PHT-bot: Deep-Learning based system for automatic risk stratification of COPD patients based upon signs of Pulmonary Hypertension

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide. Identifying those at highest risk of deterioration would allow more effective distribution of preventative and surveillance resources. Secondary pulmonary hypertension is a manifestation of advanced COPD, which can be reliably diagnosed by the main Pulmonary Artery (PA) to Ascending Aorta (Ao) ratio. In effect, a PA diameter to Ao diameter ratio of greater than 1 has been demonstrated to be a reliable marker of increased pulmonary arterial pressure. Although clinically valuable and readily visualized, the manual assessment of the PA and the Ao diameters is time consuming and under-reported. The present study describes a non invasive method to measure the diameters of both the Ao and the PA from contrast-enhanced chest Computed Tomography (CT). The solution applies deep learning techniques in order to select the correct axial slice to measure, and to segment both arteries. The system achieves test Pearson correlation coefficient scores of 93% for the Ao and 92% for the PA. To the best of our knowledge, it is the first such fully automated solution

Predicting candidate genomic sequences that correspond to synthetic functional RNA motifs

Riboswitches and RNA interference are important emerging mechanisms found in many organisms to control gene expression. To enhance our understanding of such RNA roles, finding small regulatory motifs in genomes presents a challenge on a wide scale. Many simple functional RNA motifs have been found by in vitro selection experiments, which produce synthetic target-binding aptamers as well as catalytic RNAs, including the hammerhead ribozyme. Motivated by the prediction of Piganeau and Schroeder [(2003) Chem. Biol., 10, 103–104] that synthetic RNAs may have natural counterparts, we develop and apply an efficient computational protocol for identifying aptamer-like motifs in genomes. We define motifs from the sequence and structural information of synthetic aptamers, search for sequences in genomes that will produce motif matches, and then evaluate the structural stability and statistical significance of the potential hits. Our application to aptamers for streptomycin, chloramphenicol, neomycin B and ATP identifies 37 candidate sequences (in coding and non-coding regions) that fold to the target aptamer structures in bacterial and archaeal genomes. Further energetic screening reveals that several candidates exhibit energetic properties and sequence conservation patterns that are characteristic of functional motifs. Besides providing candidates for experimental testing, our computational protocol offers an avenue for expanding natural RNA's functional repertoire

High-throughput methods for characterizing the immune repertoire

Thesis (Ph. D. in Biomedical Engineering and Computational Biology)--Harvard-MIT Program in Health Sciences and Technology, February 2013."September 2012." Cataloged from PDF version of thesis.Includes bibliographical references (p. 147-160).The adaptive immune system is one of the primary mediators in almost every major human disease, including infections, cancer, autoimmunity, and inflammation-based disorders. It fundamentally functions as a molecular classifier, and stores a memory of its previous exposures. However, until recently, methods to unlock this information or to exploit its power in the form of new therapeutic antibodies or affinity reagents have been limited by the use of traditional, low-throughput technologies. In this thesis, we leverage recent advances in high-throughput DNA sequencing technology to develop new methods to characterize and probe the immune repertoire in unprecedented detail. We use this technology to 1) characterize the rapid dynamics of the immune repertoire in response to influenza vaccination, 2) characterize elite neutralizing antibodies to HIV, to better understand the constraints for designing an HIV vaccine, and 3) develop new methodologies for discovering auto-antigens, and assaying large libraries of protein antigens in general. We hope that these projects will serve as stepping-stones towards filling the gap left by low-throughput methods in the development of antibody technologies.by Uri Laserson.Ph.D.in Biomedical Engineering and Computational Biolog

Spatial and temporal dynamics of malaria transmission in rural western Kenya

ABSTRACT: BACKGROUND: Understanding the impact of reducing Plasmodium falciparum malaria transmission requires estimates of the relationship between health outcomes and exposure to infectious mosquitoes. However, measures of exposure such as mosquito density and entomological inoculation rate (EIR) are generally aggregated over large areas and time periods, biasing the outcome-exposure relationship. There are few studies examining the extent and drivers of local variation in malaria exposure in endemic areas. METHODS: We describe the spatio-temporal dynamics of malaria transmission intensity measured by mosquito density and EIR in the KEMRI/CDC health and demographic surveillance system using entomological data collected during 2002-2004. Geostatistical zero inflated binomial and negative binomial models were applied to obtain location specific (house) estimates of sporozoite rates and mosquito densities respectively. Model-based predictions were multiplied to estimate the spatial pattern of annual entomological inoculation rate, a measure of the number of infective bites a person receive per unit of time. The models included environmental and climatic predictors extracted from satellite data, harmonic seasonal trends and parameters describing space-time correlation. RESULTS: Anopheles gambiae s.l was the main vector species accounting for 86% (n=2309) of the total collected mosquitoes with the remainder being Anopheles funestus. Sixty eight percent (757/1110) of the surveyed houses had no mosquitoes. Distance to water bodies, vegetation and day temperature were significantly associated with mosquito density. Overall annual point estimates of EIR were 6.7, 9.3 and 9.6 infectious bites per annum for 2002, 2003 and 2004 respectively. Monthly mosquito density and EIR varied over the study period peaking in May during the wet season. The predicted and observed densities and EIR showed a strong seasonal and spatial pattern over the study area. CONCLUSIONS: Spatio-temporal maps of malaria transmission intensity obtained in this study are not only useful in understanding variability in malaria epidemiology over small areas but also provides a high resolution exposure surface that can be used to analyse the impact of malaria exposure on mortalit

Анализ применения корригирующих вмешательств при ХВН

ВАРИКОЗНОЕ РАСШИРЕНИЕ ВЕН /ХИРКРОВЕНОСНЫХ СОСУДОВ БОЛЕЗНИКОНЕЧНОСТЬ НИЖНЯЯ /ХИ

RAG: RNA-As-Graphs web resource

BACKGROUND: The proliferation of structural and functional studies of RNA has revealed an increasing range of RNA's structural repertoire. Toward the objective of systematic cataloguing of RNA's structural repertoire, we have recently described the basis of a graphical approach for organizing RNA secondary structures, including existing and hypothetical motifs. DESCRIPTION: We now present an RNA motif database based on graph theory, termed RAG for RNA-As-Graphs, to catalogue and rank all theoretically possible, including existing, candidate and hypothetical, RNA secondary motifs. The candidate motifs are predicted using a clustering algorithm that classifies RNA graphs into RNA-like and non-RNA groups. All RNA motifs are filed according to their graph vertex number (RNA length) and ranked by topological complexity. CONCLUSIONS: RAG's quantitative cataloguing allows facile retrieval of all classes of RNA secondary motifs, assists identification of structural and functional properties of user-supplied RNA sequences, and helps stimulate the search for novel RNAs based on predicted candidate motifs

Menstrual hygiene management among adolescent girls in India: a systematic review and meta-analysis

Objectives To assess the status of menstrual hygiene management (MHM) among adolescent girls in India to determine unmet needs. Design Systematic review and meta-analysis. We searched PubMed, The Global Health Database, Google Scholar and references for studies published from 2000 to September 2015 on girls’ MHM. Setting India. Participants Adolescent girls. Outcome measures Information on menarche awareness, type of absorbent used, disposal, hygiene, restrictions and school absenteeism was extracted from eligible materials; a quality score was applied. Meta-analysis was used to estimate pooled prevalence (PP), and meta-regression to examine the effect of setting, region and time. Results Data from 138 studies involving 193 subpopulations and 97 070 girls were extracted. In 88 studies, half of the girls reported being informed prior to menarche (PP 48%, 95% CI 43% to 53%, I2 98.6%). Commercial pad use was more common among urban (PP 67%, 57% to 76%, I2 99.3%, n=38) than rural girls (PP 32%, 25% to 38%, I2 98.6%, n=56, p<0.0001), with use increasing over time (p<0.0001). Inappropriate disposal was common (PP 23%, 16% to 31%, I2 99.0%, n=34). Menstruating girls experienced many restrictions, especially for religious activities (PP 0.77, 0.71 to 0.83, I2 99.1%, n=67). A quarter (PP 24%, 19% to 30%, I2 98.5%, n=64) reported missing school during periods. A lower prevalence of absenteeism was associated with higher commercial pad use in univariate (p=0.023) but not in multivariate analysis when adjusted for region (p=0.232, n=53). Approximately a third of girls changed their absorbents in school facilities (PP 37%, 29% to 46%, I2 97.8%, n=17). Half of the girls’ homes had a toilet (PP 51%, 36% to 67%, I2 99.4%, n=21). The quality of studies imposed limitations on analyses and the interpretation of results (mean score 3 on a scale of 0–7). Conclusions Strengthening of MHM programmes in India is needed. Education on awareness, access to hygienic absorbents and disposal of MHM items need to be addressed

Barriers and facilitators to antenatal and delivery care in western Kenya: a qualitative study

Background In western Kenya, maternal mortality is a major public health problem estimated at 730/100,000 live births, higher than the Kenyan national average of 488/ 100,000 women. Many women do not attend antenatal care (ANC) in the first trimester, half do not receive 4 ANC visits. A high proportion use traditional birth attendants (TBA) for delivery and 1 in five deliver unassisted. The present study was carried out to ascertain why women do not fully utilise health facility ANC and delivery services. Methods A qualitative study using 8 focus group discussions each consisting of 8–10 women, aged 15–49 years. Thematic analysis identified the main barriers and facilitators to health facility based ANC and delivery. Results Attending health facility for ANC was viewed positively. Three elements of care were important; testing for disease including HIV, checking the position of the foetus, and receiving injections and / or medications. Receiving a bed net and obtaining a registration card were also valuable. Four barriers to attending a health facility for ANC were evident; attitudes of clinic staff, long clinic waiting times, HIV testing and cost, although not all women felt the cost was prohibitive being worth it for the health of the child. Most women preferred to deliver in a health facility due to better management of complications. However cost was a barrier, and a reason to visit a TBA because of flexible payment. Other barriers were unpredictable labour and transport, staff attitudes and husbands’ preference. Conclusions Our findings suggest that women in western Kenya are amenable to ANC and would be willing and even prefer to deliver in a healthcare facility, if it were affordable and accessible to them. However for this to happen there needs to be investment in health promotion, and transport, as well as reducing or removing all fees associated with antenatal and delivery care. Yet creating demand for service will need to go alongside investment in antenatal services at organisational, staffing and facility level in order to meet both current and future increase in demand

Integrating tuberculosis and HIV services in low- and middle-income countries: a systematic review.

OBJECTIVES: Given the imperative to scale up integrated tuberculosis (TB) and HIV services in settings where both are of major public health importance, we aimed to synthesise knowledge concerning implementation of TB/HIV service integration. METHODS: Systematic review of studies describing a strategy to facilitate TB and HIV service integration, searching 15 bibliographic databases including Medline, Embase and the Cochrane library; and relevant conference abstracts. RESULTS: Sixty-three of 1936 peer-reviewed articles and 70 of 170 abstracts met our inclusion criteria. We identified five models: entry via TB service, with referral for HIV testing and care; entry via TB service, on-site HIV testing, and referral for HIV care; entry via HIV service with referral for TB screening and treatment; entry via HIV service, on-site TB screening, and referral for TB diagnosis and treatment; and TB and HIV services provided at a single facility. Referral-based models are most easily implemented, but referral failure is a key risk. Closer integration requires more staff training and additional infrastructure (e.g. private space for HIV counselling; integrated records). Infection control is a major concern. More integrated models hold potential efficiencies from both provider and user perspective. Most papers report 'outcomes' (e.g. proportion of TB patients tested for HIV); few report downstream 'impacts' such as outcomes of TB treatment or antiretroviral therapy. Very few studies address the perspectives of service users or staff, or costs or cost-effectiveness. CONCLUSIONS: While scaling up integrated services, robust comparisons of the impacts of different models are needed using standardised outcome measures