complementary solutions are available for the identifier mapping problem. This creates an opportunity for bioinformatics tool developers. Tools can be made to flexibly support multiple mapping services or mapping services could be combined to get broader coverage. This approach requires an interface layer between tools and mapping services. RESULTS: Here we present BridgeDb, a software framework for gene, protein and metabolite identifier mapping. This framework provides a standardized interface layer through which bioinformatics tools can be connected to different identifier mapping services. This approach makes it easier for tool developers to support identifier mapping. Mapping services can be combined or merged to support multi-omics experiments or to integrate custom microarray annotations. BridgeDb provides its own ready-to-go mapping services, both in webservice and local database forms. However, the framework is intended for customization and adaptation to any identifier mapping service. BridgeDb has already been integrated into several bioinformatics applications. CONCLUSION: By uncoupling bioinformatics tools from mapping services, BridgeDb improves capability and flexibility of those tools. All described software is open source and available at http://www.bridgedb.org

The transcription factor 7-like 2 (TCF7L2) polymorphism may be associated with focal arteriolar narrowing in Caucasians with hypertension or without diabetes: the ARIC Study

<p>Abstract</p> <p>Background</p> <p>Transcription factor 7-like 2 (<it>TCF7L2</it>) has emerged as a consistently replicated susceptibility gene for type 2 diabetes, however, whether the <it>TCF7L2 </it>gene also has similar effects on the retinal microvasculature is less clear. We therefore aimed to investigate the association between the transcription factor 7-like 2 (<it>TCF7L2</it>) rs7903146 polymorphism and retinal microvascular phenotypes in the Atherosclerosis Risk in Communities (ARIC) Study (1993-1995).</p> <p>Methods</p> <p>This was a population-based, cross-sectional study of 10,320 middle-aged African American (n = 2,199) and Caucasian (n = 8,121) men and women selected from four United States communities to examine the association between <it>TCF7L2 </it>rs7903146 polymorphism and retinal microvascular signs (retinopathy, focal arteriolar narrowing, arteriovenous nicking, arteriolar and venular calibers). Photographs on one randomly selected eye were graded for presence of retinal microvascular signs and used to measure retinal vessel calibres.</p> <p>Results</p> <p>After adjusting for age, sex, study center, mean arterial blood pressure, total serum cholesterol, triglycerides, and other covariates, few associations of <it>TCF7L2 </it>rs7903146 and retinal microvascular signs were noted. <it>TCF7L2 </it>rs7903146 T risk allele was significantly associated with focal arteriolar narrowing in Caucasians with hypertension [odds ratio (OR)_{CT vs. CC}(95% CI) = 1.25 (1.09-1.44); OR_{TT vs. CC}= 1.56 (1.18-2.06); <it>P </it>= 0.002] and in Caucasians without diabetes [OR _{CT vs. CC}= 1.18 (1.06-1.32); OR _{TT vs. CC}= 1.40 (1.12, 1.75); <it>P </it>= 0.003]. No significant association of the <it>TCF7L2 </it>rs7903146 polymorphism and retinal vascular signs was noted among African American individuals.</p> <p>Conclusions</p> <p><it>TCF7L2 </it>rs7903146 is not consistently associated with retinal microvascular signs. However, we report an association between the <it>TCF7L2 </it>rs7903146 polymorphism and focal arteriolar narrowing in Caucasians with hypertension or without diabetes. Further research in other large, population-based studies is needed to replicate these findings.</p