Associations between FTO genotype and total energy and macronutrients intake: a systematic review and meta-analysis

Risk variants of the fat-mass and obesity-associated (FTO) gene have been associated with increased obesity. However, the evidence for associations between FTO genotype and macronutrients intake has not been reviewed systematically. Our aim was to evaluate potential associations between FTO genotype and intakes of total energy, fat, carbohydrate and protein. We undertook a systematic literature search in Medline, Scopus, EMBASE and Cochrane of associations between macronutrients intake and FTO genotype in adults. Beta coefficients and confidence intervals were used for per-allele comparisons. Random-effects models assessed the pooled effect sizes. We identified 56 eligible studies reporting on 213 173 adults. For each copy of the FTO risk allele, individuals reported 6.46 kcal/day (95% CI: 10.76, 2.16) lower total energy intake (P=0.003). Total fat (P=0.028) and protein (P=0.006), but not carbohydrate intakes, were higher in those carrying the FTO risk allele. After adjustment for body weight, total energy intakes remained significantly lower in individuals with the FTO risk genotype (P=0.028). The FTO risk allele is associated with a lower reported total energy intake and with altered patterns of macronutrients intake. Although significant, these differences are small and further research is needed to determine whether the associations are independent of dietary misreporting.

Finite sample weighting of recursive forecast errors

This paper proposes and tests a new framework for weighting recursive out-of-sample prediction errors according to their corresponding levels of in-sample estimation uncertainty. In essence, we show how to use the maximum possible amount of information from the sample in the evaluation of the prediction accuracy, by commencing the forecasts at the earliest opportunity and weighting the prediction errors. Via a Monte Carlo study, we demonstrate that the proposed framework selects the correct model from a set of candidate models considerably more often than the existing standard approach when only a small sample is available. We also show that the proposed weighting approaches result in tests of equal predictive accuracy that have much better sizes than the standard approach. An application to an exchange rate dataset highlights relevant differences in the results of tests of predictive accuracy based on the standard approach versus the framework proposed in this paper.

Social innovation and social entrepreneurship a systematic review

Corporate social responsibility (CSR) literature suggests CSR initiatives extend beyond meeting the immediate interests of stakeholders of for-profit enterprises, offering the potential to also enhance performance. Growing disillusionment of for-profit business models has drawn attention to social entrepreneurship and social innovation to ease social issues. Adopting a systematic review of relevant research, the article provides collective insights into research linking social innovation with social entrepreneurship, demonstrating growing interest in the area over the last decade. The past 5 years have seen a surge in attention with particular focus on the role of the entrepreneur, networks, systems, institutions, and cross-sectoral partnerships. Based on the findings of the review, the authors synthesize formerly dispersed fields of research into an analytical framework, signposting a “systems of innovation” approach for future studies of social innovation and social entrepreneurship.

Work Domain Analysis for understanding medication safety in care homes in England: an exploratory study

Medication safety and errors are a major concern in care homes. In addition to the identification of incidents, there is a need for a comprehensive system description to avoid the danger of introducing interventions that have unintended consequences and are therefore unsustainable. The aim of the study was to explore the impact and uniqueness of Work Domain Analysis (WDA) to facilitate an in-depth understanding of medication safety problems within the care home system and identify the potential benefits of WDA to design safety interventions to improve medication safety. A comprehensive, systematic and contextual overview of the care home medication system was developed for the first time. The novel use of the Abstraction Hierarchy (AH) to analyse medication errors revealed the value of the AH to guide a comprehensive analysis of errors and generate system improvement recommendations that took into account the contextual information of the wider system.

Glacial-interglacial temperature change in the tropical West Pacific: a comparison of stalagmite-based paleo-thermometers

In the tropics, geochemical records from stalagmites have so far mainly been used to qualitatively reconstruct changes in precipitation, but several new methods to reconstruct past temperatures from stalagmite material have emerged recently: i) liquid–vapor homogenization of fluid inclusion water ii) noble gas concentrations in fluid inclusion water, iii) the partitioning of oxygen isotopes between fluid inclusion water and calcite, and iv) the abundance of the 13C18O16O (‘clumped’) isotopologue in calcite. We present, for the first time, a direct comparison of these four paleo-thermometers by applying them to a fossil stalagmite covering nearly two glacial–interglacial cycles (Marine Isotope Stages (MIS) 12–9) and to two modern stalagmites, all from northern Borneo. The temperature estimates from the different methods agree in most cases within errors for both the old and recent samples; reconstructed formation temperatures of the recent samples match within 2-sigma errors with measured cave temperatures. However, slight but systematic deviations are observed between noble gas and liquid–vapor homogenization temperatures. Whereas the temperature sensitivity of fluid inclusion δ18O and clumped isotopes is currently debated, we find that the calibration of Tremaine et al. (2011) for fluid inclusion δ18O and a synthetic calcite-based clumped isotope calibration (Ziegler et al., in prep.) yield temperature estimates consistent with the other methods. All methods (with the potential exception of clumped isotopes) show excellent agreement on the amplitude of glacial–interglacial temperature change, indicating temperature shifts of 4–5 °C. This amplitude is similar to the amplitude of Mg/Ca-based regional sea surface temperature records, when correcting for sea level driven changes in cave elevation. Our reconstruction of tropical temperature evolution over the time period from 440 to 320 thousand years ago (ka) adds support to the view that climate sensitivity to varying greenhouse forcing is substantial also in the deep tropics.

The creation and diffusion of innovation in developing countries: a systematic literature review

In this study, we review the literature on the creation and diffusion of innovation in the private sectors (industry and services) in developing countries. In particular, we collect evidence on what are the barriers to innovation creation and diffusion and the channels of innovation diffusion to and within developing countries. We find that innovation in developing countries is about creation or adoption of new ideas and technologies; but the capacity for innovation is embedded in and constituted by dynamics between geographical, socio-economic, political and legal subsystems. We contextualize the findings from the review in the current theoretical framework of diffusion of innovations, and we emphasize how the institutional context typical of developing countries impacts the diffusion itself.

Pragmatic solutions for syntactic problems: Understanding some L2 syntactic errors in terms of discourse-pragmatic deficits

Contemporary research in generative second language (L2) acquisition has attempted to address observable target-deviant aspects of L2 grammars within a UG-continuity framework (e.g. Lardiere 2000; Schwartz 2003; Sprouse 2004; Prévost & White 1999, 2000). With the aforementioned in mind, the independence of pragmatic and syntactic development, independently observed elsewhere (e.g. Grodzinsky & Reinhart 1993; Lust et al. 1986; Pacheco & Flynn 2005; Serratrice, Sorace & Paoli 2004), becomes particularly interesting. In what follows, I examine the resetting of the Null-Subject Parameter (NSP) for English learners of L2 Spanish. I argue that insensitivity to associated discoursepragmatic constraints on the discursive distribution of overt/null subjects accounts for what appear to be particular errors as a result of syntactic deficits. It is demonstrated that despite target-deviant performance, the majority must have native-like syntactic competence given their knowledge of the Overt Pronoun Constraint (Montalbetti 1984), a principle associated with the Spanish-type setting of the NSP.

Targeting medication non-adherence behavior in selected autoimmune diseases: a systematic approach to digital health program development

Background 29 autoimmune diseases, including Rheumatoid Arthritis, gout, Crohn’s Disease, and Systematic Lupus Erythematosus affect 7.6-9.4% of the population. While effective therapy is available, many patients do not follow treatment or use medications as directed. Digital health and Web 2.0 interventions have demonstrated much promise in increasing medication and treatment adherence, but to date many Internet tools have proven disappointing. In fact, most digital interventions continue to suffer from high attrition in patient populations, are burdensome for healthcare professionals, and have relatively short life spans. Objective Digital health tools have traditionally centered on the transformation of existing interventions (such as diaries, trackers, stage-based or cognitive behavioral therapy programs, coupons, or symptom checklists) to electronic format. Advanced digital interventions have also incorporated attributes of Web 2.0 such as social networking, text messaging, and the use of video. Despite these efforts, there has not been little measurable impact in non-adherence for illnesses that require medical interventions, and research must look to other strategies or development methodologies. As a first step in investigating the feasibility of developing such a tool, the objective of the current study is to systematically rate factors of non-adherence that have been reported in past research studies. Methods Grounded Theory, recognized as a rigorous method that facilitates the emergence of new themes through systematic analysis, data collection and coding, was used to analyze quantitative, qualitative and mixed method studies addressing the following autoimmune diseases: Rheumatoid Arthritis, gout, Crohn’s Disease, Systematic Lupus Erythematosus, and inflammatory bowel disease. Studies were only included if they contained primary data addressing the relationship with non-adherence. Results Out of the 27 studies, four non-modifiable and 11 modifiable risk factors were discovered. Over one third of articles identified the following risk factors as common contributors to medication non-adherence (percent of studies reporting): patients not understanding treatment (44%), side effects (41%), age (37%), dose regimen (33%), and perceived medication ineffectiveness (33%). An unanticipated finding that emerged was the need for risk stratification tools (81%) with patient-centric approaches (67%). Conclusions This study systematically identifies and categorizes medication non-adherence risk factors in select autoimmune diseases. Findings indicate that patients understanding of their disease and the role of medication are paramount. An unexpected finding was that the majority of research articles called for the creation of tailored, patient-centric interventions that dispel personal misconceptions about disease, pharmacotherapy, and how the body responds to treatment. To our knowledge, these interventions do not yet exist in digital format. Rather than adopting a systems level approach, digital health programs should focus on cohorts with heterogeneous needs, and develop tailored interventions based on individual non-adherence patterns.

An investigation of the shortcomings of the CONSORT 2010 statement for the reporting of group sequential randomised controlled trials: a methodological systematic review

Background It can be argued that adaptive designs are underused in clinical research. We have explored concerns related to inadequate reporting of such trials, which may influence their uptake. Through a careful examination of the literature, we evaluated the standards of reporting of group sequential (GS) randomised controlled trials, one form of a confirmatory adaptive design. Methods We undertook a systematic review, by searching Ovid MEDLINE from the 1st January 2001 to 23rd September 2014, supplemented with trials from an audit study. We included parallel group, confirmatory, GS trials that were prospectively designed using a Frequentist approach. Eligible trials were examined for compliance in their reporting against the CONSORT 2010 checklist. In addition, as part of our evaluation, we developed a supplementary checklist to explicitly capture group sequential specific reporting aspects, and investigated how these are currently being reported. Results Of the 284 screened trials, 68(24%) were eligible. Most trials were published in “high impact” peer-reviewed journals. Examination of trials established that 46(68%) were stopped early, predominantly either for futility or efficacy. Suboptimal reporting compliance was found in general items relating to: access to full trials protocols; methods to generate randomisation list(s); details of randomisation concealment, and its implementation. Benchmarking against the supplementary checklist, GS aspects were largely inadequately reported. Only 3(7%) trials which stopped early reported use of statistical bias correction. Moreover, 52(76%) trials failed to disclose methods used to minimise the risk of operational bias, due to the knowledge or leakage of interim results. Occurrence of changes to trial methods and outcomes could not be determined in most trials, due to inaccessible protocols and amendments. Discussion and Conclusions There are issues with the reporting of GS trials, particularly those specific to the conduct of interim analyses. Suboptimal reporting of bias correction methods could potentially imply most GS trials stopping early are giving biased results of treatment effects. As a result, research consumers may question credibility of findings to change practice when trials are stopped early. These issues could be alleviated through a CONSORT extension. Assurance of scientific rigour through transparent adequate reporting is paramount to the credibility of findings from adaptive trials. Our systematic literature search was restricted to one database due to resource constraints.

Parents' verbal communication and childhood anxiety: a systematic review

Parents’ verbal communication to their child, particularly the expression of fear-relevant information (e.g., attributions of threat to the environment), is considered to play a key role in children’s fears and anxiety. This review considers the extent to which parental verbal communication is associated with child anxiety by examining research that has employed objective observational methods. Using a systematic search strategy, we identified 15 studies that addressed this question. These studies provided some evidence that particular fear-relevant features of parental verbal communication are associated with child anxiety under certain conditions. However, the scope for drawing reliable, general conclusions was limited by extensive methodological variation between studies, particularly in terms of the features of parental verbal communication examined and the context in which communication took place, how child anxiety was measured, and inconsistent consideration of factors that may moderate the verbal communication–child anxiety relationship. We discuss ways in which future research can contribute to this developing evidence base and reduce further methodological inconsistency so as to inform interventions for children with anxiety problems.

Higher PUFA and omega-3 PUFA, CLA, α-tocopherol and iron, but lower iodine and selenium concentrations in organic milk: a systematic literature review and meta- and redundancy analyses

Demand for organic milk is partially driven by consumer perceptions that it is more nutritious. However, there is still considerable uncertainty over whether the use of organic production standards affects milk quality. Here we report results of meta-analyses based on 170 published studies comparing the nutrient content of organic and conventional bovine milk. There were no significant differences in total SFA and MUFA concentrations between organic and conventional milk. However, concentrations of total PUFA and n-3 PUFA were significantly higher in organic milk, by an estimated 7 (95 % CI −1, 15) % and 56 (95 % CI 38, 74) %, respectively. Concentrations of α-linolenic acid (ALA), very long-chain n-3 fatty acids (EPA+DPA+DHA) and conjugated linoleic acid were also significantly higher in organic milk, by an 69 (95 % CI 53, 84) %, 57 (95 % CI 27, 87) % and 41 (95 % CI 14, 68) %, respectively. As there were no significant differences in total n-6 PUFA and linoleic acid (LA) concentrations, the n-6:n-3 and LA:ALA ratios were lower in organic milk, by an estimated 71 (95 % CI −122, −20) % and 93 (95 % CI −116, −70) %. It is concluded that organic bovine milk has a more desirable fatty acid composition than conventional milk. Meta-analyses also showed that organic milk has significantly higher α-tocopherol and Fe, but lower I and Se concentrations. Redundancy analysis of data from a large cross-European milk quality survey indicates that the higher grazing/conserved forage intakes in organic systems were the main reason for milk composition differences.

Composition differences between organic and conventional meat: a systematic literature review and meta-analysis

Demand for organic meat is partially driven by consumer perceptions that organic foods are more nutritious than non-organic foods. However, there have been no systematic reviews comparing specifically the nutrient content of organic and conventionally produced meat. In this study, we report results of a meta-analysis based on sixty-seven published studies comparing the composition of organic and non-organic meat products. For many nutritionally relevant compounds (e.g. minerals, antioxidants and most individual fatty acids (FA)), the evidence base was too weak for meaningful meta-analyses. However, significant differences in FA profiles were detected when data from all livestock species were pooled. Concentrations of SFA and MUFA were similar or slightly lower, respectively, in organic compared with conventional meat. Larger differences were detected for total PUFA and n-3 PUFA, which were an estimated 23 (95 % CI 11, 35) % and 47 (95 % CI 10, 84) % higher in organic meat, respectively. However, for these and many other composition parameters, for which meta-analyses found significant differences, heterogeneity was high, and this could be explained by differences between animal species/meat types. Evidence from controlled experimental studies indicates that the high grazing/forage-based diets prescribed under organic farming standards may be the main reason for differences in FA profiles. Further studies are required to enable meta-analyses for a wider range of parameters (e.g. antioxidant, vitamin and mineral concentrations) and to improve both precision and consistency of results for FA profiles for all species. Potential impacts of composition differences on human health are discussed.

Implementing systematic review techniques in chemical risk assessment: challenges, opportunities and recommendations

Systematic review (SR) is a rigorous, protocol-driven approach designed to minimise error and bias when summarising the body of research evidence relevant to a specific scientific question. Taking as a comparator the use of SR in synthesising research in healthcare, we argue that SR methods could also pave the way for a “step change” in the transparency, objectivity and communication of chemical risk assessments (CRA) in Europe and elsewhere. We suggest that current controversies around the safety of certain chemicals are partly due to limitations in current CRA procedures which have contributed to ambiguity about the health risks posed by these substances. We present an overview of how SR methods can be applied to the assessment of risks from chemicals, and indicate how challenges in adapting SR methods from healthcare research to the CRA context might be overcome. Regarding the latter, we report the outcomes from a workshop exploring how to increase uptake of SR methods, attended by experts representing a wide range of fields related to chemical toxicology, risk analysis and SR. Priorities which were identified include: the conduct of CRA-focused prototype SRs; the development of a recognised standard of reporting and conduct for SRs in toxicology and CRA; and establishing a network to facilitate research, communication and training in SR methods. We see this paper as a milestone in the creation of a research climate that fosters communication between experts in CRA and SR and facilitates wider uptake of SR methods into CRA.

Exploiting existing ground-based remote sensing networks to improve high-resolution weather forecasts

A new generation of high-resolution (1 km) forecast models promises to revolutionize the prediction of hazardous weather such as windstorms, flash floods, and poor air quality. To realize this promise, a dense observing network, focusing on the lower few kilometers of the atmosphere, is required to verify these new forecast models with the ultimate goal of assimilating the data. At present there are insufficient systematic observations of the vertical profiles of water vapor, temperature, wind, and aerosols; a major constraint is the absence of funding to install new networks. A recent research program financed by the European Union, tasked with addressing this lack of observations, demonstrated that the assimilation of observations from an existing wind profiler network reduces forecast errors, provided that the individual instruments are strategically located and properly maintained. Additionally, it identified three further existing European networks of instruments that are currently underexploited, but with minimal expense they could deliver quality-controlled data to national weather services in near–real time, so the data could be assimilated into forecast models. Specifically, 1) several hundred automatic lidars and ceilometers can provide backscatter profiles associated with aerosol and cloud properties and structures with 30-m vertical resolution every minute; 2) more than 20 Doppler lidars, a fairly new technology, can measure vertical and horizontal winds in the lower atmosphere with a vertical resolution of 30 m every 5 min; and 3) about 30 microwave profilers can estimate profiles of temperature and humidity in the lower few kilometers every 10 min. Examples of potential benefits from these instruments are presented.

Hydrodynamics with spin angular momentum from systematic coarse graining: a tutorial example

The derivation of time evolution equations for slow collective variables starting from a micro- scopic model system is demonstrated for the tutorial example of the classical, two-dimensional XY model. Projection operator techniques are used within a nonequilibrium thermodynamics framework together with molecular simulations in order to establish the building blocks of the hydrodynamics equations: Poisson brackets that determine the deterministic drift, the driving forces from the macroscopic free energy and the friction matrix. The approach is rather general and can be applied for deriving the equations of slow variables for a broad variety of systems.