Volume 35, Number 2, June 2015 OLAC Newsletter

Digitized June 2015 issue of the OLAC Newsletter

Volume 35, Number 4, December 2015 OLAC Newsletter

Digitized December 2015 issue of the OLAC Newsletter

Volume 35, Number 3, September 2015 OLAC Newsletter

Digitized September 2015 issue of the OLAC Newsletter

New Results from Glueball Superpotentials and Matrix Models: the Leigh-Strassler Deformation

Using the result of a matrix model computation of the exact glueball superpotential, we investigate the relevant mass perturbations of the Leigh-Strassler marginal ``q'' deformation of N=4 supersymmetric gauge theory. We recall a conjecture for the elliptic superpotential that describes the theory compactified on a circle and identify this superpotential as one of the Hamiltonians of the elliptic Ruijsenaars-Schneider integrable system. In the limit that the Leigh-Strassler deformation is turned off, the integrable system reduces to the elliptic Calogero-Moser system which describes the N=1^* theory. Based on these results, we identify the Coulomb branch of the partially mass-deformed Leigh-Strassler theory as the spectral curve of the Ruijsenaars-Schneider system. We also show how the Leigh-Strassler deformation may be obtained by suitably modifying Witten's M theory brane construction of N=2 theories.Comment: 13 pages, JHEP, amstex, changed JHEP to JHEP

Reverse sequence polymerization-induced self-assembly in aqueous media: a counter-intuitive approach to sterically-stabilized diblock copolymer nano-objects

Polymerization-induced self-assembly (PISA) is a powerful platform technology for the efficient synthesis of block copolymer nanoparticles in many types of solvents, including water. In PISA, a soluble precursor block is used to grow a second insoluble block, which leads to in situ self-assembly of the block copolymer chains. Thus, in the case of aqueous PISA, the water-soluble block is always prepared first because this confers steric stabilization. Herein, we challenge this paradigm by demonstrating that amphiphilic diblock copolymer chains can be prepared in water by preparing the hydrophobic block first via reversible addition–fragmentation chain transfer (RAFT) polymerization. This counter-intuitive reverse sequence PISA formulation utilizes an ionic RAFT agent to conduct the RAFT aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA), which results in the formation of charge-stabilized PHPMA latex particles of ∼500 nm diameter. Initial attempts to chain-extend these hydrophobic PHPMA chains with water-miscible monomers such as glycerol monomethacrylate (GMA) were unsuccessful, with only uncontrolled free radical polymerization being observed in the aqueous phase. However, using a water-immiscible monomer such as isopropylideneglycerol methacrylate (IPGMA) enabled the synthesis of charge-stabilized PHPMA-PIPGMA latex particles. Subsequent acid hydrolysis of the PIPGMA block led to the in situ formation of sterically-stabilized PHPMA-PGMA diblock copolymer spheres. Alternatively, dissolution of the precursor PHPMA latex in a methanol/water binary mixture enables RAFT solution polymerization of water-miscible monomers such as GMA or N,N′-dimethylacrylamide (DMAC) to be achieved with good control. The resulting amphiphilic diblock copolymer chains then undergo self-assembly in aqueous solution after removal of the methanol co-solvent. Finally, this reverse sequence PISA protocol can also be applied to other vinyl monomers such as 2-methoxyethyl methacrylate (MOEMA) or diacetone acrylamide (DAAM), which significantly broadens its scope

N=1* in 5 dimensions: Dijkgraaf-Vafa meets Polchinski-Strassler

One of the powerful techniques to analyze the 5 dimensional Super Yang Mills theory with a massive hypermultiplet (N=1*) is provided by the AdS/CFT correspondence. It predicts that, for certain special values of the hypermultiplet mass, this theory develops nonperturbative branches of the moduli space as well as new light degrees of freedom. We use the higher dimensional generalization of the matrix model/gauge theory correspondence and recover all the prediction of the supergravity analysis. We construct the map between the four dimensional holomorphic superpotential and the five dimensional action and explicitly show that the superpotential is flat along the nonperturbative branches. This is the first instance in which the Dijkgraaf-Vafa method is used to analyze intrinsically higher dimensional phenomena.Comment: 28 pages, Late

Cytoplasmic “ciliary inclusions” in isolation are not sufficient for the diagnosis of primary ciliary dyskinesia

Background: The diagnosis of primary ciliary dyskinesia (PCD) is difficult and requires a combination of clinical features, nasal nitric oxide testing, cilia ultrastructural analysis by electron microscopy (EM), and genetics. A recently described cytoplasmic ultrastructural change termed “ciliary inclusions” was reported to be diagnostic of PCD; however, no supporting evidence of PCD was provided. In this study, we sought to confirm, or refute, the diagnosis of PCD in subjects with “ciliary inclusions” on EM. Methods: Six subjects from five families with previous lab reports of “ciliary inclusions” on EMs of ciliated cells were identified and evaluated at a Genetic Disorders of Mucociliary Clearance Consortium site. We performed a detailed clinical history, nasal nitric oxide measurement, genetic testing including whole-exome sequencing (WES), and when possible, repeat ciliary EM study. Results: Only one of six subjects had multiple and persistent clinical features congruent with PCD. No subject had situs inversus. Only one of six subjects had a very low nasal nitric oxide level. No “ciliary inclusions” were found in three subjects who had a repeat ciliary EM, and ciliary axonemal ultrastructures were normal. Genetic testing, including WES, was negative for PCD-causing genes, and for pathogenic variants in gene pathways that might cause “ciliary inclusions,” such as ciliary biogenesis. Conclusion: “Ciliary Inclusions”, in isolation, are not sufficient to diagnosis PCD. If seen, additional studies should be done to pursue an accurate diagnosis

Solving matrix models using holomorphy

We investigate the relationship between supersymmetric gauge theories with moduli spaces and matrix models. Particular attention is given to situations where the moduli space gets quantum corrected. These corrections are controlled by holomorphy. It is argued that these quantum deformations give rise to non-trivial relations for generalized resolvents that must hold in the associated matrix model. These relations allow to solve a sector of the associated matrix model in a similar way to a one-matrix model, by studying a curve that encodes the generalized resolvents. At the level of loop equations for the matrix model, the situations with a moduli space can sometimes be considered as a degeneration of an infinite set of linear equations, and the quantum moduli space encodes the consistency conditions for these equations to have a solution.Comment: 38 pages, JHEP style, 1 figur

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding: Bill & Melinda Gates Foundation

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study Global Burden of Disease Cancer Collaboration

IMPORTANCE: Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning. OBJECTIVE: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015. EVIDENCE REVIEW: Cancer mortality was estimated using vital registration system data, cancer registry incidence data (transformed to mortality estimates using separately estimated mortality to incidence [MI] ratios), and verbal autopsy data. Cancer incidence was calculated by dividing mortality estimates through the modeled MI ratios. To calculate cancer prevalence, MI ratios were used to model survival. To calculate YLDs, prevalence estimates were multiplied by disability weights. The YLLs were estimated by multiplying age-specific cancer deaths by the reference life expectancy. DALYs were estimated as the sum of YLDs and YLLs. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. Countries were categorized by SDI quintiles to summarize results. FINDINGS: In 2015, there were 17.5 million cancer cases worldwide and 8.7 million deaths. Between 2005 and 2015, cancer cases increased by 33%, with population aging contributing 16%, population growth 13%, and changes in age-specific rates contributing 4%. For men, the most common cancer globally was prostate cancer (1.6 million cases). Tracheal, bronchus, and lung cancer was the leading cause of cancer deaths and DALYs in men (1.2 million deaths and 25.9 million DALYs). For women, the most common cancer was breast cancer (2.4 million cases). Breast cancer was also the leading cause of cancer deaths and DALYs for women (523 000 deaths and 15.1 million DALYs). Overall, cancer caused 208.3 million DALYs worldwide in 2015 for both sexes combined. Between 2005 and 2015, age-standardized incidence rates for all cancers combined increased in 174 of 195 countries or territories. Age-standardized death rates (ASDRs) for all cancers combined decreased within that timeframe in 140 of 195 countries or territories. Countries with an increase in the ASDR due to all cancers were largely located on the African continent. Of all cancers, deaths between 2005 and 2015 decreased significantly for Hodgkin lymphoma (-6.1% [95% uncertainty interval (UI), -10.6% to -1.3%]). The number of deaths also decreased for esophageal cancer, stomach cancer, and chronic myeloid leukemia, although these results were not statistically significant. CONCLUSION AND RELEVANCE: As part of the epidemiological transition, cancer incidence is expected to increase in the future, further straining limited health care resources. Appropriate allocation of resources for cancer prevention, early diagnosis, and curative and palliative care requires detailed knowledge of the local burden of cancer. The GBD 2015 study results demonstrate that progress is possible in the war against cancer. However, the major findings also highlight an unmet need for cancer prevention efforts, including tobacco control, vaccination, and the promotion of physical activity and a healthy diet