Evaluation of Interventions to Reduce Child Mortality From Acute Respiratory Infections in a Remote Community in North Eastern Afghanistan, and the Implications for the Emergence of Antibiotic Resistance in <i>Streptococcus pneumoniae</i>

There are many remote regions of the world where there are no data about the health of the community. This thesis reports on the implementation of a community health programme in Wakhan District, a remote valley in Afghanistan. This programme trained illiterate women to educate mothers to feed their children appropriately, to treat dehydration and to manage acute respiratory infections (ARI) with co-trimoxazole. The programme covered 6000 people in 28 communities, and took five years to establish. Data about births and deaths were collected in 2002, before the programme began, and during its implementation from 2005-8. ARI was a leading cause of death in children under five. Standard case management of ARI in children, using co-trimoxazole, was effective in significantly reducing mortality. A simple algorithm for appropriate use of co-trimoxazole, based on counting respiratory rate, can be implemented by health workers with limited training. Comparing data collected in 2002, before the programme was implemented, with data collected 2005-8, mortality in children under two years fell by 40%, from 262 to 158 per 1000 live births. There is little data on the consequences of using standard case management of ARI by health workers with limited training on the reduction of antibiotic susceptibility, or the clinical consequences of reduced antibiotic susceptibility. Isolating invasive Streptococcus pneumoniae, (the most common pathogen causing ARI in children) to examine its antibiotic susceptibilities is difficult. Two sets of nasopharyngeal samples were collected from healthy children to give an estimate of the proportion of Streptococcus pneumoniae with reduced antibiotic susceptibility. Streptococcus pneumoniae isolates were tested for antibiotic susceptibility in a purpose-built laboratory in Wakhan. Streptococcus pneumoniae was isolated from 47% of the children sampled. 17% of samples showed resistance to penicillin, 70% to co-trimoxazole, 9% to erythromycin and 40% to tetracycline. 16 isolates were sent back to the UK. Six of the 11 which survived were of serotypes not included in the commercially available protein conjugate vaccines. Three were novel strains of Streptococcus pneumoniae on multi-locus sequence typing, displaying two different strain types. The conclusion of this research programme is that health workers with very limited training can successfully implement a simple algorithm to treat ARI in children. It is possible to monitor antibiotic susceptibility in a remote area, with limited equipment, facilities and supplies. In vitro reductions in susceptibility to co-trimoxazole are noted, but the clinical significance of this is unclear. Unusual strains of Streptococcus pneumoniae are circulating in this community, which are not covered by vaccines currently available

Tiny

Illustration of man in suit and very tiny woman standing on a small stagehttps://scholarsjunction.msstate.edu/cht-sheet-music/5553/thumbnail.jp

Prediction of Disease and Phenotype Associations from Genome-Wide Association Studies

Genome wide association studies (GWAS) have proven useful as a method for identifying genetic variations associated with diseases. In this study, we analyzed GWAS data for 61 diseases and phenotypes to elucidate common associations based on single nucleotide polymorphisms (SNP). The study was an expansion on a previous study on identifying disease associations via data from a single GWAS on seven diseases.Adjustments to the originally reported study included expansion of the SNP dataset using Linkage Disequilibrium (LD) and refinement of the four levels of analysis to encompass SNP, SNP block, gene, and pathway level comparisons. A pair-wise comparison between diseases and phenotypes was performed at each level and the Jaccard similarity index was used to measure the degree of association between two diseases/phenotypes. Disease relatedness networks (DRNs) were used to visualize our results. We saw predominant relatedness between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis for the first three levels of analysis. Expected relatedness was also seen between lipid- and blood-related traits.The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis can be validated by clinical studies. The diseases have been proposed to share a systemic inflammation phenotype that can result in progression of additional diseases in patients with one of these three diseases. We also noticed unexpected relationships between metabolic and neurological diseases at the pathway comparison level. The less significant relationships found between diseases require a more detailed literature review to determine validity of the predictions. The results from this study serve as a first step towards a better understanding of seemingly unrelated diseases and phenotypes with similar symptoms or modes of treatment

Prevention of Postpartum Haemorrhage: Economic evaluation of the novel Butterfly device in a UK setting

ObjectivesTo explore the cost-effectiveness of a novel PPH device as compared with usual care.DesignA decision analytical model was used to explore the cost-effectiveness of the PPH Butterfly device compared with usual care. This was part of a United Kingdom, UK, clinical trial ISRCTN15452399 using a matched historical cohort who had standard PPH management without the use of the PPH Butterfly device. The economic evaluation was conducted from a UK National Health Service (NHS) perspective.SettingLiverpool Women's Hospital, UK.Participants57 women with 113 matched controls.InterventionThe PPH Butterfly is a novel device that has been invented and developed in the UK to facilitate bimanual compression of the uterus in the treatment of PPH.Main outcome measuresMain outcome measures included healthcare costs, blood loss, and maternal morbidity events.ResultsMean treatment costs in the Butterfly cohort were £3,459.66 as compared with standard care £3,223.93. Treatment with the Butterfly device resulted in decreased total blood loss in comparison with standard care. The Butterfly device had an incremental cost-effectiveness ratio of £3,795.78 per PPH progression avoided (defined as ≤ 1000 ml additional blood loss from device insertion point). If the NHS is prepared to pay £8,500 per PPH progression avoided, then the Butterfly device is cost-effective with a probability of 87 percent. In the PPH Butterfly treatment arm there were 9% fewer cases of massive obstetric haemorrhage (severe PPH of more than 2000mls or more than 4 units of blood transfusion required) recorded as compared with the standard care historical cohort. As a low-cost device, the PPH Butterfly device is cost-effective but can be cost-saving to the NHS.ConclusionThe PPH pathway can result in high-cost resource use such as blood transfusion or high dependence unit hospital stays. The Butterfly device is a relative low-cost device in a UK NHS setting with a high probability of being cost-effective. The National Institute for Health and Care Excellence (NICE) can use this evidence in considering the adoption of innovative technologies such as the Butterfly device in the NHS. Extrapolation on an international scale to lower and middle-income countries could prevent mortality associated with PPH

Central spindle self-organization and cytokinesis in artificially activated sea urchin eggs

Author Posting. © Marine Biological Laboratory, 2016. This article is posted here by permission of Marine Biological Laboratory for personal use, not for redistribution. The definitive version was published in Biological Bulletin 230, no.2 (2016): 85-95.The ability of microtubules of the mitotic apparatus to control the positioning and initiation of the cleavage furrow during cytokinesis was first established from studies on early echinoderm embryos. However, the identity of the microtubule population that imparts cytokinetic signaling is unclear. The two main––and not necessarily mutually exclusive–– candidates are the central spindle and the astral rays. In the present study, we examined cytokinesis in ammonia-activated sea urchin eggs, which lack paternally derived centrosomes and undergo mitosis mediated by unusual anastral, bipolar mini-spindles. Live cell imaging and immunolabeling for microtubules and the centralspindlin constituent and kinesin-related protein, MKLP1, demonstrated that furrowing in ammonia-activated eggs was associated with aligned arrays of centralspindlin-linked, opposed bundles of antiparallel microtubules. These autonomous, zipper- like arrays were not associated with a mitotic apparatus, but did possess characteristics similar to the central spindle region of control, fertilized embryos. Our results highlight the self-organizing nature of the central spindle region and its ability to induce cytokinesis-like furrowing, even in the absence of a complete mitotic apparatus.This research was supported by student/faculty summer research grants from the Dickinson College Research and Development Committee to JHH; Laura and Arthur Colwin Summer Research Fellowships from the MBL to JHH and CBS; a National Science Foundation Major Research Instrumentation grant to JHH (MRI-0320606); and a NSF collaborative research grant to JHH (MCB-1412688) and to CBS (MCB- 1412734)

Mega2: validated data-reformatting for linkage and association analyses.

BACKGROUND: In a typical study of the genetics of a complex human disease, many different analysis programs are used, to test for linkage and association. This requires extensive and careful data reformatting, as many of these analysis programs use differing input formats. Writing scripts to facilitate this can be tedious, time-consuming, and error-prone. To address these issues, the open source Mega2 data reformatting program provides validated and tested data conversions from several commonly-used input formats to many output formats. RESULTS: Mega2, the Manipulation Environment for Genetic Analysis, facilitates the creation of analysis-ready datasets from data gathered as part of a genetic study. It transparently allows users to process genetic data for family-based or case/control studies accurately and efficiently. In addition to data validation checks, Mega2 provides analysis setup capabilities for a broad choice of commonly-used genetic analysis programs. First released in 2000, Mega2 has recently been significantly improved in a number of ways. We have rewritten it in C++ and have reduced its memory requirements. Mega2 now can read input files in LINKAGE, PLINK, and VCF/BCF formats, as well as its own specialized annotated format. It supports conversion to many commonly-used formats including SOLAR, PLINK, Merlin, Mendel, SimWalk2, Cranefoot, IQLS, FBAT, MORGAN, BEAGLE, Eigenstrat, Structure, and PLINK/SEQ. When controlled by a batch file, Mega2 can be used non-interactively in data reformatting pipelines. Support for genetic data from several other species besides humans has been added. CONCLUSIONS: By providing tested and validated data reformatting, Mega2 facilitates more accurate and extensive analyses of genetic data, avoiding the need to write, debug, and maintain one's own custom data reformatting scripts. Mega2 is freely available at https://watson.hgen.pitt.edu/register/