Exercise Tonometry for the Diagnosis of Chronic Gastrointestinal Ischemia

This thesis investigates the role of gastrointestinal exercise tonometry as a functional diagnostic test in patients suspected of chronic gastrointestinal ischemia. In contrast with all other diagnostic modalities (angiography, duplex sonography, CT- and MRangiography) that only provide information about vessel anatomy, vessel patency or blood flow, tonometry can actually demonstrate end-organ ischemia. Measurement of gastrointestinal luminal to blood PCO2 by means of tonometry has been shown to provide exactly that information: the presence or absence of ischemia. Until now it is the only clinically feasible, i.e. minimally invasive and bedside, technique for monitoring the adequacy of gastrointestinal (mucosal) perfusion in a wide variety of conditions such as (hemorrhagic) shock, sepsis, trauma, pancreatitis, cardiovascular and gastro-esophageal surgery. In chapter two a review of the current thoughts on tonometry is given. Uncertainties about physiological background, methodology, and clinical use have hindered tonometry from gaining the status of a routine diagnostic technique. Most of the initial problems however have been addressed and solved, for instance by the introduction of automated air tonometry, and recognizing that measurements have to be done in an empty stomach and after adequate gastric acid suppression. Gastric tonometry after food provocation has been used as diagnostic test for chronic gastrointestinal ischemia. This has resulted in varying and disappointing accuracies. In a pilot study by J.J. Kolkman, using physical exercise as an alternative provocative manoeuvre, gastric (saline) tonometry showed to be a promising test for the detection of symptomatic chronic gastrointestinal ischemia. In chapters two, three and four of this thesis questions arising from this pilot study are addressed, including the intensity of exercise needed for provocation of gastrointestinal ischemia, the best way to monitor this exercise intensity and the best location in the gastrointestinal tract for tonometric measurements

Unfolding of differential energy spectra in the MAGIC experiment

The paper describes the different methods, used in the MAGIC experiment, to unfold experimental energy distributions of cosmic ray particles (gamma-rays). Questions and problems related to the unfolding are discussed. Various procedures are proposed which can help to make the unfolding robust and reliable. The different methods and procedures are implemented in the MAGIC software and are used in most of the analyses.Comment: Submitted to NIM

Implementation of the Random Forest Method for the Imaging Atmospheric Cherenkov Telescope MAGIC

The paper describes an application of the tree classification method Random Forest (RF), as used in the analysis of data from the ground-based gamma telescope MAGIC. In such telescopes, cosmic gamma-rays are observed and have to be discriminated against a dominating background of hadronic cosmic-ray particles. We describe the application of RF for this gamma/hadron separation. The RF method often shows superior performance in comparison with traditional semi-empirical techniques. Critical issues of the method and its implementation are discussed. An application of the RF method for estimation of a continuous parameter from related variables, rather than discrete classes, is also discussed.Comment: 16 pages, 8 figure

Probing quantum gravity using photons from a flare of the active galactic nucleus Markarian 501 observed by the MAGIC telescope

We analyze the timing of photons observed by the MAGIC telescope during a flare of the active galactic nucleus Mkn 501 for a possible correlation with energy, as suggested by some models of quantum gravity (QG), which predict a vacuum refractive index \simeq 1 + (E/M_{QGn})^n, n = 1,2. Parametrizing the delay between gamma-rays of different energies as \Delta t =\pm\tau_l E or \Delta t =\pm\tau_q E^2, we find \tau_l=(0.030\pm0.012) s/GeV at the 2.5-sigma level, and \tau_q=(3.71\pm2.57)x10^{-6} s/GeV^2, respectively. We use these results to establish lower limits M_{QG1} > 0.21x10^{18} GeV and M_{QG2} > 0.26x10^{11} GeV at the 95% C.L. Monte Carlo studies confirm the MAGIC sensitivity to propagation effects at these levels. Thermal plasma effects in the source are negligible, but we cannot exclude the importance of some other source effect.Comment: 12 pages, 3 figures, Phys. Lett. B, reflects published versio

Incidence of Interval Colorectal Cancer After Negative Results From First-Round Fecal Immunochemical Screening Tests, by Cutoff Value and Participant Sex and Age

Background & Aims: We evaluated the incidence of interval cancers between the first and second rounds of colorectal cancer (CRC) screening with the FOB-Gold fecal immunochemical test (FIT), and the effects of different cutoff values and patient sex and age. Methods: We collected data from participants in a population-based

Measuring the depth of invasion in vulvar squamous cell carcinoma: interobserver agreement and pitfalls

Aims: The depth of invasion is an important prognostic factor for patients with vulvar squamous cell carcinoma (SCC). The threshold of 1 mm distinguishes between FIGO stages IA and ≥IB disease and guides the need for groin surgery. Therefore, high interobserver agreement is crucial. The conventional and the alternative method are described to measure the depth of invasion. The aims of this study were to assess interobserver agreement for classifying the depth of invasion using both methods and to identify pitfalls. Methods and results: Fifty slides of vulvar SCC with a depth of invasion approximately 1 mm were selected, digitally scanned and independently assessed by 10 pathologists working in a referral or oncology centre and four pathologists in training. The depth of invasion was measured using both the conventional and alternative method in each slide and categorised into ≤1 and >1 mm. The percentage of agreement and Light’s kappa for multi-rater agreement were calculated, and 95% confidence intervals were calculated by bootstrapping (1000 runs). The agreement using the conventional method was moderate (κ = 0.57, 95% confidence interval = 0.45–0.68). The percentage of agreement among the participating pathologists using the conventional method was 85.0% versus 89.4% using the alternative method. Six pitfalls were identified: disagreement concerning which invasive nest is deepest, recognition of invasive growth and where it starts, curved surface, carcinoma situated on the edge of the tis

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD. © 2021, The Author(s).EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking