13 research outputs found
RIPOSTE: A framework for improving the design and analysis of laboratory-based research
No full textLack of reproducibility is an ongoing problem in some areas of the biomedical sciences. Poor experimental design and a failure to engage with experienced statisticians at key stages in the design and analysis of experiments are two factors that contribute to this problem. The RIPOSTE (Reducing IrreProducibility in labOratory STudiEs) framework has been developed to support early and regular discussions between scientists and statisticians in order to improve the design, conduct and analysis of laboratory studies and, therefore, reduce irreproducibility. This framework is intended for use during the early stages of a research project, when specific questions or hypotheses are proposed. The essential points within the framework are explained and illustrated using three examples (a medical equipment test, a macrophage study and a gene expression study). Sound study design minimises the possibility of bias being introduced into experiments and leads to higher quality research with more reproducible results
Prevalence and extent of infarct and microvascular obstruction following different reperfusion therapies in ST-elevation myocardial infarction
No full textBackground:
Microvascular obstruction (MVO) describes suboptimal tissue perfusion despite restoration of infarct-related artery flow. There are scarce data on Infarct Size (IS) and MVO in relation to the mode and timing of reperfusion. We sought to characterise the prevalence and extent of microvascular injury and IS using Cardiovascular magnetic resonance (CMR), in relation to the mode of reperfusion following acute ST-Elevation Myocardial Infarction (STEMI).
Methods:
CMR infarct characteristics were measured in 94 STEMI patients (age 61.0 ± 13.1 years) at 1.5 T. Seventy-three received reperfusion therapy: primary percutaneous coronary-intervention (PPCI, n = 47); thrombolysis (n = 12); rescue PCI (R-PCI, n = 8), late PCI (n = 6). Twenty-one patients presented late (>12 hours) and did not receive reperfusion therapy.
Results:
IS was smaller in PPCI (19.8 ± 13.2% of LV mass) and thrombolysis (15.2 ± 10.1%) groups compared to patients in the late PCI (40.0 ± 15.6%) and R-PCI (34.2 ± 18.9%) groups, p <0.001. The prevalence of MVO was similar across all groups and was seen at least as frequently in the non-reperfused group (15/21, [76%] v 33/59, [56%], p = 0.21) and to a similar magnitude (1.3 (0.0-2.8) v 0.4 [0.0-2.9]% LV mass, p = 0.36) compared to patients receiving early reperfusion therapy. In the 73 reperfused patients, time to reperfusion, ischaemia area at risk and TIMI grade post-PCI were the strongest independent predictors of IS and MVO.
Conclusions:
In patients with acute STEMI, CMR-measured MVO is not exclusive to reperfusion therapy and is primarily related to ischaemic time. This finding has important implications for clinical trials that use CMR to assess the efficacy of therapies to reduce reperfusion injury in STEMI
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Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
No full textIn the version of this article originally published, one of the two authors with the name Wei Zhao was omitted from the author list and the affiliations for both authors were assigned to the single Wei Zhao in the author list. In addition, the ORCID for Wei Zhao (Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA) was incorrectly assigned to author Wei Zhou. The errors have been corrected in the HTML and PDF versions of the article
The archaeology of pig domestication and husbandry: approaches and case studies
No full textThe main aim of this thesis is to present the potential of an integrated analysis for the study of past relations between humans and pigs. In particular, the advent of pig domestication and patterns of early husbandry in southern Europe will be discussed on the basis of a multidisciplinary approach. The core method is represented by abiometrical analysis of pig teeth and bones from archaeological as well as modem collections. The study of recent material provides the opportunity to detect variation in wild boar size and shape across the whole range of distribution of the species. An archaeological baseline for domestic pigs is obtained through the study of a large Neolithic assemblage from England. With the adoption of a size index scaling technique this is then used as a 'standard' reference for the analysis of southern European material. In addition to this biometrical analysis, a historical approach to the study of pig husbandry in medieval England and ethnoarchaeological work in Sardinia and Corsica provide further opportunities to build up an interpretative framework for the archaeological evidence. A number of case studies from rehistoric and historic Portugal and prehistoric Italy are then resented. In Portugal abundant data collected from late prehistoric and historic assemblages are compared with Mesolithic and Neolithic evidence and provide the opportunity to study variations in patterns of pig hunting and husbandry through a long chronologicalsequence. The evidence for this country indicates that wild boars increased in size after the Mesolithic whereas no improvement in domestic pigs can be detected until the Middle Ages, which means that practices of free-range husbandry were probably adopted for the whole of the prehistoric and early historic periods. In Italy an even larger number of sites is used to illuminate the evolution of pig exploitation in that particular country. Like in Portugal a pattern of size increase in wild boars emerges after the Mesolithic, but in Italy it is also possible to detect size decrease in domestic pigs, with intensification in pig husbandry occurring probably sometime in the late Neolithic. The similarity in size between Mesolithic and Neolithic pigs confirms the suggestion brought about by genetic analysis that pigs were domesticated locally. The use of a diversity of approaches and the large chronological and geographic scale of this analysis provides us with a unique insight into the great variety of interactions that occurred between humans and pigs and the general importance of these animals in human history
Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
No full textProtein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
No full textGenome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity
