Differential expression analysis for sequence count data

*Motivation:* High-throughput nucleotide sequencing provides quantitative readouts in assays for RNA expression (RNA-Seq), protein-DNA binding (ChIP-Seq) or cell counting (barcode sequencing). Statistical inference of differential signal in such data requires estimation of their variability throughout the dynamic range. When the number of replicates is small, error modelling is needed to achieve statistical power.

*Results:* We propose an error model that uses the negative binomial distribution, with variance and mean linked by local regression, to model the null distribution of the count data. The method controls type-I error and provides good detection power. 

*Availability:* A free open-source R software package, _DESeq_, is available from the Bioconductor project and from "http://www-huber.embl.de/users/anders/DESeq":http://www-huber.embl.de/users/anders/DESeq

Ecological Modeling of Aedes aegypti (L.) Pupal Production in Rural Kamphaeng Phet, Thailand

Background - Aedes aegypti (L.) is the primary vector of dengue, the most important arboviral infection globally. Until an effective vaccine is licensed and rigorously administered, Ae. aegypti control remains the principal tool in preventing and curtailing dengue transmission. Accurate predictions of vector populations are required to assess control methods and develop effective population reduction strategies. Ae. aegypti develops primarily in artificial water holding containers. Release recapture studies indicate that most adult Ae. aegypti do not disperse over long distances. We expect, therefore, that containers in an area of high development site density are more likely to be oviposition sites and to be more frequently used as oviposition sites than containers that are relatively isolated from other development sites. After accounting for individual container characteristics, containers more frequently used as oviposition sites are likely to produce adult mosquitoes consistently and at a higher rate. To this point, most studies of Ae. aegypti populations ignore the spatial density of larval development sites. Methodology - Pupal surveys were carried out from 2004 to 2007 in rural Kamphaeng Phet, Thailand. In total, 84,840 samples of water holding containers were used to estimate model parameters. Regression modeling was used to assess the effect of larval development site density, access to piped water, and seasonal variation on container productivity. A varying-coefficients model was employed to account for the large differences in productivity between container types. A two-part modeling structure, called a hurdle model, accounts for the large number of zeroes and overdispersion present in pupal population counts. Findings - The number of suitable larval development sites and their density in the environment were the primary determinants of the distribution and abundance of Ae. aegypti pupae. The productivity of most container types increased significantly as habitat density increased. An ecological approach, accounting for development site density, is appropriate for predicting Ae. aegypti population levels and developing efficient vector control program

A model building exercise of mortality risk for Taiwanese women with breast cancer

Abstract Background The accurate estimation of outcome in patients with malignant disease is an essential component of the optimal treatment, decision-making and patient counseling processes. The prognosis and disease outcome of breast cancer patients can differ according to geographic and ethnic factors. To our knowledge, to date these factors have never been validated in a homogenous loco-regional patient population, with the aim of achieving accurate predictions of outcome for individual patients. To clarify this topic, we created a new comprehensive prognostic and predictive model for Taiwanese breast cancer patients based on a range of patient-related and various clinical and pathological-related variables. Methods Demographic, clinical, and pathological data were analyzed from 1 137 patients with breast cancer who underwent surgical intervention. A survival prediction model was used to allow analysis of the optimal combination of variables. Results The area under the receiver operating characteristic (ROC) curve, as applied to an independent validation data set, was used as the measure of accuracy. Results were compared by comparing the area under the ROC curve. Conclusions our model building exercise of mortality risk was able to predict disease outcome for individual patients with breast cancer. This model could represent a highly accurate prognostic tool for Taiwanese breast cancer patients.</p

"Death is a better option than being treated like this" : a prevalence survey and qualitative study of depression among multi-drug resistant tuberculosis in-patients

BACKGROUND: Understanding of the relationship between multi-drug resistant tuberculosis and mental health is limited. With growing prevalence of multi-drug resistant tuberculosis, addressing mental ill-health has potential to improve treatment outcomes and well-being. In several low and middle-income contexts hospitalisation during treatment is common. Understanding of the impact on mental ill-health are required to inform interventions for patients with multi-drug resistant tuberculosis. Our aim was to identify the prevalence of comorbid depression among in-patients being treated for multi-drug resistant tuberculosis and to explore their experiences of comorbid disease and the care they received in a large specialist chest hospital in Dhaka, Bangladesh. METHODS: We conducted a quantitative cross-sectional survey among 150 multi-drug resistant tuberculosis in-patients (new cases = 34%, previously treated = 66%) in 2018. A psychiatrist assessed depression was assessed with the Structured Clinical Interview for Depression (SCID DSM-IV). We used multi-level modelling to identify associations with depression. Experience Bangladeshi researchers conducted qualitative interviews with 8 patients, 4 carers, 4 health professionals and reflective notes recorded. Qualitative data was analysed thematically. RESULTS: We found 33.8% (95% CI 26.7%; 41.7%) of patients were depressed. While more women were depressed 39.3% (95% CI 27.6%; 52.4%) than men 30.4% (95% CI 22%; 40.5%) this was not significant. After controlling for key variables only having one or more co-morbidity (adjusted odds ratio [AOR] = 2.88 [95% CI 1.13; 7.33]) and being a new rather than previously treated case (AOR = 2.33 [95% CI 1.06; 5.14]) were associated (positively) with depression. Qualitative data highlighted the isolation and despair felt by patients who described a service predominantly focused on providing medicines. Individual, familial, societal and health-care factors influenced resilience, nuanced by gender, socio-economic status and home location. CONCLUSIONS: Patients with multi-drug resistant tuberculosis are at high risk of depression, particularly those with co- and multi-morbidities. Screening for depression and psycho-social support should be integrated within routine TB services and provided throughout treatment

Obscured phylogeny and possible recombinational dormancy in Escherichia coli

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>is one of the best studied organisms in all of biology, but its phylogenetic structure has been difficult to resolve with current data and analytical techniques. We analyzed single nucleotide polymorphisms in chromosomes of representative strains to reconstruct the topology of its emergence.</p> <p>Results</p> <p>The phylogeny of <it>E. coli </it>varies according to the segment of chromosome analyzed. Recombination between extant <it>E. coli </it>groups is largely limited to only three intergroup pairings.</p> <p>Conclusions</p> <p>Segment-dependent phylogenies most likely are legacies of a complex recombination history. However, <it>E. coli </it>are now in an epoch in which they no longer broadly share DNA. Using the definition of species as organisms that freely exchange genetic material, this recombinational dormancy could reflect either the end of <it>E. coli </it>as a species, or herald the coalescence of <it>E. coli </it>groups into new species.</p

Determinants of participation in a longitudinal two-stage study of the health consequences of the Chornobyl nuclear power plant accident

<p>Abstract</p> <p>Background</p> <p>The determinants of participation in long-term follow-up studies of disasters have rarely been delineated. Even less is known from studies of events that occurred in eastern Europe. We examined the factors associated with participation in a longitudinal two-stage study conducted in Kyiv following the 1986 Chornobyl nuclear power plant accident.</p> <p>Methods</p> <p>Six hundred child-mother dyads (300 evacuees and 300 classmate controls) were initially assessed in 1997 when the children were 11 years old, and followed up in 2005–6 when they were 19 years old. A population control group (304 mothers and 327 children) was added in 2005–6. Each assessment point involved home interviews with the children and mothers (stage 1), followed by medical examinations of the children at a clinic (stage 2). Background characteristics, health status, and Chornobyl risk perceptions were examined.</p> <p>Results</p> <p>The participation rates in the follow-up home interviews were 87.8% for the children (88.6% for evacuees; 87.0% for classmates) and 83.7% for their mothers (86.4% for evacuees and 81.0% for classmates). Children's and mothers' participation was predicted by one another's study participation and attendance at the medical examination at time 1. Mother's participation was also predicted by initial concerns about her child's health, greater psychological distress, and Chornobyl risk perceptions. In 1997, 91.2% of the children had a medical examination (91.7% of evacuees and 90.7% of classmates); in 2005–6, 85.2% were examined (83.0% of evacuees, 87.7% of classmates, 85.0% of population controls). At both times, poor health perceptions were associated with receiving a medical examination. In 2005–6, clinic attendance was also associated with the young adults' risk perceptions, depression or generalized anxiety disorder, lower standard of living, and female gender.</p> <p>Conclusion</p> <p>Despite our low attrition rates, we identified several determinants of selective participation consistent with previous research. Although evacuee status was not associated with participation, Chornobyl risk perceptions were strong predictors of mothers' follow-up participation and attendance at the medical examinations. Understanding selective participation offers valuable insight for future longitudinal disaster studies that integrate psychiatric and medical epidemiologic research.</p

Classifying perinatal mortality using verbal autopsy: is there a role for nonphysicians?

<p>Abstract</p> <p>Background</p> <p>Because of a physician shortage in many low-income countries, the use of nonphysicians to classify perinatal mortality (stillbirth and early neonatal death) using verbal autopsy could be useful.</p> <p>Objective</p> <p>To determine the extent to which underlying perinatal causes of deaths assigned by nonphysicians in Guatemala, Pakistan, Zambia, and the Democratic Republic of the Congo using a verbal autopsy method are concordant with underlying perinatal cause of death assigned by physician panels.</p> <p>Methods</p> <p>Using a train-the-trainer model, 13 physicians and 40 nonphysicians were trained to determine cause of death using a standardized verbal autopsy training program. Subsequently, panels of two physicians and individual nonphysicians from this trained cohort independently reviewed verbal autopsy data from a sample of 118 early neonatal deaths and 134 stillbirths. With the cause of death assigned by the physician panel as the reference standard, sensitivity, specificity, positive and negative predictive values, and cause-specific mortality fractions were calculated to assess nonphysicians' coding responses. Robustness criteria to assess how well nonphysicians performed were used.</p> <p>Results</p> <p>Causes of early neonatal death and stillbirth assigned by nonphysicians were concordant with physician-assigned causes 47% and 57% of the time, respectively. Tetanus filled robustness criteria for early neonatal death, and cord prolapse filled robustness criteria for stillbirth.</p> <p>Conclusions</p> <p>There are significant differences in underlying cause of death as determined by physicians and nonphysicians even when they receive similar training in cause of death determination. Currently, it does not appear that nonphysicians can be used reliably to assign underlying cause of perinatal death using verbal autopsy.</p

The Uptake and Accuracy of Oral Kits for HIV Self-Testing in High HIV Prevalence Setting: A Cross-Sectional Feasibility Study in Blantyre, Malawi

Augustine Choko and colleagues assess the uptake and acceptability of home-based supervised oral HIV self-testing in Malawi, demonstrating the feasibility of this approach in a high-prevalence, low-income environment