Measuring fatigue and stress in laparoscopic surgery: validity and reliability of the star-track test

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Are Electronic Editions Inherently Obsolete?

This paper looks at some of the theoretical background behind technologies being developed at the Australian Scholarly Editions Centre for a new form of resource for the study of historical works of literature. Some of the unique features of these technologies are that they support conflicting points of view (including conflicting structural markup) and also allow simultaneous, parallel development by multiple researchers on the same parts of the work. Archivists talk about maintaining digital assets through use rather than preservation so that demand for the asset will ensure its propagation long-term. To achieve this end a digital asset must be as versatile as possible so as to meet all requirements for those who might want to use it. If it does not do this it will be superseded by something that does meet those needs creating new witness states in the record and confusion for future literary researchers. The word "edition" is a term from the print paradigm and implies a fixed publication with features proscribed by the medium. Technical and feature obsolescence will eventually cause these "electronic editions" to be either superseded or lost from the human record. A better type of resource is one that can be continually developed by its multiple users, while maintaining its textual authenticity, thereby ensuring its continued maintenance long after its original creator is gone. This paper looks at the reasoning behind the need for a new paradigm for creating and maintaining text-based digital assets and provides examples of a work in progress that solves some of the inherent limitations of the print-based "edition" paradigm.Hosted by the Scholarly Text and Imaging Service (SETIS), the University of Sydney Library, and the Research Institute for Humanities and Social Sciences (RIHSS), the University of Sydney

BENCHOP–SLV: the BENCHmarking project in Option Pricing–Stochastic and Local Volatility problems

In the recent project BENCHOP–the BENCHmarking project in Option Pricing we found that Stochastic and Local Volatility problems were particularly challenging. Here we continue the effort by introducing a set of benchmark problems for this type of problems. Eight different methods targeted for the Stochastic Differential Equation (SDE) formulation and the Partial Differential Equation (PDE) formulation of the problem, as well as Fourier methods making use of the characteristic function, were implemented to solve these problems. Comparisons are made with respect to time to reach a certain error level in the computed solution for the different methods. The implemented Fourier method was superior to all others for the two problems where it was implemented. Generally, methods targeting the PDE formulation of the problem outperformed the methods for the SDE formulation. Among the methods for the PDE formulation the ADI method stood out as the best performing one

Novel GAA Variants and Mosaicism in Pompe Disease Identified by Extended Analyses of Patients with an Incomplete DNA Diagnosis

Pompe disease is a metabolic disorder caused by a deficiency of the glycogen-hydrolyzing lysosomal enzyme acid a-glucosidase (GAA), which leads to progressive muscle wasting. This autosomal-recessive disorder is the result of disease-associated variants located in the GAA gene. In the present study, we performed extended molecular diagnostic analysis to identify novel disease-associated variants in six suspected Pompe patients from four different families for which conventional diagnostic assays were insufficient. Additional assays, such as a generic-splicing assay, minigene analysis, SNP array analysis, and targeted Sanger sequencing, allowed the identification of an exonic deletion, a promoter deletion, and a novel splicing variant located in the 5' UTR. Furthermore, we describe the diagnostic process for an infantile patient with an atypical phenotype, consisting of left ventricular hypertrophy but no signs of muscle weakness or motor problems. This led to the identification of a genetic mosaicism for a very severe GAA variant caused by a segmental uniparental isodisomy (UPD). With this study, we aim to emphasize the need for additional analyses to detect new disease-associated GAA variants and non-Mendelian genotypes in Pompe disease where conventional DNA diagnostic assays are insufficient

Segmental and total uniparental isodisomy (UPiD) as a disease mechanism in autosomal recessive lysosomal disorders : evidence from SNP arrays

Analyses in our diagnostic DNA laboratory include genes involved in autosomal recessive (AR) lysosomal storage disorders such as glycogenosis type II (Pompe disease) and mucopolysaccharidosis type I (MPSI, Hurler disease). We encountered 4 cases with apparent homozygosity for a disease-causing sequence variant that could be traced to one parent only. In addition, in a young child with cardiomyopathy, in the absence of other symptoms, a diagnosis of Pompe disease was considered. Remarkably, he presented with different enzymatic and genotypic features between leukocytes and skin fibroblasts. All cases were examined with microsatellite markers and SNP genotyping arrays. We identified one case of total uniparental disomy (UPD) of chromosome 17 leading to Pompe disease and three cases of segmental uniparental isodisomy (UPiD) causing Hurler-(4p) or Pompe disease (17q). One Pompe patient with unusual combinations of features was shown to have a mosaic segmental UPiD of chromosome 17q. The chromosome 17 UPD cases amount to 11% of our diagnostic cohort of homozygous Pompe patients (plus one case of pseudoheterozygosity) where segregation analysis was possible. We conclude that inclusion of parental DNA is mandatory for reliable DNA diagnostics. Mild or unusual phenotypes of AR diseases should alert physicians to the possibility of mosaic segmental UPiD. SNP genotyping arrays are used in diagnostic workup of patients with developmental delay. Our results show that even small Regions of Homozygosity that include telomeric areas are worth reporting, regardless of the imprinting status of the chromosome, as they might indicate segmental UPiD.Peer reviewe

The relation between motions of moored ships due to wake wash of passing vessels and the hindrance thereof

After the introduction of Fast Ferry public transport in the Netherlands a number of complaints about wake wash induced hindrance onboard moored vessels appeared. It was already possible to calculate the wake wash characteristics of fast sailing vessels, the progress of these waves in a waterway and their effect on moored vessels. This paper describes the full scale tests carried out to develop the missing relation between the wash induced motions of a moored vessel and the hindrance thereof. Many different combinations of moored ships, passing ships and shore configurations have been realised. An expert panel scored the hindrance due to the motions of the moored vessel. A guideline for maximum ship motions is developed from the results. With this guideline, it can be determined prior to the introduction of a new innovative vessel with reasonable accuracy if its wake wash will remain within acceptable limits

Response to the letter to the editor by Shek et al. on Vergeldt et al: Risk factors for pelvic organ prolapse and its recurrence: a systematic review

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Plea for routinely presenting prediction intervals in meta-analysis

OBJECTIVES: Evaluating the variation in the strength of the effect across studies is a key feature of meta-analyses. This variability is reflected by measures like tau(2) or I(2), but their clinical interpretation is not straightforward. A prediction interval is less complicated: it presents the expected range of true effects in similar studies. We aimed to show the advantages of having the prediction interval routinely reported in meta-analyses. DESIGN: We show how the prediction interval can help understand the uncertainty about whether an intervention works or not. To evaluate the implications of using this interval to interpret the results, we selected the first meta-analysis per intervention review of the Cochrane Database of Systematic Reviews Issues 2009-2013 with a dichotomous (n=2009) or continuous (n=1254) outcome, and generated 95% prediction intervals for them. RESULTS: In 72.4% of 479 statistically significant (random-effects p0), the 95% prediction interval suggested that the intervention effect could be null or even be in the opposite direction. In 20.3% of those 479 meta-analyses, the prediction interval showed that the effect could be completely opposite to the point estimate of the meta-analysis. We demonstrate also how the prediction interval can be used to calculate the probability that a new trial will show a negative effect and to improve the calculations of the power of a new trial. CONCLUSIONS: The prediction interval reflects the variation in treatment effects over different settings, including what effect is to be expected in future patients, such as the patients that a clinician is interested to treat. Prediction intervals should be routinely reported to allow more informative inferences in meta-analyses

Statistical approaches to identify subgroups in meta-analysis of individual participant data: a simulation study

BACKGROUND: Individual participant data meta-analysis (IPD-MA) is considered the gold standard for investigating subgroup effects. Frequently used regression-based approaches to detect subgroups in IPD-MA are: meta-regression, per-subgroup meta-analysis (PS-MA), meta-analysis of interaction terms (MA-IT), naive one-stage IPD-MA (ignoring potential study-level confounding), and centred one-stage IPD-MA (accounting for potential study-level confounding). Clear guidance on the analyses is lacking and clinical researchers may use approaches with suboptimal efficiency to investigate subgroup effects in an IPD setting. Therefore, our aim is to overview and compare the aforementioned methods, and provide recommendations over which should be preferred. METHODS: We conducted a simulation study where we generated IPD of randomised trials and varied the magnitude of subgroup effect (0, 25, 50% relative reduction), between-study treatment effect heterogeneity (none, medium, large), ecological bias (none, quantitative, qualitative), sample size (50,100,200), and number of trials (5,10) for binary, continuous and time-to-event outcomes. For each scenario, we assessed the power, false positive rate (FPR) and bias of aforementioned five approaches. RESULTS: Naive and centred IPD-MA yielded the highest power, whilst preserving acceptable FPR around the nominal 5% in all scenarios. Centred IPD-MA showed slightly less biased estimates than naive IPD-MA. Similar results were obtained for MA-IT, except when analysing binary outcomes (where it yielded less power and FPR < 5%). PS-MA showed similar power as MA-IT in non-heterogeneous scenarios, but power collapsed as heterogeneity increased, and decreased even more in the presence of ecological bias. PS-MA suffered from too high FPRs in non-heterogeneous settings and showed biased estimates in all scenarios. Meta-regression showed poor power (< 20%) in all scenarios and completely biased results in settings with qualitative ecological bias. CONCLUSIONS: Our results indicate that subgroup detection in IPD-MA requires careful modelling. Naive and centred IPD-MA performed equally well, but due to less bias of the estimates in the presence of ecological bias, we recommend the latter