Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors

Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.

Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia given allogeneic bone marrow transplantation from an HLA-identical sibling:results of a GITMO/EBMT randomized trial

A randomized trial was carried out comparing cyclosporin A (CsA) and short-term methotrexate (MTX) versus CsA alone for graft versus host disease (GVHD) prophylaxis in patients with severe aplastic anemia (SAA) undergoing allogeneic bone marrow transplantation (BMT) from a compatible sibling. Seventy-one patients (median age, 19 years; range, 4-46 years) were randomized to receive either CsA and MTX or CsA alone for the first 3 weeks after BMT. Subsequently, both groups received CsA orally, with gradual drug reduction until discontinuation 8 to 12 months after BMT. Patients randomized in both arms had comparable characteristics and received the same preparative regimen (ie, cyclophosphamide 200 mg/kg over 4 days). The median time for neutrophil engraftment was 17 days (range, 11-31 days) and 12 days (range, 4-45 days) for patients in the CsA/MTX group and the CsA alone group, respectively (P =.01). No significant difference was observed in the probability of either grade 2, grade 3, or grade 4 acute GVHD or chronic GVHD developing in the 2 groups. The Kaplan-Meier estimates of 1-year transplantation-related mortality rates for patients given either CsA/MTX or CsA alone were 3% and 15%, respectively (P =.07). With a median follow-up of 48 months from BMT, the 5-year survival probability is 94% for patients in the CsA/MTX group and 78% for those in the CsA alone group (P =. 05). These data indicate that the use of CsA with MTX is associated with improved survival in patients with SAA who receive transplants from compatible siblings. (Blood. 2000;96:1690-1697)

Adiposity as a cause of cardiovascular disease: a Mendelian randomization study

Background: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods.

Methods: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes.

Results: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12–1.28, P = 1.9·10−7), heart failure (HR = 1.47, 95% CI, 1.35–1.60, P = 9·10−19) and ischaemic stroke (HR = 1.15, 95% CI, 1.06–1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (β = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028–0.033, P = 3·10−107). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12–3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05–3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD.

Conclusions: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.

Designing Bare Essentials: Aldi, Lidle and the architectures of cheapness

They’re cheap. They’re in every settlement of significance in Britain, Ireland and elsewhere. We all use them but perhaps do not always admit to it. Especially, if we are architects.
Over the past decades Aldi/Lidl low cost supermarkets have escaped from middle Europe to take over large tracts of the English speaking world remaking them according to a formula of mass-produced sheds, buff-coloured cobble-lock car parks, logos in primary colours, bare-shelves and eclectic special offers. Response within architectural discourse to this phenomenon has been largely one of indifference and such places remain, perhaps reiterating Pevsner’s controversial insights into the bicycle shed, on the peripheries of what we might term architecture. This paper seeks to explore the spatial complexities of the discount supermarket and in doing so open up a discussion on the architecture of cheapness. As a road-map, it takes former managing director Dieter Brandes’ treatise on the Aldi formula, Bare Essentials: the Aldi Way to Retailing, and investigates the strategies through which economic exigencies manifest themselves in a series of spatial tactics which involve building. Central to this is the idea of architecture as system rather than form and, in Aldi/Lidl’s case, the result of a spatial network of flows. To understand the architecture of the supermarket, then, it is necessary to measure the times and spaces of supply across the scales of intersection between global and local.
Evaluating the energy, economy and precision of such systems challenges the liminal position of the commercial, the placeless and especially the cheap within architectural discourse. As is well known, architectures of mass-production and prefabrication and their origins exercised modernist thinkers such as Sigfried Giedion and Walter Gropius in the early twentieth century and has undergone a resurgence in recent times. Meanwhile, the mapping of the hitherto overlooked forms and iconography of commerce in Learning from Las Vegas (1971) was extended by Rem Koolhaas et al into an investigation of the technologies, systems and precedents of retail in the Harvard Design School Guide to Shopping, thirty years later in 2001. While obviously always a criteria for building, to find writings on architecture which explicitly celebrate cheapness as a design virtue or, indeed, even iterate the word cheap is more difficult. Walter Gropius’ essay ‘How can we build cheaper, better, more attractive houses?’ (1927), however, situates the cheap within the discussions – articulated, amongst others, by Karl Teige and Bruno Taut – surrounding the minimal dwelling and the moral benefits of absence of the 1920s and 30s.
In our contemporary age of heightened consumption, it is perhaps fitting that an architecture of bare essentials is defined in retail rather than in housing, a commercial existenzminimum where the Miesian paradox of ‘less is more’ is resold as a paradigm of ‘more for less’ in the ubiquitous yet overlooked architectures of the discount supermarket.

Optically controlled dense current structures driven by relativistic plasma aperture-induced diffraction

The collective response of charged particles to intense fields is intrinsic to plasma accelerators and radiation sources, relativistic optics and many astrophysical phenomena. Here we show that a relativistic plasma aperture is generated in thin foils by intense laser light, resulting in the fundamental optical process of diffraction. The plasma electrons collectively respond to the resulting laser near-field diffraction pattern, producing a beam of energetic electrons with a spatial structure that can be controlled by variation of the laser pulse parameters. It is shown that static electron-beam and induced-magnetic-field structures can be made to rotate at fixed or variable angular frequencies depending on the degree of ellipticity in the laser polarization. The concept is demonstrated numerically and verified experimentally, and is an important step towards optical control of charged particle dynamics in laser-driven dense plasma sources.

Objects of Transcendence: Scots Protestantism and an Anthropology of Things

This anthropological essay takes as its ethnographic point of departure two apparently contrasting deployments of the Bible within contemporary Scotland, one as observed among Brethren and Presbyterian fisher-families in Gamrie, coastal Aberdeenshire, and the other as observed among the Orange Order, a Protestant marching fraternity, in Airdrie and Glasgow. By examining how and with what effects the Bible and other objects (plastic crowns, ‘Sunday clothes’, Orange regalia) enter into and extend beyond the everyday practices of fishermen and Orangemen, my aim is to sketch different aspects of the material life of Scottish Protestantism. By offering a critique of Bruno Latour’s early writing on ‘quasi-objects’ via Alfred Gell’s notion of ‘distributed personhood’, I seek to undermine the sociological assumption that modernity and enchantment are mutually exclusive.

Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium

BACKGROUND: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality.

METHODS: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs.

RESULTS: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking.

CONCLUSIONS: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.