Newcastle University

The classification of diabetes mellitus and the tests used for its diagnosis were brought into order by the National Diabetes Data Group of the USA and the second World Health Organization Expert Committee on Diabetes Mellitus in 1979 and 1980. Apart from minor modifications by WHO in 1985, little has been changed since that time. There is however considerable new knowledge regarding the aetiology of different forms of diabetes as well as more information on the predictive value of different blood glucose values for the complications of diabetes. A WHO Consultation has therefore taken place in parallel with a report by an American Diabetes Association Expert Committee to re-examine diagnostic criteria and classification. The present document includes the conclusions of the former and is intended for wide distribution and discussion before final proposals are submitted to WHO for approval. The main changes proposed are as follows. The diagnostic fasting plasma (blood) glucose value has been lowered to > or =7.0 mmol l(-1) (6.1 mmol l(-1)). Impaired Glucose Tolerance (IGT) is changed to allow for the new fasting level. A new category of Impaired Fasting Glycaemia (IFG) is proposed to encompass values which are above normal but below the diagnostic cut-off for diabetes (plasma > or =6.1 to <7.0 mmol l(-1); whole blood > or =5.6 to <6.1 mmol l(-1)). Gestational Diabetes Mellitus (GDM) now includes gestational impaired glucose tolerance as well as the previous GDM. The classification defines both process and stage of the disease. The processes include Type 1, autoimmune and non-autoimmune, with beta-cell destruction; Type 2 with varying degrees of insulin resistance and insulin hyposecretion; Gestational Diabetes Mellitus; and Other Types where the cause is known (e.g. MODY, endocrinopathies). It is anticipated that this group will expand as causes of Type 2 become known. Stages range from normoglycaemia to insulin required for survival. It is hoped that the new classification will allow better classification of individuals and lead to fewer therapeutic misjudgements.

Background: in 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition that aimed to foster advances in identifying and caring for people with sarcopenia. In early 2018, the Working Group met again (EWGSOP2) to update the original definition in order to reflect scientific and clinical evidence that has built over the last decade. This paper presents our updated findings. Objectives: to increase consistency of research design, clinical diagnoses and ultimately, care for people with sarcopenia. Recommendations: sarcopenia is a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age but can also occur earlier in life. In this updated consensus paper on sarcopenia, EWGSOP2: (1) focuses on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarcopenia diagnosis, and identifies poor physical performance as indicative of severe sarcopenia; (2) updates the clinical algorithm that can be used for sarcopenia case-finding, diagnosis and confirmation, and severity determination and (3) provides clear cut-off points for measurements of variables that identify and characterise sarcopenia. Conclusions: EWGSOP2's updated recommendations aim to increase awareness of sarcopenia and its risk. With these new recommendations, EWGSOP2 calls for healthcare professionals who treat patients at risk for sarcopenia to take actions that will promote early detection and treatment. We also encourage more research in the field of sarcopenia in order to prevent or delay adverse health outcomes that incur a heavy burden for patients and healthcare systems.

There is increasing evidence that genome-wide association (GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study (using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined ∼2,000 individuals for each of 7 major diseases and a shared set of ∼3,000 controls. Case-control comparisons identified 24 independent association signals at P < 5 × 10-7: 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn’s disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals (including 58 loci with single-point P values between 10-5 and 5 × 10-7) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics research. With the advent of many more markers in the human genome, it has become possible to search for genes associated with human disease without having to narrow down candidate regions of the genome first. In a ground-breaking publication, the Wellcome Trust Case Control Consortium reports an exciting genome-wide association study of some 17,000 individuals for seven common familial diseases. The analysis confirms previously identified loci and provides strong evidence for many novel disease susceptibility genes. An exciting genome-wide association study in the British population for seven common diseases. This analysis confirms previously identified loci and provides strong evidence for many novel disease susceptibility loci.

Chlorophyll fluorescence analysis has become one of the most powerful and widely used techniques available to plant physiologists and ecophysiologists. This review aims to provide an introduction for the novice into the methodology and applications of chlorophyll fluorescence. After a brief introduction into the theoretical background of the technique, the methodology and some of the technical pitfalls that can be encountered are explained. A selection of examples is then used to illustrate the types of information that fluorescence can provide.

BACKGROUND: CONSORT guidelines call for precise reporting of behavior change interventions: we need rigorous methods of characterizing active content of interventions with precision and specificity. OBJECTIVES: The objective of this study is to develop an extensive, consensually agreed hierarchically structured taxonomy of techniques [behavior change techniques (BCTs)] used in behavior change interventions. METHODS: In a Delphi-type exercise, 14 experts rated labels and definitions of 124 BCTs from six published classification systems. Another 18 experts grouped BCTs according to similarity of active ingredients in an open-sort task. Inter-rater agreement amongst six researchers coding 85 intervention descriptions by BCTs was assessed. RESULTS: This resulted in 93 BCTs clustered into 16 groups. Of the 26 BCTs occurring at least five times, 23 had adjusted kappas of 0.60 or above. CONCLUSIONS: "BCT taxonomy v1," an extensive taxonomy of 93 consensually agreed, distinct BCTs, offers a step change as a method for specifying interventions, but we anticipate further development and evaluation based on international, interdisciplinary consensus.

BACKGROUND: Decision aids are interventions that support patients by making their decisions explicit, providing information about options and associated benefits/harms, and helping clarify congruence between decisions and personal values. OBJECTIVES: To assess the effects of decision aids in people facing treatment or screening decisions. SEARCH METHODS: Updated search (2012 to April 2015) in CENTRAL; MEDLINE; Embase; PsycINFO; and grey literature; includes CINAHL to September 2008. SELECTION CRITERIA: We included published randomized controlled trials comparing decision aids to usual care and/or alternative interventions. For this update, we excluded studies comparing detailed versus simple decision aids. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened citations for inclusion, extracted data, and assessed risk of bias. Primary outcomes, based on the International Patient Decision Aid Standards (IPDAS), were attributes related to the choice made and the decision-making process.Secondary outcomes were behavioural, health, and health system effects.We pooled results using mean differences (MDs) and risk ratios (RRs), applying a random-effects model. We conducted a subgroup analysis of studies that used the patient decision aid to prepare for the consultation and of those that used it in the consultation. We used GRADE to assess the strength of the evidence. MAIN RESULTS: We included 105 studies involving 31,043 participants. This update added 18 studies and removed 28 previously included studies comparing detailed versus simple decision aids. During the 'Risk of bias' assessment, we rated two items (selective reporting and blinding of participants/personnel) as mostly unclear due to inadequate reporting. Twelve of 105 studies were at high risk of bias.With regard to the attributes of the choice made, decision aids increased participants' knowledge (MD 13.27/100; 95% confidence interval (CI) 11.32 to 15.23; 52 studies; N = 13,316; high-quality evidence), accuracy of risk perceptions (RR 2.10; 95% CI 1.66 to 2.66; 17 studies; N = 5096; moderate-quality evidence), and congruency between informed values and care choices (RR 2.06; 95% CI 1.46 to 2.91; 10 studies; N = 4626; low-quality evidence) compared to usual care.Regarding attributes related to the decision-making process and compared to usual care, decision aids decreased decisional conflict related to feeling uninformed (MD -9.28/100; 95% CI -12.20 to -6.36; 27 studies; N = 5707; high-quality evidence), indecision about personal values (MD -8.81/100; 95% CI -11.99 to -5.63; 23 studies; N = 5068; high-quality evidence), and the proportion of people who were passive in decision making (RR 0.68; 95% CI 0.55 to 0.83; 16 studies; N = 3180; moderate-quality evidence).Decision aids reduced the proportion of undecided participants and appeared to have a positive effect on patient-clinician communication. Moreover, those exposed to a decision aid were either equally or more satisfied with their decision, the decision-making process, and/or the preparation for decision making compared to usual care.Decision aids also reduced the number of people choosing major elective invasive surgery in favour of more conservative options (RR 0.86; 95% CI 0.75 to 1.00; 18 studies; N = 3844), but this reduction reached statistical significance only after removing the study on prophylactic mastectomy for breast cancer gene carriers (RR 0.84; 95% CI 0.73 to 0.97; 17 studies; N = 3108). Compared to usual care, decision aids reduced the number of people choosing prostate-specific antigen screening (RR 0.88; 95% CI 0.80 to 0.98; 10 studies; N = 3996) and increased those choosing to start new medications for diabetes (RR 1.65; 95% CI 1.06 to 2.56; 4 studies; N = 447). For other testing and screening choices, mostly there were no differences between decision aids and usual care.The median effect of decision aids on length of consultation was 2.6 minutes longer (24 versus 21; 7.5% increase). The costs of the decision aid group were lower in two studies and similar to usual care in four studies. People receiving decision aids do not appear to differ from those receiving usual care in terms of anxiety, general health outcomes, and condition-specific health outcomes. Studies did not report adverse events associated with the use of decision aids.In subgroup analysis, we compared results for decision aids used in preparation for the consultation versus during the consultation, finding similar improvements in pooled analysis for knowledge and accurate risk perception. For other outcomes, we could not conduct formal subgroup analyses because there were too few studies in each subgroup. AUTHORS' CONCLUSIONS: Compared to usual care across a wide variety of decision contexts, people exposed to decision aids feel more knowledgeable, better informed, and clearer about their values, and they probably have a more active role in decision making and more accurate risk perceptions. There is growing evidence that decision aids may improve values-congruent choices. There are no adverse effects on health outcomes or satisfaction. New for this updated is evidence indicating improved knowledge and accurate risk perceptions when decision aids are used either within or in preparation for the consultation. Further research is needed on the effects on adherence with the chosen option, cost-effectiveness, and use with lower literacy populations.

IMPORTANCE: Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning. OBJECTIVE: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015. EVIDENCE REVIEW: Cancer mortality was estimated using vital registration system data, cancer registry incidence data (transformed to mortality estimates using separately estimated mortality to incidence [MI] ratios), and verbal autopsy data. Cancer incidence was calculated by dividing mortality estimates through the modeled MI ratios. To calculate cancer prevalence, MI ratios were used to model survival. To calculate YLDs, prevalence estimates were multiplied by disability weights. The YLLs were estimated by multiplying age-specific cancer deaths by the reference life expectancy. DALYs were estimated as the sum of YLDs and YLLs. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. Countries were categorized by SDI quintiles to summarize results. FINDINGS: In 2015, there were 17.5 million cancer cases worldwide and 8.7 million deaths. Between 2005 and 2015, cancer cases increased by 33%, with population aging contributing 16%, population growth 13%, and changes in age-specific rates contributing 4%. For men, the most common cancer globally was prostate cancer (1.6 million cases). Tracheal, bronchus, and lung cancer was the leading cause of cancer deaths and DALYs in men (1.2 million deaths and 25.9 million DALYs). For women, the most common cancer was breast cancer (2.4 million cases). Breast cancer was also the leading cause of cancer deaths and DALYs for women (523 000 deaths and 15.1 million DALYs). Overall, cancer caused 208.3 million DALYs worldwide in 2015 for both sexes combined. Between 2005 and 2015, age-standardized incidence rates for all cancers combined increased in 174 of 195 countries or territories. Age-standardized death rates (ASDRs) for all cancers combined decreased within that timeframe in 140 of 195 countries or territories. Countries with an increase in the ASDR due to all cancers were largely located on the African continent. Of all cancers, deaths between 2005 and 2015 decreased significantly for Hodgkin lymphoma (-6.1% [95% uncertainty interval (UI), -10.6% to -1.3%]). The number of deaths also decreased for esophageal cancer, stomach cancer, and chronic myeloid leukemia, although these results were not statistically significant. CONCLUSION AND RELEVANCE: As part of the epidemiological transition, cancer incidence is expected to increase in the future, further straining limited health care resources. Appropriate allocation of resources for cancer prevention, early diagnosis, and curative and palliative care requires detailed knowledge of the local burden of cancer. The GBD 2015 study results demonstrate that progress is possible in the war against cancer. However, the major findings also highlight an unmet need for cancer prevention efforts, including tobacco control, vaccination, and the promotion of physical activity and a healthy diet.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

Rhinosinusitis is a significant and increasing health problem which results in a large financial burden on society. This evidence based position paper describes what is known about rhinosinusitis and nasal polyps, offers evidence based recommendations on diagnosis and treatment, and considers how we can make progress with research in this area. Rhinitis and sinusitis usually coexist and are concurrent in most individuals; thus, the correct terminology is now rhinosinusitis. Rhinosinusitis (including nasal polyps) is defined as inflammation of the nose and the paranasal sinuses characterised by two or more symptoms, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), +/- facial pain/pressure, +/- reduction or loss of smell; and either endoscopic signs of polyps and/or mucopurulent discharge primarily from middle meatus and/or; oedema/mucosal obstruction primarily in middle meatus, and/or CT changes showing mucosal changes within the ostiomeatal complex and/or sinuses. The paper gives different definitions for epidemiology, first line and second line treatment and for research. Furthermore the paper describes the anatomy and (patho)physiology, epidemiology and predisposing factors, inflammatory mechanisms, evidence based diagnosis, medical and surgical treatment in acute and chronic rhinosinusitis and nasal polyposis in adults and children. Evidence based schemes for diagnosis and treatment are given for the first and second line clinicians. Moreover attention is given to complications and socio-economic cost of chronic rhinosinusitis and nasal polyps. Last but not least the relation to the lower airways is discussed.

This paper gives the main definitions relating to dependability, a generic concept including a special case of such attributes as reliability, availability, safety, integrity, maintainability, etc. Security brings in concerns for confidentiality, in addition to availability and integrity. Basic definitions are given first. They are then commented upon, and supplemented by additional definitions, which address the threats to dependability and security (faults, errors, failures), their attributes, and the means for their achievement (fault prevention, fault tolerance, fault removal, fault forecasting). The aim is to explicate a set of general concepts, of relevance across a wide range of situations and, therefore, helping communication and cooperation among a number of scientific and technical communities, including ones that are concentrating on particular types of system, of system failures, or of causes of system failures.

The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in approximately 50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 10 10 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs 71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; p interaction =0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. Funding UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

Full list of authors: Price-Whelan, Adrian M.; Lim, Pey Lian; Earl, Nicholas; Starkman, Nathaniel; Bradley, Larry; Shupe, David L.; Patil, Aarya A.; Corrales, Lia; Brasseur, C. E.; Noethe, Maximilian; Donath, Axel; Tollerud, Erik; Morris, Brett M.; Ginsburg, Adam; Vaher, Eero; Weaver, Benjamin A.; Tocknell, James; Jamieson, William; van Kerkwijk, Marten H.; Robitaille, Thomas P.; Merry, Bruce; Bachetti, Matteo; Gunther, H. Moritz; Aldcroft, Thomas L.; Alvarado-Montes, Jaime A.; Archibald, Anne M.; Bodi, Attila; Bapat, Shreyas; Barentsen, Geert; Bazan, Juanjo; Biswas, Manish; Boquien, Mederic; Burke, D. J.; Cara, Daria; Cara, Mihai; Conroy, Kyle E.; Conseil, Simon; Craig, Matthew W.; Cross, Robert M.; Cruz, Kelle L.; D'Eugenio, Francesco; Dencheva, Nadia; Devillepoix, Hadrien A. R.; Dietrich, Jorg P.; Eigenbrot, Arthur Davis; Erben, Thomas; Ferreira, Leonardo; Foreman-Mackey, Daniel; Fox, Ryan; Freij, Nabil; Garg, Suyog; Geda, Robel; Glattly, Lauren; Gondhalekar, Yash; Gordon, Karl D.; Grant, David; Greenfield, Perry; Groener, Austen M.; Guest, Steve; Gurovich, Sebastian; Handberg, Rasmus; Hart, Akeem; Hatfield-Dodds, Zac; Homeier, Derek; Hosseinzadeh, Griffin; Jenness, Tim; Jones, Craig K.; Joseph, Prajwel; Kalmbach, J. Bryce; Karamehmetoglu, Emir; Kaluszynski, Mikolaj; Kelley, Michael S. P.; Kern, Nicholas; Kerzendorf, Wolfgang E.; Koch, Eric W.; Kulumani, Shankar; Lee, Antony; Ly, Chun; Ma, Zhiyuan; MacBride, Conor; Maljaars, Jakob M.; Muna, Demitri; Murphy, N. A.; Norman, Henrik; O'Steen, Richard; Oman, Kyle A.; Pacifici, Camilla; Pascual, Sergio; Pascual-Granado, J.; Patil, Rohit R.; Perren, Gabriel, I; Pickering, Timothy E.; Rastogi, Tanuj; Roulston, Benjamin R.; Ryan, Daniel F.; Rykoff, Eli S.; Sabater, Jose; Sakurikar, Parikshit; Salgado, Jesus; Sanghi, Aniket; Saunders, Nicholas; Savchenko, Volodymyr; Schwardt, Ludwig; Seifert-Eckert, Michael; Shih, Albert Y.; Jain, Anany Shrey; Shukla, Gyanendra; Sick, Jonathan; Simpson, Chris; Singanamalla, Sudheesh; Singer, Leo P.; Singhal, Jaladh; Sinha, Manodeep; Sipocz, Brigitta M.; Spitler, Lee R.; Stansby, David; Streicher, Ole; Sumak, Jani; Swinbank, John D.; Taranu, Dan S.; Tewary, Nikita; Tremblay, Grant R.; De Val-Borro, Miguel; Vasovic, Zlatan; Van Kooten, Samuel J.; Verma, Shresth; Cardoso, Jose Vinicius de Miranda; Williams, Peter K. G.; Wilson, Tom J.; Winkel, Benjamin; Wood-Vasey, W. M.; Xue, Rui; Yoachim, Peter; Zhang, Chen; Zonca, Andrea; Astropy Project Contributors; TARDIS Collaboration; Astropy Coordination Comm.--This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

OBJECTIVES: It has become increasingly common for preference-based measures of health-related quality of life to be used in the evaluation of different health-care interventions. For one such measure, The EuroQol, designed to be used for these purposes, it was necessary to derive a single index value for each of the 243 health states it generates. The problem was that it was virtually impossible to generate direct valuations for all of these states, and thus it was necessary to find a procedure that allows the valuations of all EuroQol states to be interpolated from direct valuations on a subset of these. METHODS: In a recent study, direct valuations were elicited for 42 EuroQol health states (using the time trade-off method) from a representative sample of the UK population. This article reports on the methodology that was adopted to build up a "tariff" of EuroQol values from this data. RESULTS: A parsimonious model that fits the data well was defined as one in which valuations were explained in terms of the level of severity associated with each dimension, an intercept associated with any move away from full health, and a term that picked up whether any dimension in the state was at its most severe level. CONCLUSIONS: The model presented in this article appears to predict the values of the states for which there are direct observations and, thus, can be used to interpolate values for the states for which no direct observations exist.

Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetes-susceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI). An additive association of the variant with BMI was replicated in 13 cohorts with 38,759 participants. The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass.

The principles of shared decision making are well documented but there is a lack of guidance about how to accomplish the approach in routine clinical practice. Our aim here is to translate existing conceptual descriptions into a three-step model that is practical, easy to remember, and can act as a guide to skill development. Achieving shared decision making depends on building a good relationship in the clinical encounter so that information is shared and patients are supported to deliberate and express their preferences and views during the decision making process. To accomplish these tasks, we propose a model of how to do shared decision making that is based on choice, option and decision talk. The model has three steps: a) introducing choice, b) describing options, often by integrating the use of patient decision support, and c) helping patients explore preferences and make decisions. This model rests on supporting a process of deliberation, and on understanding that decisions should be influenced by exploring and respecting "what matters most" to patients as individuals, and that this exploration in turn depends on them developing informed preferences.

The term ‘governance’ is popular but imprecise. It has at least six uses, referring to: the minimal state; corporate governance: the new public management; ‘good governance’; socio-cybernetic systems: and self-organizing networks. I stipulate that governance refers to ‘self-organizing, interorganizational networks' and argue these networks complement markets and hierarchies as governing structures for authoritatively allocating resources and exercising control and co-ordination. I defend this definition, arguing that it throws new light on recent changes in British government, most notably: hollowing out the state, the new public management, and intergovernmental management. 1 conclude that networks are now a pervasive feature of service delivery in Britain; that such networks are characterized by trust and mutual adjustment and undermine management reforms rooted in competition; and that they are a challenge to governability because they become autonomous and resist central guidance.

Carbon capture and storage (CCS) is vital to climate change mitigation, and has application across the economy, in addition to facilitating atmospheric carbon dioxide removal resulting in emissions offsets and net negative emissions. This contribution reviews the state-of-the-art and identifies key challenges which must be overcome in order to pave the way for its large-scale deployment.

The ageing of many populations in recent years has directed increasing attention to the social, medical and biological problems of senescence. The psychological changes associated with ageing occupy a central position in inquiries in this field. The expectation of mental disorder shows a steep increase with advancing chronological age, and beyond 75 years a large part of this increase is accounted for by disorders associated with degenerative changes in the central nervous system for which we lack remedies at the present time. Larsson et al . (1963) have estimated that the aggregate morbidity risk for these disorders up to the age of 70 is 0·4 per cent., up to age 75, 1·2 per cent. and up to age 80, 5 per cent. For higher ages estimates were probably less reliable, but the calculated risk up to the age of 90 was 5·2 per cent. In a survey of a random sample of elderly people aged 65 and over in the general population, Kay et al . (1964), found a total of 4·2 per cent. of elderly subjects to be suffering from senile dementia, 2·9 per cent. being mild cases. The condition is generally recognized as being a major cause of serious infirmity among the elderly in psychiatric, geriatric, general medical and community practice alike.

The term "tipping point" commonly refers to a critical threshold at which a tiny perturbation can qualitatively alter the state or development of a system. Here we introduce the term "tipping element" to describe large-scale components of the Earth system that may pass a tipping point. We critically evaluate potential policy-relevant tipping elements in the climate system under anthropogenic forcing, drawing on the pertinent literature and a recent international workshop to compile a short list, and we assess where their tipping points lie. An expert elicitation is used to help rank their sensitivity to global warming and the uncertainty about the underlying physical mechanisms. Then we explain how, in principle, early warning systems could be established to detect the proximity of some tipping points.