How can clinicians choose between conflicting and discordant systematic reviews? A replication study of the Jadad algorithm

Introduction: The exponential growth of published systematic reviews (SRs) presents challenges for decision makers seeking to answer clinical, public health or policy questions. In 1997, an algorithm was created by Jadad et al. to choose the best SR across multiple. Our study aims to replicate author assessments using the Jadad algorithm to determine: (i) if we chose the same SR as the authors; and (ii) if we reach the same results. Methods: We searched MEDLINE, Epistemonikos, and Cochrane Database of SRs. We included any study using the Jadad algorithm. We used consensus building strategies to operationalise the algorithm and to ensure a consistent approach to interpretation. Results: We identified 21 studies that used the Jadad algorithm to choose one or more SRs. In 62% (13/21) of cases, we were unable to replicate the Jadad assessment and ultimately chose a different SR than the authors. Overall, 18 out of the 21 (86%) independent Jadad assessments agreed in direction of the findings despite 13 having chosen a different SR. Conclusions: Our results suggest that the Jadad algorithm is not reproducible between users as there are no prescriptive instructions about how to operationalise the algorithm. In the absence of a validated algorithm, we recommend that healthcare providers, policy makers, patients and researchers address conflicts between review findings by choosing the SR(s) with meta-analysis of RCTs that most closely resemble their clinical, public health, or policy question, are the most recent, comprehensive (i.e. number of included RCTs), and at the lowest risk of bias

Genetic, environmental and stochastic factors in monozygotic twin discordance with a focus on epigenetic differences

PMCID: PMC3566971This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Molecular diversity of anthracnose pathogen populations associated with UK strawberry production suggests multiple introductions of three different Colletotrichum species.

Fragaria × ananassa (common name: strawberry) is a globally cultivated hybrid species belonging to Rosaceae family. Colletotrichum acutatum sensu lato (s.l.) is considered to be the second most economically important pathogen worldwide affecting strawberries. A collection of 148 Colletotrichum spp. isolates including 67 C. acutatum s.l. isolates associated with the phytosanitary history of UK strawberry production were used to characterize multi-locus genetic variation of this pathogen in the UK, relative to additional reference isolates that represent a worldwide sampling of the diversity of the fungus. The evidence indicates that three different species C. nymphaeae, C. godetiae and C. fioriniae are associated with strawberry production in the UK, which correspond to previously designated genetic groups A2, A4 and A3, respectively. Among these species, 12 distinct haplotypes were identified suggesting multiple introductions into the country. A subset of isolates was also used to compare aggressiveness in causing disease on strawberry plants and fruits. Isolates belonging to C. nymphaeae, C. godetiae and C. fioriniae representative of the UK anthracnose pathogen populations showed variation in their aggressiveness. Among the three species, C. nymphaeae and C. fioriniae appeared to be more aggressive compared to C. godetiae. This study highlights the genetic and pathogenic heterogeneity of the C. acutatum s.l. populations introduced into the UK linked to strawberry production

Efficient TALEN-mediated gene knockout in livestock

Transcription activator-like effector nucleases (TALENs) are programmable nucleases that join FokI endonuclease with the modular DNA-binding domain of TALEs. Although zinc-finger nucleases enable a variety of genome modifications, their application to genetic engineering of livestock has been slowed by technical limitations of embryo-injection, culture of primary cells, and difficulty in producing reliable reagents with a limited budget. In contrast, we found that TALENs could easily be manufactured and that over half (23/36, 64%) demonstrate high activity in primary cells. Cytoplasmic injections of TALEN mRNAs into livestock zygotes were capable of inducing gene KO in up to 75% of embryos analyzed, a portion of which harbored biallelic modification. We also developed a simple transposon coselection strategy for TALEN-mediated gene modification in primary fibroblasts that enabled both enrichment for modified cells and efficient isolation of modified colonies. Coselection after treatment with a single TALEN-pair enabled isolation of colonies with mono- and biallelic modification in up to 54% and 17% of colonies, respectively. Coselection after treatment with two TALEN-pairs directed against the same chromosome enabled the isolation of colonies harboring large chromosomal deletions and inversions (10% and 4% of colonies, respectively). TALEN-modified Ossabaw swine fetal fibroblasts were effective nuclear donors for cloning, resulting in the creation of miniature swine containing mono- and biallelic mutations of the LDL receptor gene as models of familial hypercholesterolemia. TALENs thus appear to represent a highly facile platform for the modification of livestock genomes for both biomedical and agricultural applications

Challenging the field: Bourdieu and men's health

©2014 Macmillan Publishers Ltd. This article considers how understandings of health promotion with men may be assisted by engagement with Bourdieu's theoretical work. The article outlines leading concepts within Bourdieu's work on 'field', 'habitus' and 'capital'; considers subsequent critical debates among gender, feminist and sociological theorists around structure and agency; and links these to discussions within men's health. A particular focus concerns structural disruption of, and movement of social actors between, 'fields' such as family, work and leisure settings. The article examines, through Bourdieu's critical legacy, whether such disruption establishes conditions for transformative reflexivity among men in relation to previously held dispositions (habitus), including those inflected by masculinities, that affect men's health practices. Recent work within Bourdieu's heritage potentially facilitates a re-framing of understandings of men's health practices. The article specifically explores masculine ambivalence within accounts of reflexivity, identities and practice, and considers how social and symbolic (masculine) capital are in play. Implications of Bourdieu's leading concepts for theorising settings-focused approaches to men's health promotion are exemplified with reference to a men's health project in a football stadium leisure setting. The article considers the benefits and challenges of applying gendered critical insights drawing on Bourdieu's work to men's health promotion, and discusses emerging theoretical dilemmas

Precision genetics for complex objectives in animal agriculture

Indirect modification of animal genomes by interspecific hybridization, cross-breeding, and selection has produced an enormous spectrum of phenotypic diversity over more than 10,000 yr of animal domestication. Using these established technologies, the farming community has successfully increased the yield and efficiency of production in most agricultural species while utilizing land resources that are often unsuitable for other agricultural purposes. Moving forward, animal well-being and agricultural sustainability are moral and economic priorities of consumers and producers alike. Therefore, these considerations will be included in any strategy designed to meet the challenges produced by global climate change and an expanding world population. Improvements in the efficiency and precision of genetic technologies will enable a timely response to meet the multifaceted food requirements of a rapidly increasing world population

Milk Lacking α-Casein Leads to Permanent Reduction in Body Size in Mice

The major physiological function of milk is the transport of amino acids, carbohydrates, lipids and minerals to mammalian offspring. Caseins, the major milk proteins, are secreted in the form of a micelle consisting of protein and calcium-phosphate