Baptist home missions in North America

In a volume lettered: China and the Chinese: a collection of pamphlets relating thereto. Volume 63

The Costs, Benefits, and Cost-Effectiveness of Interventions to Reduce Maternal Morbidity and Mortality in Mexico

Background: In Mexico, the lifetime risk of dying from maternal causes is 1 in 370 compared to 1 in 2,500 in the U.S. Although national efforts have been made to improve maternal services in the last decade, it is unclear if Millennium Development Goal 5 - to reduce maternal mortality by three-quarters by 2015 - will be met. Methodology/Principal Findings: We developed an empirically calibrated model that simulates the natural history of pregnancy and pregnancy-related complications in a cohort of 15-year-old women followed over their lifetime. After synthesizing national and sub-national trends in maternal mortality, the model was calibrated to current intervention-specific coverage levels and validated by comparing model-projected life expectancy, total fertility rate, crude birth rate and maternal mortality ratio with Mexico-specific data. Using both published and primary data, we assessed the comparative health and economic outcomes of alternative strategies to reduce maternal morbidity and mortality. A dual approach that increased coverage of family planning by 15%, and assured access to safe abortion for all women desiring elective termination of pregnancy, reduced mortality by 43% and was cost saving compared to current practice. The most effective strategy added a third component, enhanced access to comprehensive emergency obstetric care for at least 90% of women requiring referral. At a national level, this strategy reduced mortality by 75%, cost less than current practice, and had an incremental cost-effectiveness ratio of $300 per DALY relative to the next best strategy. Analyses conducted at the state level yielded similar results. Conclusions/Significance: Increasing the provision of family planning and assuring access to safe abortion are feasible, complementary and cost-effective strategies that would provide the greatest benefit within a short-time frame. Incremental improvements in access to high-quality intrapartum and emergency obstetric care will further reduce maternal deaths and disability

Constructing evidence-based clinical intrapartum care algorithms for decision-support tools

AimTo describe standardised iterative methods used by a multidisciplinary group to develop evidence-based clinical intrapartum care algorithms for the management of uneventful and complicated labours.PopulationSingleton, term pregnancies considered to be at low risk of developing complications at admission to the birthing facility.SettingHealth facilities in low- and middle-income countries.Search strategyLiterature reviews were conducted to identify standardised methods for algorithm development and examples from other fields, and evidence and guidelines for intrapartum care. Searches for different algorithm topics were last updated between January and October 2020 and included a combination of terms such as 'labour', 'intrapartum', 'algorithms' and specific topic terms, using Cochrane Library and MEDLINE/PubMED, CINAHL, National Guidelines Clearinghouse and Google.Case scenariosNine algorithm topics were identified for monitoring and management of uncomplicated labour and childbirth, identification and management of abnormalities of fetal heart rate, liquor, uterine contractions, labour progress, maternal pulse and blood pressure, temperature, urine and complicated third stage of labour. Each topic included between two and four case scenarios covering most common deviations, severity of related complications or critical clinical outcomes.ConclusionsIntrapartum care algorithms provide a framework for monitoring women, and identifying and managing complications during labour and childbirth. These algorithms will support implementation of WHO recommendations and facilitate the development by stakeholders of evidence-based, up to date, paper-based or digital reminders and decision-support tools. The algorithms need to be field tested and may need to be adapted to specific contexts.Tweetable abstractEvidence-based intrapartum care clinical algorithms for a safe and positive childbirth experience

The organisational response of a hospital critical care service to the COVID-19 pandemic: The Groote Schuur Hospital experience.

Background: There are limited data about the coronavirus disease-19 (COVID-19)-related organisational responses and the challenges of expanding a critical care service in a resource-limited setting. Objectives: To describe the ICU organisational response to the pandemic and the main outcomes of the intensive care service of a large state teaching hospital in South Africa. Methods: Data were extracted from administrative records and a prospective patient database with ethical approval. An ICU expansion plan was developed, and resource constraints identified. A triage tool was distributed to referring wards and hospitals. Intensive care was reserved for patients who required invasive mechanical ventilation (IMV). The total number of ICU beds was increased from 25 to 54 at peak periods, with additional non-COVID ICU capacity required during the second wave. The availability of nursing staff was the main factor limiting expansion. A ward-based high flow nasal oxygen (HFNO) service reduced the need for ICU admission of patients who failed conventional oxygen therapy. A team was established to intubate and transfer patients requiring ICU admission but was only available for the first wave. Results: We admitted 461 COVID-19 patients to the ICU over a 13-month period from 5 April 2020 to 5 May 2021 spanning two waves of admissions. The median age was 50 years and duration of ICU stay was 9 days. More than a third of the patients (35%; n=161) survived to hospital discharge. Conclusion: Pre-planning, leadership, teamwork, flexibility and good communication were essential elements for an effective response. A shortage of nurses was the main constraint on ICU expansion. HFNO may have reduced the requirement for ICU admission, but patients intubated after failing HFNO had a poor prognosis. Contributions of the study: We describe the organisational requirements to successfully expand critical care facilities and strategies to reduce the need for invasive mechanical ventilation in COVID-19 pneumonia. We also present the intensive care outcomes of these patients in a resource-constrained environment

A method for estimation of elasticities in metabolic networks using steady state and dynamic metabolomics data and linlog kinetics

BACKGROUND: Dynamic modeling of metabolic reaction networks under in vivo conditions is a crucial step in order to obtain a better understanding of the (dis)functioning of living cells. So far dynamic metabolic models generally have been based on mechanistic rate equations which often contain so many parameters that their identifiability from experimental data forms a serious problem. Recently, approximative rate equations, based on the linear logarithmic (linlog) format have been proposed as a suitable alternative with fewer parameters. RESULTS: In this paper we present a method for estimation of the kinetic model parameters, which are equal to the elasticities defined in Metabolic Control Analysis, from metabolite data obtained from dynamic as well as steady state perturbations, using the linlog kinetic format. Additionally, we address the question of parameter identifiability from dynamic perturbation data in the presence of noise. The method is illustrated using metabolite data generated with a dynamic model of the glycolytic pathway of Saccharomyces cerevisiae based on mechanistic rate equations. Elasticities are estimated from the generated data, which define the complete linlog kinetic model of the glycolysis. The effect of data noise on the accuracy of the estimated elasticities is presented. Finally, identifiable subset of parameters is determined using information on the standard deviations of the estimated elasticities through Monte Carlo (MC) simulations. CONCLUSION: The parameter estimation within the linlog kinetic framework as presented here allows the determination of the elasticities directly from experimental data from typical dynamic and/or steady state experiments. These elasticities allow the reconstruction of the full kinetic model of Saccharomyces cerevisiae, and the determination of the control coefficients. MC simulations revealed that certain elasticities are potentially unidentifiable from dynamic data only. Addition of steady state perturbation of enzyme activities solved this problem

Climatic and topographic changes since the Miocene influenced the diversification and biogeography of the tent tortoise (Psammobates tentorius) species complex in Southern Africa

Background: Climatic and topographic changes function as key drivers in shaping genetic structure and cladogenic radiation in many organisms. Southern Africa has an exceptionally diverse tortoise fauna, harbouring one-third of the world’s tortoise genera. The distribution of Psammobates tentorius (Kuhl, 1820) covers two of the 25 biodiversity hotspots in the world, the Succulent Karoo and Cape Floristic Region. The highly diverged P. tentorius represents an excellent model species for exploring biogeographic and radiation patterns of reptiles in Southern Africa. Results: We investigated genetic structure and radiation patterns against temporal and spatial dimensions since the Miocene in the Psammobates tentorius species complex, using multiple types of DNA markers and niche modelling analyses. Cladogenesis in P. tentorius started in the late Miocene (11.63–5.33 Ma) when populations dispersed from north to south to form two geographically isolated groups. The northern group diverged into a clade north of the Orange River (OR), followed by the splitting of the group south of the OR into a western and an interior clade. The latter divergence corresponded to the intensifcation of the cold Benguela current, which caused western aridifcation and rainfall seasonality. In the south, tectonic uplift and subsequent exhumation, together with climatic fuctuations seemed responsible for radiations among the four southern clades since the late Miocene. We found that each clade occurred in a habitat shaped by diferent climatic parameters, and that the niches difered substantially among the clades of the northern group but were similar among clades of the southern group. Conclusion: Climatic shifts, and biome and geographic changes were possibly the three major driving forces shaping cladogenesis and genetic structure in Southern African tortoise species. Our results revealed that the cladogenesis of the P. tentorius species complex was probably shaped by environmental cooling, biome shifts and topographic uplift in Southern Africa since the late Miocene. The Last Glacial Maximum (LGM) may have impacted the distribution of P. tentorius substantially. We found the taxonomic diversify of the P. tentorius species complex to be highest in the Greater Cape Floristic Region. All seven clades discovered warrant conservation attention, particularly Ptt-B–Ptr, Ptt-A and Pv-

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference