Global hypoellipticity and global solvability for vector fields on compact Lie groups

We present necessary and sufficient conditions to have global hypoellipticity and global solvability for a class of vector fields defined on a product of compact Lie groups. In view of Greenfield's and Wallach's conjecture, about the non-existence of globally hypoelliptic vector fields on compact manifolds different from tori, we also investigate different notions of regularity weaker than global hypoellipticity and describe completely the global hypoellipticity and global solvability of zero-order perturbations of our vector fields. We also present a class of vector fields with variable coefficients whose operators can be reduced to a normal form, and we prove that the study of the global properties of such operators is equivalent to the study of the respective properties for their normal forms.Comment: 43 page

A novel role for the 3′-5′ exoribonuclease Dis3L2 in controlling cell proliferation and tissue growth

In a complex organism, cell proliferation and apoptosis need to be precisely controlled in order for tissues to develop correctly. Excessive cell proliferation can lead to diseases such as cancer. We have shown that the exoribonuclease Dis3L2 is required for the correct regulation of proliferation in a natural tissue within the model organism Drosophila melanogaster. Dis3L2 is a member of a highly conserved family of exoribonucleases that degrade RNA in a 3′-5′ direction. We show that knockdown of dis3L2 in the Drosophila wing imaginal discs results in substantial wing overgrowth due to increased cellular proliferation rather than an increase in cell size. Imaginal discs are specified in the embryo before proliferating and differentiating to form the adult structures of the fly. Using RNA-seq we identified a small set of mRNAs that are sensitive to Dis3L2 activity. Of the mRNAs which increase in levels and are therefore potential targets of Dis3L2, we identified 2 that change at the post-transcriptional level but not at the transcriptional level, namely CG2678 (a transcription factor) and pyrexia (a TRP cation channel). We also demonstrate a compensatory effect between Dis3L2 and the 5′-3′ exoribonuclease Pacman demonstrating that these 2 exoribonucleases function to regulate opposing pathways within the developing tissue. This work provides the first description of the molecular and developmental consequences of Dis3L2 inactivation in a non-human animal model. The work is directly relevant to the understanding of human overgrowth syndromes such as Perlman syndrome

Tubulohelical membrane arrays: From the initial observation to the elucidation of nanophysical properties and cellular function

Lipids undergo self-assembly to form ordered nonlamellar, nanoperiodic arrays both in vitro and in vivo. While engineering of such membrane arrays for technical devices is envisaged, we know little about their cellular function. Do they represent building blocks of an inherent cellular nanotechnology? Prospects for answering this question could be improved if the nanophysical properties of the membrane arrays could be studied in the context of specific cellular functions. Therefore, we draw attention to exceptional complex membrane arrays found in the renal epithelial cell line PtK2 that could provide perfect conditions for both biophysical and cell functional studies. The so-called tubulohelical membrane arrays (TUHMAs) combine nanoperiodicity of lipid membranes with that of helix-like proteinaceous core structures. Strikingly, they show several characteristics of dynamic, microtubule-associated single organelles. Our initial data indicate that TUHMA formation occurs in the depth of the cytoplasm under participation of cytoplasmic nucleoporins. Once matured, they may fuse with the nuclear membrane in polarized positions, either perpendicularly or in parallel to the nucleus. As a starting point for the initiation of functional studies we found a connection between TUHMAs and primary cilia, indicated by immunolabeling patterns of detyrosynated tubulin and cytoplasmic nucleoporins. We discuss these observations in the context of the ciliary cycle and of the specific requirement of ciliated renal epithelial cells for oriented cell division. Finally, we raise the question of whether putative nanooptical properties of TUHMAs could serve for communicating orientation between dividing cells

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

SummaryBackground 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

Human H5N1 influenza infections in Cambodia 2005-2011: case series and cost-of-illness.

BACKGROUND: Southeast Asia has been identified as a potential epicentre of emerging diseases with pandemic capacity, including highly pathogenic influenza. Cambodia in particular has the potential for high rates of avoidable deaths from pandemic influenza due to large gaps in health system resources. This study seeks to better understand the course and cost-of-illness for cases of highly pathogenic avian influenza in Cambodia. METHODS: We studied the 18 laboratory-confirmed cases of avian influenza subtype H5N1 identified in Cambodia between January 2005 and August 2011. Medical records for all patients were reviewed to extract information on patient characteristics, travel to hospital, time to admission, diagnostic testing, treatment and disease outcomes. Further data related to costs was collected through interviews with key informants at district and provincial hospitals, the Ministry of Health and non-governmental organisations. An ingredient-based approach was used to estimate the total economic cost for each study patient. Costing was conducted from a societal perspective and included both financial and opportunity costs to the patient or carer. Sensitivity analysis was undertaken to evaluate potential change or variation in the cost-of-illness. RESULTS: Of the 18 patients studied, 11 (61%) were under the age of 18 years. The majority of patients (16, 89%) died, eight (44%) within 24 hours of hospital admission. There was an average delay of seven days between symptom onset and hospitalisation with patients travelling an average of 148 kilometres (8-476 km) to the admitting hospital. Five patients were treated with oseltamivir of whom two received the recommended dose. For the 16 patients who received all their treatment in Cambodia the average per patient cost of H5N1 influenza illness was US$300 of which 85.0$45 per patient (15.0%) of total economic cost. CONCLUSION: Cases of avian influenza in Cambodia were characterised by delays in hospitalisation, deficiencies in some aspects of treatment and a high fatality rate. The costs associated with medical care, particularly diagnostic testing and pharmaceutical therapy, were major contributors to the relatively high cost-of-illness

Before and after study of bar workers' perceptions of the impact of smoke-free workplace legislation in the Republic of Ireland

<p>Abstract</p> <p>Background</p> <p><it>Objectives</it>: To compare support for, and perceptions of, the impacts of smoke-free workplace legislation among bar workers in the Republic of Ireland (ROI) pre- and post-implementation, and to identify predictors of support for the legislation.</p> <p>Methods</p> <p><it>Setting</it>: Public houses (pubs) in three areas of the ROI.</p> <p><it>Design</it>: Comparisons pre- and post-implementation of smoke-free workplace legislation.</p> <p><it>Participants</it>: From a largely non-random selection, 288 bar workers volunteered for the baseline survey; 220 were followed up one year later (76.4%).</p> <p><it>Outcome measures: </it>Level of support for the legislation, attitude statements concerning potential impacts of the law and modelled predictors of support for the legislation.</p> <p>Results</p> <p>Pre-implementation 59.5% of participants supported the legislation, increasing to 76.8% post-implementation. Support increased among smokers by 27.3 percentage points from 39.4% to 66.7% (p < 0.001) and among non-smokers by 12.4% percentage points from 68.8% to 81.2% (p = 0.003).</p> <p>Pre-legislation three-quarters of participants agreed that the legislation would make bars more comfortable and was needed to protect workers' health. Post-legislation these proportions increased to over 90% (p < 0.001). However, negative perceptions also increased, particularly for perceptions that the legislation has a negative impact on business (from 50.9% to 62.7%, p = 0.008) and that fewer people would visit pubs (41.8% to 62.7%, p < 0.001). After adjusting for relevant covariates, including responses to the attitude statements, support for the ban increased two to three-fold post-implementation. Regardless of their views on the economic impact, most participants agreed, both pre- and post-implementation, that the legislation was needed to protect bar workers' health.</p> <p>Conclusion</p> <p>Smoke-free legislation had the support of three-quarters of a large sample of bar workers in the ROI. However, this group holds complex sets of both positive and negative perspectives on the legislation. Of particular importance is that negative economic perceptions did not diminish the widely held perception that the ban is needed to protect workers' health.</p

Effect of training on the use of long-lasting insecticide-treated bed nets on the burden of malaria among vulnerable groups, south-west Ethiopia: baseline results of a cluster randomized trial

<p>Abstract</p> <p>Background</p> <p>In Ethiopia, the utilization of long-lasting insecticide-treated bed nets (LLITN) is hampered by behavioural factors such as low awareness and negative attitude of the community. The aim of this study was to present the design and baseline results of a cluster randomized trial on the effect of training of household heads on the use of LLITN.</p> <p>Methods</p> <p>This baseline survey was undertaken from February to March, 2009 as part of a randomized cluster trial. A total of 11 intervention and 11 control <it>Gots </it>(villages) were included in the Gilgel Gibe Field Research Centre, south-west Ethiopia. House to house visit was done in 4135 households to collect information about the use of LLITN and socio-demographic variables. For the diagnosis of malaria and anaemia, blood samples were collected from 2410 under-five children and 242 pregnant women.</p> <p>Results</p> <p>One fourth of the households in the intervention and control <it>Gots </it>had functional LLITN. Only 30% of the observed LLITN in the intervention and 28% in the control <it>Gots </it>were hanged properly. Adults were more likely to utilize LLITN than under-five children in the control and intervention <it>Gots</it>. The prevalence of malaria in under-five children in the intervention and control <it>Gots </it>was 10.5% and 8.3% respectively. The intervention and control <it>Gots </it>had no significant difference concerning the prevalence of malaria in under-five children, [OR = 1.28, (95%CI: 0.97, 1.69)]. Eight (6.1%) pregnant women in the intervention and eight (7.2%) in the control <it>Gots </it>were positive for malaria (P = 0.9). Children in the intervention <it>Gots </it>were less likely to have anaemia than children in the control <it>Gots</it>, [OR = 0.75, (95%CI: 0.62, 0.85)].</p> <p>Conclusion</p> <p>The availability and utilization of LLITN was low in the study area. The prevalence of malaria and anaemia was high. Intervention strategies of malaria should focus on high risk population and vulnerable groups.</p

One year of smokefree bars and restaurants in New Zealand: Impacts and responses

BACKGROUND: New Zealand introduced a smokefree bars and restaurants policy in December 2004. We reviewed the data available at December 2005 on the main public health, societal and political impacts and responses within New Zealand to the new law. METHODS: Data were collected from publicly available survey reports, and from government departments and interviews. This included data on smoking in bars, attitudes to smokefree bars, bar patronage, socially cued smoking, and perceived rights to smokefree workplaces. RESULTS: The proportion of surveyed bars with smoking occurring decreased from 95% to 3% during July 2004 – April 2005. Between 2004 and 2005, public support for smokefree bars rose from 56% to 69%. In the same period, support for the rights of bar workers to have smokefree workplaces rose from 81% to 91%. During the first ten months of the smokefree bars policy, there were only 196 complaints to officials about smoking in the over 9900 licensed premises. The proportion of smokers who reported that they smoked more than normal at bars, nightclubs, casinos and cafés halved between 2004 and 2005 (from 58% to 29%). Seasonally adjusted sales in bars and clubs changed little (0.6% increase) between the first three quarters of 2004 and of 2005, while café and restaurant sales increased by 9.3% in the same period. Both changes continued existing trends. Compared to the same period in 2004, average employment during the first three quarters of 2005 was up 24% for 'pubs, taverns and bars', up 9% for cafés/restaurants, and down 8% for clubs (though employment in 'pubs, taverns and bars' may have been affected by unusually high patronage around a major sports-series). The proportion of bar managers who approved of smokefree bars increased from 44% to 60% between November 2004 and May 2005. Bar managers also reported increased agreement with the rights of bar workers and patrons to smokefree environments. The main reported concerns of the national and regional Hospitality Associations, in 2005, were the perceived negative effects on rural and traditional pubs. CONCLUSION: As in other jurisdictions, the introduction of smokefree bars in New Zealand has had positive overall health protection, economic and social effects; in contrast to the predictions of opponents

Cervical squamous carcinoma cells are resistant to the combined action of tumor necrosis factor-α and histamine whereas normal keratinocytes undergo cytolysis

<p>Abstract</p> <p>Background</p> <p>Previous reports showed that mast cells can typically be found in the peritumoral stroma of cervix carcinomas as well as in many other cancers. Both histamine and TNF-α are potent preformed mast cell mediators and they can act simultaneously after release from mast cells. Thus, the effect of TNF-α and histamine on cervical carcinoma cell lines was studied.</p> <p>Methods and results</p> <p>TNF-α alone induced slight growth inhibition and cell cycle arrest at G0/G1 phase in SiHa cells, but increased their migration. Histamine alone had no effect on cells. In addition, TNF-α and histamine in combination showed no additional effect over that by TNF-α alone, although SiHa cells were even pretreated with a protein synthesis inhibitor. Furthermore, TNF-α-sensitive ME-180 carcinoma cells were also resistant to the combination effect of TNF-α and histamine. In comparison, TNF-α or histamine alone induced growth inhibition in a non-cytolytic manner in normal keratinocytes, an effect that was further enhanced to cell cytolysis when both mediators acted in combination. Keratinocytes displayed strong TNF receptor (TNFR) I and II immunoreactivity, whereas SiHa and ME-180 cells did not. Furthermore, cervix carcinoma specimens revealed TNF-α immunoreactivity in peritumoral cells and carcinoma cells. However, the immunoreactivity of both TNFRs was less intense in carcinoma cells than that in epithelial cells in cervical specimens with non-specific inflammatory changes.</p> <p>Conclusion</p> <p>SiHa and ME-180 cells are resistant to the cytolytic effect of TNF-α and histamine whereas normal keratinocytes undergo cytolysis, possibly due to the smaller amount of TNFRs in SiHa and ME-180 cells. In the cervix carcinoma, the malignant cells may resist this endogenous cytolytic action and TNF-α could even enhance carcinoma cell migration.</p