Solar power satellite cost estimate

The solar power configuration costed is the 5 GW silicon solar cell reference system. The subsystems identified by work breakdown structure elements to the lowest level for which cost information was generated. This breakdown divides into five sections: the satellite, construction, transportation, the ground receiving station and maintenance. For each work breakdown structure element, a definition, design description and cost estimate were included. An effort was made to include for each element a reference that more thoroughly describes the element and the method of costing used. All costs are in 1977 dollars

Making co-enrolment feasible for randomised controlled trials in paediatric intensive care.

Enrolling children into several trials could increase recruitment and lead to quicker delivery of optimal care in paediatric intensive care units (PICU). We evaluated decisions taken by clinicians and parents in PICU on co-enrolment for two large pragmatic trials: the CATCH trial (CATheters in CHildren) comparing impregnated with standard central venous catheters (CVCs) for reducing bloodstream infection in PICU and the CHIP trial comparing tight versus standard control of hyperglycaemia

Dryland salinity: a multi-disciplinary conceptual model designed for on-farm salinity control

Non-Peer Reviewe

Measuring disadvantage in the early years in the UK: A systematic scoping review

Background: The relationship between disadvantage and child health in the early years is well established. For this evidence base to most helpfully inform services, we need to better understand how disadvantage is conceptualised and measured in the literature. We aimed to conceptualise disadvantage measured in child health literature and explore the associations between disadvantage and child health using these measures. Method: We conducted a scoping review using systematic methods to identify key concepts of disadvantage used in empirical child health literature. We searched MEDLINE, Scopus, and grey literature for studies exploring the association between disadvantage and child health outcomes for children aged 0-5 in the United Kingdom. We extracted and analysed data from 86 studies. Results: We developed a framework describing two domains, each with two attributes conceptualising disadvantage: level of disadvantage indicator (individual and area) and content of disadvantage indicator (social and economic). Individual-level measures of disadvantage tended to identify stronger associations between disadvantage and child health compared with area-level measures. Conclusion: The choice of disadvantage indicators, particularly whether individual- or area-level, can affect the inferences made about the relationship between disadvantage and child health. Better access to individual-level disadvantage indicators in administrative data could support development and implementation of interventions aimed at reducing child health inequalities in the early years

Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy

Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation corresponding to a mutational “hotspot” in the human DMD gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (n = 2) or 8 weeks after systemic delivery (n = 2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90% of normal, depending on muscle type. In cardiac muscle, dystrophin levels in the dog receiving the highest dose reached 92% of normal. The treated dogs also showed improved muscle histology. These large-animal data support the concept that, with further development, gene editing approaches may prove clinically useful for the treatment of DMD

Cost-effectiveness of strategies preventing late-onset infection in preterm infants

OBJECTIVE: Developing a model to analyse the cost-effectiveness of interventions preventing late-onset infection (LOI) in preterm infants and applying it to the evaluation of anti-microbial impregnated peripherally inserted central catheters (AM-PICCs) compared with standard PICCs (S-PICCs). DESIGN: Model-based cost-effectiveness analysis, using data from the Preventing infection using Antimicrobial Impregnated Long Lines (PREVAIL) randomised controlled trial linked to routine healthcare data, supplemented with published literature. The model assumes that LOI increases the risk of neurodevelopmental impairment (NDI). SETTING: Neonatal intensive care units in the UK National Health Service (NHS). PATIENTS: Infants born ≤32 weeks gestational age, requiring a 1 French gauge PICC. INTERVENTIONS: AM-PICC and S-PICC. MAIN OUTCOME MEASURES: Life expectancy, quality-adjusted life years (QALYs) and healthcare costs over the infants' expected lifetime. RESULTS: Severe NDI reduces life expectancy by 14.79 (95% CI 4.43 to 26.68; undiscounted) years, 10.63 (95% CI 7.74 to 14.02; discounted) QALYs and costs £19 057 (95% CI £14 197; £24697; discounted) to the NHS. If LOI causes NDI, the maximum acquisition price of an intervention reducing LOI risk by 5% is £120. AM-PICCs increase costs (£54.85 (95% CI £25.95 to £89.12)) but have negligible impact on health outcomes (-0.01 (95% CI -0.09 to 0.04) QALYs), compared with S-PICCs. The NHS can invest up to £2.4 million in research to confirm that AM-PICCs are not cost-effective. CONCLUSIONS: The model quantifies health losses and additional healthcare costs caused by NDI and LOI during neonatal care. Given these consequences, interventions preventing LOI, even by a small extent, can be cost-effective. AM-PICCs, being less effective and more costly than S-PICC, are not likely to be cost-effective. TRIAL REGISTRATION NUMBER: NCT03260517

Relaxin gene family in teleosts: phylogeny, syntenic mapping, selective constraint, and expression analysis

<p>Abstract</p> <p>Background</p> <p>In recent years, the relaxin family of signaling molecules has been shown to play diverse roles in mammalian physiology, but little is known about its diversity or physiology in teleosts, an infraclass of the bony fishes comprising ~ 50% of all extant vertebrates. In this paper, 32 relaxin family sequences were obtained by searching genomic and cDNA databases from eight teleost species; phylogenetic, molecular evolutionary, and syntenic data analyses were conducted to understand the relationship and differential patterns of evolution of relaxin family genes in teleosts compared with mammals. Additionally, real-time quantitative PCR was used to confirm and assess the tissues of expression of five relaxin family genes in <it>Danio rerio </it>and <it>in situ </it>hybridization used to assess the site-specific expression of the insulin 3-like gene in <it>D. rerio </it>testis.</p> <p>Results</p> <p>Up to six relaxin family genes were identified in each teleost species. Comparative syntenic mapping revealed that fish possess two paralogous copies of human <it>RLN3</it>, which we call <it>rln3a </it>and <it>rln3b</it>, an orthologue of human <it>RLN2</it>, <it>rln</it>, two paralogous copies of human <it>INSL5</it>, <it>insl5a and insl5b</it>, and an orthologue of human <it>INSL3</it>, <it>insl3</it>. Molecular evolutionary analyses indicated that: <it>rln3a, rln3b </it>and <it>rln </it>are under strong evolutionary constraint, that <it>insl3 </it>has been subject to moderate rates of sequence evolution with two amino acids in <it>insl3/INSL3 </it>showing evidence of positively selection, and that <it>insl5b </it>exhibits a higher rate of sequence evolution than its paralogue <it>insl5a </it>suggesting that it may have been neo-functionalized after the teleost whole genome duplication. Quantitative PCR analyses in <it>D. rerio </it>indicated that <it>rln3a </it>and r<it>ln3b </it>are expressed in brain, <it>insl3 </it>is highly expressed in gonads, and that there was low expression of both <it>insl5 </it>genes in adult zebrafish. Finally, <it>in situ </it>hybridization of <it>insl3 </it>in <it>D. rerio </it>testes showed highly specific hybridization to interstitial Leydig cells.</p> <p>Conclusions</p> <p>Contrary to previous studies, we find convincing evidence that teleosts contain orthologues of four relaxin family peptides. Overall our analyses suggest that in teleosts: 1) <it>rln3 </it>exhibits a similar evolution and expression pattern to mammalian <it>RLN3</it>, 2) <it>insl3 </it>has been subject to positive selection like its mammalian counterpart and shows similar tissue-specific expression in Leydig cells, 3) <it>insl5 </it>genes are highly represented and have a relatively high rate of sequence evolution in teleost genomes, but they exhibited only low levels of expression in adult zebrafish, 4) <it>rln </it>is evolving under very different selective constraints from mammalian <it>RLN</it>. The results presented here should facilitate the development of hypothesis-driven experimental work on the specific roles of relaxin family genes in teleosts.</p

Dengue in pregnancy and maternal mortality: a cohort analysis using routine data.

Dengue is a mosquito-borne disease with major public health importance due to its growing incidence and geographical spread. There is a lack of knowledge on its contribution to maternal death. We conducted a population-based cohort study to investigate the association between symptomatic dengue during pregnancy and deaths in Brazil from 2007 to 2012. We did this by linking routine records of confirmed dengue cases to records of deaths of women who had a live birth. Using the Firth method, we estimated odds ratios for maternal deaths associated with dengue during pregnancy. Dengue increased the risk of maternal death by 3 times (95%CI,1.5-5.8) and dengue haemorrhagic fever increased the risk of maternal death by 450 times (95%CI,186.9-1088.4) when compared to mortality of pregnant women without dengue. The increase in risk occurred mostly during acute dengue 71.5 (95%CI,32.8-155.8), compared with no dengue cases. This study showed an increased risk of adverse outcomes in pregnant women with dengue. Therefore in areas where dengue is circulating, the health of pregnant women should be not only a public health priority, but health professionals attending pregnant women with dengue should more closely observe these patients to be able to intervene in a timely way and avoid deaths