Exposure to Amosite-Containing Ceiling Boards in a Public School in Switzerland: A Case Study.

The measurement of an airborne concentration in Amosite fibers above 5035 F/m <sup>3</sup> in a school prompted a retrospective quantitative health risk assessment. Dose estimates were built using air measurements, laboratory experiments, previous exposure data, and interviews. A dose response model was adapted for amosite-only exposure and adjusted for the life expectancy and lung cancer incidence in the Swiss population. The average yearly concentrations found were 52-320 F/m <sup>3</sup> . The high concentration previously observed was not representative of the average exposure in the building. Overall, the risk estimates for the different populations of the school were low and in the range of 2 × 10 <sup>-6</sup> to 3 × 10 <sup>-5</sup> for mesothelioma and 4 × 10 <sup>-7</sup> to 8 × 10 <sup>-6</sup> for lung cancer. The results evidenced however that children have to be considered at higher risk when exposed to asbestos, and that the current reference method and target values are of limited use for amphibole-only exposures. This study confirmed that quantitative health risk assessments and participatory approaches are powerful tools to support public decisions and build constructive communication between exposed people, experts, and policy-makers

Ceftazidime in severe infections: a Swiss multicentre study

A total of 105 patients (mean age 57, range 15 to 90) with serious infections were treated with intravenous ceftazidime, usually 2 g 8-hourly. Most patients had complicating factors such as major surgery, cancer, chronic obstructive lung disease, catheters or anatomical abnormalities. Eighty-seven infectious episodes in 77 patients could be assessed for efficacy. Bacteraemia was diagnosed in 26% of these episodes. Seventy-five per cent of infections were due to Gram-negative bacteria, Pseudomonas aeruginosa being the most frequent. The major sites of infections were the lower respiratory tract (30), the urinary tract (28), the soft tissues (9), the biliary tract (4), bones (4) and the ears (4). Overall, 67% of the patients were cured, 20% improved, 7% relapsed and 6% failed to respond. Among the 27 infections due to Ps aeruginosa, only two failures (in the same patient) and four relapses were recorded. However, in the two failures and in three other cases with persistent Ps. aeruginosa colonisation, the organism had become resistant to ceftazidime. Three failures were recorded in the seven Staphylococcus aureus infections included in this study. Superinfection occurred in four patients. Adverse events included rash (6), Clostridium difficile toxin-induced diarrhoea (3), transaminase elevation (3), weakly positive Coombs test (10). Ceftazidime appears to be safe and effective for the treatment of severe Gram-negative infections, including those caused by Ps. aeruginosa

Ceftazidime in severe infections: a Swiss multicentre study

A total of 105 patients (mean age 57, range 15 to 90) with serious infections were treated with intravenous ceftazidime, usually 2 g 8-hourly. Most patients had complicating factors such as major surgery, cancer, chronic obstructive lung disease, catheters or anatomical abnormalities. Eighty-seven infectious episodes in 77 patients could be assessed for efficacy. Bacteraemia was diagnosed in 26% of these episodes. Seventy-five per cent of infections were due to Gram-negative bacteria, Pseudomonas aeruginosa being the most frequent. The major sites of infections were the lower respiratory tract (30), the urinary tract (28), the soft tissues (9), the biliary tract (4), bones (4) and the ears (4). Overall, 67% of the patients were cured, 20% improved, 7% relapsed and 6% failed to respond. Among the 27 infections due to Ps aeruginosa, only two failures (in the same patient) and four relapses were recorded. However, in the two failures and in three other cases with persistent Ps. aeruginosa colonisation, the organism had become resistant to ceftazidime. Three failures were recorded in the seven Staphylococcus aureus infections included in this study. Superinfection occurred in four patients. Adverse events included rash (6), Clostridium difficile toxin-induced diarrhoea (3), transaminase elevation (3), weakly positive Coombs test (10). Ceftazidime appears to be safe and effective for the treatment of severe Gram-negative infections, including those caused by Ps. aeruginos

Sustainable land use in mountain regions under global change: synthesis across scales and disciplines

Mountain regions provide essential ecosystem goods and services (EGS) for both mountain dwellers and people living outside these areas. Global change endangers the capacity of mountain ecosystems to provide key services. The Mountland project focused on three case study regions in the Swiss Alps and aimed to propose land-use practices and alternative policy solutions to ensure the provision of key EGS under climate and land-use changes. We summarized and synthesized the results of the project and provide insights into the ecological, socioeconomic, and political processes relevant for analyzing global change impacts on a European mountain region. In Mountland, an integrative approach was applied, combining methods from economics and the political and natural sciences to analyze ecosystem functioning from a holistic human-environment system perspective. In general, surveys, experiments, and model results revealed that climate and socioeconomic changes are likely to increase the vulnerability of the EGS analyzed. We regard the following key characteristics of coupled human-environment systems as central to our case study areas in mountain regions: thresholds, heterogeneity, trade-offs, and feedback. Our results suggest that the institutional framework should be strengthened in a way that better addresses these characteristics, allowing for (1) more integrative approaches, (2) a more network-oriented management and steering of political processes that integrate local stakeholders, and (3) enhanced capacity building to decrease the identified vulnerability as central elements in the policy process. Further, to maintain and support the future provision of EGS in mountain regions, policy making should also focus on project-oriented, cross-sectoral policies and spatial planning as a coordination instrument for land use in general

Human bocavirus (HBoV) in children with respiratory tract infection by enzyme linked immunosorbent assay (ELISA) and qualitative polymerase chain reaction (PCR)

<p>Abstract</p> <p>Background</p> <p>Human bocavirus (HBoV) is a recently discovered parvovirus associated with mild to severe lower respiratory tract infections in children, the aim of the work was determination of human bocavirus in nasopharyngeal aspirate (NPA) of infants by qualitative PCR and determination of acute human bocavirus infection by estimation of immunoglobulin M (IgM) antibodies in serum by enzyme linked immunosorbent assay.</p> <p>Results</p> <p>Twenty two (22%) out of the 100 NPA specimens of the patients with respiratory manifestations were positive for HBoV by qualitative PCR, while ELISA revealed positive HBoV IgM antibodies in 18 (18%) patients who were also positive by PCR. Non of the controls were positive by both techniques. The correlation study between ELISA and PCR revealed high significant association, (p < 0.001, X²= 36 and agreement = 96%). Also PCR detected 4 (18.1%) NPA samples as HBoV positive cases among the patients that were not identified by ELISA. This could be due to high sensitivity and efficacy of PCR. ELISA being less sensitive than RT-PCR, sensitivity was (81.8% vs 100%), the efficacy was 97.7% in ELISA versus 99.7% for RT-PCR.</p> <p>Conclusion</p> <p>HBoV infections could be diagnosed in NPA of children by conventional PCR as a rapid and sensitive technique. While ELISA was a reliable serologic analysis for diagnosis of acute HBoV infection by estimation IgM antibodies in serum.</p

Kaposi's sarcoma‐associated herpesvirus serology in Europe and Uuganda: Multicentre study with multiple and novel assays

AbstractA multicentre study was undertaken to define novel assays with increased inter‐assay concordance, sensitivity, specificity and predictive value for serological diagnosis of human herpesvirus type 8 (HHV‐8) infection. A total of 562 sera from European and Ugandan human immunodeficiency virus (HIV)‐infected or uninfected individuals with or without Kaposi's sarcoma (KS) and blood donors were examined under code by 18 different assays in seven European laboratories. Sera from KS patients and all non‐KS sera found positive by at least 70%, 80%, or 90% of the assays were considered "true positive." The validity of the assays was then evaluated by univariate logistic regression analysis. Two immunofluorescence assays (IFA) for detection of antibodies against HHV‐8 lytic (Rlyt) or latent (LLANA) antigens and two enzyme‐linked‐immunosorbent assays (ELISA) (M2, EK8.1) for detection of antibodies against HHV‐8 structural proteins were found to be highly concordant, specific, and sensitive, with odds ratios that indicated a high predictive value. When used together, the two IFA (Rlyt‐LLANA) showed the best combination of sensitivity (89.1%) and specificity (94.9%). The performance of these assays indicate that they may be used for the clinical management of individuals at risk of developing HHV‐8 associated tumours such as allograft recipients. J. Med. Virol. 65:123–132, 2001. © 2001 Wiley‐Liss, Inc

Detection of Human Bocavirus mRNA in Respiratory Secretions Correlates with High Viral Load and Concurrent Diarrhea

Human bocavirus (HBoV) is a parvovirus recently identified in association with acute respiratory infections (ARI). Despite its worldwide occurrence, little is known on the pathogenesis of HBoV infections. In addition, few systematic studies of HBoV in ARI have been conducted in Latin America. Therefore, in order to test whether active viral replication of human bocavirus is associated with respiratory diseases and to understand the clinical impact of this virus in patients with these diseases, we performed a 3-year retrospective hospital-based study of HBoV in outpatients and inpatients with symptoms of Acute Respiratory Infections (ARI) in Brazil. Nasopharyngeal aspirates (NPAs) from 1015 patients with respiratory symptoms were tested for HBoV DNA by PCR. All samples positive for HBoV were tested by PCR for all other respiratory viruses, had HBoV viral loads determined by quantitative real time PCR and, when possible, were tested by RT-PCR for HBoV VP1 mRNA, as evidence of active viral replication. HBoV was detected in 4.8% of patients, with annual rates of 10.0%, 3.0% and 3.0% in 2005, 2006 and 2007, respectively. The range of respiratory symptoms was similar between HBoV-positive and HBoV-negative ARI patients. However, a higher rate of diarrhea was observed in HBoV-positive patients. High HBoV viral loads (>108 copies/mL) and diarrhea were significantly more frequent in patients with exclusive infection by HBoV and in patients with detection of HBoV VP1 mRNA than in patients with viral co-infection, detected in 72.9% of patients with HBoV. In summary, our data demonstrated that active HBoV replication was detected in a small percentage of patients with ARI and was correlated with concurrent diarrhea and lack of other viral co-infections

TRAIP/RNF206 is required for recruitment of RAP80 to sites of DNA damage

RAP80 localizes to sites of DNA insults to enhance the DNA-damage responses. Here we identify TRAIP/RNF206 as a novel RAP80-interacting protein and find that TRAIP is necessary for translocation of RAP80 to DNA lesions. Depletion of TRAIP results in impaired accumulation of RAP80 and functional downstream partners, including BRCA1, at DNA lesions. Conversely, accumulation of TRAIP is normal in RAP80-depleted cells, implying that TRAIP acts upstream of RAP80 recruitment to DNA lesions. TRAIP localizes to sites of DNA damage and cells lacking TRAIP exhibit classical DNA-damage response-defect phenotypes. Biochemical analysis reveals that the N terminus of TRAIP is crucial for RAP80 interaction, while the C terminus of TRAIP is required for TRAIP localization to sites of DNA damage through a direct interaction with RNF20-RNF40. Taken together, our findings demonstrate that the novel RAP80-binding partner TRAIP regulates recruitment of the damage signalling machinery and promotes homologous recombinationopen

Pulmonary epithelial barrier and immunological functions at birth and in early life - key determinants of the development of asthma? A description of the protocol for the Breathing Together study

Acknowledgements The authors are indebted to the participants and parents who have already been recruited. We also acknowledge the enthusiasm and endeavour of the research nurse team which includes: Stephen Main, Margaret Connon, Catherine Beveridge, Julie Baggott, Kay Riding, Ellie McCamie, Maria Larsson, Lynda Melvin, Mumtaz Idris, Tara Murray, Nicky Tongue, Nicolene Plaatjies, Sheila Mortimer, Sally Spedding, Susy Grevatt, Victoria Welch, Morag Zelisko, Jillian Doherty, Jane Martin, Emma Macleod and Cilla Snape. We are also delighted to be working alongside the following colleagues in laboratories: Marie Craigon, Marie McWilliam, Maria Zarconi, Judit Barabas, Lindsay Broadbent, Ceyda Oksel and Sheerien Manzoor. Grant information The study is supported by the Wellcome Trust [108818]; and the PHA HSC R&D Division, Northern Ireland.Peer reviewedPublisher PD

Effects of TLR Agonists on the Hypoxia-Regulated Transcription Factor HIF-1α and Dendritic Cell Maturation under Normoxic Conditions

Dendritic cells (DC) are professional antigen presenting cells that represent an important link between innate and adaptive immunity. Danger signals such as toll-like receptor (TLR) agonists induce maturation of DC leading to a T-cell mediated adaptive immune response. In this study, we show that exogenous as well as endogenous inflammatory stimuli for TLR4 and TLR2 induce the expression of HIF-1α in human monocyte-derived DC under normoxic conditions. On the functional level, inhibition of HIF-1α using chetomin (CTM), YC-1 and digoxin lead to no consistent effect on MoDC maturation, or cytokine secretion despite having the common effect of blocking HIF-1α stabilization or activity through different mechanisms. Stabilization of HIF-1α protein by hypoxia or CoCl2 did not result in maturation of human DC. In addition, we could show that TLR stimulation resulted in an increase of HIF-1α controlled VEGF secretion. These results show that stimulation of human MoDC with exogenous as well as endogenous TLR agonists induces the expression of HIF-1α in a time-dependent manner. Hypoxia alone does not induce maturation of DC, but is able to augment maturation after TLR ligation. Current evidence suggests that different target genes may be affected by HIF-1α under normoxic conditions with physiological roles that differ from those induced by hypoxia