Distance to health services influences insecticide-treated net possession and use among six to 59 month-old children in Malawi

<p>Abstract</p> <p>Background</p> <p>Health ministries and providers are rapidly scaling up insecticide-treated nets (ITN) distribution to control malaria, yet possession and proper use typically remain below targeted levels. In Malawi, health facilities (HFs) are currently the principal points of ITN distribution, making it important to understand how access to these ITN sources affects ownership, possession, and use. The authors evaluated the association between proximity to HFs and ITN possession or use among Malawian children six to 59 months of age.</p> <p>Methods</p> <p>A household malaria survey undertaken in eight districts of Malawi during 2007 was used to characterize ITN possession and use. The location of each respondent's household was geocoded as was those of Ministry of Health (MoH) HFs and other health centres. Euclidean distance from each household to the nearest HF was calculated. Patterns of net possession and use were determined through descriptive methods. The authors then analysed the significance of distance and ITN possession/use through standard statistical tests, including logistic regression.</p> <p>Results</p> <p>Median distance to HFs was greater among households that did not possess ITNs and did not use an ITN the previous evening. Descriptive statistical methods confirmed a pattern of decreasing ITN possession and use with increasing distance from HFs. Logistic regression showed the same statistically significant association of distance to HFs, even when controlling for age and gender of the child, ratio of nets to children in household, community net possession and use, and household material wealth.</p> <p>Conclusions</p> <p>Strategies that exclusively distribute ITNs through HFs are likely to be less effective in increasing possession and use in communities that are more distant from those health services. Health providers should look towards community-based distribution services that take ITNs directly to community members to more effectively scale up ITN possession and regular use aimed at protecting children from malaria.</p

Clinical and laboratory characteristics in juvenile-onset systemic lupus erythematosus across age groups

BACKGROUND Systemic lupus erythematous (SLE) is a systemic autoimmune/inflammatory condition. Approximately 15–20% of patients develop symptoms before their 18th birthday and are diagnosed with juvenile-onset SLE (JSLE). Gender distribution, clinical presentation, disease courses and outcomes vary significantly between JSLE patients and individuals with adult-onset SLE. This study aimed to identify age-specific clinical and/or serological patterns in JSLE patients enrolled to the UK JSLE Cohort Study. METHODS Patient records were accessed and grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8–13 years) and adolescent (14–18 years). The presence of American College of Rheumatology (ACR) classification criteria, laboratory results, disease activity [British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores] and damage [Systemic Lupus International Collaborating Clinics (SLICC) damage index] were evaluated at diagnosis and last follow up. RESULTS A total of 418 JSLE patients were included in this study: 43 (10.3%) with pre-pubertal disease onset; 240 (57.4%) with peri-pubertal onset and 135 (32.3%) were diagnosed during adolescence. At diagnosis, adolescent JSLE patients presented with a higher number of ACR criteria when compared with pre-pubertal and peri-pubertal patients [pBILAG2004 scores: 9(4–20] vs. 7(3–13] vs. 7(3–14], respectively, p = 0.015] with increased activity in the following BILAG domains: mucocutaneous (p = 0.025), musculoskeletal (p = 0.029), renal (p = 0.027) and cardiorespiratory (p = 0.001). Furthermore, adolescent JSLE patients were more frequently ANA-positive (p = 0.034) and exhibited higher anti-dsDNA titres (p = 0.001). Pre-pubertal individuals less frequently presented with leukopenia (p = 0.002), thrombocytopenia (p = 0.004) or low complement (p = 0.002) when compared with other age groups. No differences were identified in disease activity (pBILAG2004 score), damage (SLICC damage index) and the number of ACR criteria fulfilled at last follow up. CONCLUSIONS Disease presentations and laboratory findings vary significantly between age groups within a national cohort of JSLE patients. Patients diagnosed during adolescence exhibit greater disease activity and “classic” autoantibody, immune cell and complement patterns when compared with younger patients. This supports the hypothesis that pathomechanisms may vary between patient age groups

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

Proposal of a Nutritional Quality Index (NQI) to Evaluate the Nutritional Supplementation of Sportspeople

Background: Numerous supplements are used by sportspeople. They are not always appropriate for the individual or the sports activity and may do more harm than good. Vitamin and mineral supplements are unnecessary if the energy intake is sufficient to maintain body weight and derives from a diet with an adequate variety of foods. The study objectives were to evaluate the main nutrients used as supplements in sports and to propose a nutritional quality index (NQI) that enables sportspeople to optimize their use of supplements and detect and remedy possible nutritional deficits. Material and Methods: A nutritional study was performed in 485 sportspeople recruited from Centros Andaluces de Medicina del Deporte, (CAMD). All completed socio-demographic, food frequency, and lifestyle questionnaires. The nutritional quality of their diet and need for supplementation were evaluated by scoring their dietary intake with and without supplementation, yielding two NQI scores (scales of 0-21 points) for each participant. Results: A superior mean NQI score was obtained when the supplements taken by participants were not included (16. 28 (SD of 3.52)) than when they were included (15.47 (SD: 3.08)), attributable to an excessive intake of some nutrients through supplementation. Conclusions: These results indicate that sportspeople with a varied and balanced diet do not need supplements, which appear to offer no performance benefits and may pose a health risk.The authors are grateful to the Junta de Andalucía, Spain (Research Group AGR-255“Nutrition. Diet and Risk Assessment”), a collaboration agreement with the Andalusian Centres of Sports Medicine (Junta de Andalucía) and the FPU program of the Spanish Ministry of Education and Science. Study participants were recruited through the project “Nutritional and diet assessment methodologies applied to the Andalusian sportsperson in Andalusian Sports centres”, Research project FMD2010SC0071 of the Junta de Andalucía

A cross-lingual adaptation approach for rapid development of speech recognizers for learning disabled users

Building a voice-operated system for learning disabled users is a difficult task that requires a considerable amount of time and effort. Due to the wide spectrum of disabilities and their different related phonopathies, most approaches available are targeted to a specific pathology. This may improve their accuracy for some users, but makes them unsuitable for others. In this paper, we present a cross-lingual approach to adapt a general-purpose modular speech recognizer for learning disabled people. The main advantage of this approach is that it allows rapid and cost-effective development by taking the already built speech recognition engine and its modules, and utilizing existing resources for standard speech in different languages for the recognition of the users’ atypical voices. Although the recognizers built with the proposed technique obtain lower accuracy rates than those trained for specific pathologies, they can be used by a wide population and developed more rapidly, which makes it possible to design various types of speech-based applications accessible to learning disabled users.This research was supported by the project ‘Favoreciendo la vida autónoma de discapacitados intelectuales con problemas de comunicación oral mediante interfaces personalizados de reconocimiento automático del habla’, financed by the Centre of Initiatives for Development Cooperation (Centro de Iniciativas de Cooperación al Desarrollo, CICODE), University of Granada, Spain. This research was supported by the Student Grant Scheme 2014 (SGS) at the Technical University of Liberec

Nicotine patch preloading for smoking cessation (the preloading trial): study protocol for a randomized controlled trial

Background: The use of nicotine replacement therapy before quitting smoking is called nicotine preloading. Standard smoking cessation protocols suggest commencing nicotine replacement therapy only on the first day of quitting smoking (quit day) aiming to reduce withdrawal symptoms and craving. However, other, more successful smoking cessation pharmacotherapies are used prior to the quit day as well as after. Nicotine preloading could improve quit rates by reducing satisfaction from smoking prior to quitting and breaking the association between smoking and reward. A systematic literature review suggests that evidence for the effectiveness of preloading is inconclusive and further trials are needed. Methods/Design: This is a study protocol for a multicenter, non-blinded, randomized controlled trial based in the United Kingdom, enrolling 1786 smokers who want to quit, funded by the National Institute for Health Research, Health Technology Assessment program, and sponsored by the University of Oxford. Participants will primarily be recruited through general practices and smoking cessation clinics, and randomized (1:1) either to use 21 mg nicotine patches, or not, for four weeks before quitting, whilst smoking as normal. All participants will be referred to receive standard smoking cessation service support. Follow-ups will take place at one week, four weeks, six months and 12 months after quit day. The primary outcome will be prolonged, biochemically verified six-month abstinence. Additional outcomes will include point prevalence abstinence and abstinence of four-week and 12-month duration, side effects, costs of treatment, and markers of potential mediators and moderators of the preloading effect. Discussion: This large trial will add substantially to evidence on the effectiveness of nicotine preloading, but also on its cost effectiveness and potential mediators, which have not been investigated in detail previously. A range of recruitment strategies have been considered to try and compensate for any challenges encountered in recruiting the large sample, and the multicentre design means that knowledge can be shared between recruitment teams. The pragmatic study design means that results will give a realistic estimate of the success of the intervention if it were to be rolled out as part of standard smoking cessation service practice. Trial registration: Current Controlled Trials ISRCTN33031001. Registered 27 April 2012

miRNA-Mediated Relationships between Cis-SNP Genotypes and Transcript Intensities in Lymphocyte Cell Lines

In metazoans, miRNAs regulate gene expression primarily through binding to target sites in the 3′ UTRs (untranslated regions) of messenger RNAs (mRNAs). Cis-acting variants within, or close to, a gene are crucial in explaining the variability of gene expression measures. Single nucleotide polymorphisms (SNPs) in the 3′ UTRs of genes can affect the base-pairing between miRNAs and mRNAs, and hence disrupt existing target sites (in the reference sequence) or create novel target sites, suggesting a possible mechanism for cis regulation of gene expression. Moreover, because the alleles of different SNPs within a DNA sequence of limited length tend to be in strong linkage disequilibrium (LD), we hypothesize the variants of miRNA target sites caused by SNPs potentially function as bridges linking the documented cis-SNP markers to the expression of the associated genes. A large-scale analysis was herein performed to test this hypothesis. By systematically integrating multiple latest information sources, we found 21 significant gene-level SNP-involved miRNA-mediated post-transcriptional regulation modules (SNP-MPRMs) in the form of SNP-miRNA-mRNA triplets in lymphocyte cell lines for the CEU and YRI populations. Among the cognate genes, six including ALG8, DGKE, GNA12, KLF11, LRPAP1, and MMAB are related to multiple genetic diseases such as depressive disorder and Type-II diabetes. Furthermore, we found that ∼35% of the documented transcript intensity-related cis-SNPs (∼950) in a recent publication are identical to, or in significant linkage disequilibrium (LD) (p<0.01) with, one or multiple SNPs located in miRNA target sites. Based on these associations (or identities), 69 significant exon-level SNP-MPRMs and 12 disease genes were further determined for two populations. These results provide concrete in silico evidence for the proposed hypothesis. The discovered modules warrant additional follow-up in independent laboratory studies

New Functions of Ctf18-RFC in Preserving Genome Stability outside Its Role in Sister Chromatid Cohesion

Expansion of DNA trinucleotide repeats causes at least 15 hereditary neurological diseases, and these repeats also undergo contraction and fragility. Current models to explain this genetic instability invoke erroneous DNA repair or aberrant replication. Here we show that CAG/CTG tracts are stabilized in Saccharomyces cerevisiae by the alternative clamp loader/unloader Ctf18-Dcc1-Ctf8-RFC complex (Ctf18-RFC). Mutants in Ctf18-RFC increased all three forms of triplet repeat instability—expansions, contractions, and fragility—with effect over a wide range of allele lengths from 20–155 repeats. Ctf18-RFC predominated among the three alternative clamp loaders, with mutants in Elg1-RFC or Rad24-RFC having less effect on trinucleotide repeats. Surprisingly, chl1, scc1-73, or scc2-4 mutants defective in sister chromatid cohesion (SCC) did not increase instability, suggesting that Ctf18-RFC protects triplet repeats independently of SCC. Instead, three results suggest novel roles for Ctf18-RFC in facilitating genomic stability. First, genetic instability in mutants of Ctf18-RFC was exacerbated by simultaneous deletion of the fork stabilizer Mrc1, but suppressed by deletion of the repair protein Rad52. Second, single-cell analysis showed that mutants in Ctf18-RFC had a slowed S phase and a striking G2/M accumulation, often with an abnormal multi-budded morphology. Third, ctf18 cells exhibit increased Rad52 foci in S phase, often persisting into G2, indicative of high levels of DNA damage. The presence of a repeat tract greatly magnified the ctf18 phenotypes. Together these results indicate that Ctf18-RFC has additional important functions in preserving genome stability, besides its role in SCC, which we propose include lesion bypass by replication forks and post-replication repair

Efficient Genetic Method for Establishing Drosophila Cell Lines Unlocks the Potential to Create Lines of Specific Genotypes

Analysis of cells in culture has made substantial contributions to biological research. The versatility and scale of in vitro manipulation and new applications such as high-throughput gene silencing screens ensure the continued importance of cell-culture studies. In comparison to mammalian systems, Drosophila cell culture is underdeveloped, primarily because there is no general genetic method for deriving new cell lines. Here we found expression of the conserved oncogene RasV12 (a constitutively activated form of Ras) profoundly influences the development of primary cultures derived from embryos. The cultures become confluent in about three weeks and can be passaged with great success. The lines have undergone more than 90 population doublings and therefore constitute continuous cell lines. Most lines are composed of spindle-shaped cells of mesodermal type. We tested the use of the method for deriving Drosophila cell lines of a specific genotype by establishing cultures from embryos in which the warts (wts) tumor suppressor gene was targeted. We successfully created several cell lines and found that these differ from controls because they are primarily polyploid. This phenotype likely reflects the known role for the mammalian wts counterparts in the tetraploidy checkpoint. We conclude that expression of RasV12 is a powerful genetic mechanism to promote proliferation in Drosophila primary culture cells and serves as an efficient means to generate continuous cell lines of a given genotype