The UK Clinical Research Collaboration (UKCRC) Tissue Directory and Coordination Centre: the UK’s centre for facilitating the usage of human samples for medical research

The UKCRC Tissue Directory and Coordination Centre was established to improve access to and utilisation of UK human tissue samples for medical research. The key output of the Centre is the creation of the UK’s first pan-disease Tissue Directory (https://directory.biobankinguk.org/). Any researcher can search the Directory based on a series of simple key words including disease classification, age, sex, sample type, preservation details, quality indicators and datasets available. The Directory as of April 2017 contains 100 Bioresources. Researchers seeking fresh samples can also search for facilities that offer bespoke collection services. Future work of the Centre will be to explore greater standardisation of biobanking activities across the UK and to facilitate an inter-connected research infrastructure related to the use of human biosamples

Oceanic adults, coastal juveniles: tracking the habitat use of whale sharks off the Pacific coast of Mexico

Eight whale sharks tagged with pop-up satellite archival tags off the Gulf of California, Mexico, were tracked for periods of 14–134 days. Five of these sharks were adults, with four females visually assessed to be pregnant. At least for the periods they were tracked, juveniles remained in the Gulf of California while adults moved offshore into the eastern Pacific Ocean. We propose that parturition occurs in these offshore waters. Excluding two juveniles that remained in the shallow tagging area for the duration of tracking, all sharks spent 65 ± 20.7% (SD) of their time near the surface, even over deep water, often in association with frontal zones characterized by cool-water upwelling. While these six sharks all made dives into the meso- or bathypelagic zones, with two sharks reaching the maximum depth recordable by the tags (1285.8 m), time spent at these depths represented a small proportion of the overall tracks. Most deep dives (72.7%) took place during the day, particularly during the early morning and late afternoon. Pronounced habitat differences by ontogenetic stage suggest that adult whale sharks are less likely to frequent coastal waters after the onset of maturity

CJCheck Stage 1: development and testing of a checklist for reporting community juries – Delphi process and analysis of studies published in 1996–2015

Background Opportunities for community members to actively participate in policy development are increasing. Community/citizen's juries (CJs) are a deliberative democratic process aimed to illicit informed community perspectives on difficult topics. But how comprehensive these processes are reported in peer-reviewed literature is unknown. Adequate reporting of methodology enables others to judge process quality, compare outcomes, facilitate critical reflection and potentially repeat a process. We aimed to identify important elements for reporting CJs, to develop an initial checklist and to review published health and health policy CJs to examine reporting standards. Design Using the literature and expertise from CJ researchers and policy advisors, a list of important CJ reporting items was suggested and further refined. We then reviewed published CJs within the health literature and used the checklist to assess the comprehensiveness of reporting. Results CJCheck was developed and examined reporting of CJ planning, juror information, procedures and scheduling. We screened 1711 studies and extracted data from 38. No studies fully reported the checklist items. The item most consistently reported was juror numbers (92%, 35/38), while least reported was the availability of expert presentations (5%, 2/38). Recruitment strategies were described in 66% of studies (25/38); however, the frequency and timing of deliberations was inadequately described (29%, 11/38). Conclusions Currently CJ publications in health and health policy literature are inadequately reported, hampering their use in policy making. We propose broadening the CJCheck by creating a reporting standards template in collaboration with international CJ researchers, policy advisors and consumer representatives to ensure standardized, systematic and transparent reporting.RT was supported by a NHMRC Screening and Test Evaluation Program (STEP) Grant (#633033). RS was supported by a Bond University Vice Chancellor’s Research Grant Scheme. CD, SMC and LR received funding support from NHMRC Project Grant (#1023197). CD received funding support from a NHMRC Project Grant (#1083079). SMC is funded through NHMRC Career Development Fellowship (#1032963). JMS was funded by an Australian National Preventive Health Agency Fellowship (20STR2013F) and an NHMRC Capacity Building Grant (565501)

Quarterly U.S. unemployment: cycles, seasons and asymmetries

This paper documents three stylized facts for the quarterly unemployment rate in the United States. Firstly, unemployment is asymmetric over the business cycle, i.e. it rises sharply in recessions and it falls slowly in expansions. Secondly, its seasonal fluctuations are not constant across the two business cycle stages in the sense that there is less seasonality in recession periods. Thirdly, the effect of shocks to the unemployment rate in expansions seem transitory, while this effect is permanent in recessions. Some implications of these stylized facts for empirical macroeconomics and seasonal adjustment are discussed

Impact of metabolic comorbidity on the association between body mass index and heatlh-related quality of life: a Scotland-wide cross-sectional study of 5,608 participants

<p/>Background: The prevalence of obesity is rising in Scotland and globally. Overall, obesity is associated with increased morbidity, mortality and reduced health-related quality of life. Studies suggest that "healthy obesity" (obesity without metabolic comorbidity) may not be associated with morbidity or mortality. Its impact on health-related quality of life is unknown. <p/>Methods: We extracted data from the Scottish Health Survey on self-reported health-related quality of life, body mass index (BMI), demographic information and comorbidity. SF-12 responses were converted into an overall health utility score. Linear regression analyses were used to explore the association between BMI and health utility, stratified by the presence or absence of metabolic comorbidity (diabetes, hypertension, hypercholesterolemia or cardiovascular disease), and adjusted for potential confounders (age, sex and deprivation quintile). <p/>Results: Of the 5,608 individuals, 3,744 (66.8%) were either overweight or obese and 921 (16.4%) had metabolic comorbidity. There was an inverted U-shaped relationship whereby health utility was highest among overweight individuals and fell with increasing BMI. There was a significant interaction with metabolic comorbidity (p = 0.007). Individuals with metabolic comorbidty had lower utility scores and a steeper decline in utility with increasing BMI (morbidly obese, adjusted coefficient: -0.064, 95% CI -0.115, -0.012, p = 0.015 for metabolic comorbidity versus -0.042, 95% CI -0.067, -0.018, p = 0.001 for no metabolic comorbidity). <p/>Conclusions: The adverse impact of obesity on health-related quality of life is greater among individuals with metabolic comorbidity. However, increased BMI is associated with reduced health-related quality of life even in the absence of metabolic comorbidity, casting doubt on the notion of "healthy obesity"

Direct integration of intensity-level data from Affymetrix and Illumina microarrays improves statistical power for robust reanalysis

<p>Abstract</p> <p>Background</p> <p>Affymetrix GeneChips and Illumina BeadArrays are the most widely used commercial single channel gene expression microarrays. Public data repositories are an extremely valuable resource, providing array-derived gene expression measurements from many thousands of experiments. Unfortunately many of these studies are underpowered and it is desirable to improve power by combining data from more than one study; we sought to determine whether platform-specific bias precludes direct integration of probe intensity signals for combined reanalysis.</p> <p>Results</p> <p>Using Affymetrix and Illumina data from the microarray quality control project, from our own clinical samples, and from additional publicly available datasets we evaluated several approaches to directly integrate intensity level expression data from the two platforms. After mapping probe sequences to Ensembl genes we demonstrate that, ComBat and cross platform normalisation (XPN), significantly outperform mean-centering and distance-weighted discrimination (DWD) in terms of minimising inter-platform variance. In particular we observed that DWD, a popular method used in a number of previous studies, removed systematic bias at the expense of genuine biological variability, potentially reducing legitimate biological differences from integrated datasets.</p> <p>Conclusion</p> <p>Normalised and batch-corrected intensity-level data from Affymetrix and Illumina microarrays can be directly combined to generate biologically meaningful results with improved statistical power for robust, integrated reanalysis.</p

Young off-axis volcanism along the ultraslow-spreading Southwest Indian Ridge

Author Posting. © The Authors, 2010. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 3 (2010): 286-292, doi:10.1038/ngeo824.Mid-ocean ridge crustal accretion occurs continuously at all spreading rates through a combination of magmatic and tectonic processes. Fast to slow spreading ridges are largely built by adding magma to narrowly focused neovolcanic zones. In contrast, ultraslow spreading ridge construction significantly relies on tectonic accretion, which is characterized by thin volcanic crust, emplacement of mantle peridotite directly to the seafloor, and unique seafloor fabrics with variable segmentation patterns. While advances in remote imaging have enhanced our observational understanding of crustal accretion at all spreading rates, temporal information is required in order to quantitatively understand mid-ocean ridge construction. However, temporal information does not exist for ultraslow spreading environments. Here, we utilize U-series eruption ages to investigate crustal accretion at an ultraslow spreading ridge for the first time. Unexpectedly young eruption ages throughout the Southwest Indian ridge rift valley indicate that neovolcanic activity is not confined to the spreading axis, and that magmatic crustal accretion occurs over a wider zone than at faster spreading ridges. These observations not only suggest that crustal accretion at ultraslow spreading ridges is distinct from faster spreading ridges, but also that the magma transport mechanisms may differ as a function of spreading rate.This work was supported by the following NSF grants: NSF-OCE 0137325; NSF-OCE 060383800; and NSF-OCE 062705300

Deriving a mutation index of carcinogenicity using protein structure and protein interfaces

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/

The SOS Pilot Study: a RCT of routine oxygen supplementation early after acute stroke—effect on recovery of neurological function at one week

Mild hypoxia is common after stroke and associated with poor long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no significant benefit at 7 and 12 months. This pilot study reports the effects of routine oxygen supplementation for 72 hours on oxygen saturation and neurological outcomes at 1 week after a stroke

Adaptive Lévy Walks in Foraging Fallow Deer

Background: Lévy flights are random walks, the step lengths of which come from probability distributions with heavy power-law tails, such that clusters of short steps are connected by rare long steps. Lévy walks maximise search efficiency of mobile foragers. Recently, several studies raised some concerns about the reliability of the statistical analysis used in previous analyses. Further, it is unclear whether Lévy walks represent adaptive strategies or emergent properties determined by the interaction between foragers and resource distribution. Thus two fundamental questions still need to be addressed: the presence of Lévy walks in the wild and whether or not they represent a form of adaptive behaviour. Methodology/Principal Findings: We studied 235 paths of solitary and clustered (i.e. foraging in group) fallow deer (Dama dama), exploiting the same pasture. We used maximum likelihood estimation for discriminating between a power-tailed distribution and the exponential alternative and rank/frequency plots to discriminate between Lévy walks and composite Brownian walks. We showed that solitary deer perform Lévy searches, while clustered animals did not adopt that strategy. Conclusion/Significance: Our demonstration of the presence of Lévy walks is, at our knowledge, the first available which adopts up-to-date statistical methodologies in a terrestrial mammal. Comparing solitary and clustered deer, we concluded that the Lévy walks of solitary deer represent an adaptation maximising encounter rates with forage resources and not a