Optimising computer aided detection to identify intra-thoracic tuberculosis on chest x-ray in South African children

Diagnostic tools for paediatric tuberculosis remain limited, with heavy reliance on clinical algorithms which include chest x-ray. Computer aided detection (CAD) for tuberculosis on chest x-ray has shown promise in adults. We aimed to measure and optimise the performance of an adult CAD system, CAD4TB, to identify tuberculosis on chest x-rays from children with presumptive tuberculosis. Chest x-rays from 620 children <13 years enrolled in a prospective observational diagnostic study in South Africa, were evaluated. All chest x-rays were read by a panel of expert readers who attributed each with a radiological reference of either 'tuberculosis' or 'not tuberculosis'. Of the 525 chest x-rays included in this analysis, 80 (40 with a reference of 'tuberculosis' and 40 with 'not tuberculosis') were allocated to an independent test set. The remainder made up the training set. The performance of CAD4TB to identify 'tuberculosis' versus 'not tuberculosis' on chest x-ray against the radiological reference read was calculated. The CAD4TB software was then fine-tuned using the paediatric training set. We compared the performance of the fine-tuned model to the original model. Our findings were that the area under the receiver operating characteristic curve (AUC) of the original CAD4TB model, prior to fine-tuning, was 0.58. After fine-tuning there was an improvement in the AUC to 0.72 (p = 0.0016). In this first-ever description of the use of CAD to identify tuberculosis on chest x-ray in children, we demonstrate a significant improvement in the performance of CAD4TB after fine-tuning with a set of well-characterised paediatric chest x-rays. CAD has the potential to be a useful additional diagnostic tool for paediatric tuberculosis. We recommend replicating the methods we describe using a larger chest x-ray dataset from a more diverse population and evaluating the potential role of CAD to replace a human-read chest x-ray within treatment-decision algorithms for paediatric tuberculosis

Toward a conceptual framework of the acceptability of tuberculosis treatment in children using a theory generative approach

To describe an early-stage holistic framework towards evaluating factors that impact the overall acceptability of TB treatment along the TB care cascade in children. We developed a conceptual framework utilising a theory generative approach. Domains were developed through review of existing definitions and analysis of existing qualitative data undertaken in acceptability studies of TB treatment in children. Clarity of domain definitions was achieved through iterative refinement among the research team. Three domains, each comprising several dimensions, were identified to holistically evaluate treatment acceptability: (1) usability, which involves the alignment between the requirements of treatment use and caregivers’ and children’s ability to integrate TB treatment into their everyday routines, (2) receptivity, which describes the end-user’s perception and expectations of treatment and its actual use, and (3) integration, which describes the relationship between available health services and caregivers/children’s capacity to make use of those services. Our framework addresses the gaps in current research which do not account for the influence of caregivers’ and children’s contexts on TB treatment uptake and overall acceptability. This approach may support the development of more standard, holistic measures to improve TB treatment delivery and experiences and future research in children

Unicircular structure of the Brassica hirta mitochondrial genome

Restriction mapping studies reveal that the mitochondrial genome of white mustard ( Brassica hirta ) exists in the form of a single circular 208 kb chromosome. The B. hirta genome has only one copy of the two sequences which, in several related Brassica species, are duplicated and undergo intramolecular recombination. This first report of a plant mitochondrial DNA that does not exist in a multipartite structure indicates that high frequency intramolecular recombination is not an obligatory feature of plant mitochondrial genomes. Heterologous filter hybridizatios reveal that the mitochondrial genomes of B. hirta and B. campestris have diverged radically in sequence arrangement, as the result of approximately 10 large inversions. At the same time, however, the two genomes are similar in size, sequence content, and primary sequence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46962/1/294_2004_Article_BF00384620.pd

Cold water and harmful algal blooms linked to coral reef collapse in the Eastern Tropical Pacific

Background: With conventional coral reef conservation methods proving ineffective against intensifying climate change, efforts have focussed on augmenting coral tolerance to warmer water—the primary driver of coral declines. We document coral cover and composition in relation to sea surface temperature (SST) over 25-years, of six marginal reefs in an upwelling area of Costa Rica’s Eastern Tropical Pacific. Methods: Using reef survey data and sea surface temperature (SST) dating back over 25-years, we document coral cover and composition of six marginal reefs in an upwelling area of Costa Rica’s Eastern Tropical Pacific in relation to thermal highs and lows. Results.: A ubiquitous and catastrophic coral die-off event occurred in 2009, driven by SST minima and likely by the presence of extreme harmful algal blooms. Coral cover was dramatically reduced and coral composition shifted from dominant branching Pocillopora to massive Pavona, Porites, and Gardineroseris. The lack of coral recovery in the decade since indicates a breach in ecosystem tipping-point and highlights a need for resilience-based management (RBM) and restoration. We propose a locally tailored and globally scalable approach to coral reef declines that is founded in RBM and informed by coral health dynamics

An international Delphi consensus regarding best practice recommendations for hyperkalaemia across the cardiorenal spectrum.

AIMS: Renin-angiotensin-aldosterone system inhibitors (RAASi) are guideline-recommended therapy for individuals with cardiorenal disease. They are associated with increased risk of hyperkalaemia, a common and life-threatening disorder for this population. RAASi-induced hyperkalaemia often leads to dose reduction or discontinuation, reducing cardiorenal protection. Guideline recommendations differ between specialties for the clinical management of hyperkalaemia. Using a modified Delphi method, we developed consensus recommendations for optimal management of hyperkalaemia in adults with cardiorenal disease. METHODS AND RESULTS: An international steering group of cardiologists and nephrologists developed 39 statements regarding hyperkalaemia care, including risk factors and risk stratification, prevention, correction, and cross-specialty coordination. Consensus was determined by agreement on an online questionnaire administered to cardiorenal specialists across Europe and North America. The threshold for consensus agreement was established a priori by the steering group at 67%. Across November 2021, 520 responses were received from Canada (n = 50), France (n = 50), Germany (n = 54), Italy (n = 58), Spain (n = 57), the UK (n = 49), and the US (n = 202); 268 from cardiologists and 252 from nephrologists. Twenty-nine statements attained very high agreement (≥90%) and 10 attained high agreement (≥67%-<90%), with strong alignment between cardiologists and nephrologists. CONCLUSION: A high degree of consensus regarding hyperkalaemia evaluation and management exists among healthcare professionals. Based on high levels of agreement, the steering group derived six key recommendations for hyperkalaemia prevention and management in people with cardiorenal disease. Future studies examining the quality of hyperkalaemia care delivery are required

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

A cross-country review of strategies of the German development cooperation to strengthen human resources

ABSTRACT: BACKGROUND: Recent years have seen growing awareness of the importance of human resources for health in health systems and with it an intensifying of the international and national policies in place to steer a response. This paper looks at how governments and donors in five countries - Cameroon, Indonesia, Malawi, Rwanda and Tanzania - have translated such policies into action. More detailed information with regard to initiatives of German development cooperation brings additional depth to the range and entry doors of human resources for health initiatives from the perspective of donor cooperation. METHODS: This qualitative study systematically presents different approaches and stages to human resources for health development in a cross-country comparison. An important reference to capture implementation at country level was grey literature such as policy documents and programme reports. In-depth interviews along a predefined grid with national and international stakeholders in the five countries provided information on issues related to human resources for health policy processes and implementation. RESULTS: All five countries have institutional entities in place and have drawn up national policies to address human resources for health. Only some of the countries have translated policies into strategies with defined targets and national programmes with budgets and operational plans. Traditional approaches of supporting training for individual health professionals continue to dominate. In some cases partners have played an advocacy and technical role to promote human resources for health development at the highest political levels, but usually they still focus on the provision of ad hoc training within their programmes, which may not be in line with national human resources for health development efforts or may even be counterproductive to them. Countries that face an emergency, such as Malawi, have intensified their efforts within a relatively short time and by using donor funding support also through new initiatives such as the Global Fund to Fight AIDS, Tuberculosis and Malaria. CONCLUSIONS: The country case studies illustrate the range of initiatives that have surged in recent years and some main trends in terms of donor initiatives. Though attention and priority attributed to human resources for health is increasing, there is still a focus on single initiatives and programmes. This can be explained in part by the complexity of the issue, and in part by its need to be addressed through a long-term approach including public sector and salary reforms that go beyond the health secto