Modelling of Quaternary Glacier Extent and Climate in Tasmania, Australia

The aim of this study was to improve our understanding of Quaternary glaciations in Tasmania, and to assess their climatic significance. During the Quaternary, Tasmania experienced ice cap development in the West Coast Range and Central Plateau, with smaller cirque and valley glaciers developing on surrounding mountains. Geomorphic evidence indicates at least four glacial advances occurred. A 500 m resolution, three-dimensional thermomechanical ice-sheet model was used to reconstruct and simulate these glacier fluctuations. The model, while a simplification of reality, provided a framework in which to understand the genesis of contemporary landforms and former glacial climate conditions in Tasmania. Input specifications of basal topography, temperature and precipitation were required, with the latter two interpolated from present-day datasets. Numerous experiments were carried out, involving systematic alterations to temperature and precipitation, basal sliding and atmospheric temperature lapse-rates. Modelled output was compared to empirical evidence with the aim of optimizing the parameters (temperature, precipitation) from which model mismatch was minimised. An annual temperature reduction of 6' C is required for glaciers to form in Tasmania. When temperatures cool beyond this threshold, an ice mass develops over the Central Highlands, Central Plateau, West Coast Range and other mountains. In all but the most extensive glaciations, the Central Plateau ice field consists of a relatively thin carapace of ice, and the thickest and most dynamic glaciers develop in the deep valleys of the Central Highlands. The model shows that ice readily flows down the west-facing valleys from the Central Highlands to join with West Coast Range glaciers. A temperature reduction between 7 and 9' C, with corresponding regional precipitation changes of between +/-50% and an increase in orographic precipitation is required to simulate the Last Glacial Maximum (LGM) ice cover. Earlier glacial advances require larger coolings of up to 11.25' C depending on the regional precipitation conditions prescribed. Mismatches between geomorphic evidence and modelled reconstructions probably result from model grid size issues and parameters not accommodated by the model such as wind-blown snow redistribution. This means that temperature reductions derived from the model may have been overestimated. Despite these limitations, reconstructed temperatures compare well to some multi-proxy palaeo-temperature records from Tasmania, although the cooling identified was larger than that recorded in nearby ocean sediments

Abordando la exposición a las emisiones del tabaco y de los cigarrillos electrónicos: protocolo del proyecto TackSHS

Objective The TackSHS project aims to comprehensively elucidate the impact that exposure to second-hand smoke (SHS) from cigarettes and second-hand aerosols (SHA) from electronic cigarettes have on the respiratory health of the European population according to socioeconomic characteristics and other determinants. Method The TackSHS project involves a series of coordinated studies carried out by 11 academic and public health organisations from six European countries. The project will investigate: a) the determinants of SHS and SHA exposure assessed at the individual level (surveys on representative general population samples) and in common environments (environmental sampling in specific settings); b) the overall disease burden, mortality and morbidity attributable to such exposure; and c) its economic impact in terms of direct health care costs. The project will also examine specific acute respiratory health changes in healthy individuals and patients with respiratory diseases exposed to SHS and SHA. In addition, the project will examine the effectiveness of a novel intervention to reduce SHS exposure in households where smoking is permitted. All these studies are inter-related and involve collaborative coordination among the participant organisations. Conclusion The comprehensive, integrated approach of the TackSHS project will enable a significant step forward from the current status quo in the understanding of the impact of SHS and SHA exposure on health and provide the basis for health policy recommendations to help European countries to further reduce the harm caused by SHS and SHA exposure.Additional co-authors: Montse Ballbè, Beladenta Amalia, Olena Tigova, Xavier Continente, Teresa Arechávala, Elisabet Henderson, Alessandra Lugo, Xiaoqiu Liu, Cristina Bosetti, Enrico Davoli, Paolo Colombo, Sheila Keogan, Shashsa Li, Elizabeth Breslin, Hannah Byrne, Anna Tzortzi, Constantine Vardavas, Vergina Konstantina Vyzikidou, Stephanie Teloniatis, Gerasimos Bakelas, George Mattiampa, Roberto Boffi, Cinzia De Marco, Alessandro Borgini, Chiara Veronese, Martina Bertoldi, Andrea Tittarelli, Giulia Carreras, Barbara Cortini, Simona Verdi, Alessio Lachi, Elisabetta Chellini, Marta Trapero-Bertran, Daniel Celdrán Guerrero, Dominick Nguyen, Polina Starchenko, Julio Ancochea, Tamara Alonso, María Teresa Pastor, Marta Erro, Ana Roca, Patricia Pére

Estimates of Pandemic Influenza Vaccine Effectiveness in Europe, 2009–2010: Results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) Multicentre Case-Control Study

Results from a European multicentre case-control study reported by Marta Valenciano and colleagues suggest good protection by the pandemic monovalent H1N1 vaccine against pH1N1 and no effect of the 2009–2010 seasonal influenza vaccine on H1N1

A Comprehensive Phenotypic and Functional Immune Analysis Unravels Circulating Anti-Phospholipase A2 Receptor Antibody Secreting Cells in Membranous Nephropathy Patients

Introduction: Primary membranous nephropathy (MN) is characterized by the presence of antipodocyte antibodies, but studies describing phenotypic and functional abnormalities in circulating lymphocytes are limited. Methods: We analyzed 68 different B- and T-cell subsets using flow cytometry in 30 MN patients (before initiating immunosuppression) compared with 31 patients with non-immune-mediated chronic kidney disease (CKD) and 12 healthy individuals. We also measured 19 serum cytokines in MN patients and in healthy controls. Lastly, we quantified the ex vivo production of phospholipase A2 receptor (PLA2R)-specific IgG by plasmablasts (measuring antibodies in culture supernatants and by the newly developed FluoroSpot assay [AutoImmun Diagnostika, Strasberg, Germany]) and assessed the circulating antibody repertoire by phage immunoprecipitation sequencing (PhIP-Seq). Results: After adjusting for multiple testing, plasma cells and regulatory B cells (BREG) were significantly higher (P < 0.05) in MN patients compared with both control groups. The percentages of circulating plasma cells correlated with serum anti-PLA2R antibody levels (P = 0.042) and were associated with disease activity. Ex vivo-expanded PLA2R-specific IgG-producing plasmablasts generated from circulating PLA2R-specific memory B cells (mBCs) correlated with serum anti-PLA2R IgG antibodies (P < 0.001) in MN patients. Tumor necrosis factor-alpha (TNF-alpha) was the only significantly increased cytokine in MN patients (P < 0.05), whereas there was no significant difference across study groups in the autoantibody and antiviral antibody repertoire. Conclusion: This extensive phenotypic and functional immune characterization shows that autoreactive plasma cells are present in the circulation of MN patients, providing a new therapeutic target and a candidate biomarker of disease activity

Health and economic impact of seasonal influenza mass vaccination strategies in European settings: A mathematical modelling and cost-effectiveness analysis

Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861572/Introduction: Despite seasonal influenza vaccination programmes in most countries targeting individuals aged ≥ 65 (or ≥ 55) years and high risk-groups, significant disease burden remains. We explored the impact and cost-effectiveness of 27 vaccination programmes targeting the elderly and/or children in eight European settings (n = 205.8 million). Methods: We used an age-structured dynamic-transmission model to infer age- and (sub-)type-specific seasonal influenza virus infections calibrated to England, France, Ireland, Navarra, The Netherlands, Portugal, Scotland, and Spain between 2010/11 and 2017/18. The base-case vaccination scenario consisted of non-adjuvanted, non-high dose trivalent vaccines (TV) and no universal paediatric vaccination. We explored i) moving the elderly to "improved" (i.e., adjuvanted or high-dose) trivalent vaccines (iTV) or non-adjuvanted non-high-dose quadrivalent vaccines (QV); ii) adopting mass paediatric vaccination with TV or QV; and iii) combining the elderly and paediatric strategies. We estimated setting-specific costs and quality-adjusted life years (QALYs) gained from the healthcare perspective, and discounted QALYs at 3.0%. Results: In the elderly, the estimated numbers of infection per 100,000 population are reduced by a median of 261.5 (range across settings: 154.4, 475.7) when moving the elderly to iTV and by 150.8 (77.6, 262.3) when moving them to QV. Through indirect protection, adopting mass paediatric programmes with 25% uptake achieves similar reductions in the elderly of 233.6 using TV (range: 58.9, 425.6) or 266.5 using QV (65.7, 477.9), with substantial health gains from averted infections across ages. At €35,000/QALY gained, moving the elderly to iTV plus adopting mass paediatric QV programmes provides the highest mean net benefits and probabilities of being cost-effective in all settings and paediatric coverage levels. Conclusion: Given the direct and indirect protection, and depending on the vaccine prices, model results support a combination of having moved the elderly to an improved vaccine and adopting universal paediatric vaccination programmes across the European settings.Highlights: Seasonal influenza vaccine programmes usually target at-risk and older individuals; We used an age-structured dynamic-transmission model for eight European settings; Older people benefit from adjuvanted or high-dose trivalent or quadrivalent vaccines; Adopting mass paediatric influenza vaccination is also likely to be cost-effective; Results rest on vaccine costs, willingness to vaccinate and unknown long-term effects.I-MOVE+ (Integrated Monitoring of Vaccines in Europe) project, received a grant from the European Commission Horizon 2020 research and innovation programme (grant agreement No 634446).info:eu-repo/semantics/publishedVersio

I-MOVE Multi-Centre Case Control Study 2010-11: Overall and Stratified Estimates of Influenza Vaccine Effectiveness in Europe

BACKGROUND: In the third season of I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe), we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in eight European Union (EU) member states to estimate 2010/11 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. METHODS: Using systematic sampling, practitioners swabbed ILI/ARI patients within seven days of symptom onset. We compared influenza-positive to influenza laboratory-negative patients among those meeting the EU ILI case definition. A valid vaccination corresponded to > 14 days between receiving a dose of vaccine and symptom onset. We used multiple imputation with chained equations to estimate missing values. Using logistic regression with study as fixed effect we calculated influenza VE adjusting for potential confounders. We estimated influenza VE overall, by influenza type, age group and among the target group for vaccination. RESULTS: We included 2019 cases and 2391 controls in the analysis. Adjusted VE was 52% (95% CI 30-67) overall (N = 4410), 55% (95% CI 29-72) against A(H1N1) and 50% (95% CI 14-71) against influenza B. Adjusted VE against all influenza subtypes was 66% (95% CI 15-86), 41% (95% CI -3-66) and 60% (95% CI 17-81) among those aged 0-14, 15-59 and ≥60 respectively. Among target groups for vaccination (N = 1004), VE was 56% (95% CI 34-71) overall, 59% (95% CI 32-75) against A(H1N1) and 63% (95% CI 31-81) against influenza B. CONCLUSIONS: Results suggest moderate protection from 2010-11 trivalent influenza vaccines against medically-attended ILI laboratory-confirmed as influenza across Europe. Adjusted and stratified influenza VE estimates are possible with the large sample size of this multi-centre case-control. I-MOVE shows how a network can provide precise summary VE measures across Europe

A Dynamic Pathway for Calcium-Independent Activation of CaMKII by Methionine Oxidation

SummaryCalcium/calmodulin (Ca2+/CaM)-dependent protein kinase II (CaMKII) couples increases in cellular Ca2+ to fundamental responses in excitable cells. CaMKII was identified over 20 years ago by activation dependence on Ca2+/CaM, but recent evidence shows that CaMKII activity is also enhanced by pro-oxidant conditions. Here we show that oxidation of paired regulatory domain methionine residues sustains CaMKII activity in the absence of Ca2+/CaM. CaMKII is activated by angiotensin II (AngII)-induced oxidation, leading to apoptosis in cardiomyocytes both in vitro and in vivo. CaMKII oxidation is reversed by methionine sulfoxide reductase A (MsrA), and MsrA−/− mice show exaggerated CaMKII oxidation and myocardial apoptosis, impaired cardiac function, and increased mortality after myocardial infarction. Our data demonstrate a dynamic mechanism for CaMKII activation by oxidation and highlight the critical importance of oxidation-dependent CaMKII activation to AngII and ischemic myocardial apoptosis

Exposure to secondhand aerosol from electronic cigarettes at homes: A real-life study in four European countries

Electronic cigarette (e-cigarette) use emits potentially hazardous compounds and deteriorates indoor air quality. Home is a place where e-cigarettes may frequently be used amid its increasing prohibition in public places. This study assessed the real-life scenario of bystanders' exposure to secondhand e-cigarette aerosol (SHA) at home. A one-week observational study was conducted within the TackSHS project in four countries (Greece, Italy, Spain, and the United Kingdom) in 2019 including: 1) homes of e-cigarette users living together with a non-user/non-smoker; and 2) control homes with no smokers nor e-cigarette users. Indoor airborne nicotine, PM2.5, and PM1.0 concentrations were measured as environmental markers of SHA. Biomarkers, including nicotine and its metabolites, tobacco -specific nitrosamines, propanediol, glycerol, and metals were measured in participants' saliva and urine samples. E-cigarette use characteristics, such as e-cigarette refill liquid's nicotine concentration, e-cigarette type, place of e-cigarette use at home, and frequency of ventilation, were also collected. A total of 29 e-cigarette users' homes and 21 control homes were included. The results showed that the seven-day concentrations of airborne nicotine were quantifiable in 21 (72.4 %) out of 29 e-cigarette users' homes; overall, they were quite low (geometric mean: 0.01 mu g/m3; 95 % CI: 0.01-0.02 mu g/m(3)) and were all below the limit of quantification in control homes. Seven-day concentrations of PM2.5 and PM1.0 in e-cigarette and control homes were similar. Airborne nicotine and PM concentrations did not differ according to different e-cigarette use characteristics. Non-users residing with e-cigarette users had low but significantly higher levels of cotinine, 3 '-OH-cotinine and 1,2-propanediol in saliva, and cobalt in urine than non-users living in control homes. In conclusion, e-cigarette use at home created bystanders' exposure to SHA regardless of the e-cigarette use characteristics. Further studies are warranted to assess the implications of SHA exposure for smoke-free policy

Burden of disease attributable to second-hand smoke exposure: a systematic review

Our aim was to provide a systematic review of studies on the burden of disease due to second-hand smoke (SHS) exposure, reviewing methods, exposure assessment, diseases causally linked to SHS, health outcomes, and estimates available to date. A literature review of studies on the burden of disease from SHS exposure, available in PubMed and SCOPUS, published 2007–2018 in English language, was carried out following the PRISMA recommendations. Overall, 588 studies were first identified, and 94 were eligible. Seventy-two studies were included in the systematic review. Most of them were based on the comparative risk assessment approach, assessing SHS exposure using mainly surveys on exposure at home/workplaces. Diseases more frequently studied were: lung cancer, ischemic heart disease, stroke, chronic obstructive pulmonary disease, asthma and breast cancer in adults; lower respiratory tract infection, otitis media, asthma, sudden infant death syndrome and low birth weight in children. The SHS exposure assessment and the reported population attributable fractions (PAF) were largely heterogeneous. As an example, the PAF from lung cancer varied between 0.6% and 20.5%. Moreover, PAF were estimated applying relative risks and SHS exposures with no consistent definitions or with different age classes. The research gap on the SHS exposure burden is shrinking. However, estimates are not yet available for a number of countries, particularly the Middle Eastern and African countries, and not all diseases with the strongest evidence of causation, such as sudden infant death syndrome, have been explored. Moreover, in some cases the applied methodology revealed relatively low quality of data