Young and vulnerable: Spatial-temporal trends and risk factors for infant mortality in rural South Africa (Agincourt), 1992-2007

<p>Abstract</p> <p>Background</p> <p>Infant mortality is an important indicator of population health in a country. It is associated with several health determinants, such as maternal health, access to high-quality health care, socioeconomic conditions, and public health policy and practices.</p> <p>Methods</p> <p>A spatial-temporal analysis was performed to assess changes in infant mortality patterns between 1992-2007 and to identify factors associated with infant mortality risk in the Agincourt sub-district, rural northeast South Africa. Period, sex, refugee status, maternal and fertility-related factors, household mortality experience, distance to nearest primary health care facility, and socio-economic status were examined as possible risk factors. All-cause and cause-specific mortality maps were developed to identify high risk areas within the study site. The analysis was carried out by fitting Bayesian hierarchical geostatistical negative binomial autoregressive models using Markov chain Monte Carlo simulation. Simulation-based Bayesian kriging was used to produce maps of all-cause and cause-specific mortality risk.</p> <p>Results</p> <p>Infant mortality increased significantly over the study period, largely due to the impact of the HIV epidemic. There was a high burden of neonatal mortality (especially perinatal) with several hot spots observed in close proximity to health facilities. Significant risk factors for all-cause infant mortality were mother's death in first year (most commonly due to HIV), death of previous sibling and increasing number of household deaths. Being born to a Mozambican mother posed a significant risk for infectious and parasitic deaths, particularly acute diarrhoea and malnutrition.</p> <p>Conclusions</p> <p>This study demonstrates the use of Bayesian geostatistical models in assessing risk factors and producing smooth maps of infant mortality risk in a health and socio-demographic surveillance system. Results showed marked geographical differences in mortality risk across a relatively small area. Prevention of vertical transmission of HIV and survival of mothers during the infants' first year in high prevalence villages needs to be urgently addressed, including expanded antenatal testing, prevention of mother-to-child transmission, and improved access to antiretroviral therapy. There is also need to assess and improve the capacity of district hospitals for emergency obstetric and newborn care. Persisting risk factors, including inadequate provision of clean water and sanitation, are yet to be fully addressed.</p

SIGffRid: A tool to search for sigma factor binding sites in bacterial genomes using comparative approach and biologically driven statistics

<p>Abstract</p> <p>Background</p> <p>Many programs have been developed to identify transcription factor binding sites. However, most of them are not able to infer two-word motifs with variable spacer lengths. This case is encountered for RNA polymerase Sigma (<it>σ</it>) Factor Binding Sites (SFBSs) usually composed of two boxes, called -35 and -10 in reference to the transcription initiation point. Our goal is to design an algorithm detecting SFBS by using combinational and statistical constraints deduced from biological observations.</p> <p>Results</p> <p>We describe a new approach to identify SFBSs by comparing two related bacterial genomes. The method, named SIGffRid (SIGma Factor binding sites Finder using R'MES to select Input Data), performs a simultaneous analysis of pairs of promoter regions of orthologous genes. SIGffRid uses a prior identification of over-represented patterns in whole genomes as selection criteria for potential -35 and -10 boxes. These patterns are then grouped using pairs of short seeds (of which one is possibly gapped), allowing a variable-length spacer between them. Next, the motifs are extended guided by statistical considerations, a feature that ensures a selection of motifs with statistically relevant properties. We applied our method to the pair of related bacterial genomes of <it>Streptomyces coelicolor </it>and <it>Streptomyces avermitilis</it>. Cross-check with the well-defined SFBSs of the SigR regulon in <it>S. coelicolor </it>is detailed, validating the algorithm. SFBSs for HrdB and BldN were also found; and the results suggested some new targets for these <it>σ </it>factors. In addition, consensus motifs for BldD and new SFBSs binding sites were defined, overlapping previously proposed consensuses. Relevant tests were carried out also on bacteria with moderate GC content (i.e. <it>Escherichia coli</it>/<it>Salmonella typhimurium </it>and <it>Bacillus subtilis</it>/<it>Bacillus licheniformis </it>pairs). Motifs of house-keeping <it>σ </it>factors were found as well as other SFBSs such as that of SigW in <it>Bacillus </it>strains.</p> <p>Conclusion</p> <p>We demonstrate that our approach combining statistical and biological criteria was successful to predict SFBSs. The method versatility autorizes the recognition of other kinds of two-box regulatory sites.</p

SIGffRid: A tool to search for sigma factor binding sites in bacterial genomes using comparative approach and biologically driven statistics

<p>Abstract</p> <p>Background</p> <p>Many programs have been developed to identify transcription factor binding sites. However, most of them are not able to infer two-word motifs with variable spacer lengths. This case is encountered for RNA polymerase Sigma (<it>σ</it>) Factor Binding Sites (SFBSs) usually composed of two boxes, called -35 and -10 in reference to the transcription initiation point. Our goal is to design an algorithm detecting SFBS by using combinational and statistical constraints deduced from biological observations.</p> <p>Results</p> <p>We describe a new approach to identify SFBSs by comparing two related bacterial genomes. The method, named SIGffRid (SIGma Factor binding sites Finder using R'MES to select Input Data), performs a simultaneous analysis of pairs of promoter regions of orthologous genes. SIGffRid uses a prior identification of over-represented patterns in whole genomes as selection criteria for potential -35 and -10 boxes. These patterns are then grouped using pairs of short seeds (of which one is possibly gapped), allowing a variable-length spacer between them. Next, the motifs are extended guided by statistical considerations, a feature that ensures a selection of motifs with statistically relevant properties. We applied our method to the pair of related bacterial genomes of <it>Streptomyces coelicolor </it>and <it>Streptomyces avermitilis</it>. Cross-check with the well-defined SFBSs of the SigR regulon in <it>S. coelicolor </it>is detailed, validating the algorithm. SFBSs for HrdB and BldN were also found; and the results suggested some new targets for these <it>σ </it>factors. In addition, consensus motifs for BldD and new SFBSs binding sites were defined, overlapping previously proposed consensuses. Relevant tests were carried out also on bacteria with moderate GC content (i.e. <it>Escherichia coli</it>/<it>Salmonella typhimurium </it>and <it>Bacillus subtilis</it>/<it>Bacillus licheniformis </it>pairs). Motifs of house-keeping <it>σ </it>factors were found as well as other SFBSs such as that of SigW in <it>Bacillus </it>strains.</p> <p>Conclusion</p> <p>We demonstrate that our approach combining statistical and biological criteria was successful to predict SFBSs. The method versatility autorizes the recognition of other kinds of two-box regulatory sites.</p

The Treatment of Experimental Iliofemoral Venous Thrombosis with Isolated Arteriovenous Limb Perfusion

Iliofemoral venous thrombosis poses a triple threat to the afflicted individual. Should a fragment of thrombus become dislodged, pulmonary embolism results. A second immediate complication may be the development of phlegmasia cerulea dolens, possibly due to massive extension of the thrombosis. The morbidity and mortality of this disease, in terms of gangrenous extremities necessitating amputation, . or shock as a result of extensive sequestration of fluid into the involved limb, are disastrous. Thirdly is the postphlebitic syndrome. This complex represents the late sequela of the crippling valvular destruction which results from thrombosis and re-canalization of veins. Thrombectomy has been proposed as a means of management of iliofemoral thrombophlebitis. There is, however, poor correlation between the early postoperative clinical course, and angiographic studies; that is, a significant incidence of re-thrombosis has been found. The reasons for this high incidence have not been fully elucidated, however venous trauma, residual thrombus, a hypercoagulable state, and the fact that the original focus of phlebitis is still present, all may be factors. It was thought that attention might be directed towards more effective cleansing of the venous tree, in order to decrease the amount of residual thrombus which might serve as a nidus of thrombus propagation. ..

Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids.

Corticosteroids mediate a variety of immunological actions and are commonly utilized in the treatment of a wide range of diseases. Unfortunately, therapy with this class of medications is associated with a large proportion of non-responders and significant side effects. Inhaled corticosteroids are the most commonly used asthma controller therapy. However, asthmatic response to corticosteroids also varies widely between individuals. We investigated the genetic contribution to the variation in response to inhaled corticosteroid therapy in asthma. The association of longitudinal change in lung function and single nucleotide polymorphisms from candidate genes crucial to the biologic actions of corticosteroids were evaluated in three independent asthmatic clinical trial populations utilizing inhaled corticosteroids as the primary therapy in at least one treatment arm. Variation in one gene, corticotropin-releasing hormone receptor 1 (CRHR1) was consistently associated with enhanced response to therapy in each of our three populations. Individuals homozygous for the variants of interest manifested a doubling to quadrupling of the lung function response to corticosteroids compared with lack of the variants (P-values ranging from 0.006 to 0.025 for our three asthmatic populations). As the primary receptor mediating the release of adrenocorticotropic hormone, which regulates endogenous cortisol levels, CRHR1 plays a pivotal, pleiotropic role in steroid biology. These data indicate that genetic variants in CRHR1 have pharmacogenetic effects influencing asthmatic response to corticosteroids, provide a rationale for predicting therapeutic response in asthma and other corticosteroid-treated diseases, and suggests this gene pathway as a potential novel therapeutic target