Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

Exercise and psychosocial interventions in breast cancer survivors: Preliminary results of a randomized controlled trial

Physical and psychological decline is common in the post-treatment breast cancer population, yet the efficacy of concurrent interventions to meet both physical- psychosocial needs in this population has not been extensively examined. PURPOSE: This study explores the effects of a combined exercise and psychosocial intervention model on selected physiological-psychological parameters in post-treated breast cancer. METHODS: Forty-one breast cancer survivors were randomly assigned to one of four groups for an 8-week intervention: exercise only [EX, n=13] (aerobic and resistance training), psychosocial therapy only [PS, n=11] (biofeedback), combined EX and PS [EX+PS, n=11], or to control conditions [CO, n=6]. Mean delta score (post-intervention - baseline) were calculated for each of the following: body weight, % body fat (skin folds), predicted VO2max (Modified Bruce Protocol), overall dynamic muscular endurance [OME] (RMCRI protocol), static balance (Single leg stance test), dynamic balance (360° turn and 4-square step test), fatigue (Revised Piper Scale), and quality of life (FACT-B). A one-way ANOVA was used to analyze the preliminary results of this on-going randomized trial. RESULTS: Overall, there were significant differences in the delta scores for predicted VO2max, OME, and dynamic balance among the 4 groups (p<0.05). The EX+PS group showed a significant improvement in VO2max compared with the PS group (4.2 ± 3.8 vs. -0.9 ± 4.2 mL/kg/min; p<0.05). Both the EX+PS and EX groups showed significant improvements in OME compared with the PS and CO groups (44.5 ± 23.5 and 43.4 ± 22.1 vs. -3.9 ± 15.2 and 2.7 ± 13.7 repetitions; p<0.05). All 3 intervention groups showed significant improvements in dynamic balance compared with the CO group (-0.8 ± 0.6, -0.6 ± 0.8, and -0.6 ±1.0 vs. 0.6 ± 0.6 seconds; p<0.05). Overall, changes in fatigue tended towards significance among the 4 groups (p = 0.08), with decreased fatigue in the intervention groups and increased fatigue in the CO group. CONCLUSIONS: Our preliminary findings suggest that EX and PS seem to produce greater positive changes in the outcome measures than CO. However, at this point no definite conclusions can be made on the additive effects of combining the EX and PS interventions.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 +/- 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 +/- 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 +/- 0.06 s.e.), and ADHD and major depressive disorder (0.32 +/- 0.07 s.e.), low between schizophrenia and ASD (0.16 +/- 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

International contact lens prescribing in 2014

Since the late 1990s, the International Contact Lens Prescribing Survey Consortium has prospectively gathered information about 285,000 contact lens fits from more than 50 countries. This article presents our 14th annual summary of current trends published in Contact Lens Spectrum. With only minor differences in the distribution of our surveys among markets, we have continued to adopt the same approach throughout the past 18 years. Through national coordinators, we approach contact lens prescribers in each country and ask them to record information about the first 10 patients whom they fit with contact lenses after receipt of our survey form. The information collected is generic, and respondents are weighted to reflect the volume of contact lens fits undertaken by each. For this 2014 report, we present information about 25,179 contact lens fits from 32 countries...

Defects in the IFT-B component IFT172 cause Jeune and Mainzer-Saldino syndromes in humans

Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease. To identify additional IFT-B components defective in ciliopathies, we independently performed different mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in 1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome resequencing in 63 individuals with ATD. We thereby detected biallelic mutations in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals displayed abnormalities of the thorax and/or long bones, as well as renal, hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS. Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert syndrome was present in 2 out of 12 families. Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. Knockdown of ift172 in zebrafish recapitulated the human phenotype and demonstrated a genetic interaction between ift172 and ift80. In summary, we have identified defects in IFT172 as a cause of complex ATD and MZSDS. Our findings link the group of skeletal ciliopathies to an additional IFT-B component, IFT172, similar to what has been shown for IFT-A.

Illuminating the glass box: The lighting designs of Richard Kelly

A promotional brochure celebrating the completion of the Seagram Building in spring 1957 features on its cover intense portraits of seven men bisected by a single line of bold text that asks, “Who are these Men?” The answer appears on the next page: “They Dreamed of a Tower of Light” (Figures 1, 2). Each photograph is reproduced with the respective man’s name and project credit: architects, Mies van der Rohe and Philip Johnson; associate architect, Eli Jacques Kahn; electrical contractor, Harry F. Fischbach; lighting consultant, Richard Kelly; and electrical engineer, Clifton E. Smith. To the right, a rendering of the new Seagram Tower anchors the composition, standing luminous against a star-speckled night sky; its glass walls and bronze mullions are transformed into a gossamer skin that reveals the tower’s structural skeleton. Lightolier, the contract lighting manufacturer, produced the brochure to promote its role in the lighting of the Seagram Building, but Lightolier’s promotional copy was not far from the truth.

The Science and Art of Light

Architecture today often is praised for its tectonics, floating volumes, and sensational, gravity-defying stunts of “starchitecture.” Yet, very so often there is a building that inspires descriptions of the sublime, the experiential, and the power of light and architecture to transcend our expectations. The new Meinel Optical Sciences Research Building, designed by Phoenix-based Richärd+Bauer for the University of Arizona, Tucson, is one of these architectural rarities. Already drawing comparisons to Louis Kahn's 1965 Salk Institute for Biological Studies in La Jolla, California, the indescribable quality of light that characterizes the best of Kahn's work also resonates in Richärd+Bauer's new building. Both an expansion and renovation of the existing College of Optical Sciences facilities, the Meinel building includes teaching and research laboratories, six floors of offices, discussion areas, conference rooms, and an auditorium. The new 47,000 square-foot cast-in-place concrete structure, wrapped on three-sides in copper-alloy panels, harmonizes with the largely brick vocabulary of the campus while reflecting the ethereal quality of the wide Arizona sky. The façade, however, is merely a prelude for what awaits inside—where light and architecture seamlessly combine to create moments of pure awe.

Highlight: Yale University Art Gallery

Modern architecture, with its exposed concrete, glass, and steel expanses, does not age gracefully. The Yale University Art Gallery, designed by architecture great Louis Kahn, is no exception. As Yale's first modernist building, completed in 1953, and Kahn's first major commission and collaboration with pioneering lighting designer, Richard Kelly, the gallery is an important part of American architecture. Yet, despite its iconic status, the building suffered numerous architectural indignities in the years following its completion, including the insertion of permanent gallery partitions, which divided Kahn's open plan, and the enclosure of an exterior court, which blocked daylight to the lower galleries.