A tale of two cities: effects of air pollution on hospital admissions in Hong Kong and London compared.

The causal interpretation of reported associations between daily air pollution and daily admissions requires consideration of residual confounding, correlation between pollutants, and effect modification. If results obtained in Hong Kong and London--which differ in climate, lifestyle, and many other respects--were similar, a causal association would be supported. We used identical statistical methods for the analysis in each city. Associations between daily admissions and pollutant levels were estimated using Poisson regression. Nonparametric smoothing methods were used to model seasonality and the nonlinear dependence of admissions on temperature, humidity, and influenza admissions. For respiratory admissions (> or = 65 years of age), significant positive associations were observed with particulate matter < 10 microm in aerodynamic diameter (PM(10), nitrogen dioxide, sulfur dioxide, and ozone in both cities. These associations tended to be stronger at shorter lags in Hong Kong and at longer lags in London. Associations were stronger in the cool season in Hong Kong and in the warm season in London, periods during which levels of humidity are at their lowest in each city. For cardiac admissions (all ages) in both cities, significant positive associations were observed for PM(10), NO(2), and SO(2) with similar lag patterns. Associations tended to be stronger in the cool season. The associations with NO(2) and SO(2) were the most robust in two-pollutant models. Patterns of association for pollutants with ischemic heart disease were similar in the two cities. The associations between O(3) and cardiac admissions were negative in London but positive in Hong Kong. We conclude that air pollution has remarkably similar associations with daily cardiorespiratory admissions in both cities, in spite of considerable differences between cities in social, lifestyle, and environmental factors. The results strengthen the argument that air pollution causes detrimental short-term health effects

Evaluating the Benefits of Restricted Grazing to Protect Wet Pasture Soils in Two Dairy Regions of New Zealand

Many dairy farms in the Manawatu and Southland regions of New Zealand have poorly drained soils that are prone to treading damage, an undesirable outcome on grazed pastures during the wetter months of the year. Removing cows to a stand-off pad during wet conditions can reduce damage, but incurs costs. The objective of this study was to evaluate the impact of different levels of restricted grazing (from 0 to 10 hours grazing time/day for lactating cows) on pasture yield, damage and wastage, feed and stand-off expenses, and farm operating profit. A simulated farm from each region was used in a farm systems model. This model simulated pasture-cow-management interactions, using site-specific climate data as inputs for the soil-pasture sub-models. Days to recover previous yield potential for damaged paddocks can vary widely. A sensitivity analysis (40 to 200 days to recover) was conducted to evaluate the effect of this parameter on results. Full protection when there is risk of damage (0 grazing hours/day) appeared to be less profitable compared with some level of grazing, because the advantages of reduced damage were outweighed by the disadvantages of managing infrequently grazed pastures. The differences in operating profit between full protection and some level of grazing became less as the recovery time increased, but for both regions grazing durations of 6-8 hours/day when a risk of damage is present appeared to be a sensible strategy irrespective of recovery time

Replication Stress Drives Constitutive Activation of the DNA Damage Response and Radioresistance in Glioblastoma Stem-like Cells

Glioblastoma (GBM) is a lethal primary brain tumor characterized by treatment resistance and inevitable tumor recurrence, both of which are driven by a subpopulation of GBM cancer stem-like cells (GSC) with tumorigenic and self-renewal properties. Despite having broad implications for understanding GSC phenotype, the determinants of upregulated DNA damage response (DDR) and subsequent radiation resistance in GSC are unknown and represent a significant barrier to developing effective GBM treatments. In this study, we show that constitutive DDR activation and radiation resistance are driven by high levels of DNA replication stress (RS). CD133+ GSC exhibited reduced DNA replication velocity and a higher frequency of stalled replication forks than CD133- non-GSC in vitro; immunofluorescence studies confirmed these observations in a panel of orthotopic xenografts and human GBM specimens. Exposure of non-GSC to low-level exogenous RS generated radiation resistance in vitro, confirming RS as a novel determinant of radiation resistance in tumor cells. GSC exhibited DNA double strand breaks (DSB) which co-localized with 'replication factories' and RNA: DNA hybrids. GSC also demonstrated increased expression of long neural genes (&gt;1Mbp) containing common fragile sites, supporting the hypothesis that replication/transcription collisions are the likely cause of RS in GSC. Targeting RS by combined inhibition of ATR and PARP (CAiPi) provided GSC-specific cytotoxicity and complete abrogation of GSC radiation resistance in vitro. These data identify RS as a cancer stem cell-specific target with significant clinical potential

Japan Tobacco International: : To ‘be the most successful and respected tobacco company in the world’

Japan Tobacco International (JTI) is the international division of Japan Tobacco Incorporated, and the world's third largest transnational tobacco company. Founded in 1999, JTI's rapid growth has been the result of a global business strategy that potentially serves as a model for other Asian tobacco companies. This paper analyses Japan Tobacco Incorporated's global expansion since the 1980s in response to market opening, foreign competition, and declining share of a contracting domestic market. Key features of its global strategy include the on-going central role and investment by the Japanese government, and an expansion agenda based on mergers and acquisitions. The paper also discusses the challenges this global business strategy poses for global tobacco control and public health. This paper is part of the special issue 'The Emergence of Asian Tobacco Companies: Implications for Global Health Governance'.19 page(s

‘Preparing Ourselves to Become an International Organization’: Thailand Tobacco Monopoly’s Regional and Global Strategies

The Thailand Tobacco Monopoly (TTM) controlled the country\u27s tobacco industry from its formation in the 1940s, until the government dropped restrictions on imported cigarettes in the late 1980s in response to pressure from the United States. The TTM has since competed with transnational tobacco companies (TTCs) in a semi-monopoly market in which TTCs have steadily increased their market share. Coupled with a decline in national smoking prevalence, the result of Thailand\u27s stringent tobacco control agenda, the TTM now accounts for a diminishing share of a contracting market. In response, the monopoly has looked to regional trade liberalisation, and proximity to markets with some of the world\u27s highest smoking rates to expand its operations. Expansion strategies have gone largely unrealised however, and the TTM effectively remains a domestic operation. Using TTM publications, market and trade reports, industry publications, tobacco industry documents and other resources, this paper analyses TTM expansion strategies, and the limited extent to which they have been achieved. This inability to expand its operations has left the monopoly potentially vulnerable to global strategies of its transnational competitors. This article is part of the special issue \u27The Emergence of Asian Tobacco Companies: Implications for Global Health Governance\u27

Association of Alleles Carried at TNFA -850 and BAT1 -22 with Alzheimer\u27s Disease

Background: Inflammatory changes are a prominent feature of brains affected by Alzheimer\u27s disease (AD). Activated glial cells release inflammatory cytokines which modulate the neurodegenerative process. These cytokines are encoded by genes representing several interleukins and TNFA, which are associated with AD. The gene coding for HLA-B associated transcript 1 (BAT1) lies adjacent to TNFA in the central major histocompatibility complex (MHC). BAT1, a member of the DEAD-box family of RNA helicases, appears to regulate the production of inflammatory cytokines associated with AD pathology. In the current study TNFA and BAT1 promoter polymorphisms were analysed in AD and control cases and BAT1 mRNA levels were investigated in brain tissue from AD and control cases. Methods: Genotyping was performed for polymorphisms at positions -850 and -308 in the proximal promoter of TNFA and position -22 in the promoter of BAT1. These were investigated singly or in haplotypic association in a cohort of Australian AD patients with AD stratified on the basis of their APOE ε4 genotype. Semi-quantitative RT-PCR was also performed for BAT1 from RNA isolated from brain tissue from AD and control cases. Results: APOE ε4 was associated with an independent increase in risk for AD in individuals with TNFA -850*2, while carriage of BAT1 -22*2 reduced the risk for AD, independent of APOE ε4 genotype. Semi-quantitative mRNA analysis in human brain tissue showed elevated levels of BAT1 mRNA in frontal cortex of AD cases. Conclusion: These findings lend support to the application of TNFA and BAT1 polymorphisms in early diagnosis or risk assessment strategies for AD and suggest a potential role for BAT1 in the regulation of inflammatory reactions in AD pathology

HIV infection and stroke:current perspectives and future directions

HIV infection can result in stroke via several mechanisms, including opportunistic infection, vasculopathy, cardioembolism, and coagulopathy. However, the occurrence of stroke and HIV infection might often be coincidental. HIV-associated vasculopathy describes various cerebrovascular changes, including stenosis and aneurysm formation, vasculitis, and accelerated atherosclerosis, and might be caused directly or indirectly by HIV infection, although the mechanisms are controversial. HIV and associated infections contribute to chronic inflammation. Combination antiretroviral therapies (cART) are clearly beneficial, but can be atherogenic and could increase stroke risk. cART can prolong life, increasing the size of the ageing population at risk of stroke. Stroke management and prevention should include identification and treatment of the specific cause of stroke and stroke risk factors, and judicious adjustment of the cART regimen. Epidemiological, clinical, biological, and autopsy studies of risk, the pathogenesis of HIV-associated vasculopathy (particularly of arterial endothelial damage), the long-term effects of cART, and ideal stroke treatment in patients with HIV are needed, as are antiretrovirals that are without vascular risk

Principles of Periodontology

Periodontal diseases are among the most common diseases affecting humans. Dental biofilm is a contributor to the etiology of most periodontal diseases. It is also widely accepted that immunological and inflammatory responses to biofilm components are manifested by signs and symptoms of periodontal disease. The outcome of such interaction is modulated by risk factors (modifiers), either inherent (genetic) or acquired (environmental), significantly affecting the initiation and progression of different periodontal disease phenotypes. While definitive genetic determinants responsible for either susceptibility or resistance to periodontal disease have yet to be identified, many factors affecting the pathogenesis have been described, including smoking, diabetes, obesity, medications, and nutrition. Currently, periodontal diseases are classified based upon clinical disease traits using radiographs and clinical examination. Advances in genomics, molecular biology, and personalized medicine may result in new guidelines for unambiguous disease definition and diagnosis in the future. Recent studies have implied relationships between periodontal diseases and systemic conditions. Answering critical questions regarding host‐parasite interactions in periodontal diseases may provide new insight in the pathogenesis of other biomedical disorders. Therapeutic efforts have focused on the microbial nature of the infection, as active treatment centers on biofilm disruption by non‐surgical mechanical debridement with antimicrobial and sometimes anti‐inflammatory adjuncts. The surgical treatment aims at gaining access to periodontal lesions and correcting unfavorable gingival/osseous contours to achieve a periodontal architecture that will provide for more effective oral hygiene and periodontal maintenance. In addition, advances in tissue engineering have provided innovative means to regenerate/repair periodontal defects, based upon principles of guided tissue regeneration and utilization of growth factors/biologic mediators. To maintain periodontal stability, these treatments need to be supplemented with long‐term maintenance (supportive periodontal therapy) programs

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Outcome of cardiac surgery in patients with low preoperative ejection fraction

Background: In patients undergoing cardiac surgery, a reduced preoperative left ventricular ejection fraction (LVEF) is common and is associated with a worse outcome. Available outcome data for these patients address specific surgical procedures, mainly coronary artery bypass graft (CABG). Aim of our study was to investigate perioperative outcome of surgery on patients with low pre-operative LVEF undergoing a broad range of cardiac surgical procedures. Methods: Data from patients with pre-operative LVEF ≤40 % undergoing cardiac surgery at a university hospital were reviewed and analyzed. A subgroup analysis on patients with pre-operative LVEF ≤30 % was also performed. Results: A total of 7313 patients underwent cardiac surgery during the study period. Out of these, 781 patients (11 %) had a pre-operative LVEF ≤40 % and were included in the analysis. Mean pre-operative LVEF was 33.9 ± 6.1 % and in 290 patients (37 %) LVEF was ≤30 %. The most frequently performed operation was CABG (31 % of procedures), followed by mitral valve surgery (22 %) and aortic valve surgery (19 %). Overall perioperative mortality was 5.6 %. Mitral valve surgery was more frequent among patients who did not survive, while survivors underwent more frequently CABG. Post-operative myocardial infarction occurred in 19 (2.4 %) of patients, low cardiac output syndrome in 271 (35 %). Acute kidney injury occurred in 195 (25 %) of patients. Duration of mechanical ventilation was 18 (12-48) hours. Incidence of complications was higher in patients with LVEF ≤30 %. Stepwise multivariate analysis identified chronic obstructive pulmonary disease, pre-operative insertion of intra-aortic balloon pump, and pre-operative need for inotropes as independent predictors of mortality among patients with LVEF ≤40 %. Conclusions: We confirmed that patients with low pre-operative LVEF undergoing cardiac surgery are at higher risk of post-operative complications. Cardiac surgery can be performed with acceptable mortality rates; however, mitral valve surgery, was found to be associated with higher mortality rates in this population. Accurate selection of patients, risk/benefit evaluation, and planning of surgical and anesthesiological management are mandatory to improve outcome