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Although prognostic gene expression signatures for survival in early stage lung cancer have been proposed, for clinical application it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training-testing, multi-site blinded validation study to characterize the performance of several prognostic models based on gene expression for 442 lung adenocarcinomas. The hypotheses proposed examined whether microarray measurements of gene expression either alone or combined with basic clinical covariates (stage, age, sex) can be used to predict overall survival in lung cancer subjects. Several models examined produced risk scores that substantially correlated with actual subject outcome. Most methods performed better with clinical data, supporting the combined use of clinical and molecular information when building prognostic models for early stage lung cancer. This study also provides the largest available set of microarray data with extensive pathological and clinical annotation for lung adenocarcinomas.

Soil property and class maps for the continent of Africa were so far only available at very generalised scales, with many countries not mapped at all. Thanks to an increasing quantity and availability of soil samples collected at field point locations by various government and/or NGO funded projects, it is now possible to produce detailed pan-African maps of soil nutrients, including micro-nutrients at fine spatial resolutions. In this paper we describe production of a 30 m resolution Soil Information System of the African continent using, to date, the most comprehensive compilation of soil samples ( N ≈ 150 , 000 ) and Earth Observation data. We produced predictions for soil pH, organic carbon (C) and total nitrogen (N), total carbon, effective Cation Exchange Capacity (eCEC), extractable—phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg), sulfur (S), sodium (Na), iron (Fe), zinc (Zn)—silt, clay and sand, stone content, bulk density and depth to bedrock, at three depths (0, 20 and 50 cm) and using 2-scale 3D Ensemble Machine Learning framework implemented in the mlr (Machine Learning in R) package. As covariate layers we used 250 m resolution (MODIS, PROBA-V and SM2RAIN products), and 30 m resolution (Sentinel-2, Landsat and DTM derivatives) images. Our fivefold spatial Cross-Validation results showed varying accuracy levels ranging from the best performing soil pH (CCC = 0.900) to more poorly predictable extractable phosphorus (CCC = 0.654) and sulphur (CCC = 0.708) and depth to bedrock. Sentinel-2 bands SWIR (B11, B12), NIR (B09, B8A), Landsat SWIR bands, and vertical depth derived from 30 m resolution DTM, were the overall most important 30 m resolution covariates. Climatic data images—SM2RAIN, bioclimatic variables and MODIS Land Surface Temperature—however, remained as the overall most important variables for predicting soil chemical variables at continental scale. This publicly available 30-m Soil Information System of Africa aims at supporting numerous applications, including soil and fertilizer policies and investments, agronomic advice to close yield gaps, environmental programs, or targeting of nutrition interventions.

Understanding the influence of the changing Arctic on mid-latitude weather is complex, and a challenge for researchers. This Perspective considers current approaches and proposes a way forward based on accepting the chaotic nature of the atmospheric circulation. Are continuing changes in the Arctic influencing wind patterns and the occurrence of extreme weather events in northern mid-latitudes? The chaotic nature of atmospheric circulation precludes easy answers. The topic is a major science challenge, as continued Arctic temperature increases are an inevitable aspect of anthropogenic climate change. We propose a perspective that rejects simple cause-and-effect pathways and notes diagnostic challenges in interpreting atmospheric dynamics. We present a way forward based on understanding multiple processes that lead to uncertainties in Arctic and mid-latitude weather and climate linkages. We emphasize community coordination for both scientific progress and communication to a broader public.

This study examined the extent to which the association between increased student absence and lower achievement outcomes varied by student and school-level socioeconomic characteristics. Analyses were based on the enrolment, absence and achievement records of 89,365 Year 5, 7 and 9 students attending government schools in Western Australian between 2008 and 2012. Multivariate multi-level modelling methods were used to estimate numeracy, writing and reading outcomes based on school absence, and interactions between levels of absence and school socioeconomic index (SEI), prior achievement, gender, ethnicity, language background, parent education and occupation status. While the effects of absence on achievement were greater for previously high-achieving students, there were few significant interactions between absence and any of the socioeconomic measures on achievement outcomes. The results of first-difference regression models indicated that the negative effect of an increase in absence was marginally larger for students attending more advantaged schools, though most effects were very small. While students from disadvantaged schools have, on average, more absences than their advantaged peers, there is very little evidence to suggest that the effects of absence are greater for those attending lower-SEI schools. School attendance should therefore be a priority for all schools, and not just those with high rates of absence or low average achievement.

Children with persistent hearing loss due to otitis media with effusion are commonly managed by surgical intervention. A safe, cheap, and effective medical treatment would enhance treatment options. Underpowered, poor-quality trials have found short-term benefit from oral steroids. We aimed to investigate whether a short course of oral steroids would achieve acceptable hearing in children with persistent otitis media with effusion and hearing loss. In this individually randomised, parallel, double-blinded, placebo-controlled trial we recruited children aged 2–8 years with symptoms attributable to otitis media with effusion for at least 3 months and with confirmed bilateral hearing loss. Participants were recruited from 20 ear, nose, and throat (ENT), paediatric audiology, and audiovestibular medicine outpatient departments in England and Wales. Participants were randomly allocated (1:1) to sequentially numbered identical prednisolone (oral steroid) or placebo packs by use of computer-generated random permuted block sizes stratified by site and child's age. The primary outcome was audiometry-confirmed acceptable hearing at 5 weeks. All analyses were by intention to treat. This trial is registered with the ISRCTN Registry, number ISRCTN49798431. Between March 20, 2014, and April 5, 2016, 1018 children were screened, of whom 389 were randomised. 200 were assigned to receive oral steroids and 189 to receive placebo. Hearing at 5 weeks was assessed in 183 children in the oral steroid group and in 180 in the placebo group. Acceptable hearing was observed in 73 (40%) children in the oral steroid group and in 59 (33%) in the placebo group (absolute difference 7% [95% CI −3 to 17], number needed to treat 14; adjusted odds ratio 1·36 [95% CI 0·88–2·11]; p=0·16). There was no evidence of any significant differences in adverse events or quality-of-life measures between the groups. Otitis media with effusion in children with documented hearing loss and attributable symptoms for at least 3 months has a high rate of spontaneous resolution. A short course of oral prednisolone is not an effective treatment for most children aged 2–8 years with persistent otitis media with effusion, but is well tolerated. One in 14 children might achieve improved hearing but not quality of life. Discussions about watchful waiting and other interventions will be supported by this evidence. National Institute for Health Research (NIHR) Health Technology Assessment programme.

[BACKGROUND:] The burden of mental health problems among Aboriginal and Torres Strait Islander children is a major public health problem in Australia. While socioeconomic factors are implicated as important determinants of mental health problems in mainstream populations, their bearing on the mental health of Indigenous Australians remains largely uncharted across all age groups. [METHODS:] We examined the relationship between the risk of clinically significant emotional or behavioural difficulties (CSEBD) and a range of socioeconomic measures for 3993 Indigenous children aged 4–17 years in Western Australia, using a representative survey conducted in 2000–02. Analysis was conducted using multivariate logistic regression within a multilevel framework. [RESULTS:] Almost one quarter (24%) of Indigenous children were classified as being at high risk of CSEBD. Our findings generally indicate that higher socioeconomic status is associated with a reduced risk of mental health problems in Indigenous children. Housing quality and tenure and neighbourhood-level disadvantage all have a strong direct effect on child mental health. Further, the circumstances of families with Indigenous children (parenting quality, stress, family composition, overcrowding, household mobility, racism and family functioning) emerged as an important explanatory mechanism underpinning the relationship between child mental health and measures of material wellbeing such as carer employment status and family financial circumstances. [CONCLUSIONS:] Our results provide incremental evidence of a social gradient in the mental health of Aboriginal and Torres Strait Islander children. Improving the social, economic and psychological conditions of families with Indigenous children has considerable potential to reduce the mental health inequalities within Indigenous populations and, in turn, to close the substantial racial gap in mental health. Interventions that target housing quality, home ownership and neighbourhood-level disadvantage are likely to be particularly beneficial.

The first trial of the efficacy of a human immunodeficiency virus (HIV)–1 vaccine was conducted in North America and The Netherlands between 1998 and 2003. This multicenter, randomized, placebo-controlled trial of a recombinant glycoprotein 120 vaccine included 5403 initially HIV-negative volunteers who were monitored for 3 years. The 368 subjects who acquired HIV-1 infection were monitored for 2 years by use of the following postinfection end points: plasma HIV-1 RNA level (viral load), CD4+ lymphocyte count, initiation of antiretroviral therapy (ART), and HIV-1–related clinical outcomes. This article reports the study results that pertain to the effect of vaccination on the postinfection end points. The time until initiation of ART and the time until virologic failure or initiation of ART were similar in the vaccine arm and the placebo arm. The pre-ART viral load and CD4+ lymphocyte count trajectories were also comparable between the groups. Evidently, the vaccine did not affect HIV-1 disease progression

IntroductionCare home residents are at increased risk of infections and antibiotic prescription. Reduced antibiotic use from fewer infections would improve quality of life. The Probiotics to Reduce Infections iN CarE home reSidentS (PRINCESS) trial aims to determine the efficacy and investigate mechanisms of daily probiotics on antibiotic use and incidence of infections in care home residents.Methods and analysisPRINCESS is a double-blind, individually randomised, placebo-controlled trial that will assess the effect of a daily oral probiotic combination of Lactobacillus rhamnosus, GG (LGG) and Bifidobacterium animalis subsp. lactis, BB-12 (BB-12) on cumulative antibiotic administration days (CAADs) (primary outcome) for infection in up to 330 care home residents aged ≥65 years over up to 12 months. Secondary outcomes include: Infection: Total number of days of antibiotic administration for each infection type (respiratory tract infection, urinary tract infection, gastrointestinal infection, unexplained fever and other); number, site, duration of infection; estimation of incidence and duration of diarrhoea and antibiotic-associated diarrhoea; Stool microbiology: Clostridium difficile infection; Gram-negative Enterobacteriaceae and vancomycin-resistant enterococci; LGG and BB-12. Oral microbiology: Candida spp. Health and well-being: Self and/or proxy health-related quality of life EQ5D (5 L); self-and/or proxy-reported ICEpop CAPability measure for older people. Hospitalisations: number and duration of all-cause hospital stays. Mortality: deaths. Mechanistic immunology outcomes: influenza vaccine efficacy (haemagglutination inhibition assay and antibody titres); full blood count and immune cell phenotypes, plasma cytokines and chemokines; cytokine and chemokine response in whole blood stimulated ex vivo by toll-like receptor 2 and 4 agonists; monocyte and neutrophil phagocytosis of Escherichia coli; serum vitamin D.Ethics and disseminationEthics approval is from the Wales Research Ethics Committee 3. Findings will be disseminated through peer-reviewed journals and conferences; results will be of interest to patient and policy stakeholders.Trial registration number ISRCTN16392920; Pre-results.