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Showing papers by "Dalhousie University published in 2013"


Journal ArticleDOI
TL;DR: The results demonstrate that phylogeny and function are sufficiently linked that this 'predictive metagenomic' approach should provide useful insights into the thousands of uncultivated microbial communities for which only marker gene surveys are currently available.
Abstract: Profiling phylogenetic marker genes, such as the 16S rRNA gene, is a key tool for studies of microbial communities but does not provide direct evidence of a community's functional capabilities. Here we describe PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states), a computational approach to predict the functional composition of a metagenome using marker gene data and a database of reference genomes. PICRUSt uses an extended ancestral-state reconstruction algorithm to predict which gene families are present and then combines gene families to estimate the composite metagenome. Using 16S information, PICRUSt recaptures key findings from the Human Microbiome Project and accurately predicts the abundance of gene families in host-associated and environmental communities, with quantifiable uncertainty. Our results demonstrate that phylogeny and function are sufficiently linked that this 'predictive metagenomic' approach should provide useful insights into the thousands of uncultivated microbial communities for which only marker gene surveys are currently available.

6,860 citations


Journal ArticleDOI
TL;DR: Developing more efficient methods to detect frailty and measure its severity in routine clinical practice would greatly inform the appropriate selection of elderly people for invasive procedures or drug treatments and would be the basis for a shift in the care of frail elderly people towards more appropriate goal-directed care.

5,456 citations



Journal ArticleDOI
TL;DR: The refined Quality In Prognosis Studies tool is described, which includes questions related to these areas that can inform judgments of risk of bias in prognostic research.
Abstract: Previous work has identified 6 important areas to consider when evaluating validity and bias in studies of prognostic factors: participation, attrition, prognostic factor measurement, confounding measurement and account, outcome measurement, and analysis and reporting. This article describes the Quality In Prognosis Studies tool, which includes questions related to these areas that can inform judgments of risk of bias in prognostic research.A working group comprising epidemiologists, statisticians, and clinicians developed the tool as they considered prognosis studies of low back pain. Forty-three groups reviewing studies addressing prognosis in other topic areas used the tool and provided feedback. Most reviewers (74%) reported that reaching consensus on judgments was easy. Median completion time per study was 20 minutes; interrater agreement (κ statistic) reported by 9 review teams varied from 0.56 to 0.82 (median, 0.75). Some reviewers reported challenges making judgments across prompting items, which were addressed by providing comprehensive guidance and examples. The refined Quality In Prognosis Studies tool may be useful to assess the risk of bias in studies of prognostic factors.

1,997 citations


Journal ArticleDOI
TL;DR: The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009, and this third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunctionWith the previous publications.
Abstract: The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009. This third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunction with the previous publications.The recommendations for the management of acute mania remain largely unchanged. Lithium, valproate, and several atypical antipsychotic agents continue to be first-line treatments for acute mania. Monotherapy with asenapine, paliperidone extended release (ER), and divalproex ER, as well as adjunctive asenapine, have been added as first-line options.For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, as well as olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. Lurasidone monotherapy and the combination of lurasidone or lamotrigine plus lithium or divalproex have been added as a second-line options. Ziprasidone alone or as adjunctive therapy, and adjunctive levetiracetam have been added as not-recommended options for the treatment of bipolar depression. Lithium, lamotrigine, valproate, olanzapine, quetiapine, aripiprazole, risperidone long-acting injection, and adjunctive ziprasidone continue to be first-line options for maintenance treatment of bipolar disorder. Asenapine alone or as adjunctive therapy have been added as third-line options.

1,369 citations


Journal ArticleDOI
TL;DR: How prognostic models are developed and validated are reviewed and assessed for their impact on practice and patient outcomes are addressed, illustrating these ideas with examples.
Abstract: Prognostic models are abundant in the medical literature yet their use in practice seems limited In this article, the third in the PROGRESS series, the authors review how such models are developed and validated, and then address how prognostic models are assessed for their impact on practice and patient outcomes, illustrating these ideas with examples

1,016 citations


Journal ArticleDOI
13 Sep 2013-Science
TL;DR: Using nearly 50 years of coastal survey data on >350 marine taxa, Pinsky et al. found that climate velocity was a much better predictor of patterns of change than individual species' characteristics or life histories.
Abstract: Organisms are expected to adapt or move in response to climate change, but observed distribution shifts span a wide range of directions and rates. Explanations often emphasize biological distinctions among species, but general mechanisms have been elusive. We tested an alternative hypothesis: that differences in climate velocity—the rate and direction that climate shifts across the landscape—can explain observed species shifts. We compiled a database of coastal surveys around North America from 1968 to 2011, sampling 128 million individuals across 360 marine taxa. Climate velocity explained the magnitude and direction of shifts in latitude and depth much more effectively than did species characteristics. Our results demonstrate that marine species shift at different rates and directions because they closely track the complex mosaic of local climate velocities.

964 citations


Journal ArticleDOI
TL;DR: There is agreement on the usefulness of defining frailty in clinical settings as well as on its main dimensions, however, additional research is needed before an operative definition of frailty can be established.
Abstract: BACKGROUND: There is no consensus regarding the definition of frailty for clinical uses. METHODS: A modified Delphi process was used to attempt to achieve consensus definition. Experts were selected from different fields and organized into five Focus Groups. A questionnaire was developed and sent to experts in the area of frailty. Responses and comments were analyzed using a pre-established strategy. Statements with an agreement more than or equal to 80% were accepted. RESULTS: Overall, 44% of the statements regarding the concept of frailty and 18% of the statements regarding diagnostic criteria were accepted. There was consensus on the value of screening for frailty and about the identification of six domains of frailty for inclusion in a clinical definition, but no agreement was reached concerning a specific set of clinical/laboratory biomarkers useful for diagnosis. CONCLUSIONS: There is agreement on the usefulness of defining frailty in clinical settings as well as on its main dimensions. However, additional research is needed before an operative definition of frailty can be established.

929 citations


Journal ArticleDOI
TL;DR: Key changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants.
Abstract: Introduction: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved. Methods: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. Results: Key changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. Conclusions: A comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.

800 citations


Journal ArticleDOI
08 Aug 2013-Nature
TL;DR: A semi-automated pipeline using electron microscopy is developed to reconstruct a connectome, containing 379 neurons and 8,637 chemical synaptic contacts, within the Drosophila optic medulla, and it is demonstrated that connectomes can provide key insights into neuronal computations.
Abstract: Animal behaviour arises from computations in neuronal circuits, but our understanding of these computations has been frustrated by the lack of detailed synaptic connection maps, or connectomes. For example, despite intensive investigations over half a century, the neuronal implementation of local motion detection in the insect visual system remains elusive. Here we develop a semi-automated pipeline using electron microscopy to reconstruct a connectome, containing 379 neurons and 8,637 chemical synaptic contacts, within the Drosophila optic medulla. By matching reconstructed neurons to examples from light microscopy, we assigned neurons to cell types and assembled a connectome of the repeating module of the medulla. Within this module, we identified cell types constituting a motion detection circuit, and showed that the connections onto individual motion-sensitive neurons in this circuit were consistent with their direction selectivity. Our results identify cellular targets for future functional investigations, and demonstrate that connectomes can provide key insights into neuronal computations. Reconstruction of a connectome within the fruitfly visual medulla, containing more than 300 neurons and over 8,000 chemical synapses, reveals a candidate motion detection circuit; such a circuit operates by combining displaced visual inputs, an operation consistent with correlation based motion detection. Three papers in this issue of Nature use the retina as a model for mapping neuronal circuits from the level of individual synaptic contacts to the long-range scale of dendritic interactions. Helmstaedter et al. used electron microscopy to map a mammalian retinal circuit of close to a thousand neurons. The work reveals a new type of retinal bipolar neuron and suggests functional mechanisms for known visual computations. The other two groups study the detection of visual motion in the Drosophila visual system — a classic neural computation model. Takemura et al. used semi-automated electron microscopy to reconstruct the basic connectome (8,637 chemical synapses among 379 neurons) of Drosophila's optic medulla. Their results reveal a candidate motion detection circuit with a wiring plan consistent with direction selectivity. Maisak et al. used calcium imaging to show that T4 and T5 neurons are divided into specific subpopulations responding to motion in four cardinal directions, and are specific to 'ON' versus 'OFF' edges, respectively.

687 citations


Journal ArticleDOI
TL;DR: The Canadian Hypertension Education Program reviews the hypertension literature annually and provides detailed recommendations regarding hypertension diagnosis, assessment, prevention, and treatment, and 4 new recommendations were added and 2 existing recommendations were modified this year.

Journal ArticleDOI
TL;DR: The overall evidence warrants moderate confidence in this large relative risk reduction of C. difficile infection in adults and children, and the overall quality of evidence for CDAD is downgraded to 'moderate' due to imprecision.
Abstract: Background Antibiotics are widely prescribed; however they can cause disturbances in gastrointestinal flora which may lead to reduced resistance to pathogens such as Clostridium difficile (C. difficile). Probiotics are live organisms thought to balance the gastrointestinal flora. Objectives The primary objectives were to assess the efficacy and safety of probiotics for preventing Clostridium difficile-associated diarrhea (CDAD) or C. difficile infection in adults and children. Search methods On February 21, 2013 we searched PubMed (1966-2013), EMBASE (1966-2013), Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 1), CINAHL (1982-2013), AMED (1985-2013), and ISI Web of Science. Additionally, we conducted an extensive grey literature search including contact with industry representatives. Selection criteria Randomized controlled (placebo, alternative prophylaxis, or no treatment control) trials investigating probiotics (any strain, any dose) for prevention of CDAD, or C. difficile infection were considered for inclusion. Data collection and analysis Two authors independently and in duplicate extracted data and assessed risk of bias using pre-constructed, and piloted, data extraction forms. Any disagreements were resolved by a third adjudicator. For articles published in abstract form only, further information was sought by contacting principal authors. The primary outcome was the incidence of CDAD. Secondary outcomes included the incidence of C. difficile infection, adverse events, antibiotic-associated diarrhea (AAD) and length of hospital stay. Dichotomous outcomes (e.g. incidence of CDAD) were pooled using a random-effects model to calculate the relative risk and corresponding 95% confidence interval (95% CI). Continuous outcomes (e.g. length of hospital) were pooled using a random-effects model to calculate the mean difference and corresponding 95% CI. Sensitivity analyses were conducted to explore the impact of missing data on efficacy and safety outcomes. For the sensitivity analyses, we assumed that the event rate for those participants in the control group who had missing data was the same as the event rate for those participants in the control group who were successfully followed. For the probiotic group we calculated effects using the following assumed ratios of event rates in those with missing data in comparison to those successfully followed: 1.5:1, 2:1, 3:1, and 5:1. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic species, dose, adult versus pediatric population, and risk of bias.The overall quality of the evidence supporting each outcome was assessed using the GRADE criteria. Main results A total of 1871 studies were identified with 31 (4492 participants) meeting eligibility requirements for our review. Overall 11 studies were rated as a high risk of bias due mostly to missing outcome data. A complete case analysis (i.e. participants who completed the study) of those trials investigating CDAD (23 trials, 4213 participants) suggests that probiotics significantly reduce this risk by 64%. The incidence of CDAD was 2.0% in the probiotic group compared to 5.5% in the placebo or no treatment control group (RR 0.36; 95% CI 0.26 to 0.51). Sixteen of 23 trials had missing CDAD data ranging from 5% to 45%. These results proved robust to sensitivity analyses of plausible and worst-plausible assumptions regarding missing outcome data and were similar whether considering trials in adults versus children, lower versus higher doses, different probiotic species, or higher versus lower risk of bias. Our judgment is that the overall evidence warrants moderate confidence in this large relative risk reduction. We downgraded the overall quality of evidence for CDAD to ‘moderate’ due to imprecision. There were few events (154) and the calculated optimal information size (n = 8218) was more than the total sample size. With respect to the incidence of C. difficile infection, a secondary outcome, pooled complete case results from 13 trials (961 participants) did not show a statistically significant reduction. The incidence of C. difficile infection was 12.6% in the probiotics group compared to 12.7% in the placebo or no treatment control group (RR 0.89; 95% CI 0.64 to 1.24). Adverse events were assessed in 26 studies (3964 participants) and our pooled complete case analysis indicates probiotics reduce the risk of adverse events by 20% (RR 0.80; 95% CI 0.68 to 0.95). In both treatment and control groups the most common adverse events included abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance. For the short-term use of probiotics in patients that are not immunocompromised or severely debilitated, we consider the strength of this evidence to be moderate. Authors' conclusions Based on this systematic review and meta-analysis of 23 randomized controlled trials including 4213 patients, moderate quality evidence suggests that probiotics are both safe and effective for preventing Clostridium difficile-associated diarrhea.

Journal ArticleDOI
TL;DR: The role of prognostic factors in current clinical practice, randomised trials, and developing new interventions are discussed, and why and how prognostic factor research should be improved are explained.
Abstract: Prognostic factor research aims to identify factors associated with subsequent clinical outcome in people with a particular disease or health condition. In this article, the second in the PROGRESS series, the authors discuss the role of prognostic factors in current clinical practice, randomised trials, and developing new interventions, and explain why and how prognostic factor research should be improved.

Journal ArticleDOI
TL;DR: Using this multisystemic social-ecological theory of resilience can inform a deeper understanding of the processes that contribute to positive development under stress and offer practitioners and policy makers a broader perspective on principles for the design and implementation of effective interventions.
Abstract: Background: The development of Bronfenbrenner’s bio-social-ecological systems model of human development parallels advances made to the theory of resilience that progressively moved from a more in ...

Journal ArticleDOI
TL;DR: The second Diabetes Attitudes, Wishes and Needs (DAWN2) study aimed to assess psychosocial outcomes in people with diabetes across countries for benchmarking.
Abstract: Aims The second Diabetes Attitudes, Wishes and Needs (DAWN2) study aimed to assess psychosocial outcomes in people with diabetes across countries for benchmarking. Methods Surveys included new and adapted questions from validated questionnaires that assess health-related quality of life, self-management, attitudes/beliefs, social support and priorities for improving diabetes care. Questionnaires were conducted online, by telephone or in person. Results Participants were 8596 adults with diabetes across 17 countries. There were significant between-country differences for all benchmarking indicators; no one country's outcomes were consistently better or worse than others. The proportion with likely depression [WHO-5 Well-Being Index (WHO-5) score ≤ 28] was 13.8% (country range 6.5–24.1%). Diabetes-related distress [Problem Areas in Diabetes Scale 5 (PAID-5) score ≥ 40] was reported by 44.6% of participants (17.2–67.6%). Overall quality of life was rated ‘poor’ or ‘very poor’ by 12.2% of participants (7.6–26.1%). Diabetes had a negative impact on all aspects investigated, ranging from 20.5% on relationship with family/friends to 62.2% on physical health. Approximately 40% of participants (18.6–64.9%) reported that their medication interfered with their ability to live a normal life. The availability of person-centred chronic illness care and support for active involvement was rated as low. Following self-care advice for medication and diet was most common, and least common for glucose monitoring and foot examination, with marked country variation. Only 48.8% of respondents had participated in diabetes educational programmes/activities to help manage their diabetes. Conclusions Cross-national benchmarking using psychometrically validated indicators can help identify areas for improvement and best practices to drive changes that improve outcomes for people with diabetes.

Journal ArticleDOI
03 Jan 2013-Nature
TL;DR: Radial velocity measurements reveal that the satellites in this structure have the same sense of rotation about their host, and shows conclusively that substantial numbers of dwarf satellite galaxies share the same dynamical orbital properties and direction of angular momentum.
Abstract: Dwarf satellite galaxies are thought to be the remnants of the population of primordial structures that coalesced to form giant galaxies like the Milky Way. It has previously been suspected that dwarf galaxies may not be isotropically distributed around our Galaxy, because several are correlated with streams of H I emission, and may form coplanar groups. These suspicions are supported by recent analyses. It has been claimed that the apparently planar distribution of satellites is not predicted within standard cosmology, and cannot simply represent a memory of past coherent accretion. However, other studies dispute this conclusion. Here we report the existence of a planar subgroup of satellites in the Andromeda galaxy (M 31), comprising about half of the population. The structure is at least 400 kiloparsecs in diameter, but also extremely thin, with a perpendicular scatter of less than 14.1 kiloparsecs. Radial velocity measurements reveal that the satellites in this structure have the same sense of rotation about their host. This shows conclusively that substantial numbers of dwarf satellite galaxies share the same dynamical orbital properties and direction of angular momentum. Intriguingly, the plane we identify is approximately aligned with the pole of the Milky Way's disk and with the vector between the Milky Way and Andromeda.

Journal ArticleDOI
TL;DR: High coverage of essential interventions did not imply reduced maternal mortality in the health-care facilities the authors studied, and the maternal severity index (MSI) had good accuracy for maternal death prediction in women with markers of organ dysfunction.

Journal ArticleDOI
TL;DR: T attempts to improve their bioavailability in order to improve the efficacy of flavonoids are being studied as it is a determining factor for flavonoid biological activity.
Abstract: Flavonoids are a group of phytochemicals that have shown numerous health effects and have therefore been studied extensively. Of the six common food flavonoid classes, flavonols are distributed ubiquitously among different plant foods whereas appreciable amounts of isoflavones are found in leguminous plant-based foods. Flavonoids have shown promising health promoting effects in human cell culture, experimental animal and human clinical studies. They have shown antioxidant, hypocholesterolemic, anti-inflammatory effects as well as ability to modulate cell signaling and gene expression related disease development. Low bioavailability of flavonoids has been a concern as it can limit or even hinder their health effects. Therefore, attempts to improve their bioavailability in order to improve the efficacy of flavonoids are being studied. Further investigations on bioavailability are warranted as it is a determining factor for flavonoid biological activity.

Journal ArticleDOI
TL;DR: This article reviews the relationship between factors associated with resilience, and aspects of the individual’s social ecology (environment) that promote and protect against the negative impact of exposure to traumatic events.
Abstract: This article reviews the relationship between factors associated with resilience, and aspects of the individual's social ecology (environment) that promote and protect against the negative impact of exposure to traumatic events. It is shown that the Environment × Individual interactions related to resilience can be understood using three principles: (1) Resilience is not as much an individual construct as it is a quality of the environment and its capacity to facilitate growth (nurture trumps nature); (2) resilience looks both the same and different within and between populations, with the mechanisms that predict positive growth sensitive to individual, contextual, and cultural variation (differential impact); and (3) the impact that any single factor has on resilience differs by the amount of risk exposure, with the mechanisms that protect against the impact of trauma showing contextual and cultural specificity for particular individuals (cultural variation). A definition of resilience is provided that highlights the need for environments to facilitate the navigations and negotiations of individuals for the resources they need to cope with adversity. The relative nature of resilience is discussed, emphasizing that resilience can manifest as either prosocial behaviors or pathological adaptation depending on the quality of the environment.

Journal ArticleDOI
TL;DR: There is strong evidence supporting the efficacy of distraction and hypnosis for needle-related pain and distress in children and adolescents, with no evidence currently available for preparation and information or both, combined CBT, parent coaching plus distraction, suggestion, or virtual reality.
Abstract: Background This review is an updated version of the original Cochrane review published in Issue 4, 2006. Needle-related procedures are a common source of pain and distress for children. Our previous review on this topic indicated that a number of psychological interventions were efficacious in managing pediatric needle pain, including distraction, hypnosis, and combined cognitive behavioural interventions. Considerable additional research in the area has been published since that time. Objectives To provide an update to our 2006 review assessing the efficacy of psychological interventions for needle-related procedural pain and distress in children and adolescents. Search methods Searches of the following databases were conducted for relevant randomized controlled trials (RCTs): Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; PsycINFO; the Cumulative Index to Nursing and Allied Health Literature (CINAHL); and Web of Science. Requests for relevant studies were also posted on various electronic list servers. We ran an updated search in March 2012, and again in March 2013. Selection criteria Participants included children and adolescents aged two to 19 years undergoing needle-related procedures. Only RCTs with at least five participants in each study arm comparing a psychological intervention group with a control or comparison group were eligible for inclusion. Data collection and analysis Two review authors extracted data and assessed trial quality and a third author helped with data extraction and coding for one non-English study. Included studies were coded for quality using the Cochrane Risk of bias tool. Standardized mean differences with 95% confidence intervals were computed for all analyses using Review Manager 5.2 software. Main results Thirty-nine trials with 3394 participants were included. The most commonly studied needle procedures were venipuncture, intravenous (IV) line insertion, and immunization. Studies included children aged two to 19 years, with the most evidence available for children under 12 years of age. Consistent with the original review, the most commonly studied psychological interventions for needle procedures were distraction, hypnosis, and cognitive behavioural therapy (CBT). The majority of included studies (19 of 39) examined distraction only. The additional studies from this review update continued to provide strong evidence for the efficacy of distraction and hypnosis. No evidence was available to support the efficacy of preparation and information, combined CBT (at least two or more cognitive or behavioural strategies combined), parent coaching plus distraction, suggestion, or virtual reality for reducing children's pain and distress. No conclusions could be drawn about interventions of memory alteration, parent positioning plus distraction, blowing out air, or distraction plus suggestion, as evidence was available from single studies only. In addition, the Risk of bias scores indicated several domains with high or unclear bias scores (for example, selection, detection, and performance bias) suggesting that the methodological rigour and reporting of RCTs of psychological interventions continue to have considerable room for improvement. Authors' conclusions Overall, there is strong evidence supporting the efficacy of distraction and hypnosis for needle-related pain and distress in children and adolescents, with no evidence currently available for preparation and information or both, combined CBT, parent coaching plus distraction, suggestion, or virtual reality. Additional research is needed to further assess interventions that have only been investigated in one RCT to date (that is, memory alteration, parent positioning plus distraction, blowing out air, and distraction plus suggestion). There are continuing issues with the quality of trials examining psychological interventions for needle-related pain and distress.

Journal ArticleDOI
TL;DR: Global total shark mortality needs to be reduced drastically in order to rebuild depleted populations and restore marine ecosystems with functional top predators.

Journal ArticleDOI
TL;DR: To operationalize frailty using eight scales and to compare their content validity, feasibility, prevalence estimates of frailty, and ability to predict all‐cause mortality, it is shown that the former are more reliable than the latter.
Abstract: Objectives: To operationalize frailty using eight scales and to compare their content validity, feasibility, prevalence estimates of frailty, and ability to predict all-cause mortality. Design: Secondary analysis of the Survey of Health, Ageing and Retirement in Europe (SHARE). Setting: Eleven European countries. Participants: Individuals aged 50 to 104 (mean age 65.3 ± 10.5, 54.8% female, N = 27,527). Measurements: Frailty was operationalized using SHARE data based on the Groningen Frailty Indicator, the Tilburg Frailty Indicator, a 70-item Frailty Index (FI), a 44-item FI based on a Comprehensive Geriatric Assessment (FI-CGA), the Clinical Frailty Scale, frailty phenotype (weighted and unweighted versions), the Edmonton Frail Scale, and the FRAIL scale. Results: All scales had fewer than 6% of cases with at least one missing item, except the SHARE-frailty phenotype (11.1%) and the SHARE-Tilburg (12.2%). In the SHARE-Groningen, SHARE-Tilburg, SHARE-frailty phenotype, and SHARE-FRAIL scales, death rates were 3 to 5 times as high in excluded cases as in included ones. Frailty prevalence estimates ranged from 6% (SHARE-FRAIL) to 44% (SHARE-Groningen). All scales categorized 2.4% of participants as frail. Of unweighted scales, the SHARE-FI and SHARE-Edmonton scales most accurately predicted mortality at 2 (SHARE-FI area under the receiver operating characteristic curve (AUC) = 0.77, 95% confidence interval (CI) = 0.75�0.79); SHARE-Edmonton AUC = 0.76, 95% CI = 0.74�0.79) and 5 (both AUC = 0.75, 95% CI = 0.74�0.77) years. The continuous score of the weighted SHARE-frailty phenotype (AUC = 0.77, 95% CI = 0.75�0.78) predicted 5-year mortality better than the unweighted SHARE-frailty phenotype (AUC = 0.70, 95% CI = 0.68�0.71), but the categorical score of the weighted SHARE-frailty phenotype did not (AUC = 0.70, 95% CI = 0.68�0.72). Conclusion: Substantive differences exist between scales in their content validity, feasibility, and ability to predict all-cause mortality. These frailty scales capture related but distinct groups. Weighting items in frailty scales can improve their predictive ability, but the trade-off between specificity, predictive power, and generalizability requires additional evaluation.

Journal ArticleDOI
TL;DR: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity, which emphasizes the importance of real-time radiation quality assurance for IMRT trials.
Abstract: Purpose A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. Methods and Materials T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy ≤3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator's ability to perform DP-IMRT. Results Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P =.032), grade 3+ gastrointestinal, 21% (9811 36%, P =.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P Conclusions Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials.

Journal ArticleDOI
05 Feb 2013-BMJ
TL;DR: A framework of four interrelated themes in prognosis research is introduced, describing the importance of the first of these themes (understanding future outcomes in relation to current diagnostic and treatment practices), and recommendations for the field of prognosisResearch are introduced.
Abstract: Understanding and improving the prognosis of a disease or health condition is a priority in clinical research and practice. In this article, the authors introduce a framework of four interrelated themes in prognosis research, describe the importance of the first of these themes (understanding future outcomes in relation to current diagnostic and treatment practices), and introduce recommendations for the field of prognosis research

Journal ArticleDOI
03 Jul 2013-Nature
TL;DR: Humanity depends on fewer than a dozen of the approximately 300,000 species of flowering plants for 80% of its caloric intake and capitalize on only a fraction of the genetic diversity that resides within each of these species.
Abstract: Humanity depends on fewer than a dozen of the approximately 300,000 species of flowering plants for 80% of its caloric intake. And we capitalize on only a fraction of the genetic diversity that resides within each of these species. This is not enough to support our food system in the future. Food availability must double in the next 25 years to keep pace with population and income growth around the world. Already, food-production systems are precarious in the face of intensifying demand, climate change, soil degradation and water and land shortages. Farmers have saved the seeds of hundreds of crop species and hundreds of thousands of ‘primitive’ varieties (local domesticates called landraces), as well as the wild relatives of crop species and modern varieties no longer in use. These are stored in more than 1,700 gene banks worldwide. Maintaining the 11 international gene-bank collections alone costs about US$18 million a year.

Journal ArticleDOI
TL;DR: In this article, the extent of land-cover change caused by people is analyzed. But the authors focus on the terrestrial water cycle and do not consider the effects of human impacts on it.
Abstract: Human impacts on the terrestrial water cycle have the potential to influence hazards such as flooding and drought, so understanding the extent of our influence is an important research goal. A study utilizing estimates of evapotranspiration for different types of land cover and a database of changes in use now shows that the extent of land-cover change caused by people is already an important factor affecting the terrestrial water cycle.

Journal ArticleDOI
TL;DR: This paper introduces the application of probability adapting in dynamic safety analysis rather than probability updating, and illustrates how Bayesian network (BN) helps to overcome limitations in BT.

Journal ArticleDOI
TL;DR: Despite the breadth of the literature on the epidemiology of MS in Europe, inter-study comparisons are hampered by the lack of standardization and further research should focus on regions not yet studied and the evaluation of ethnic differences in MS prevalence and incidence.
Abstract: Multiple sclerosis (MS) is the most common cause of neurological disability in young adults worldwide and approximately half of those affected are in Europe. The assessment of differential incidence and prevalence across populations can reveal spatial, temporal and demographic patterns which are important for identifying genetic and environmental factors contributing to MS. However, study methodologies vary and the quality of the methods can influence the estimates. This study aimed to systematically review European studies of incidence and prevalence of MS and to provide a quantitative assessment of their methodological quality. A comprehensive literature search was performed to obtain all original population-based studies of MS incidence and prevalence in European populations conducted and published between January 1985 and January 2011. Only peer-reviewed full-text articles published in English or French were included. All abstracts were screened for eligibility and two trained reviewers abstracted the data and graded the quality of each study using a tool specifically designed for this study. There were 123 studies that met the inclusion criteria. The study estimates were highly heterogeneous, even within regions or countries. Quality was generally higher in the more recent studies, which also tended to use current diagnostic criteria. Prevalence and incidence estimates tended to be higher in the more recent studies and were higher in the Nordic countries and in northern regions of the British Isles. With rare exceptions, prevalence and incidence estimates were higher in women with ratios as high as 3:1. Few studies examined ethnicity. Epidemiological data at the national level was uncommon and there were marked geographical disparities in available data, with large areas of Europe unrepresented and other regions well-represented in the literature. Only 37% of the studies provided standardized estimates. Despite the breadth of the literature on the epidemiology of MS in Europe, inter-study comparisons are hampered by the lack of standardization. Further research should focus on regions not yet studied and the evaluation of ethnic differences in MS prevalence and incidence. National-level studies using current diagnostic criteria, validated case definitions and similar age- and sex-standardization would allow better geographical comparisons.

Journal ArticleDOI
Betsy A. Read1, Jessica Kegel2, Mary J. Klute3, Alan Kuo4, Stephane C. Lefebvre5, Florian Maumus6, Christoph Mayer7, John P. Miller8, Adam Monier9, Asaf Salamov4, Jeremy R. Young10, María Aguilar3, Jean-Michel Claverie11, Stephan Frickenhaus2, Karina Gonzalez12, Emily K. Herman3, Yao-Cheng Lin13, Johnathan A. Napier14, Hiroyuki Ogata11, Analissa F. Sarno1, Jeremy Shmutz4, Declan C. Schroeder, Colomban de Vargas15, Frédéric Verret16, Peter von Dassow17, Klaus Valentin2, Yves Van de Peer13, Glen L. Wheeler18, Joel B. Dacks3, Charles F. Delwiche8, Sonya T. Dyhrman2, Sonya T. Dyhrman19, Sonya T. Dyhrman20, Gernot Glöckner21, Uwe John2, Thomas A. Richards22, Alexandra Z. Worden9, Xiaoyu Zhang1, Igor V. Grigoriev23, Andrew E. Allen24, Kay D. Bidle11, Kay D. Bidle25, Mark Borodovsky11, Chris Bowler15, Colin Brownlee1, Colin Brownlee26, J. Mark Cock12, Marek Eliáš27, Vadim N. Gladyshev28, Marco Groth1, Chittibabu Guda, Ahmad R. Hadaegh29, M. D. Iglesias-Rodriguez30, Jerry Jenkins16, Bethan M. Jones31, Tracy Lawson32, Florian Leese33, Erika Lindquist34, Alexei Lobanov27, Alexandre Lomsadze25, Shehre-Banoo Malik35, Mary E. Marsh36, Luke C. M. Mackinder15, Thomas Mock11, Bernd Mueller-Roeber37, António Pagarete38, Micaela S. Parker39, Ian Probert11, Hadi Quesneville15, Christine A. Raines31, Stefan A. Rensing15, Stefan A. Rensing2, Diego Mauricio Riaño-Pachón40, Sophie Richier41, Sophie Richier40, Sebastian D. Rokitta42, Yoshihiro Shiraiwa43, Darren M. Soanes42, Mark van der Giezen39, Thomas M. Wahlund41, Bryony A. P. Williams44, Willie Wilson43, Gordon Wolfe41, Louie L. Wurch42, Louie L. Wurch40 
11 Jul 2013-Nature
TL;DR: Comparisons across strains demonstrate that E. huxleyi, which has long been considered a single species, harbours extensive genome variability reflected in different metabolic repertoires, and reveals a pan genome (core genes plus genes distributed variably between strains) probably supported by an atypical complement of repetitive sequence in the genome.
Abstract: Coccolithophores have influenced the global climate for over 200 million years(1). These marine phytoplankton can account for 20 per cent of total carbon fixation in some systems(2). They form blooms that can occupy hundreds of thousands of square kilometres and are distinguished by their elegantly sculpted calcium carbonate exoskeletons (coccoliths), rendering them visible from space(3). Although coccolithophores export carbon in the form of organic matter and calcite to the sea floor, they also release CO2 in the calcification process. Hence, they have a complex influence on the carbon cycle, driving either CO2 production or uptake, sequestration and export to the deep ocean(4). Here we report the first haptophyte reference genome, from the coccolithophore Emiliania huxleyi strain CCMP1516, and sequences from 13 additional isolates. Our analyses reveal a pan genome (core genes plus genes distributed variably between strains) probably supported by an atypical complement of repetitive sequence in the genome. Comparisons across strains demonstrate that E. huxleyi, which has long been considered a single species, harbours extensive genome variability reflected in different metabolic repertoires. Genome variability within this species complex seems to underpin its capacity both to thrive in habitats ranging from the equator to the subarctic and to form large-scale episodic blooms under a wide variety of environmental conditions.

Journal ArticleDOI
TL;DR: The theoretical basis of several approaches towards debiasing share a common feature that involves a deliberate decoupling from Type 1 intuitive processing and moving to Type 2 analytical processing so that eventually unexamined intuitive judgments can be submitted to verification.
Abstract: Numerous studies have shown that diagnostic failure depends upon a variety of factors. Psychological factors are fundamental in influencing the cognitive performance of the decision maker. In this first of two papers, we discuss the basics of reasoning and the Dual Process Theory (DPT) of decision making. The general properties of the DPT model, as it applies to diagnostic reasoning, are reviewed. A variety of cognitive and affective biases are known to compromise the decision-making process. They mostly appear to originate in the fast intuitive processes of Type 1 that dominate (or drive) decision making. Type 1 processes work well most of the time but they may open the door for biases. Removing or at least mitigating these biases would appear to be an important goal. We will also review the origins of biases. The consensus is that there are two major sources: innate, hard-wired biases that developed in our evolutionary past, and acquired biases established in the course of development and within our working environments. Both are associated with abbreviated decision making in the form of heuristics. Other work suggests that ambient and contextual factors may create high risk situations that dispose decision makers to particular biases. Fatigue, sleep deprivation and cognitive overload appear to be important determinants. The theoretical basis of several approaches towards debiasing is then discussed. All share a common feature that involves a deliberate decoupling from Type 1 intuitive processing and moving to Type 2 analytical processing so that eventually unexamined intuitive judgments can be submitted to verification. This decoupling step appears to be the critical feature of cognitive and affective debiasing.