The continuing challenge of familial hypercholesterolaemia.

This editorial refers to ‘Prediction of cardiovascular risk in patients with familial hypercholesterolaemia’, by G. Villa et al., on page 274

Cardiovascular disease risk assessment and reduction: summary of updated NICE guidance

NICE recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the guideline committee's (GC's) experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. Definitions of evidence certainty are given in box 1

Online self-assessment of cardiovascular risk using the Joint British Societies (JBS3)-derived heart age tool: a descriptive study.

OBJECTIVE: A modified version of the Joint British Societies (JBS3) 'heart age' tool was introduced online to broaden access to personalised risk assessment to the general population and encourage participation in the National Health Service (NHS) Health Check programme. This study reports on its early uptake and the profiles of those who used the self-assessment tool to determine their own cardiovascular risk. DESIGN: Observational, retrospective analysis of online tool use. SETTING: Between February and July 2015, user data collected from the NHS Choices website, where the tool was hosted, were analysed anonymously using standard analytic packages. RESULTS: The online tool landing page was viewed 1.4 million times in the first 5 months, with increased activity following limited media coverage. Of the 575 782 users completing the data journey with a valid 'heart age' result, their demographic and risk factor profiles broadly resembled the population of England, although both younger users and males (60%) were over-represented. Almost 50% and 79% did not know or enter their blood pressure or total cholesterol values, respectively. Estimated heart age was higher than chronological age for 79% of all users, and also for 69% of younger users under 40 years who are at low 10-year risk and not invited for NHS Health Checks. CONCLUSIONS: These data suggest a high level of public interest in self-assessment of cardiovascular risk when an easily understood metric is used, although a large number of users lack awareness of their own risk factors. The heart age tool was accessed by a group not easily reached by conventional approaches yet is at high cardiovascular risk and would benefit most from early and sustained risk reduction. These are both important opportunities for interventions to educate and empower the public to manage better their cardiovascular risk and promote population-level prevention

A sense of place, many times over - pattern formation and evolution of repetitive morphological structures

Fifty years ago, Lewis Wolpert introduced the concept of "positional information" to explain how patterns form in a multicellular embryonic field. Using morphogen gradients, whose continuous distributions of positional values are discretized via thresholds into distinct cellular states, he provided, at the theoretical level, an elegant solution to the "French Flag problem." In the intervening years, many experimental studies have lent support to Wolpert's ideas. However, the embryonic patterning of highly repetitive morphological structures, as often occurring in nature, can reveal limitations in the strict implementation of his initial theory, given the number of distinct threshold values that would have to be specified. Here, we review how positional information is complemented to circumvent these inadequacies, to accommodate tissue growth and pattern periodicity. In particular, we focus on functional anatomical assemblies composed of such structures, like the vertebrate spine or tetrapod digits, where the resulting segmented architecture is intrinsically linked to periodic pattern formation and unidirectional growth. These systems integrate positional information and growth with additional patterning cues that, we suggest, increase robustness and evolvability. We discuss different experimental and theoretical models to study such patterning systems, and how the underlying processes are modulated over evolutionary timescales to enable morphological diversification

Resolved Multi-element Stellar Chemical Abundances in the Brightest Quiescent Galaxy at z ∼ 2

Measuring the chemical composition of galaxies is crucial to our understanding of galaxy formation and evolution models. However, such measurements are extremely challenging for quiescent galaxies at high redshifts, which have faint stellar continua and compact sizes, making it difficult to detect absorption lines and nearly impossible to spatially resolve them. Gravitational lensing offers the opportunity to study these galaxies with detailed spectroscopy that can be spatially resolved. In this work, we analyze deep spectra of MRG-M0138, a lensed quiescent galaxy at z = 1.98, which is the brightest of its kind, with an H-band magnitude of 17.1. Taking advantage of full spectral fitting, we measure [Mg/Fe] = 0.51 ± 0.05, [Fe/H] = 0.26 ± 0.04, and, for the first time, the stellar abundances of six other elements in this galaxy. We further constrained, also for the first time in a z ~ 2 galaxy, radial gradients in stellar age, [Fe/H], and [Mg/Fe]. We detect no gradient in age or [Mg/Fe] and a slightly negative gradient in [Fe/H], which has a slope comparable to that seen in local early-type galaxies. Our measurements show that not only is MRG-M0138 very Mg-enhanced compared to the centers of local massive early-type galaxies, it is also very iron rich. These dissimilar abundances suggest that even the inner regions of massive galaxies have experienced significant mixing of stars in mergers, in contrast to a purely inside-out growth model. The abundance pattern observed in MRG-M0138 challenges simple galactic chemical evolution models that vary only the star formation timescale and shows the need for more elaborate models

Variation in Interleukin 6 Receptor Gene Associates with Risk of Crohn’s Disease and Ulcerative Colitis

Interleukin 6 (IL6) is an inflammatory cytokine; signaling via its receptor (IL6R) is believed to contribute to development of inflammatory bowel diseases (IBD). The single nucleotide polymorphism rs2228145 in IL6R associates with increased levels of soluble IL6R (s-IL6R), as well as reduced IL6R signaling and risk of inflammatory disorders; its effects are similar to those of a therapeutic monoclonal antibody that blocks IL6R signaling. We used the effect of rs2228145 on s-IL6R level as an indirect marker to investigate whether reduced IL6R signaling associates with risk of ulcerative colitis (UC) or Crohn’s disease (CD). In a genome-wide meta-analysis of 20,550 patients with CD, 17647 patients with UC, and more than 40,000 individuals without IBD (controls), we found that rs2228145 (scaled to a 2-fold increase in s-IL6R) was associated with reduced risk of CD (odds ratio, 0.876; 95% CI, 0.822–0.933; P=.00003) or UC (odds ratio, 0.932; 95% CI, 0.875–0.996; P=.036). These findings indicate that therapeutics designed to block IL6R signaling might be effective in treatment of IBD

Economic evaluation of a task-shifting intervention for common mental disorders in India

OBJECTIVE: To carry out an economic evaluation of a task-shifting intervention for the treatment of depressive and anxiety disorders in primary-care settings in Goa, India. METHODS: Cost-utility and cost-effectiveness analyses based on generalized linear models were performed within a trial set in 24 public and private primary-care facilities. Subjects were randomly assigned to an intervention or a control arm. Eligible subjects in the intervention arm were given psycho-education, case management, interpersonal psychotherapy and/or antidepressants by lay health workers. Subjects in the control arm were treated by physicians. The use of health-care resources, the disability of each subject and degree of psychiatric morbidity, as measured by the Revised Clinical Interview Schedule, were determined at 2, 6 and 12 months. FINDINGS: Complete data, from all three follow-ups, were collected from 1243 (75.4%) and 938 (81.7%) of the subjects enrolled in the study facilities from the public and private sectors, respectively. Within the public facilities, subjects in the intervention arm showed greater improvement in all the health outcomes investigated than those in the control arm. Time costs were also significantly lower in the intervention arm than in the control arm, whereas health system costs in the two arms were similar. Within the private facilities, however, the effectiveness and costs recorded in the two arms were similar. CONCLUSION: Within public primary-care facilities in Goa, the use of lay health workers in the care of subjects with common mental disorders was not only cost-effective but also cost-saving