The GABRIEL Advanced Surveys: study design, participation and evaluation of bias

Exposure to farming environments has been shown to protect substantially against asthma and atopic disease across Europe and in other parts of the world. The GABRIEL Advanced Surveys (GABRIELA) were conducted to determine factors in farming environments which are fundamental to protecting against asthma and atopic disease. The GABRIEL Advanced Surveys have a multi-phase stratified design. In a first-screening phase, a comprehensive population-based survey was conducted to assess the prevalence of exposure to farming environments and of asthma and atopic diseases (n = 103,219). The second phase was designed to ascertain detailed exposure to farming environments and to collect biomaterial and environmental samples in a stratified random sample of phase 1 participants (n = 15,255). A third phase was carried out in a further stratified sample only in Bavaria, southern Germany, aiming at in-depth respiratory disease and exposure assessment including extensive environmental sampling (n = 895). Participation rates in phase 1 were around 60% but only about half of the participating study population consented to further study modules in phase 2. We found that consenting behaviour was related to familial allergies, high parental education, wheeze, doctor diagnosed asthma and rhinoconjunctivitis, and to a lesser extent to exposure to farming environments. The association of exposure to farm environments with asthma or rhinoconjunctivitis was not biased by participation or consenting behaviour. The GABRIEL Advanced Surveys are one of the largest studies to shed light on the protective 'farm effect' on asthma and atopic disease. Bias with regard to the main study question was able to be ruled out by representativeness and high participation rates in phases 2 and 3. The GABRIEL Advanced Surveys have created extensive collections of questionnaire data, biomaterial and environmental samples promising new insights into this area of research.

Defining "Drunk" in Early Modern Germany

Explores the role of the drinking of alcoholic beverages in early modern Germany. Definition of drunkenness; Notions on harm caused by alcohol consumption on different types of persons; Recommendation of occasional immoderate drinking to rid the body of impurities.

Rates of disease progression according to initial highly active antiretroviral therapy regimen: a collaborative analysis of 12 prospective cohort studies

BACKGROUND: No large clinical end-point trials have been conducted comparing regimens among human immunodeficiency virus type 1-positive persons starting antiretroviral therapy. We examined clinical progression according to initial regimen in the Antiretroviral Therapy Cohort Collaboration, which is based on 12 European and North American cohort studies. METHODS: We analyzed progression to death from any cause and to AIDS or death (AIDS/death), comparing efavirenz (EFV), nevirapine (NVP), nelfinavir, idinavir, ritonavir (RTV), RTV-boosted protease inhibitors (PIs), saquinavir, and abacavir. We also compared nucleoside reverse-transcriptase inhibitor pairs: zidovudine/lamivudine (AZT/3TC), stavudine (D4T)/3TC, D4T/didanosine (DDI), and others. RESULTS: A total of 17,666 treatment-naive patients, 55,622 person-years at risk, 1,617 new AIDS events, and 895 deaths were analyzed. Compared with EFV, the adjusted hazard ratio (HR) for AIDS/death was 1.28 (95% confidence interval [CI], 1.03-1.60) for NVP, 1.31 (95% CI, 1.01-1.71) for RTV, and 1.45 (95% CI, 1.15-1.81) for RTV-boosted PIs. For death, the adjusted HR for NVP was 1.65 (95% CI, 1.16-2.36). The adjusted HR for death for D4T/3TC was 1.35 (95% CI, 1.14-1.59), compared with AZT/3TC. CONCLUSIONS: Outcomes may vary across initial regimens. Results are observational and may have been affected by bias due to unmeasured or residual confounding. There is a need for large, randomized, clinical end-point trials.

Sirolimus- vs paclitaxel-eluting stents in de novo coronary artery lesions: the REALITY trial: a randomized controlled trial

CONTEXT: Compared with bare metal stents, sirolimus-eluting and paclitaxel-eluting stents have been shown to markedly improve angiographic and clinical outcomes after percutaneous coronary revascularization, but their performance in the treatment of de novo coronary lesions has not been compared in a prospective multicenter study. OBJECTIVE: To compare the safety and efficacy of sirolimus-eluting vs paclitaxel-eluting coronary stents. DESIGN: Prospective, randomized comparative trial (the REALITY trial) conducted between August 2003 and February 2004, with angiographic follow-up at 8 months and clinical follow-up at 12 months. SETTING: Ninety hospitals in Europe, Latin America, and Asia. PATIENTS: A total of 1386 patients (mean age, 62.6 years; 73.1% men; 28.0% with diabetes) with angina pectoris and 1 or 2 de novo lesions (2.25-3.00 mm in diameter) in native coronary arteries. INTERVENTION: Patients were randomly assigned in a 1:1 ratio to receive a sirolimus-eluting stent (n = 701) or a paclitaxel-eluting stent (n = 685). MAIN OUTCOME MEASURES: The primary end point was in-lesion binary restenosis (presence of a more than 50% luminal-diameter stenosis) at 8 months. Secondary end points included 1-year rates of target lesion and vessel revascularization and a composite end point of cardiac death, Q-wave or non-Q-wave myocardial infarction, coronary artery bypass graft surgery, or repeat target lesion revascularization. RESULTS: In-lesion binary restenosis at 8 months occurred in 86 patients (9.6%) with a sirolimus-eluting stent vs 95 (11.1%) with a paclitaxel-eluting stent (relative risk [RR], 0.84; 95% confidence interval [CI], 0.61-1.17; P = .31). For sirolimus- vs paclitaxel-eluting stents, respectively, the mean (SD) in-stent late loss was 0.09 (0.43) mm vs 0.31 (0.44) mm (difference, -0.22 mm; 95% CI, -0.26 to -0.18 mm; P<.001), mean (SD) in-stent diameter stenosis was 23.1% (16.6%) vs 26.7% (15.8%) (difference, -3.60%; 95% CI, -5.12% to -2.08%; P<.001), and the number of major adverse cardiac events at 1 year was 73 (10.7%) vs 76 (11.4%) (RR, 0.94; 95% CI, 0.69-1.27; P = .73). CONCLUSION: In this trial comparing sirolimus- and paclitaxel-eluting coronary stents, there were no differences in the rates of binary restenosis or major adverse cardiac events. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00235092.

Effect of transcutaneous electrical muscle stimulation and passive cycling movements on blood pressure and removal of urea and phosphate during hemodialysis

BACKGROUND: Intradialytic exercise has been described to improve blood pressure stability and dialysis efficacy. However, comorbid conditions in the dialysis population often preclude the widespread use of active intradialytic exercise. Therefore, we investigated the effect of intradialytic transcutaneous muscle stimulation (TEMS) and passive cycling movements (PCMs) on blood pressure and dialysis efficacy in patients. STUDY DESIGN: Prospective, controlled, randomized, crossover investigation. SETTING ; PARTICIPANTS: Ten patients were randomly allocated to TEMS, PCMs, or no intervention (NI) for 9 consecutive dialysis sessions. INTERVENTION: Participants were studied with NI, PCMs using a motor-driven ergometer, and bilateral TEMS of the leg musculature. Individual dialysis prescriptions were unchanged during the investigation. OUTCOMES ; MEASUREMENTS: The effect of TEMS and PCMs on blood pressure and dialysis efficacy in patients was assessed. RESULTS: Mean blood pressure increased from 121/64 +/- 21/15 mm Hg with NI to 132/69 +/- 21/15 mm Hg (P < 0.001) during sessions with PCMs and 125/66 +/- 22/16 mm Hg (P < 0.05) during sessions with TEMS. Urea and phosphate removal during dialysis were significantly (P < 0.001) greater with TEMS (19.4 +/- 3.7 g/dialysis and 1,197 +/- 265 mg/dialysis) or PCMs (20.1 +/- 3.4 g/dialysis and 1,172 +/- 315 mg/dialysis) than with NI (15.1 +/- 3.9 g/dialysis and 895 +/- 202 mg/dialysis). Body weight, ultrafiltration, Kt/V, and increases in hemoglobin and albumin levels during dialysis did not differ among the NI, PCMs, and TEMS groups. LIMITATIONS: The study design does not allow extension of the findings to prolonged treatment. CONCLUSION: Future studies during longer observation periods will have to prove the persistence of these acute findings. Both TEMS and PCMs deserve future investigations in dialysis patients because they increase intradialytic blood pressure and facilitate urea and phosphate removal when applied short term.

CHARACTERIZATION OF ELECTRODEPOSITED POLYANILINE BIOSENSOR PLATFORM FOR ESCHERICHIA COLI O157:H7 DETECTION

Amperometric electrodeposition has been used to obtain uniform, conductive, and repeatable polyaniline (PANi) thin films for use in nano scaled biochemical sensors. This report describes the characterization of these films. Techniques such as ellipsometry were used to test repeatability of the deposition and the uniformity of the deposited thin films. Raman spectroscopy was utilized to confirm the composition of the deposited PANi thin films. Fluorescence microscopy was used to determine the immobilization of antibodies to the PANi thin films using biotin-avidin interactions, as well as the density of active binding sites. Ellipsometry results demonstrated that biomolecules could be immobilized on PANi films as thin as 9nm. Evidence from the Raman spectroscopy demonstrated the conductive nature of the PANi films. The fluorescence microscopy demonstrated that antibodies could be immobilized on PANi films, although the experiment also demonstrated a low density of binding sites. The characterization demonstrates the utility of the PANi thin films as a conductive interface between the inorganic sensor platform and biochemical molecules.

Temporal patterns in lacustrine stable isotopes as evidence for climate change during the late glacial in the Southern European Alps

We investigated oxygen and carbon isotopes of bulk carbonate and of benthic freshwater ostracods (Candona candida) in a sediment core of Lago Piccolo di Avigliana that was previously analyzed for pollen and loss-on-ignition, in order to reconstruct environmental changes during the late glacial and early Holocene. The depth-age relationship of the sediment core was established using 14 AMS C-14 dates and the Laacher See Tephra. While stable isotopes of bulk carbonates may have been affected by detrital input and, therefore, only indirectly reflect climatic changes, isotopes measured on ostracod shells provide unambiguous evidence for major environmental changes. Oxygen isotope ratios of ostracod shells (delta O-18(C)) increased by similar to 6 parts per thousand at the onset of the Bolling (similar to 14,650 cal BP) and were similar to 2 parts per thousand lower during the Younger Dryas (similar to 12,850 to 11,650 cal BP), indicating a temporal pattern of climate changes similar to the North Atlantic region. However, in contrast to records in that region, delta O-18(C) gradually decreased during the early Holocene, suggesting that compared to the Younger Dryas more humid conditions occurred and that the lake received gradually increasing input of O-18-depleted groundwater or river water.

Fibromatosis in a young Bernese Mountain Dog: clinical, imaging, and histopathological findings

A young, intact, male Bernese Mountain Dog was presented to the animal hospital for lameness and diffuse thickening of the soft tissue in the right hind limb. Magnetic resonance imaging revealed multiple, multilobular, space-occupying lesions within and between the muscles of the right femur. Biopsies taken from the lesions revealed an infiltrative mass composed mainly of collagen fibers and a low density of benign-appearing fibroblasts. These findings were compatible with a diagnosis of a fibromatosis. Taking the age of onset into account, infantile fibromatosis was most likely. A deep fibromatosis, similar to that seen in adults, could not be excluded based on histology.

When to start antiretroviral therapy in children aged 2-5 years: a collaborative causal modelling analysis of cohort studies from southern Africa

BACKGROUND There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2-5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2-5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4 percentage (CD4%) <25%. METHODS AND FINDINGS ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm(3) (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1-6.5) (no ART) to 2.1% (95% CI: 1.3%-3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%-3.5%) and 2.2% (95% CI: 1.4%-3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data. CONCLUSIONS The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm(3) or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors' Summary.

DEVELOPING A METHOD FOR IDENTIFYING AND REDUCING FUNCTIONAL DISCREPANCIES OF INFORMATION SYSTEMS

Currently more than half of Electronic Health Record (EHR) projects fail. Most of these failures are not due to flawed technology, but rather due to the lack of systematic considerations of human issues. Among the barriers for EHR adoption, function mismatching among users, activities, and systems is a major area that has not been systematically addressed from a human-centered perspective. A theoretical framework called Functional Framework was developed for identifying and reducing functional discrepancies among users, activities, and systems. The Functional Framework is composed of three models – the User Model, the Designer Model, and the Activity Model. The User Model was developed by conducting a survey (N = 32) that identified the functions needed and desired from the user’s perspective. The Designer Model was developed by conducting a systemic review of an Electronic Dental Record (EDR) and its functions. The Activity Model was developed using an ethnographic method called shadowing where EDR users (5 dentists, 5 dental assistants, 5 administrative personnel) were followed quietly and observed for their activities. These three models were combined to form a unified model. From the unified model the work domain ontology was developed by asking users to rate the functions (a total of 190 functions) in the unified model along the dimensions of frequency and criticality in a survey. The functional discrepancies, as indicated by the regions of the Venn diagrams formed by the three models, were consistent with the survey results, especially with user satisfaction. The survey for the Functional Framework indicated the preference of one system over the other (R=0.895). The results of this project showed that the Functional Framework provides a systematic method for identifying, evaluating, and reducing functional discrepancies among users, systems, and activities. Limitations and generalizability of the Functional Framework were discussed.

Resolving Cl and SO4 Profiles in a Clay-Rich Rock Sequence

The chloride and sulfate concentration profiles in a 260 m thick clay-rich Mesozoic sediment sequence have been analyzed by various methods. Chloride data generally indicate a good consistency between different methods if anion exclusion is accounted for in leaching tests. For sulfate, however, there is an apparent inconsistency between leaching data and those obtained from the other methods, which points to the dissolution of a sulfur-bearing mineral. Traces of diagenetic gypsum seem to be a likely source, but other sulfur minerals cannot be ruled out.