The histological significance of atypical glandular cells on cervical cytology: Experience at Groote Schuur Hospital, Cape Town, South Africa

Background. Atypical glandular cells (AGC) identified on Pap tests may be markers for potentially significant pathology.Objectives. Primarily, to correlate AGC findings at Groote Schuur Hospital (GSH), Cape Town, South Africa, with subsequent histological investigations and attempt to identify predictors of pathology relevant to the clinical management of women with a cytological diagnosis of AGC. Secondly, to compare the GSH data with data from similar international studies.Methods. Records of AGC Pap tests were retrieved from the laboratory database in the anatomical pathology laboratory at GSH and clinically relevant information was summarised based on the available information. Standard descriptive statistics were used to summarise the study data, and Fisher’s exact test was used to compare categorical outcomes, where possible.Results. Of the 237 women with a cytological diagnosis of AGC and who had subsequent histological diagnoses, 120 (50.6%) had significant pathology (cervical intraepithelial neoplasia (CIN) 2 or worse). Significant cervical pathology was most common in women aged <50 years, while significant endometrial pathology predominated in women aged ≥50 years. The results of the GSH study were largely consistent with international findings, but the risk of malignancy was six times higher in the GSH population than in a comparable international group.Conclusion. AGC identified on Pap tests may be markers for potentially significant pathology. Human papillomavirus DNA testing is recommended for younger women diagnosed with AGC to reduce invasive investigations and minimise expenses in a resource-poor setting

Critical Currents and Vortex States at Fractional Matching Fields in Superconductors with Periodic Pinning

We study vortex states and dynamics in 2D superconductors with periodic pinning at fractional sub-matching fields using numerical simulations. For square pinning arrays we show that ordered states form at 1/1, 1/2, and 1/4 filling fractions while only partially ordered states form at other filling fractions, such as 1/3 and 1/5, in agreement with recent imaging experiments. For triangular pinning arrays we observe matching effects at filling fractions of 1/1, 6/7, 2/3, 1/3, 1/4, 1/6, and 1/7. For both square and triangular pinning arrays we also find that, for certian sub-matching fillings, vortex configurations depend on pinning strength. For weak pinning, ordering in which a portion of the vortices are positioned between pinning sites can occur. Depinning of the vortices at the matching fields, where the vortices are ordered, is elastic while at the incommensurate fields the motion is plastic. At the incommensurate fields, as the applied driving force is increased, there can be a transition to elastic flow where the vortices move along the pinning sites in 1D channels and a reordering transition to a triangular or distorted triangular lattice. We also discuss the current-voltage curves and how they relate to the vortex ordering at commensurate and incommensurate fields.Comment: 14 figure

A lower bound on the mass of Dark Matter particles

We discuss the bounds on the mass of Dark Matter (DM) particles, coming from the analysis of DM phase-space distribution in dwarf spheroidal galaxies (dSphs). After reviewing the existing approaches, we choose two methods to derive such a bound. The first one depends on the information about the current phase space distribution of DM particles only, while the second one uses both the initial and final distributions. We discuss the recent data on dSphs as well as astronomical uncertainties in relevant parameters. As an application, we present lower bounds on the mass of DM particles, coming from various dSphs, using both methods. The model-independent bound holds for any type of fermionic DM. Stronger, model-dependent bounds are quoted for several DM models (thermal relics, non-resonantly and resonantly produced sterile neutrinos, etc.). The latter bounds rely on the assumption that baryonic feedback cannot significantly increase the maximum of a distribution function of DM particles. For the scenario in which all the DM is made of sterile neutrinos produced via non-resonant mixing with the active neutrinos (NRP) this gives m_nrp > 1.7 keV. Combining these results in their most conservative form with the X-ray bounds of DM decay lines, we conclude that the NRP scenario remains allowed in a very narrow parameter window only. This conclusion is independent of the results of the Lyman-alpha analysis. The DM model in which sterile neutrinos are resonantly produced in the presence of lepton asymmetry remains viable. Within the minimal neutrino extension of the Standard Model (the nuMSM), both mass and the mixing angle of the DM sterile neutrino are bounded from above and below, which suggests the possibility for its experimental search.Comment: 20 pages, published in JCA

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

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele