Quantifizierung des perioperativen Risikos [Quantifications of perioperative risk]

In this paper standardized and quantitative definitions of perioperative risk and risk factor using probabilities are given. A calculation of risk and risk factors is performed using data from a study on perioperative risk in colon resection and a study on a preoperative risk check in general surgery. The problem of one risk factor, a combination of two risk factors and the use of many risk factors to quantify preoperative risk is discussed. Confidence intervals are recommended as a standard method for presenting statistical results on perioperative risk

Lessons to be Learned for Gastroenterology from Recent Issues in Clinical Trial Methodology

Randomized trials are the preferred tool for patient-oriented research, and their main role is to enable the transfer of results from basic research to routine application. While the need for randomized trials is evident, conducting these trials is becoming increasingly difficult and complex. This article reviews actual and conflicting issues of clinical trials with respect to gastroenterology. Major problems in trial design are neglect of previous research, inadequate sample size calculations and irrelevant outcome criteria. Significant trial management problems include subversion of random allocation, and the design of systems and procedures that are inefficient, ineffective and inflexible. One of the major challenges in conducting randomized, controlled trials is obtaining informed consent because of the differing perspectives and languages of physicians and patients. Recommendations include practical guidance in obtaining informed consent, feedback of trial results to patients and support of research related to obtaining informed consent. Despite statistical guidance, several critical issues persist with respect to trial analysis. The use of confidence intervals is under-represented, the presentation of baseline data is often omitted and postsubgroup analysis is performed. Another controversial but relevant issue is the intention-to-treat analysis. Despite the formulation of standards, there is consistently poor quality of trial reporting, poor registration of unpublished trials and limited registration of ongoing trials. The authors conclude that there is a need for more randomized trials in gastroenterology. While the complexity of trial conduction has increased, so have the means of methodological and practical support. Thus, all problems can be professionally tackled, resulting in good clinical research

Features of Blastocystis spp. in xenic culture revealed by deconvolutional microscopy.

Blastocystis spp. are common human enteric parasites with complex morphology and have been reported to cause irritable bowel syndrome (IBS). Deconvolutional microscopy with time-lapse imaging and fluorescent spectroscopy of xenic cultures of Blastocystis spp. from stool samples of IBS patients and from asymptomatic, healthy pigs allowed observations of living organisms in their natural microbial environment. Blastocystis organisms of the vacuolated, granular, amoebic and cystic forms were observed to autofluorescence in the 557/576 emission spectra. Autofluorescence could be distinguished from fluorescein-conjugated Blastocystis-specific antibody labelling in vacuolated and granular forms. This antibody labelled Blastocystis subtypes 1, 3 and 4 but not 5. Surface pores of 1 μm in diameter were observed cyclically opening and closing over 24 h. Vacuolated forms extruded a viscous material from a single surface point with coincident deflation that may demonstrate osmoregulation. Tear-shaped granules were observed exiting from the surface of an amoebic form, but their origin and identity remain unknown

Universal Evolution of CKM Matrix Elements

We derive the two-loop evolution equations for the Cabibbo-Kobayashi-Maskawa matrix. We show that to leading order in the mass and CKM hierarchies the scaling of the mixings $|V_{ub}|^2$, $|V_{cb}|^2$, $|V_{td}|^2$, $|V_{ts}|^2$ and of the rephase-invariant CP-violating parameter $J$ is universal to all orders in perturbation theory. In leading order the other CKM elements do not scale. Imposing the constraint $\lambda _b=\lambda _{\tau}$ at the GUT scale determines the CKM scaling factor to be $\simeq 0.58$ in the MSSM.Comment: 17 pages + 2 figures not included (available upon request), revised version fixes discrepancy between S and S^{1/2}, no other changes, MAD/PH/72

Spin-Polarized STM for a Kondo adatom

We investigate the bias dependence of the tunneling conductance between a spin-polarized (SP) scanning tunneling microscope (STM) tip and the surface conduction states of a normal metal with a Kondo adatom. Quantum interference between tip-host metal and tip-adatom-host metal conduction paths is studied in the full range of the Fano parameter $q$. The spin-polarized STM gives rise to a splitting of the Kondo peak and asymmetry in the zero-bias anomaly depending on the lateral tip-adatom distance. For increasing lateral distances, the Kondo peak-splitting shows a strong suppression and the spin-polarized conductance exhibits the standard Fano-Kondo profile.Comment: new version with improved discussion. added one figure. 12 pages (one-column) + 5 figure

Prospective Study in a Porcine Model of Sarcoptes scabiei Indicates the Association of Th2 and Th17 Pathways with the Clinical Severity of Scabies

BackgroundUnderstanding of scabies immunopathology has been hampered by the inability to undertake longitudinal studies in humans. Pigs are a useful animal model for scabies, and show clinical and immunologic changes similar to those in humans. Crusted scabies can be readily established in pigs by treatment with the glucocorticoid dexamethasone (Dex).Methodology/ Principal FindingsProspective study of 24 pigs in four groups: a) Scabies+/Dex+, b) Scabies+/Dex-, c) Scabies-/Dex+ and d) Scabies-/Dex-. Clinical symptoms were monitored. Histological profiling and transcriptional analysis of skin biopsies was undertaken to compare changes in cell infiltrates and representative cytokines. A range of clinical responses to Sarcoptes scabiei were observed in Dex treated and non-immunosuppressed pigs. An association was confirmed between disease severity and transcription of the Th2 cytokines IL-4 and IL-13, and up-regulation of the Th17 cytokines IL-17 and IL-23 in pigs with crusted scabies. Immunohistochemistry revealed marked infiltration of lymphocytes and mast cells, and strong staining for IL-17.Conclusions/ SignificanceWhile an allergic Th2 type response to scabies has been previously described, these results suggest that IL-17 related pathways may also contribute to immunopathology of crusted scabies. This may lead to new strategies to protect vulnerable subjects from contracting recurrent crusted scabies

Strain background determines lymphoma incidence in Atm knockout mice

About 10% to 30% of patients with ataxia-telangiectasia (A-T) develop leukemias or lymphomas. There is considerable interpatient variation in the age of onset and leukemia/lymphoma type. The incomplete penetrance and variable age of onset may be attributable to several factors. These include competing mortality from other A-T-associated pathologies, particularly neurodegeneration and interstitial lung disease, and allele-specific effects of ataxia-telangiectasia mutated (ATM) gene mutations. There is also limited evidence from clinical observations and studies using Atm knockout mice that modifier genes may account for some variation in leukemia/lymphoma susceptibility. We have introgressed the Atm knockout allele (Atm) onto several inbred murine strains and observed differences in thymic lymphoma incidence and latency between Atm mice on the different strain backgrounds and between their F1 hybrids. The lymphomas that arose in these mice had a pattern of sequence gains and losses that were similar to those previously described by others. These results provide further evidence for the existence of modifier genes controlling lymphomagenesis in individuals carrying defective copies of Atm, at least in mice, and the characterized Atm- congenic strain set provides a resource with which to identify these genes. In addition, we found that fewer than expected Atm pups were weaned on two strain backgrounds and that there was no correlation between body weight of young Atm mice and lymphoma incidence or latency