Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes.

The PROGRESS series (www.progress-partnership.org) sets out a framework of four interlinked prognosis research themes and provides examples from several disease fields to show why evidence from prognosis research is crucial to inform all points in the translation of biomedical and health related research into better patient outcomes. Recommendations are made in each of the four papers to improve current research standards What is prognosis research? Prognosis research seeks to understand and improve future outcomes in people with a given disease or health condition. However, there is increasing evidence that prognosis research standards need to be improved Why is prognosis research important? More people now live with disease and conditions that impair health than at any other time in history; prognosis research provides crucial evidence for translating findings from the laboratory to humans, and from clinical research to clinical practice This first article introduces the framework of four interlinked prognosis research themes and then focuses on the first of the themes - fundamental prognosis research, studies that aim to describe and explain future outcomes in relation to current diagnostic and treatment practices, often in relation to quality of care Fundamental prognosis research provides evidence informing healthcare and public health policy, the design and interpretation of randomised trials, and the impact of diagnostic tests on future outcome. It can inform new definitions of disease, may identify unanticipated benefits or harms of interventions, and clarify where new interventions are required to improve prognosis

Hydraulic and biotic impacts on neutralisation of high-pH waters

The management of alkaline (pH 11–12.5) leachate is an important issue associated with the conditioning, afteruse or disposal of steel slags. Passive in-gassing of atmospheric CO₂ is a low cost option for reducing Ca(OH)₂ alkalinity, as Ca(OH)₂ is neutralised by carbonic acid to produce CaCO₃. The relative effectiveness of such treatment can be affected by both the system geometry (i.e. stepped cascades versus settlement ponds) and biological colonization. Sterilized mesocosm experiments run over periods of 20 days showed that, due to more water mixing and enhanced CO₂ dissolution at the weirs, the cascade systems (pH 11.2 → 9.6) are more effective than settlement ponds (pH 11.2 → 11.0) for lowering leachate alkalinity in all the tested conditions. The presence of an active microbial biofilm resulted in significantly more pH reduction in ponds (pH 11.2 → 9.5), but had a small impact on the cascade systems (pH 11.2 → 9.4). The pH variation in biofilm colonized systems shows a diurnal cycle of 1 to 1.5 pH units due to CO₂ uptake and release associated with respiration and photosynthesis. The results demonstrate that, where gradient permits, aeration via stepped cascades are the best option for neutralisation of steel slag leachates, and where feasible, the development of biofilm communities can also help reduce alkalinity

Prognosis research strategy (PROGRESS) 4: Stratified medicine research

In patients with a particular disease or health condition, stratified medicine seeks to identify thosewho will have the most clinical benefit or least harm from a specific treatment. In this article, thefourth in the PROGRESS series, the authors discuss why prognosis research should form acornerstone of stratified medicine, especially in regard to the identification of factors that predictindividual treatment respons

The science of clinical practice: disease diagnosis or patient prognosis? Evidence about "what is likely to happen" should shape clinical practice.

BACKGROUND: Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful. DISCUSSION: Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous 'yes' or 'no' is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient's future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome. SUMMARY: Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care

REVIEW The social, economic, and environmental importance of inland fish and fisheries

Abstract: Though reported capture fisheries are dominated by marine production, inland fish and fisheries make substantial contributions to meeting the challenges faced by individuals, society, and the environment in a changing global landscape. Inland capture fisheries and aquaculture contribute over 40% to the world's reported finfish production from less than 0.01% of the total volume of water on earth. These fisheries provide food for billions and livelihoods for millions of people worldwide. Herein, using supporting evidence from the literature, we review 10 reasons why inland fish and fisheries are important to the individual (food security, economic security, empowerment), to society (cultural services, recreational services, human health and well-being, knowledge transfer and capacity building), and to the environment (ecosystem function and biodiversity, as aquatic "canaries", the "green food" movement). However, the current limitations to valuing the services provided by inland fish and fisheries make comparison with other water resource users extremely difficult. This list can serve to demonstrate the importance of inland fish and fisheries, a necessary first step to better incorporating them into agriculture, land-use, and water resource planning, where they are currently often underappreciated or ignored. Key words: food security, freshwater ecosystems, importance of fish, inland fisheries. Résumé : Bien que la capture de poissons rapportée par les pêcheries soit dominée par la production marine, les poissons et les pêcheries de l'intérieur des terres apportent des contributions substantielles pour rencontrer les défis rencontrés par les individus, les sociétés et l'environnement dans un paysage en changement global. Les captures des pêcheries de l'intérieur et l'aquaculture contribuent à la hauteur de 40 % à la production mondiale rapportée pour les poissons à nageoires, à partir de moins de 0,01 % du volume total de l'eau sur terre. Ces pêcheries fournissent de la nourriture pour des milliards et un moyen de subsistance pour des millions de gens, partout au monde. Dans cette revue, en utilisant des preuves venant de la littérature, les auteurs examinent 10 raisons pour lesquelles, les pêcheries et les poissons de l'intérieur sont importants pour les individus (sécurité alimentaire, sécurité économique, l'autonomisation), pour la société (services culturels, services récréatifs, santé humaine et bien-être, transfert de connaissances et capacité à construire) et pour l'environnement (fonction écosystémique et biodiversité, comme « canaris » aquatiques, pour le mouvement « aliments verts »). Cependant, les limitations actuelles pour évaluer les services fournis par les poissons et les pêcheries intérieures rendent les comparaisons avec les autres utilisateurs de la ressource en eau extrêmement difficile. Cette liste peut servir à démontrer l'importance des poissons et des pêcheries de l'intérieur, une première étape essentielle pour mieux les incorporer avec l'agriculture, l'utilisation du territoire et la planification des ressources en eau, où elles sont actuellement sous-estimées, voire totalement ignorées. [Traduit par la Rédaction] Mots-clés : sécurité alimentaire, écosystèmes d'eau douce, importance des poissons, pêcheries de l'intérieur

Hydration of dicalcium silicate and diffusion through neo-formed calcium-silicate-hydrates at weathered surfaces control the long-term leaching behaviour of basic oxygen furnace (BOF) steelmaking slag

Alkalinity generation and toxic trace metal (such as vanadium) leaching from basic oxygen furnace (BOF) steel slag particles must be properly understood and managed by pre-conditioning if beneficial reuse of slag is to be maximised. Water leaching under aerated conditions was investigated using fresh BOF slag at three different particle sizes (0.5–1.0, 2–5 and 10 × 10 × 20 mm blocks) and a 6-month pre-weathered block. There were several distinct leaching stages observed over time associated with different phases controlling the solution chemistry: (1) free-lime (CaO) dissolution (days 0–2); (2) dicalcium silicate (Ca₂SiO₄) dissolution (days 2–14) and (3) Ca–Si–H and CaCO₃ formation and subsequent dissolution (days 14–73). Experiments with the smallest size fraction resulted in the highest Ca, Si and V concentrations, highlighting the role of surface area in controlling initial leaching. After ~2 weeks, the solution Ca/Si ratio (0.7–0.9) evolved to equal those found within a Ca–Si–H phase that replaced dicalcium silicate and free-lime phases in a 30- to 150-μm altered surface region. V release was a two-stage process; initially, V was released by dicalcium silicate dissolution, but V also isomorphically substituted for Si into the neo-formed Ca–Si–H in the alteration zone. Therefore, on longer timescales, the release of V to solution was primarily controlled by considerably slower Ca–Si–H dissolution rates, which decreased the rate of V release by an order of magnitude. Overall, the results indicate that the BOF slag leaching mechanism evolves from a situation initially dominated by rapid hydration and dissolution of primary dicalcium silicate/free-lime phases, to a slow diffusion limited process controlled by the solubility of secondary Ca–Si–H and CaCO₃ phases that replace and cover more reactive primary slag phases at particle surfaces

Alkaline residues and the environment: A review of impacts, management practices and opportunities

Around two billion tonnes of alkaline residues are produced globally each year by industries such as steel production, alumina refining and coal-fired power generation, with a total production estimate of 90 billion tonnes since industrialization. These wastes are frequently stored in waste piles or landfills, and can be an environmental hazard if allowed to generate dust, or if rainwater infiltrates the waste. This review will focus on the environmental impacts associated with alkaline residues, with emphasis on the leachates produced by rainwater ingress. Many alkaline industrial wastes can produce leachates that are enriched with trace metals that form oxyanions (e.g. As, Cr, Mo, Se, V), which can be very mobile in alkaline water. The management options for the residues and their leachates are also discussed, distinguishing active and passive treatment options. Potential reuses of these materials, in construction materials, as agricultural amendments, and in environmental applications are identified. The mechanisms of carbon sequestration by alkaline residues are assessed, and the potential for enhancing its rate as a climate change off-setting measure for the industry is evaluated. The potential for recovery of metals critical to e-technologies, such as vanadium, cobalt, lithium and rare earths, from alkaline residues is considered. Finally research needs are identified, including the need to better understand the biogeochemistry of highly alkaline systems in order to develop predictable passive remediation and metal recovery technologies

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity