Admissions to a Low-Resource Neonatal Unit in Malawi Using a Mobile App and Dashboard: A 1-Year Digital Perinatal Outcome Audit

Introduction: Understanding the extent and cause of high neonatal deaths rates in Sub-Saharan Africa is a challenge, especially in the presence of poor-quality and inaccurate data. The NeoTree digital data capture and quality improvement system has been live at Kamuzu Central Hospital, Neonatal Unit, Malawi, since April 2019. Objective: To describe patterns of admissions and outcomes in babies admitted to a Malawian neonatal unit over a 1-year period via a prototype data dashboard. Methods: Data were collected prospectively at the point of care, using the NeoTree app, which includes digital admission and outcome forms containing embedded clinical decision and management support and education in newborn care according to evidence-based guidelines. Data were exported and visualised using Microsoft Power BI. Descriptive and inferential analysis statistics were executed using R. Results: Data collected via NeoTree were 100% for all mandatory fields and, on average, 96% complete across all fields. Coverage of admissions, discharges, and deaths was 97, 99, and 91%, respectively, when compared with the ward logbook. A total of 2,732 neonates were admitted and 2,413 (88.3%) had an electronic outcome recorded: 1,899 (78.7%) were discharged alive, 12 (0.5%) were referred to another hospital, 10 (0.4%) absconded, and 492 (20%) babies died. The overall case fatality rate (CFR) was 204/1,000 admissions. Babies who were premature, low birth weight, out born, or hypothermic on admission, and had significantly higher CFR. Lead causes of death were prematurity with respiratory distress (n = 252, 51%), neonatal sepsis (n = 116, 23%), and neonatal encephalopathy (n = 80, 16%). The most common perceived modifiable factors in death were inadequate monitoring of vital signs and suboptimal management of sepsis. Two hundred and two (8.1%) neonates were HIV exposed, of whom a third [59 (29.2%)] did not receive prophylactic nevirapine, hence vulnerable to vertical infection. Conclusion: A digital data capture and quality improvement system was successfully deployed in a low resource neonatal unit with high (1 in 5) mortality rates providing and visualising reliable, timely, and complete data describing patterns, risk factors, and modifiable causes of newborn mortality. Key targets for quality improvement were identified. Future research will explore the impact of the NeoTree on quality of care and newborn survival

Yang-Mills instantons and dyons on homogeneous G_2-manifolds

We consider Lie G-valued Yang-Mills fields on the space R x G/H, where G/H is a compact nearly K"ahler six-dimensional homogeneous space, and the manifold R x G/H carries a G_2-structure. After imposing a general G-invariance condition, Yang-Mills theory with torsion on R x G/H is reduced to Newtonian mechanics of a particle moving in R^6, R^4 or R^2 under the influence of an inverted double-well-type potential for the cases G/H = SU(3)/U(1)xU(1), Sp(2)/Sp(1)xU(1) or G_2/SU(3), respectively. We analyze all critical points and present analytical and numerical kink- and bounce-type solutions, which yield G-invariant instanton configurations on those cosets. Periodic solutions on S^1 x G/H and dyons on iR x G/H are also given.Comment: 1+26 pages, 14 figures, 6 miniplot

Estimating the risk of rabies transmission to humans in the U.S.: a delphi analysis

<p>Abstract</p> <p>Background</p> <p>In the United States, the risk of rabies transmission to humans in most situations of possible exposure is unknown. Controlled studies on rabies are clearly not possible. Thus, the limited data on risk has led to the frequent administration of rabies post-exposure prophylaxis (PEP), often in inappropriate circumstances.</p> <p>Methods</p> <p>We used the Delphi method to obtain an expert group consensus estimate of the risk of rabies transmission to humans in seven scenarios of potential rabies exposure. We also surveyed and discussed the merits of recommending rabies PEP for each scenario.</p> <p>Results</p> <p>The median risk of rabies transmission without rabies PEP for a bite exposure by a skunk, bat, cat, and dog was estimated to be 0.05, 0.001, 0.001, and 0.00001, respectively. Rabies PEP was unanimously recommended in these scenarios. However, rabies PEP was overwhelmingly not recommended for non-bite exposures (e.g. dog licking hand but unavailable for subsequent testing), estimated to have less than 1 in 1,000,000 (0.000001) risk of transmission.</p> <p>Conclusions</p> <p>Our results suggest that there are many common situations in which the risk of rabies transmission is so low that rabies PEP should not be recommended. These risk estimates also provide a key parameter for cost-effective models of human rabies prevention and can be used to educate health professionals about situation-specific administration of rabies PEP.</p

Dental management considerations for the patient with an acquired coagulopathy. Part 1: Coagulopathies from systemic disease

Current teaching suggests that many patients are at risk for prolonged bleeding during and following invasive dental procedures, due to an acquired coagulopathy from systemic disease and/or from medications. However, treatment standards for these patients often are the result of long-standing dogma with little or no scientific basis. The medical history is critical for the identification of patients potentially at risk for prolonged bleeding from dental treatment. Some time-honoured laboratory tests have little or no use in community dental practice. Loss of functioning hepatic, renal, or bone marrow tissue predisposes to acquired coagulopathies through different mechanisms, but the relationship to oral haemostasis is poorly understood. Given the lack of established, science-based standards, proper dental management requires an understanding of certain principles of pathophysiology for these medical conditions and a few standard laboratory tests. Making changes in anticoagulant drug regimens are often unwarranted and/or expensive, and can put patients at far greater risk for morbidity and mortality than the unlikely outcome of postoperative bleeding. It should be recognised that prolonged bleeding is a rare event following invasive dental procedures, and therefore the vast majority of patients with suspected acquired coagulopathies are best managed in the community practice setting

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Plasma levels of nitric oxide related amino acids in demented subjects with Down syndrome are related to neopterin concentrations

Subjects with Down syndrome (DS) have abnormalities in virtually all aspects of the immune system and almost all will be affected with Alzheimer’s disease (AD). It is thought that nitric oxide (NO) is involved in the pathophysiology of AD. In the present study, including a total of 401 elderly DS subjects, the spectrum of plasma amino acids and neopterin was investigated and related to development of AD. Concentrations of nearly all amino acids in DS subjects differed significantly from those of healthy controls. Neopterin was increased in DS subjects, especially in dementia. The production of NO as reflected by an increased citrulline/arginine ratio (Cit/Arg ratio) was enhanced during development of clinical dementia. Neopterin concentrations correlated to the Cit/Arg ratio only in the group of prevalent demented subjects (ρ = 0.48, P = 0.006). The results of this study are suggestive for an increase in oxidative processes in DS subjects with AD

Circulating C-peptide levels in living children and young people and pancreatic beta cell loss in pancreas donors across type 1 diabetes disease duration.

This is the author accepted manuscript. The final version is available from the American Diabetes Association via the DOI in this record Data Availability: Further information about the data is available from the corresponding author upon request.C-peptide declines in type 1 diabetes although many long-duration patients retain low, but detectable levels. Histological analyses confirm that beta cells can remain following type 1 diabetes onset. We explored the trends observed in C-peptide decline in UK Genetic Resource Investigating Diabetes (UK GRID) cohort (N=4,079), with beta cell loss in pancreas donors from the network for Pancreatic Organ donors with Diabetes (nPOD) biobank and the Exeter Archival Diabetes Biobank (EADB) (combined N=235), stratified by recently reported age at diagnosis endotypes (< 7, 7-12, ≥ 13 years) across increasing diabetes durations. The proportion of individuals with detectable C-peptide declined beyond the first year after diagnosis, but this was most marked in the youngest age group (< 1 year duration: age < 7 years: 18/20 (90%), 7-12 years: 107/110 (97%), ≥ 13 years: 58/61 (95%) versus. 1-5 years post diagnosis: < 7 years: 172/522 (33%), 7-12 years: 604/995 (61%), ≥ 13 years: 225/289 (78%)). A similar profile was observed in beta cell loss, with those diagnosed at younger ages experiencing more rapid loss of islets containing insulin-positive (insulin+) beta cells < 1 year post diagnosis: age < 7 years: 23/26 (88%), 7-12 years: 32/33 (97%), ≥ 13 years: 22/25 (88%) versus. 1-5 years post diagnosis: < 7 years: 1/12 (8.3%) ,7-12 years: 7/13 (54%), ≥ 13 years: 7/8 (88%)). These data should be considered in the planning and interpretation of intervention trials designed to promote beta cell retention and function.Diabetes UKDiabetes UKDiabetes UKThe Leona M. & Harry B. Helmsley Charitable TrustJuvenile Diabetes Research FoundationWellcome Trus

GeneTools – application for functional annotation and statistical hypothesis testing

BACKGROUND: Modern biology has shifted from "one gene" approaches to methods for genomic-scale analysis like microarray technology, which allow simultaneous measurement of thousands of genes. This has created a need for tools facilitating interpretation of biological data in "batch" mode. However, such tools often leave the investigator with large volumes of apparently unorganized information. To meet this interpretation challenge, gene-set, or cluster testing has become a popular analytical tool. Many gene-set testing methods and software packages are now available, most of which use a variety of statistical tests to assess the genes in a set for biological information. However, the field is still evolving, and there is a great need for "integrated" solutions. RESULTS: GeneTools is a web-service providing access to a database that brings together information from a broad range of resources. The annotation data are updated weekly, guaranteeing that users get data most recently available. Data submitted by the user are stored in the database, where it can easily be updated, shared between users and exported in various formats. GeneTools provides three different tools: i) NMC Annotation Tool, which offers annotations from several databases like UniGene, Entrez Gene, SwissProt and GeneOntology, in both single- and batch search mode. ii) GO Annotator Tool, where users can add new gene ontology (GO) annotations to genes of interest. These user defined GO annotations can be used in further analysis or exported for public distribution. iii) eGOn, a tool for visualization and statistical hypothesis testing of GO category representation. As the first GO tool, eGOn supports hypothesis testing for three different situations (master-target situation, mutually exclusive target-target situation and intersecting target-target situation). An important additional function is an evidence-code filter that allows users, to select the GO annotations for the analysis. CONCLUSION: GeneTools is the first "all in one" annotation tool, providing users with a rapid extraction of highly relevant gene annotation data for e.g. thousands of genes or clones at once. It allows a user to define and archive new GO annotations and it supports hypothesis testing related to GO category representations. GeneTools is freely available through www.genetools.n

American Step-Up and Step-Down Default Swaps under Levy Models

This paper studies the valuation of a class of default swaps with the embedded option to switch to a different premium and notional principal anytime prior to a credit event. These are early exercisable contracts that give the protection buyer or seller the right to step-up, step-down, or cancel the swap position. The pricing problem is formulated under a structural credit risk model based on Levy processes. This leads to the analytic and numerical studies of several optimal stopping problems subject to early termination due to default. In a general spectrally negative Levy model, we rigorously derive the optimal exercise strategy. This allows for instant computation of the credit spread under various specifications. Numerical examples are provided to examine the impacts of default risk and contractual features on the credit spread and exercise strategy.Comment: 35 pages, 5 figure