Evaluation of a service intervention to improve awareness and uptake of bowel cancer screening in ethnically-diverse areas

The Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis receives funding for a research programme from the UK Department of Health Policy Research Programme (grant no. 106/0001). It is a collaboration between researchers from seven institutions (the Queen Mary University of London, the UCL, the King’s College London, the London School of Hygiene and Tropical Medicine, the Hull York Medical School, the Durham University and the Peninsula Medical School)

Multiple and Multidimensional life transitions in the context of life-limiting health conditions:Longitudinal study focussing on perspectives of Young Adults, Families and Professionals

Background: There is a dearth of literature that investigates life transitions of young adults (YAs) with life-limiting conditions, families and professionals. The scant literature that is available has methodological limitations, including not listening to the voice of YAs, collecting data retrospectively, at one time point, from one group’s perspective and single case studies. The aim of this study was to address the gaps found in our literature review and provide a clearer understanding of the multiple and multi-dimensional life transitions experienced by YAs and significant others, over a period of time. Methods: This qualitative study used a longitudinal design and data were collected using semi-structured interviews over a 6-month period at 3 time points. Participants included 12 YAs with life-limiting conditions and their nominated significant others (10 family members and 11 professionals). Data were analysed using a thematic analysis approach. Results: Life transitions of YA and significant others are complex; they experience multiple and multi-dimensional transitions across several domains. The findings challenge the notion that all life transitions are triggered by health transitions of YAs, and has highlighted environmental factors (attitudinal and systemic) that can be changed to facilitate smoother transitions in various aspects of their lives. Conclusions: This study makes a unique and significant contribution to literature. It provides evidence and rich narratives for policy makers and service providers to change policies and practices that are in line with the needs of YAs with life-limiting conditions as they transition to adulthood. Families and professionals have specific training needs that have not yet been met fully

Effect of the Mediterranean diet on blood pressure in the PREDIMED trial: results from a randomized controlled trial

BackgroundHypertension can be prevented by adopting healthy dietary patterns. Our aim was to assess the 4-year effect on blood pressure (BP) control of a randomized feeding trial promoting the traditional Mediterranean dietary pattern.MethodsThe PREDIMED primary prevention trial is a randomized, single-blinded, controlled trial conducted in Spanish primary healthcare centers. We recruited 7,447 men (aged 55 to 80 years) and women (aged 60 to 80 years) who had high risk for cardiovascular disease. Participants were assigned to a control group or to one of two Mediterranean diets. The control group received education on following a low-fat diet, while the groups on Mediterranean diets received nutritional education and also free foods; either extra virgin olive oil, or nuts. Trained personnel measured participants’ BP at baseline and once yearly during a 4-year follow-up. We used generalized estimating equations to assess the differences between groups during the follow-up.ResultsThe percentage of participants with controlled BP increased in all three intervention groups (P-value for within-group changes: P<0.001). Participants allocated to either of the two Mediterranean diet groups had significantly lower diastolic BP than the participants in the control group (−1.53 mmHg (95% confidence interval (CI) −2.01 to −1.04) for the Mediterranean diet supplemented with extra virgin olive oil, and −0.65 mmHg (95% CI -1.15 to −0.15) mmHg for the Mediterranean diet supplemented with nuts). No between-group differences in changes of systolic BP were seen.ConclusionsBoth the traditional Mediterranean diet and a low-fat diet exerted beneficial effects on BP and could be part of advice to patients for controlling BP. However, we found lower values of diastolic BP in the two groups promoting the Mediterranean diet with extra virgin olive oil or with nuts than in the control group.Trial registrationCurrent Controlled Trials ISRCTN3573963

A novel widespread cryptic species and phylogeographic patterns within several giant clam species (Cardiidae: Tridacna) from the Indo-Pacific Ocean

Giant clams (genus Tridacna) are iconic coral reef animals of the Indian and Pacific Oceans, easily recognizable by their massive shells and vibrantly colored mantle tissue. Most Tridacna species are listed by CITES and the IUCN Redlist, as their populations have been extensively harvested and depleted in many regions. Here, we survey Tridacna crocea and Tridacna maxima from the eastern Indian and western Pacific Oceans for mitochondrial (COI and 16S) and nuclear (ITS) sequence variation and consolidate these data with previous published results using phylogenetic analyses. We find deep intraspecific differentiation within both T. crocea and T. maxima. In T. crocea we describe a previously undocumented phylogeographic division to the east of Cenderawasih Bay (northwest New Guinea), whereas for T. maxima the previously described, distinctive lineage of Cenderawasih Bay can be seen to also typify western Pacific populations. Furthermore, we find an undescribed, monophyletic group that is evolutionarily distinct from named Tridacna species at both mitochondrial and nuclear loci. This cryptic taxon is geographically widespread with a range extent that minimally includes much of the central Indo-Pacific region. Our results reinforce the emerging paradigm that cryptic species are common among marine invertebrates, even for conspicuous and culturally significant taxa. Additionally, our results add to identified locations of genetic differentiation across the central Indo-Pacific and highlight how phylogeographic patterns may differ even between closely related and co-distributed species

Meta-analysis of four new genome scans for lipid parameters and analysis of positional candidates in positive linkage regions

Lipid levels in plasma strongly influence the risk for coronary heart disease. To localise and subsequently identify genes affecting lipid levels, we performed four genome-wide linkage scans followed by combined linkage/association analysis. Genome-scans were performed in 701 dizygotic twin pairs from four samples with data on plasma levels of HDL- and LDL-cholesterol and their major protein constituents, apolipoprotein AI (ApoAI) and Apolipoprotein B (ApoB). To maximise power, the genome scans were analysed simultaneously using a well-established meta-analysis method that was newly applied to linkage analysis. Overall LOD scores were estimated using the means of the sample-specific quantitative trait locus (QTL) effects inversely weighted by the standard errors obtained using an inverse regression method. Possible heterogeneity was accounted for with a random effects model. Suggestive linkage for HDL-C was observed on 8p23.1 and 12q21.2 and for ApoAI on 1q21.3. For LDL-C and ApoB, linkage regions frequently coincided (2p24.1, 2q32.1, 19p13.2 and 19q13.31). Six of the putative QTLs replicated previous findings. After fine mapping, three maximum LOD scores mapped within 1cM of major candidate genes, namely APOB (LOD =2.1), LDLR (LOD =1.9) and APOE (LOD =1.7). APOB haplotypes explained 27% of the QTL effect observed for LDL-C on 2p24.1 and reduced the LOD-score by 0.82. Accounting for the effect of the LDLR and APOE haplotypes did not change the LOD score close to the LDLR gene but abolished the linkage signal at the APOE gene. In conclusion, application of a new meta-analysis approach maximised the power to detect QTLs for lipid levels and improved the precision of their location estimate. © 2005 Nature Publishing Group. All rights reserved

The role of gonadotrophin-releasing hormone antagonists in the treatment of patients with advanced hormone-dependent prostate cancer in the UK.

PURPOSE: Comparing gonadotrophin-releasing hormone (GnRH) antagonists and agonists as androgen deprivation therapy for advanced prostate cancer (PC). METHODS: This article stems from a round-table meeting in December 2014 to compare the properties of GnRH agonists and antagonists in the published literature in order to identify the patient groups most likely to benefit from GnRH antagonist therapy. A broad PubMed and congress abstract search was carried out in preparation for the meeting to ensure that the latest data and opinion were available for the discussions. RESULTS: In randomised, controlled trials, GnRH antagonist therapy provides more rapid suppression of luteinising hormone, follicle-stimulating hormone and testosterone than GnRH agonist treatment. Compared with the GnRH agonist, there is evidence of improved disease control by a GnRH antagonist, with longer interval to prostate-specific antigen progression and greater reduction of serum alkaline phosphatase. In a post hoc analysis of six randomised trials, the risk of cardiac events within 1 year of initiating therapy was significantly lower among men receiving GnRH antagonist than agonist. Pre-clinical laboratory data suggest a number of mechanisms whereby GnRH antagonist therapy may benefit men with pre-existing cardiovascular disease (CVD), the most plausible hypothesis being that, unlike GnRH agonists, GnRH antagonists do not activate T lymphocytes, which act to increase atherosclerotic plaque rupture. CONCLUSION: When making treatment decisions, clinicians should consider comorbidities, particularly CVD, in addition to effects on PC. GnRH antagonists may be appropriate in patients with significant CV risk, existing osteopenia, lower urinary tract symptoms and significant metastatic disease

Shake a tail feather: the evolution of the theropod tail into a stiff aerodynamic surface

Theropod dinosaurs show striking morphological and functional tail variation; e.g., a long, robust, basal theropod tail used for counterbalance, or a short, modern avian tail used as an aerodynamic surface. We used a quantitative morphological and functional analysis to reconstruct intervertebral joint stiffness in the tail along the theropod lineage to extant birds. This provides new details of the tail's morphological transformation, and for the first time quantitatively evaluates its biomechanical consequences. We observe that both dorsoventral and lateral joint stiffness decreased along the non-avian theropod lineage (between nodes Theropoda and Paraves). Our results show how the tail structure of non-avian theropods was mechanically appropriate for holding itself up against gravity and maintaining passive balance. However, as dorsoventral and lateral joint stiffness decreased, the tail may have become more effective for dynamically maintaining balance. This supports our hypothesis of a reduction of dorsoventral and lateral joint stiffness in shorter tails. Along the avian theropod lineage (Avialae to crown group birds), dorsoventral and lateral joint stiffness increased overall, which appears to contradict our null expectation. We infer that this departure in joint stiffness is specific to the tail's aerodynamic role and the functional constraints imposed by it. Increased dorsoventral and lateral joint stiffness may have facilitated a gradually improved capacity to lift, depress, and swing the tail. The associated morphological changes should have resulted in a tail capable of producing larger muscular forces to utilise larger lift forces in flight. Improved joint mobility in neornithine birds potentially permitted an increase in the range of lift force vector orientations, which might have improved flight proficiency and manoeuvrability. The tail morphology of modern birds with tail fanning capabilities originated in early ornithuromorph birds. Hence, these capabilities should have been present in the early Cretaceous, with incipient tail-fanning capacity in the earliest pygostylian birds

Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility.

Heterogeneity of embryological origins is a hallmark of vascular smooth muscle cells (SMCs) and may influence the development of vascular disease. Differentiation of human pluripotent stem cells (hPSCs) into developmental origin-specific SMC subtypes remains elusive. Here we describe a chemically defined protocol in which hPSCs were initially induced to form neuroectoderm, lateral plate mesoderm or paraxial mesoderm. These intermediate populations were further differentiated toward SMCs (>80% MYH11(+) and ACTA2(+)), which displayed contractile ability in response to vasoconstrictors and invested perivascular regions in vivo. Derived SMC subtypes recapitulated the unique proliferative and secretory responses to cytokines previously documented in studies using aortic SMCs of distinct origins. Notably, this system predicted increased extracellular matrix degradation by SMCs derived from lateral plate mesoderm, which was confirmed using rat aortic SMCs from corresponding origins. This differentiation approach will have broad applications in modeling origin-dependent disease susceptibility and in developing bioengineered vascular grafts for regenerative medicine

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Resolution of inflammation: a new therapeutic frontier

Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes — a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field