Increasing understanding of the relationship between geographic access and gendered decision-making power for treatment-seeking for febrile children in the Chikwawa district of Malawi

Background: This study used qualitative methods to investigate the relationship between geographic access and gendered intra-household hierarchies and how these influence treatment-seeking decision-making for childhood fever within the Chikwawa district of Malawi. Previous cross-sectional survey findings in the district indicated that distance from facility and associated costs are important determinants of health facility attendance in the district. This paper uses qualitative data to add depth of understanding to these findings by exploring the relationship between distance from services, anticipated costs and cultural norms of intra-household decision-making, and to identify potential intervention opportunities to reduce challenges experienced by those in remote locations. Qualitative data collection included 12 focus group discussions and 22 critical incident interviews conducted in the local language, with primary caregivers of children who had recently experienced a febrile episode. Results: Low geographic accessibility to facilities inhibited care-seeking, sometimes by extending the ‘assessment period’ for a child’s illness episode, and led to delays in seeking formal treatment, particularly when the illness occurred at night. Although carers attempted to avoid incurring costs, cash was often needed for transport and food. Whilst in all communities fathers were normatively responsible for treatment costs, mothers generally had greater access to and control over resources and autonomy in decision-making in the matrilineal and matrilocal communities in the central part of the district, which were also closer to formal facilities. Conclusions: This study illustrates the complex interplay between geographic access and gender dynamics in shaping decisions on whether and when formal treatment is sought for febrile children in Chikwawa District. Geographic marginality and cultural norms intersect in remote areas both to increase the logistical and anticipated financial barriers to utilising services and to reduce caretakers’ autonomy to act quickly once they recognize the need for formal care. Health education campaigns should be based within communities, engaging all involved in treatment-seeking decision-making, including men and grandmothers, and should aim to promote the ability of junior women to influence the treatment-seeking process. Both mothers’ financial autonomy and fathers financial contributions are important to enable timely access to effective healthcare for children with malaria

Dynamics of direct inter-pack encounters in endangered African wild dogs

Aggressive encounters may have important life history consequences due to the potential for injury and death, disease transmission, dispersal opportunities or exclusion from key areas of the home range. Despite this, little is known of their detailed dynamics, mainly due to the difficulties of directly observing encounters in detail. Here, we describe detailed spatial dynamics of inter-pack encounters in African wild dogs (Lycaon pictus), using data from custom-built high-resolution GPS collars in 11 free-ranging packs. On average, each pack encountered another pack approximately every 7 weeks and met each neighbour twice each year. Surprisingly, intruders were more likely to win encounters (winning 78.6% of encounters by remaining closer to the site in the short term). However, intruders did tend to move farther than residents toward their own range core in the short-term (1 h) post-encounter, and if this were used to indicate losing an encounter, then the majority (73.3%) of encounters were won by residents. Surprisingly, relative pack size had little effect on encounter outcome, and injuries were rare (<15% of encounters). These results highlight the difficulty of remotely scoring encounters involving mobile participants away from static defendable food resources. Although inter-pack range overlap was reduced following an encounter, encounter outcome did not seem to drive this, as both packs shifted their ranges post-encounter. Our results indicate that inter-pack encounters may be lower risk than previously suggested and do not appear to influence long-term movement and ranging

QiSampler: evaluation of scoring schemes for high-throughput datasets using a repetitive sampling strategy on gold standards

<p>Abstract</p> <p>Background</p> <p>High-throughput biological experiments can produce a large amount of data showing little overlap with current knowledge. This may be a problem when evaluating alternative scoring mechanisms for such data according to a gold standard dataset because standard statistical tests may not be appropriate.</p> <p>Findings</p> <p>To address this problem we have implemented the QiSampler tool that uses a repetitive sampling strategy to evaluate several scoring schemes or experimental parameters for any type of high-throughput data given a gold standard. We provide two example applications of the tool: selection of the best scoring scheme for a high-throughput protein-protein interaction dataset by comparison to a dataset derived from the literature, and evaluation of functional enrichment in a set of tumour-related differentially expressed genes from a thyroid microarray dataset.</p> <p>Conclusions</p> <p>QiSampler is implemented as an open source R script and a web server, which can be accessed at <url>http://cbdm.mdc-berlin.de/tools/sampler/</url>.</p

Group II Introns Break New Boundaries: Presence in a Bilaterian's Genome

Group II introns are ribozymes, removing themselves from their primary transcripts, as well as mobile genetic elements, transposing via an RNA intermediate, and are thought to be the ancestors of spliceosomal introns. Although common in bacteria and most eukaryotic organelles, they have never been reported in any bilaterian animal genome, organellar or nuclear. Here we report the first group II intron found in the mitochondrial genome of a bilaterian worm. This location is especially surprising, since animal mitochondrial genomes are generally distinct from those of plants, fungi, and protists by being small and compact, and so are viewed as being highly streamlined, perhaps as a result of strong selective pressures for fast replication while establishing germ plasm during early development. This intron is found in the mtDNA of an annelid worm, (an undescribed species of Nephtys), where the complete sequence revealed a 1819 bp group II intron inside the cox1 gene. We infer that this intron is the result of a recent horizontal gene transfer event from a viral or bacterial vector into the mitochondrial genome of Nephtys sp. Our findings hold implications for understanding mechanisms, constraints, and selective pressures that account for patterns of animal mitochondrial genome evolutio

Comprehensive Analysis of MGMT Promoter Methylation: Correlation with MGMT Expression and Clinical Response in GBM

O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR  = 5.23, 95% CI [2.089–13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR  = 3.076, 95% CI [1.301–7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting

Incidence and Prediction of Falls in Dementia: A Prospective Study in Older People

Falls are a major cause of morbidity and mortality in dementia, but there have been no prospective studies of risk factors for falling specific to this patient population, and no successful falls intervention/prevention trials. This prospective study aimed to identify modifiable risk factors for falling in older people with mild to moderate dementia.179 participants aged over 65 years were recruited from outpatient clinics in the UK (38 Alzheimer's disease (AD), 32 Vascular dementia (VAD), 30 Dementia with Lewy bodies (DLB), 40 Parkinson's disease with dementia (PDD), 39 healthy controls). A multifactorial assessment of baseline risk factors was performed and fall diaries were completed prospectively for 12 months. Dementia participants experienced nearly 8 times more incident falls (9118/1000 person-years) than controls (1023/1000 person-years; incidence density ratio: 7.58, 3.11-18.5). In dementia, significant univariate predictors of sustaining at least one fall included diagnosis of Lewy body disorder (proportional hazard ratio (HR) adjusted for age and sex: 3.33, 2.11-5.26), and history of falls in the preceding 12 months (HR: 2.52, 1.52-4.17). In multivariate analyses, significant potentially modifiable predictors were symptomatic orthostatic hypotension (HR: 2.13, 1.19-3.80), autonomic symptom score (HR per point 0-36: 1.055, 1.012-1.099), and Cornell depression score (HR per point 0-40: 1.053, 1.01-1.099). Higher levels of physical activity were protective (HR per point 0-9: 0.827, 0.716-0.956).The management of symptomatic orthostatic hypotension, autonomic symptoms and depression, and the encouragement of physical activity may provide the core elements for the most fruitful strategy to reduce falls in people with dementia. Randomised controlled trials to assess such a strategy are a priority

Genotyping of Bacillus cereus Strains by Microarray-Based Resequencing

The ability to distinguish microbial pathogens from closely related but nonpathogenic strains is key to understanding the population biology of these organisms. In this regard, Bacillus anthracis, the bacterium that causes inhalational anthrax, is of interest because it is closely related and often difficult to distinguish from other members of the B. cereus group that can cause diverse diseases. We employed custom-designed resequencing arrays (RAs) based on the genome sequence of Bacillus anthracis to generate 422 kb of genomic sequence from a panel of 41 Bacillus cereus sensu lato strains. Here we show that RAs represent a “one reaction” genotyping technology with the ability to discriminate between highly similar B. anthracis isolates and more divergent strains of the B. cereus s.l. Clade 1. Our data show that RAs can be an efficient genotyping technology for pre-screening the genetic diversity of large strain collections to selected the best candidates for whole genome sequencing

Why caretakers bypass Primary Health Care facilities for child care - a case from rural Tanzania

<p>Abstract</p> <p>Background</p> <p>Research on health care utilization in low income countries suggests that patients frequently bypass PHC facilities in favour of higher-level hospitals - despite substantial additional time and financial costs. There are limited number of studies focusing on user's experiences at such facilities and reasons for bypassing them. This study aimed to identify factors associated with bypassing PHC facilities among caretakers seeking care for their underfive children and to explore experiences at such facilities among those who utilize them.</p> <p>Methods</p> <p>The study employed a mixed-method approach consisting of an interviewer administered questionnaires and in-depth interviews among selected care-takers seeking care for their underfive children at Korogwe and Muheza district hospitals in north-eastern Tanzania.</p> <p>Results</p> <p>The questionnaire survey included 560 caretakers. Of these 30 in-depth interviews were conducted. Fifty nine percent (206/348) of caretakers had not utilized their nearer PHC facilities during the index child's sickness episode. The reasons given for bypassing PHC facilities were lack of possibilities for diagnostic facilities (42.2%), lack of drugs (15.5%), closed health facility (10.2%), poor services (9.7%) and lack of skilled health workers (3.4%). In a regression model, the frequency of bypassing a PHC facility for child care increased significantly with decreasing travel time to the district hospital, shorter duration of symptoms and low disease severity.</p> <p>Findings from the in-depth interviews revealed how the lack of quality services at PHC facilities caused delays in accessing appropriate care and how the experiences of inadequate care caused users to lose trust in them.</p> <p>Conclusion</p> <p>The observation that people are willing to travel long distances to get better quality services calls for health policies that prioritize quality of care before quantity. In a situation with limited resources, utilizing available resources to improve quality of care at available facilities could be more appropriate for improving access to health care than increasing the number of facilities. This would also improve equity in health care access since the poor who can not afford travelling costs will then get access to quality services at their nearer PHC facilities.</p