Effect of Population Heterogenization on the Reproducibility of Mouse Behavior: A Multi-Laboratory Study

In animal experiments, animals, husbandry and test procedures are traditionally standardized to maximize test sensitivity and minimize animal use, assuming that this will also guarantee reproducibility. However, by reducing within-experiment variation, standardization may limit inference to the specific experimental conditions. Indeed, we have recently shown in mice that standardization may generate spurious results in behavioral tests, accounting for poor reproducibility, and that this can be avoided by population heterogenization through systematic variation of experimental conditions. Here, we examined whether a simple form of heterogenization effectively improves reproducibility of test results in a multi-laboratory situation. Each of six laboratories independently ordered 64 female mice of two inbred strains (C57BL/6NCrl, DBA/2NCrl) and examined them for strain differences in five commonly used behavioral tests under two different experimental designs. In the standardized design, experimental conditions were standardized as much as possible in each laboratory, while they were systematically varied with respect to the animals' test age and cage enrichment in the heterogenized design. Although heterogenization tended to improve reproducibility by increasing within-experiment variation relative to between-experiment variation, the effect was too weak to account for the large variation between laboratories. However, our findings confirm the potential of systematic heterogenization for improving reproducibility of animal experiments and highlight the need for effective and practicable heterogenization strategies.

Long-term outcome of ablative therapy of post-operative atrial tachyarrhythmias in patients with tetralogy of Fallot: a European multi-centre study

Post-operative atrial tachyarrhythmias (AT) in patients with tetralogy of Fallot (ToF) are associated with congestive heart failure, stroke, and cardiac death. Effective treatment is therefore essential. The aim of the study is to evaluate long-term outcome of ablative therapy of AT in ToF patients and to study characteristics of AT recurrences.

First serial assessment at 6 months and 2 years of the second generation of absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study

Nonserial observations have shown this bioresorbable scaffold to have no signs of area reduction at 6 months and recovery of vasomotion at 1 year. Serial observations at 6 months and 2 years have to confirm the absence of late restenosis or unfavorable imaging outcomes.

Bacterial GDGTs in Holocene sediments and catchment soils of a high Alpine lake: application of the MBT/CBT-paleothermometer

A novel proxy for continental mean annual air temperature (MAAT) and soil pH, the MBT/CBT-paleothermometer, is based on the temperature (T) and pH-dependent distribution of specific bacterial membrane lipids (branched glycerol dialkyl glycerol tetraethers – GDGTs) in soil organic matter. Here, we tested the applicability of the MBT/CBT-paleothermometer to sediments from Lake Cadagno, a high Alpine lake in southern Switzerland with a small catchment of 2.4 km2. We analysed the distribution of bacterial GDGTs in catchment soils and in a radiocarbon-dated sediment core from the centre of the lake, covering the past 11 000 yr. The distribution of bacterial GDGTs in the catchment soils is very similar to that in the lake's surface sediments, indicating a common origin of the lipids. Consequently, their transfer from the soils into the sediment record seems undisturbed, probably without any significant alteration of their distribution through in situ production in the lake itself or early diagenesis of branched GDGTs. The MBT/CBT-inferred MAAT estimates from soils and surface sediments are in good agreement with instrumental values for the Lake Cadagno region (~0.5 °C). Moreover, downcore MBT/CBT-derived MAAT estimates match in timing and magnitude other proxy-based T reconstructions from nearby locations for the last two millennia. Major climate anomalies recorded by the MBT/CBT-paleothermometer are, for instance, the Little Ice Age (~14th to 19th century) and the Medieval Warm Period (MWP, ~9th to 14th century). Together, our observations indicate the quantitative applicability of the MBT/CBT-paleothermometer to Lake Cadagno sediments. In addition to the MWP, our lacustrine paleo T record indicates Holocene warm phases at about 3, 5, 7 and 11 kyr before present, which agrees in timing with other records from both the Alps and the sub-polar North-East Atlantic Ocean. The good temporal match of the warm periods determined for the central Alpine region with north-west European winter precipitation strength implies a strong and far-reaching influence of the North Atlantic Oscillation on continental European T variations during the Holocene.

The arterial switch operation in Europe for transposition of the great arteries: a multi-institutional study from the European Congenital Heart Surgeons Association

OBJECTIVES: This study analyzes the results of the arterial switch operation for transposition of the great arteries in member institutions of the European Congenital Heart Surgeons Association. METHODS: The records of 613 patients who underwent primary arterial switch operations in each of 19 participating institutions in the period from January 1998 through December 2000 were reviewed retrospectively. RESULTS: A ventricular septal defect was present in 186 (30%) patients. Coronary anatomy was type A in 69% of the patients, and aortic arch pathology was present in 20% of patients with ventricular septal defect. Rashkind septostomy was performed in 75% of the patients, and 69% received prostaglandin. There were 37 hospital deaths (operative mortality, 6%), 13 (3%) for patients with an intact ventricular septum and 24 (13%) for those with a ventricular septal defect (P < .001). In 36% delayed sternal closure was performed, 8% required peritoneal dialysis, and 2% required mechanical circulatory support. Median ventilation time was 58 hours, and intensive care and hospital stay were 6 and 14 days, respectively. Although of various preoperative risk factors the presence of a ventricular septal defect, arch pathology, and coronary anomalies were univariate predictors of operative mortality, only the presence of a ventricular septal defect approached statistical significance (P = .06) on multivariable analysis. Of various operative parameters, aortic crossclamp time and delayed sternal closure were also univariate predictors; however, only the latter was an independent statistically significant predictor of death. CONCLUSIONS: Results of the procedure in European centers are compatible with those in the literature. The presence of a ventricular septal defect is the clinically most important preoperative risk factor for operative death, approaching statistical significance on multivariable analysis.

Ozone and Mortality: A Meta-Analysis of Time-Series Studies and Comparison to a Multi-City Study (The National Morbidity, Mortality, and Air Pollution Study)

While many time-series studies of ozone and daily mortality identified positive associations,others yielded null or inconclusive results. We performed a meta-analysis of 144 effect estimates from 39 time-series studies, and estimated pooled effects by lags, age groups,cause-specific mortality, and concentration metrics. We compared results to estimates from the National Morbidity, Mortality, and Air Pollution Study (NMMAPS), a time-series study of 95 large U.S. cities from 1987 to 2000. Both meta-analysis and NMMAPS results provided strong evidence of a short-term association between ozone and mortality, with larger effects for cardiovascular and respiratory mortality, the elderly, and current day ozone exposure as compared to other single day lags. In both analyses, results were not sensitive to adjustment for particulate matter and model specifications. In the meta-analysis we found that a 10 ppb increase in daily ozone is associated with a 0.83 (95% confidence interval: 0.53, 1.12%) increase in total mortality, whereas the corresponding NMMAPS estimate is 0.25%(0.12, 0.39%). Meta-analysis results were consistently larger than those from NMMAPS,indicating publication bias. Additional publication bias is evident regarding the choice of lags in time-series studies, and the larger heterogeneity in posterior city-specific estimates in the meta-analysis, as compared with NMAMPS.

[A descriptive epidemiological study on canine babesiosis in the Lake Geneva region]

A descriptive study was carried out in the district of the Lake Geneva between March 1, 2005 and August 31,2006 to assess the incidence and prevalence of canine babesiosis, to genotype the Babesia species occurring, to assess the most frequently clinical signs found and to address the potential of autochthonous transmission. This included a data assessment on the different tick-populations occurring in the area and on the prevalence of Babesia-DNA in these ticks. A total of 56 veterinary practices participated in the study. By blood smear and PCR, Babesia canis canis was found in 12 out of 21 cases with suspected babesiosis. In an additional 13th case, the parasite could only be detected by PCR. All autochthonous cases originated from the Western part of the Lake Geneva region. Clinical signs in affected dogs included inappetence, apathy, anemia, fever, hemoglobinuria and thrombocytopenia. There were no risk factors with regard to age, sex and breed. Most cases were diagnosed during the spring periods of 2005 and 2006 (11 cases) and two cases in autumn 2005, coinciding with the main activity period of Dermacentor reticulatus, the main vector of B. canis canis. A total of 495 ticks were collected on patients by the veterinarians, 473 were identified as Ixodes sp., 7 as Rhipicephalus sanguineus and 15 as Dermacentor reticulatus. While Ixodes sp. was found in the whole study area, D. reticulatus and R. sanguineus occurred only in the Western part till Lausanne. PCR and sequencing yielded B. canis canis positivity in 3 D. reticulatus specimen, these three ticks were collected from two different dogs both suffering from babesiosis. All R. sanguineus were negative by Babesia-PCR. Global warming, ecological changes in the potential habitat of ticks, increasing host- and vector-populations and increasing mobility of dog owners may be responsible for an emergence situation of infection risk for Babesia spp. by time. E.g., Dermacentor reticulatus has become autochtonously prevalent already till Lausanne in the Lake Geneva region, and further surveillance is suggested to tackle this problem.

[On quality of life after surgical therapy of oral cancer - a retrospective multi-center study: the connection between dedentition, denture, quality of life, and dysphagia, and the resulting rehabilitation schemes]

PURPOSE: The surgical treatment of oral cancer results in functional and aesthetical impairments. Patients' quality of life is considerably impaired by oral symptoms resulting from therapy of oral cancer. In many cases the inevitable resection of the tumor, as well as the adjuvant radiochemotherapy will cause the destruction of physiologically and anatomically important structures. One focus of research was the specific rehabilitation of dental loss by functional dentures. Another was the course of 19 impairments (comprehension of speech for unknown others, comprehension of speech for familiar others, eating/swallowing, mobility of the tongue, opening range of the mouth, mobility of lower jaw, mobility of neck, mobility of arms and shoulders, sense of taste, sense of smell, appearance, strength, appetite, respiration, pain, swelling, xerostomia, halitosis). METHODS: Commissioned by the German, Austrian and Swiss cooperative group on tumors of the maxillofacial region (DOSAK), data were collected in 3.894 questionnaires at 43 hospitals in Germany, Austria and Switzerland. The catalogue comprised 147 items in 9 chapters. At the end of the enquiry, 1.761 anonymous questionnaires were returned by 38 hospitals. 1.652 of these could be evaluated regarding the question. RESULTS: The sum score of the 19 impairments was highly increased immediately after the operation and recovered over the next 6 months, without, however, reaching the pre-surgery level. Of 1.652 patients, only 35% did not lose any teeth during therapy. 23% lost up to 5, 17% up to 10 teeth. A quarter of the patients lost more than 10 teeth. The more teeth were lost, the greater the decline of quality of life (p < or = 0.001), although this could be allayed by the functionality of the dentures (p < or = 0.001). There is a reciprocal dependence between the functionality of dental prosthetics and impairment by eating/swallowing (p < or = 0.001). CONCLUSIONS: Patients' quality of life after radical surgery of a carcinoma of the oral cavity depends not only on the functionality of dentures and the specificity of rehabilitation, but also from the initial findings, the extent and location of the resection, the chosen therapy, the general circumstances of the patient's life as well as their strategies of coping. These factors, however, unlike those of functionality of dental prosthesis and rehabilitation, are not modifiable.

Conversion of CT numbers into tissue parameters for Monte Carlo dose calculations: a multi-centre study

The conversion of computed tomography (CT) numbers into material composition and mass density data influences the accuracy of patient dose calculations in Monte Carlo treatment planning (MCTP). The aim of our work was to develop a CT conversion scheme by performing a stoichiometric CT calibration. Fourteen dosimetrically equivalent tissue subsets (bins), of which ten bone bins, were created. After validating the proposed CT conversion scheme on phantoms, it was compared to a conventional five bin scheme with only one bone bin. This resulted in dose distributions D(14) and D(5) for nine clinical patient cases in a European multi-centre study. The observed local relative differences in dose to medium were mostly smaller than 5%. The dose-volume histograms of both targets and organs at risk were comparable, although within bony structures D(14) was found to be slightly but systematically higher than D(5). Converting dose to medium to dose to water (D(14) to D(14wat) and D(5) to D(5wat)) resulted in larger local differences as D(5wat) became up to 10% higher than D(14wat). In conclusion, multiple bone bins need to be introduced when Monte Carlo (MC) calculations of patient dose distributions are converted to dose to water.