Search

BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.

Premature ovarian insufficiency (POI) – the loss of ovarian function before the age of 40 years, a decade before natural menopause – is a life-changing diagnosis for women. POI causes significant short-term and long-term morbidity related to estrogen deficiency. The condition is managed by providing exogenous estrogen replacement, usually as the oral contraceptive pill or hormone therapy. These preparations have different estrogen formulations and may have differing benefits and risks. At present, there are no robust data to inform clinical recommendations and women's decision-making about treatment that they may be taking for many years. The POISE study (Premature Ovarian Insufficiency Study of Effectiveness of hormonal therapy) has been designed to determine whether hormone therapy is superior to combined oral contraceptives on important clinical outcomes and patient-reported symptoms, based on the hypothesis that hormone therapy provides more physiological continuous hormone supplementation with natural estrogens. The study is an open and pragmatic, parallel, randomized controlled trial. The primary outcome is absolute bone mineral density assessed by dual-energy X-ray absorptiometry of the lumbar spine after 2 years of treatment. The study will also investigate cardiovascular markers, symptom relief and acceptability of treatment, and will continue to collect long-term data on fractures and cardiovascular events. Results will inform future guidance on management of POI. [ABSTRACT FROM AUTHOR]

Tropical peat swamp forests provide important ecosystem services, ranging from carbon storage and fire prevention to fish provision. In the Sebangau catchment of Central Kalimantan, Indonesia, we completed the first detailed spatial and temporal assessments of local fish biodiversity in peat swamp forest and blackwater river habitats. Monthly environmental and fish data were collected over a 15-month period in both riverine and forest habitats. This resulted in a species list of 55 species from 16 different families. Species richness in the river was almost 1.5 times higher than in the forest, probably due to the sampling methods and trap selectivity. Average monthly river fish catches were negatively correlated with average monthly river depth. River fish surveys were conducted pre- and post- fire in 2015, with results showing increased river acidity and reduced fish catches post-fire. The fish and environmental data presented form a baseline for future monitoring projects and highlight a previously overlooked potential impact of fire on local biodiversity in Indonesia, namely that fire is likely to have negative impacts on the sizes of fish populations and catches. There are direct implications for human communities that depend on fishing for their livelihoods. Because peatlands and their rivers face continued human disturbance and degradation, assessments of fish biodiversity and water quality are of high priority. [ABSTRACT FROM AUTHOR]

Lumpy skin disease, sheeppox and goatpox are high-impact diseases of domestic ruminants with a devastating effect on cattle, sheep and goat farming industries in endemic regions. In this article, we review the current geographical distribution, economic impact of an outbreak, epidemiology, transmission and immunity of capripoxvirus. The special focus of the article is to scrutinize the use of currently available vaccines to investigate the resource needs and challenges that will have to be overcome to improve disease control and eradication, and progress on the development of safer and more effective vaccines. In addition, field evaluation of the efficacy of the vaccines and the genomic database available for poxviruses are discussed. [ABSTRACT FROM AUTHOR]

When seeking near-optimal solutions for complex scheduling problems, meta-heuristics demonstrate good performance with affordable computational effort. This has resulted in a gravitation towards these approaches when researching industrial use-cases such as energy-efficient production planning. However, much of the previous research makes assumptions about softer constraints that affect planning strategies and about how human planners interact with the algorithm in a live production environment. This article describes a job-shop problem that focuses on minimizing energy consumption across a production facility of shared resources. The application scenario is based on real facilities made available by the Irish Center for Manufacturing Research. The formulated problem is tackled via harmony search heuristics with random keys encoding. Simulation results are compared to a genetic algorithm, a simulated annealing approach and a first-come-first-served scheduling. The superior performance obtained by the proposed scheduler paves the way towards its practical implementation over industrial production chains. [ABSTRACT FROM AUTHOR]

Intereferon-γ (IFN-γ) has some anti-tumour activity in human ovarian cancer. This cytokine inhibited proliferation in three of four ovarian cancer cell lines in vitro. We then compared the action of IFN-γ in two cell lines, one sensitive and one resistant to its growth inhibitory effects. IFN-γ signalling appeared normal in both cell lines, with stat1 DNA binding activity detectable at 30 min. Continuous exposure to IFN-γ for 2–3 days was necessary for an irreversible effect on cell growth and apoptosis in cells sensitive to growth inhibition. During this time there was an increase in mRNA for the CKI p21, but no alterations in mRNA levels for other members of the CKI family. Maintenance of p21 mRNA required continuous mRNA synthesis. mRNA for the transcription factor IRF-1 was also induced in growth inhibited cells with similar kinetics to those observed for p21. Maximal induction of both p21 and IRF-1 mRNA was observed after 2–3 days IFN-γ exposure as the cells became committed to cell death. There was also a rapid increase in p21 and IRF-1 mRNA in cells resistant to the growth inhibitory effects of IFN-γ, but this increase was not maintained. Thus, continuous interaction with the IFN-γ receptor, together with a sustained induction of p21 and IRF-1, is associated with growth inhibitory and apoptotic effects of IFN-γ in ovarian cancer cells. © 1999 Cancer Research Campaign [ABSTRACT FROM AUTHOR]

Describes the method of construction of a diagram used as a classificatory tool in an election wherein three parties are involved. Reasons over the selection of an equilateral triangle over a right-angle triangle in a diagrammatic representation; Methods on how to plot an individual constituency result; Use of an index to constituency groups; Explanation of the representation and classification of voting change.

Twenty four preterm infants (median birth weight 1120 g and gestation 29 weeks) were studied on 83 occasions by measuring upper airway airflow. Airway patency was detected by the transmission of cardiac impulse up the airway and airway closure by its absence. A total of 309 apnoeas of at least five seconds' duration were recorded. One hundred and eighty (58.0%) were central, 109 (35.5%) mixed, and 20 (6.5%) obstructive. Airway closure was noted in 47% of apparently central apnoeas. Airway closure occurred as apnoea lengthened; the airway remained patent in 38% of apnoeas of 5-9 seconds, 17% of those 10-14 seconds, and 11% of those 15-19 seconds' duration. Airway closure occurred in every apnoea of greater than or equal to 20 seconds. As a consequence, closed apnoeas were longer than open apnoeas (mean 9.7 v 6.6 seconds). In 72% of mixed apnoeas, airway closure was recorded during the central element and this usually preceded obstructive breaths. In 20% of mixed apnoeas and 15.5% of the total group the airways closed, having previously been patent. This occurred after a mean of 3.5 seconds (range 1-17). Mixed apnoea produced a significantly greater drop in arterial oxygen saturation than central apnoea, but only because of the greater duration of mixed apnoea. Airway closure occurs in both central and mixed apnoea and appears to be important in the pathophysiology of mixed apnoea. Central and mixed apnoea are part of a continuum of airway closure and not separate entities. [ABSTRACT FROM AUTHOR]