The characterisation of the hydrodynamic loads on tidal turbines due to turbulence

An improved characterisation of the hydrodynamic blade loads due to onset turbulence is essential in order to mitigate premature failures, reduce excessive levels of conservativeness and ultimately ensure the commercial viability of tidal turbines. The literature focussing on the turbulence in fast flowing tidal streams and of the unsteady loads that are subsequently imparted to rotors has previously been very limited. However, increased activity in the tidal energy community has led to new investigations and insights which are reported in this paper. It has been found that through the use of acoustic Doppler-based sensors, the streamwise turbulence intensities generally tend to a value of approximately 6–8% at the mid-depth of proposed tidal energy sites. Evidence that the anisotropic structure and scales of the turbulence are more consistent with open-channel-based models than atmospheric-based correlations has also been found. Rapid distortion theory has been applied to estimate that the standard deviation of the streamwise turbulent velocity fluctuations in the onset free-stream flow may be amplified significantly by 15% due to the presence of a turbine. The turbulent fluctuations have also been predicted to remain well correlated over the outer span of the blades at the rotational frequency of the rotor. Recent model-scale experiments have enabled the unsteady hydrodynamic loading to be isolated from the steady-flow loading. For cases where the boundary layer remains primarily attached across the blades, this has enabled linear transfer functions to be developed and applied to model the response to a multi-frequency forcing. It has also been found that phenomena consistent with delayed separation and dynamic stall can result in a blade root bending moment that exceeds the steady value by 25%, and this needs to be taken into account in design to reduce the probability of failure

Ideal Stars and General Relativity

We study a system of differential equations that governs the distribution of matter in the theory of General Relativity. The new element in this paper is the use of a dynamical action principle that includes all the degrees of freedom, matter as well as metric. The matter lagrangian defines a relativistic version of non-viscous, isentropic hydrodynamics. The matter fields are a scalar density and a velocity potential; the conventional, four-vector velocity field is replaced by the gradient of the potential and its scale is fixed by one of the eulerian equations of motion, an innovation that significantly affects the imposition of boundary conditions. If the density is integrable at infinity, then the metric approaches the Schwarzschild metric at large distances. There are stars without boundary and with finite total mass; the metric shows rapid variation in the neighbourhood of the Schwarzschild radius and there is a very small core where a singularity indicates that the gas laws break down. For stars with boundary there emerges a new, critical relation between the radius and the gravitational mass, a consequence of the stronger boundary conditions. Tentative applications are suggested, to certain Red Giants, and to neutron stars, but the investigation reported here was limited to polytropic equations of state. Comparison with the results of Oppenheimer and Volkoff on neutron cores shows a close agreement of numerical results. However, in the model the boundary of the star is fixed uniquely by the required matching of the interior metric to the external Schwarzschild metric, which is not the case in the traditional approach.Comment: 26 pages, 7 figure

The General Solution of Bianchi Type VIIhVII_h Vacuum Cosmology

The theory of symmetries of systems of coupled, ordinary differential equations (ODE) is used to develop a concise algorithm in order to obtain the entire space of solutions to vacuum Bianchi Einstein Field Equations (EFEs). The symmetries used are the well known automorphisms of the Lie algebra for the corresponding isometry group of each Bianchi Type, as well as the scaling and the time re-parametrization symmetry. The application of the method to Type VII_h results in (a) obtaining the general solution of Type VII_0 with the aid of the third Painlev\'{e} transcendental (b) obtaining the general solution of Type $VII_h$ with the aid of the sixth Painlev\'{e} transcendental (c) the recovery of all known solutions (six in total) without a prior assumption of any extra symmetry (d) The discovery of a new solution (the line element given in closed form) with a G_3 isometry group acting on T_3, i.e. on time-like hyper-surfaces, along with the emergence of the line element describing the flat vacuum Type VII_0 Bianchi Cosmology.Comment: latex2e source file, 27 pages, 2 tables, no fiure

Stellar structure and compact objects before 1940: Towards relativistic astrophysics

Since the mid-1920s, different strands of research used stars as "physics laboratories" for investigating the nature of matter under extreme densities and pressures, impossible to realize on Earth. To trace this process this paper is following the evolution of the concept of a dense core in stars, which was important both for an understanding of stellar evolution and as a testing ground for the fast-evolving field of nuclear physics. In spite of the divide between physicists and astrophysicists, some key actors working in the cross-fertilized soil of overlapping but different scientific cultures formulated models and tentative theories that gradually evolved into more realistic and structured astrophysical objects. These investigations culminated in the first contact with general relativity in 1939, when J. Robert Oppenheimer and his students George Volkoff and Hartland Snyder systematically applied the theory to the dense core of a collapsing neutron star. This pioneering application of Einstein's theory to an astrophysical compact object can be regarded as a milestone in the path eventually leading to the emergence of relativistic astrophysics in the early 1960s.Comment: 83 pages, 4 figures, submitted to the European Physical Journal

Heterogeneity of luminal breast cancer characterised by immunohistochemical expression of basal markers

Background: Luminal A breast cancer defined as hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative is known to be heterogeneous. Previous study showed that luminal A tumours with the expression of basal markers ((cytokeratin (CK) 5 or CK5/6) or epidermal growth factor receptor (EGFR)) were associated with poorer prognosis compared with those that stained negative for basal markers. Prompted by this study, we assessed whether tumour characteristics and risk factors differed by basal marker status within luminal A tumours. Methods: We pooled 5040 luminal A cases defined by immunohistochemistry (4490 basal-negative ((CK5 (or CK5/6))− and EGFR−) and 550 basal-positive ((CK5 (or CK5/6+)) or EGFR+)) from eight studies participating in the Breast Cancer Association Consortium. Case–case comparison was performed using unconditional logistic regression. Results: Tumour characteristics and risk factors did not vary significantly by the expression of basal markers, although results suggested that basal-positive luminal tumours tended to be smaller and node negative, and were more common in women with a positive family history and lower body mass index. Conclusions: Most established breast cancer risk factors were similar in basal-positive and basal-negative luminal A tumours. The non-significant but suggestive differences in tumour features and family history warrant further investigations

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies

Background: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. Objective: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. Method: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. Results: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing >= 60 g/d with = 25 g/d with Conclusion: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation

Quantitative gait and balance outcomes for ataxia trials: consensus recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers

With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait and balance disturbances most often present as the first signs of degenerative cerebellar ataxia and are the most reported disabling features in disease progression. Thus, digital gait and balance measures constitute promising and relevant performance outcomes for clinical trials.This narrative review with embedded consensus will describe evidence for the sensitivity of digital gait and balance measures for evaluating ataxia severity and progression, propose a consensus protocol for establishing gait and balance metrics in natural history studies and clinical trials, and discuss relevant issues for their use as performance outcomes

Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1

Peer reviewe

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.UK funding includes Cancer Research UK and NIH.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13058-016-0718-