Micro-to-macro transition accounting for general imperfect interfaces

The objective of this contribution is to establish a micro-to-macro transition framework to study the behavior of heterogeneous materials whereby the influence of interfaces at the microscale is taken into account. The term “interface” refers to a zero-thickness model that represents the finite thickness “interphase” between the constituents of the micro-structure. For geometrically equivalent samples, due to increasing area-to-volume ratio with decreasing size, interfaces demonstrate a more pronounced effect on the material response at small scales. A remarkable outcome is that including interfaces introduces a length-scale and our interface-enhanced computational homogenization captures a size effect in the material response even if linear prolongation conditions are considered. Furthermore, the interface model in this contribution is general imperfect in the sense that it allows for both jumps of the deformation as well as for the traction across the interface. Both cohesive zone model and interface elasticity theory can be derived as two limit cases of this general model. We establish a consistent computational homogenization scheme accounting for general imperfect interfaces. Suitable boundary conditions to guarantee meaningful averages are derived. Clearly, this general framework reduces to classical computational homogenization if the effect of interfaces is ignored. Finally, the proposed theory is elucidated via a series of numerical examples. © 2016 Elsevier B.V

Which factors differentiate athletes with hip/groin pain from those without? A systematic review with meta-analysis

Background: Hip and groin injuries are common in many sports. Understanding the factors differentiating athletes with hip/groin pain from those without these injuries could facilitate management and prevention. Objective: Conduct a systematic review and meta-analysis of the literature on factors differentiating athletes with and without hip/groin pain. Methods: The review was registered as PROSPERO CRD42014007416 and a comprehensive, systematic search was conducted in June 2014. Inclusion criteria were: cross-sectional, cohort or case-control study designs of n>10 that examined outcome measures differentiating athletes with and without hip/groin pain. Two authors independently screened search results, assessed study quality, and performed data extraction. Methodological heterogeneity was determined and data pooled for meta-analysis when appropriate. A best evidence synthesis was performed on the remaining outcome measures. Results: Of 2251 titles identified, 17 articles were included of which 10 were high quality. Sixty two different outcome measures were examined, 8 underwent meta-analysis. Pooled data showed strong evidence that athletes with hip/groin pain demonstrated: pain and lower strength on the adductor squeeze test, reduced range of motion in hip internal rotation and bent knee fall out; however, hip external rotation range was equivalent to controls. Strong evidence was found that lower patient-reported outcome (PRO) scores, altered trunk muscle function, and moderate evidence of bone oedema and secondary cleft sign were associated with hip/groin pain. Conclusions: PROs, pain and reduced strength on the adductor squeeze test, reduced range of motion in internal rotation and bent knee fall out are the outcome measures that best differentiate athletes with hip/groin pain from those without this pain

Multivariate risks and depth-trimmed regions

We describe a general framework for measuring risks, where the risk measure takes values in an abstract cone. It is shown that this approach naturally includes the classical risk measures and set-valued risk measures and yields a natural definition of vector-valued risk measures. Several main constructions of risk measures are described in this abstract axiomatic framework. It is shown that the concept of depth-trimmed (or central) regions from the multivariate statistics is closely related to the definition of risk measures. In particular, the halfspace trimming corresponds to the Value-at-Risk, while the zonoid trimming yields the expected shortfall. In the abstract framework, it is shown how to establish a both-ways correspondence between risk measures and depth-trimmed regions. It is also demonstrated how the lattice structure of the space of risk values influences this relationship.Comment: 26 pages. Substantially revised version with a number of new results adde

The UK's Global Health Respiratory Network: Improving respiratory health of the world's poorest through research collaborations.

Respiratory disorders are responsible for considerable morbidity, health care utilisation, societal costs and approximately one in five deaths worldwide [1-4]. Yet, despite this substantial health and societal burden – which particularly affects the world’s poorest populations and as such is a major contributor to global health inequalities – respiratory disorders have historically not received the policy priority they warrant. For example, despite causing an estimated 1000 deaths per day, less than half of the world’s countries collect data on asthma prevalence (http://www.globalasthmareport.org/). This is true for both communicable and non-communicable respiratory disorders, many of which are either amenable to treatment or preventable

Centerpoints: a link between optimization and convex geometry

We introduce a concept that generalizes several different notions of a “centerpoint” in the literature. We develop an oracle-based algorithm for convex mixed-integer optimization based on centerpoints. Further, we show that algorithms based on centerpoints are “best possible” in a certain sense. Motivated by this, we establish several structural results about this concept and provide efficient algorithms for computing these points

Prognostic Value of Number and Site of Calcified Coronary Lesions Compared With the Total Score

ObjectivesThis study sought to evaluate the long-term prognostic value of the number and sites of calcified coronary lesions and to compare the accuracy of number of calcified lesions with the extent of total calcium score.BackgroundThere is a strong relationship between mortality and total coronary artery calcium (CAC) score. It is not known whether the number of calcified lesions or their location influences outcome.MethodsA total of 14,759 asymptomatic patients were referred for evaluation of CAC scanning using electron beam tomography. Univariable and multivariable Cox proportional hazards models were developed to estimate time to all-cause mortality at, on average, 6.8 years (n = 281).ResultsRisk-adjusted annual mortality was 0.19% (95% confidence interval 0.18% to 0.21%) for patients without any calcified lesions. For patients with >20 lesions, annual risk-adjusted mortality exceeded 2% per year. Mortality rates were significantly higher for left main lesions as compared to other coronary arteries with annual mortality rates of 1.3%, 2.1%, 9.2%, and 13.6% for 1 to 2, 3 to 5, and ≥6 lesions, respectively (p < 0.0001). For left main CAC scores of 0 to 10, 11 to 100, 101 to 399, and 400 to 999, annual risk-adjusted mortality was 0.33%, 0.81%, 1.73%, and 7.71%, respectively (p < 0.0001). All 4 patients with a CAC score of ≥1,000 in the left main died during follow-up. However, patients with more frequent calcified lesions also had higher CAC scores. Specifically, ≥81% of patients with >10 calcified lesions also had a CAC score ≥100. With exception, for patients with CAC scores ≥1,000, annual mortality was dramatically higher at 3.0% to 4.5% for those with 1 to 5 calcified lesions as compared with 1.1% to 2.0% for those with 6 or more lesions (p < 0.0001).ConclusionsWe report that mortality rates increased proportionally with the number of calcified lesions. Although predictive information is contained in the number of calcified lesions, its added statistical value is minimal. With exception, patients with frequent lesions in the left main or those with a few large calcified lesions have a particularly high mortality risk

Chronic irradiation of human cells reduces histone levels and deregulates gene expression

Abstract: Over the past decades, there have been huge advances in understanding cellular responses to ionising radiation (IR) and DNA damage. These studies, however, were mostly executed with cell lines and mice using single or multiple acute doses of radiation. Hence, relatively little is known about how continuous exposure to low dose ionising radiation affects normal cells and organisms, even though our cells are constantly exposed to low levels of radiation. We addressed this issue by examining the consequences of exposing human primary cells to continuous ionising γ-radiation delivered at 6–20 mGy/h. Although these dose rates are estimated to inflict fewer than a single DNA double-strand break (DSB) per hour per cell, they still caused dose-dependent reductions in cell proliferation and increased cellular senescence. We concomitantly observed histone protein levels to reduce by up to 40%, which in contrast to previous observations, was not mainly due to protein degradation but instead correlated with reduced histone gene expression. Histone reductions were accompanied by enlarged nuclear size paralleled by an increase in global transcription, including that of pro-inflammatory genes. Thus, chronic irradiation, even at low dose-rates, can induce cell senescence and alter gene expression via a hitherto uncharacterised epigenetic route. These features of chronic radiation represent a new aspect of radiation biology

Chronic irradiation of human cells reduces histone levels and deregulates gene expression

Abstract: Over the past decades, there have been huge advances in understanding cellular responses to ionising radiation (IR) and DNA damage. These studies, however, were mostly executed with cell lines and mice using single or multiple acute doses of radiation. Hence, relatively little is known about how continuous exposure to low dose ionising radiation affects normal cells and organisms, even though our cells are constantly exposed to low levels of radiation. We addressed this issue by examining the consequences of exposing human primary cells to continuous ionising γ-radiation delivered at 6–20 mGy/h. Although these dose rates are estimated to inflict fewer than a single DNA double-strand break (DSB) per hour per cell, they still caused dose-dependent reductions in cell proliferation and increased cellular senescence. We concomitantly observed histone protein levels to reduce by up to 40%, which in contrast to previous observations, was not mainly due to protein degradation but instead correlated with reduced histone gene expression. Histone reductions were accompanied by enlarged nuclear size paralleled by an increase in global transcription, including that of pro-inflammatory genes. Thus, chronic irradiation, even at low dose-rates, can induce cell senescence and alter gene expression via a hitherto uncharacterised epigenetic route. These features of chronic radiation represent a new aspect of radiation biology