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

Representation of decision-making in European agricultural agent-based models

The use of agent-based modelling approaches in ex-post and ex-ante evaluations of agricultural policies has been progressively increasing over the last few years. There are now a sufficient number of models that it is worth taking stock of the way these models have been developed. Here, we review 20 agricultural agent-based models (ABM) addressing heterogeneous decision-making processes in the context of European agriculture. The goals of this review were to i) develop a framework describing aspects of farmers' decision-making that are relevant from a farm-systems perspective, ii) reveal the current state-of-the-art in representing farmers' decision-making in the European agricultural sector, and iii) provide a critical reflection of underdeveloped research areas and on future opportunities in modelling decision-making. To compare different approaches in modelling farmers' behaviour, we focused on the European agricultural sector, which presents a specific character with its family farms, its single market and the common agricultural policy (CAP). We identified several key properties of farmers' decision-making: the multi-output nature of production; the importance of non-agricultural activities; heterogeneous household and family characteristics; and the need for concurrent short- and long-term decision-making. These properties were then used to define levels and types of decision-making mechanisms to structure a literature review. We find most models are sophisticated in the representation of farm exit and entry decisions, as well as the representation of long-term decisions and the consideration of farming styles or types using farm typologies. Considerably fewer attempts to model farmers' emotions, values, learning, risk and uncertainty or social interactions occur in the different case studies. We conclude that there is considerable scope to improve diversity in representation of decision-making and the integration of social interactions in agricultural agent-based modelling approaches by combining existing modelling approaches and promoting model inter-comparisons. Thus, this review provides a valuable entry point for agent-based modellers, agricultural systems modellers and data driven social scientists for the re-use and sharing of model components, code and data. An intensified dialogue could fertilize more coordinated and purposeful combinations and comparisons of ABM and other modelling approaches as well as better reconciliation of empirical data and theoretical foundations, which ultimately are key to developing improved models of agricultural systems.Swiss National Science Foundatio

Decongestion improving right heart function ameliorates prognosis after an acute heart failure episode.

The prognostic role of decongestion-related change of cardiac morphology and in particular right heart function has not been investigated comprehensively in AHF patients. This prospective observational single-centre study included consecutive patients hospitalized for treatment of AHF with reduced, mildly-reduced or preserved left ventricular ejection fraction (LVEF). Comprehensive transthoracic echocardiography at admission and discharge assessed decongestion-related change of cardiac function and morphology. The combined endpoint of 1 year all-cause mortality and cardiovascular rehospitalization explored the prognostic importance of decongestion-related change. The 176 study participants were 83 years old [74-87] and 54% were men. Fifty one (29%) had rLVEF, 65 (37%) mrLVEF, and 60 (34%) pLVEF. The proportion of de novo or worsening chronic HF was not different between LVEF groups. HF aetiology and cardiovascular risk factors were equally distributed across all groups except for a higher BMI in the pLVEF group. Decongestion equally reduced body weight, heart rate, systolic and diastolic blood pressure, tricuspid regurgitation gradient, and inferior vena cava diameter across all groups (P < 0.004 for all). Decongestion-related increase in TAPSE independent of the LVEF was associated with improvement of right-ventricular-pulmonary artery coupling and a lower incidence of the combined outcome in the Cox proportional hazard risk analysis (unadjusted HR 0.50 95% CI 0.33-0.78, P = 0.002; adjusted HR 0.46 95% CI: 0.33-0.78, P = 0.001). Decongestion-related increase in TAPSE and recovery of RV/pulmonary artery coupling was observed across all LVEF groups and associated with a risk reduction for the combined endpoint highlighting the important prognostic role of right heart recovery after an AHF episode

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

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

Extracting key information from historical data to quantify the transmission dynamics of smallpox

<p>Abstract</p> <p>Background</p> <p>Quantification of the transmission dynamics of smallpox is crucial for optimizing intervention strategies in the event of a bioterrorist attack. This article reviews basic methods and findings in mathematical and statistical studies of smallpox which estimate key transmission parameters from historical data.</p> <p>Main findings</p> <p>First, critically important aspects in extracting key information from historical data are briefly summarized. We mention different sources of heterogeneity and potential pitfalls in utilizing historical records. Second, we discuss how smallpox spreads in the absence of interventions and how the optimal timing of quarantine and isolation measures can be determined. Case studies demonstrate the following. (1) The upper confidence limit of the 99th percentile of the incubation period is 22.2 days, suggesting that quarantine should last 23 days. (2) The highest frequency (61.8%) of secondary transmissions occurs 3–5 days after onset of fever so that infected individuals should be isolated before the appearance of rash. (3) The U-shaped age-specific case fatality implies a vulnerability of infants and elderly among non-immune individuals. Estimates of the transmission potential are subsequently reviewed, followed by an assessment of vaccination effects and of the expected effectiveness of interventions.</p> <p>Conclusion</p> <p>Current debates on bio-terrorism preparedness indicate that public health decision making must account for the complex interplay and balance between vaccination strategies and other public health measures (e.g. case isolation and contact tracing) taking into account the frequency of adverse events to vaccination. In this review, we summarize what has already been clarified and point out needs to analyze previous smallpox outbreaks systematically.</p

The Min System and Nucleoid Occlusion Are Not Required for Identifying the Division Site in Bacillus subtilis but Ensure Its Efficient Utilization

Precise temporal and spatial control of cell division is essential for progeny survival. The current general view is that precise positioning of the division site at midcell in rod-shaped bacteria is a result of the combined action of the Min system and nucleoid (chromosome) occlusion. Both systems prevent assembly of the cytokinetic Z ring at inappropriate places in the cell, restricting Z rings to the correct site at midcell. Here we show that in the bacterium Bacillus subtilis Z rings are positioned precisely at midcell in the complete absence of both these systems, revealing the existence of a mechanism independent of Min and nucleoid occlusion that identifies midcell in this organism. We further show that Z ring assembly at midcell is delayed in the absence of Min and Noc proteins, while at the same time FtsZ accumulates at other potential division sites. This suggests that a major role for Min and Noc is to ensure efficient utilization of the midcell division site by preventing Z ring assembly at potential division sites, including the cell poles. Our data lead us to propose a model in which spatial regulation of division in B. subtilis involves identification of the division site at midcell that requires Min and nucleoid occlusion to ensure efficient Z ring assembly there and only there, at the right time in the cell cycle