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1.  Minimally invasive, imaging guided virtual autopsy compared to conventional autopsy in foetal, newborn and infant cases: study protocol for the paediatric virtual autopsy trial 
BMC Pediatrics  2014;14:15.
Background
In light of declining autopsy rates around the world, post-mortem MR imaging is a promising alternative to conventional autopsy in the investigation of infant death. A major drawback of this non-invasive autopsy approach is the fact that histopathological and microbiological examination of the tissue is not possible. The objective of this prospective study is to compare the performance of minimally invasive, virtual autopsy, including CT-guided biopsy, with conventional autopsy procedures in a paediatric population.
Methods/Design
Foetuses, newborns and infants that are referred for autopsy at three different institutions associated with the University of Zurich will be eligible for recruitment. All bodies will be examined with a commercial CT and a 3 Tesla MRI scanner, masked to the results of conventional autopsy. After cross-sectional imaging, CT-guided tissue sampling will be performed by a multifunctional robotic system (Virtobot) allowing for automated post-mortem biopsies. Virtual autopsy results will be classified with regards to the likely final diagnosis and major pathological findings and compared to the results of conventional autopsy, which remains the diagnostic gold standard.
Discussion
There is an urgent need for the development of alternative post-mortem examination methods, not only as a counselling tool for families and as a quality control measure for clinical diagnosis and treatment but also as an instrument to advance medical knowledge and clinical practice. This interdisciplinary study will determine whether virtual autopsy will narrow the gap in information between non-invasive and traditional autopsy procedures.
Trial Registration
ClinicalTrials.gov: NCT01888380
doi:10.1186/1471-2431-14-15
PMCID: PMC3897955  PMID: 24438163
Autopsy; Post-mortem imaging; Minimally invasive virtual autopsy; Guided biopsy; Virtopsy®; Foetus; Stillbirth; Newborn; Infant
2.  Reduction of Thromboembolic Events in Meningioma Surgery: A Cohort Study of 724 Consecutive Patients 
PLoS ONE  2013;8(11):e79170.
Background
Meningiomas are associated with the highest postoperative rate of venous thromboembolic events (VTE) among all intracranial tumors. The aim of this study is to compare two entirely different VTE prophylaxis regimens in 724 consecutive patients undergoing meningioma surgery.
Methods
Two cohorts at a single institution treated with different regimens to prevent VTE were reviewed retrospectively. Cohort A (n = 482; 314 females, mean age 57 years, range: 11–87 years) received our institutional regimen during the years 1999–2006, consisting of low-molecular-weight heparin (LMWH) and compression stockings. For cohort B (n = 242; 163 females, mean age 56.8 years, range: 16–90 years), during the years 2008–2010, the management included intraoperative 10°–20° leg elevation with intermittent pneumatic compression (IPC), heparin and LMWH administration. We compared the incidence of the endpoints pulmonary embolism (PE), deep venous thrombosis (DVT), hemorrhage and death, taking into account several known associated risk factors.
Results
For all endpoints, we observed a more favorable outcome with the new regimen. The difference in incidence of PEs (cohort A: 38/482, 8%; cohort B: 6/242, 2.5%) reached statistical significance (p = 0.002). In general, patients with skull base meningiomas had a higher risk for PE (OR 2.77). Regarding VTE prophylaxis, an adjusted subgroup analysis suggests that the new regimen is particularly beneficial for patients with skull base meningiomas.
Conclusions
We recommend perioperative prophylaxis using a management composed of intraoperative leg-elevation, IPC, early heparin administration and LMWH to reduce the risk for PE.
doi:10.1371/journal.pone.0079170
PMCID: PMC3828295  PMID: 24244441
3.  Validating and updating a risk model for pneumonia – a case study 
Background
The development of risk prediction models is of increasing importance in medical research - their use in practice, however, is rare. Among other reasons this might be due to the fact that thorough validation is often lacking. This study focuses on two Bayesian approaches of how to validate a prediction rule for the diagnosis of pneumonia, and compares them with established validation methods.
Methods
Expert knowledge was used to derive a risk prediction model for pneumonia. Data on more than 600 patients presenting with cough and fever at a general practitioner’s practice in Switzerland were collected in order to validate the expert model and to examine the predictive performance of it. Additionally, four modifications of the original model including shrinkage of the regression coefficients, and two Bayesian approaches with the expert model used as prior mean and different weights for the prior covariance matrix were fitted. We quantify the predictive performance of the different methods with respect to calibration and discrimination, using cross-validation.
Results
The predictive performance of the unshrinked regression coefficients was poor when applied to the Swiss cohort. Shrinkage improved the results, but a Bayesian model formulation with unspecified weight of the informative prior lead to large AUC and small Brier score, naïve and after cross-validation. The advantage of this approach is the flexibility in case of a prior-data conflict.
Conclusions
Published risk prediction rules in clinical research need to be validated externally before they can be used in new settings. We propose to use a Bayesian model formulation with the original risk prediction rule as prior. The posterior means of the coefficients, given the validation data showed best predictive performance with respect to cross-validated calibration and discriminative ability.
doi:10.1186/1471-2288-12-99
PMCID: PMC3441433  PMID: 22817850
Validation; Predictive performance; Bayesian model; g-factor; Pneumonia
4.  Relief from Zmp1-Mediated Arrest of Phagosome Maturation Is Associated with Facilitated Presentation and Enhanced Immunogenicity of Mycobacterial Antigens▿ 
Pathogenic mycobacteria escape host innate immune responses by blocking phagosome-lysosome fusion. Avoiding lysosomal delivery may also be involved in the capacity of mycobacteria to evade major histocompatibility complex (MHC) class I- or II-dependent T-cell responses. In this study, we used a genetic mutant of Mycobacterium bovis BCG that is unable to escape lysosomal transfer and show that presentation of mycobacterial antigens is affected by the site of intracellular residence. Compared to infection with wild-type BCG, infection of murine bone marrow-derived dendritic cells with a mycobacterial mutant deficient in zinc metalloprotease 1 (Zmp1) resulted in increased presentation of MHC class II-restricted antigens, as assessed by activation of mycobacterial Ag85A-specific T-cell hybridomas. The zmp1 deletion mutant was more immunogenic in vivo, as measured by delayed-type hypersensitivity (DTH), antigen-specific lymphocyte proliferation, and the frequency of antigen-specific gamma interferon (IFN-γ)-producing lymphocytes of both CD4 and CD8 subsets. In conclusion, our results suggest that phagosome maturation and lysosomal delivery of BCG facilitate mycobacterial antigen presentation and enhance immunogenicity.
doi:10.1128/CVI.00015-11
PMCID: PMC3122614  PMID: 21471301
5.  A nomogram for P values 
Background
P values are the most commonly used tool to measure evidence against a hypothesis. Several attempts have been made to transform P values to minimum Bayes factors and minimum posterior probabilities of the hypothesis under consideration. However, the acceptance of such calibrations in clinical fields is low due to inexperience in interpreting Bayes factors and the need to specify a prior probability to derive a lower bound on the posterior probability.
Methods
I propose a graphical approach which easily translates any prior probability and P value to minimum posterior probabilities. The approach allows to visually inspect the dependence of the minimum posterior probability on the prior probability of the null hypothesis. Likewise, the tool can be used to read off, for fixed posterior probability, the maximum prior probability compatible with a given P value. The maximum P value compatible with a given prior and posterior probability is also available.
Results
Use of the nomogram is illustrated based on results from a randomized trial for lung cancer patients comparing a new radiotherapy technique with conventional radiotherapy.
Conclusion
The graphical device proposed in this paper will enhance the understanding of P values as measures of evidence among non-specialists.
doi:10.1186/1471-2288-10-21
PMCID: PMC2851703  PMID: 20233437

Results 1-5 (5)