The impact of short-selling in financial markets

This dissertation empirically examines the impact of short-selling in financial markets. Given the increasing participation of short-sellers in financial markets, this research provides empirical evidence on an increasingly important issue. Each chapter addresses a research question with scarce or conflicting prior research findings to provide evidence which can assist researchers, investors and regulators to understand and manage the impact of short-selling in financial markets

Does 4D transperineal ultrasound have additional value over 2D transperineal ultrasound for diagnosing posterior pelvic floor disorders in women with obstructed defecation syndrome?

Objective To establish the diagnostic test accuracy of two‐dimensional (2D) and four‐dimensional (4D) transperineal ultrasound (TPUS) for diagnosis of posterior pelvic floor disorders in women with obstructed defecation syndrome (ODS), in order to assess if 4D ultrasound imaging provides additional value. Methods This was a prospective cohort study of 121 consecutive women with ODS. Symptoms of ODS and pelvic organ prolapse on clinical examination were assessed using validated methods. All women underwent both 2D‐ and 4D‐TPUS. Imaging analysis was performed by two blinded observers. Posterior pelvic floor disorders were dichotomized into presence or absence, according to predefined cut‐off values. In the absence of a reference standard, a composite reference standard was created from a combination of results of evacuation proctography, magnetic resonance imaging and endovaginal ultrasound. Primary outcome measures were diagnostic test characteristics of 2D‐ and 4D‐TPUS for rectocele, enterocele, intussusception and anismus. Secondary outcome measures were interobserver agreement, agreement between the two imaging techniques, and association of severity of ODS symptoms and degree of posterior vaginal wall prolapse with conditions observed on imaging. Results For diagnosis of all four posterior pelvic floor disorders, there was no difference in sensitivity or specificity between 2D‐ and 4D‐TPUS (P = 0.131–1.000). Good agreement between 2D‐ and 4D‐TPUS was found for diagnosis of rectocele (κ = 0.675) and moderate agreement for diagnoses of enterocele, intussusception and anismus (κ = 0.465–0.545). There was no difference in rectocele depth measurements between the techniques (19.9 mm for 2D vs 19.0 mm for 4D, P = 0.802). Interobserver agreement was comparable for both techniques, although 2D‐TPUS had excellent interobserver agreement for diagnosis of enterocele and rectocele depth measurements, while this was only moderate and good, respectively, for 4D‐TPUS. Diagnoses of rectocele and enterocele on both 2D‐ and 4D‐TPUS were significantly associated with degree of posterior vaginal wall prolapse on clinical examination (odds ratio (OR) = 1.89–2.72). The conditions observed using either imaging technique were not associated with severity of ODS symptoms (OR = 0.82–1.13). Conclusions There is no evidence of superiority of 4D ultrasound acquisition to dynamic 2D ultrasound acquisition for the diagnosis of posterior pelvic floor disorders. 2D‐ and 4D‐TPUS could be used interchangeably to screen women with symptoms of ODS

Laparoscopic subtotal hysterectomy versus laparoscopic total hysterectomy: a decade of experience

At present, there are only few data on the surgical outcomes of laparoscopic hysterectomy (LH). Up till now, it has been unclear whether there is a difference in number of complications among the subcategories of laparoscopic total hysterectomy and laparoscopic subtotal hysterectomy (LSH). Therefore, we have performed a retrospective analysis to evaluate the peri- and postoperative outcomes in women undergoing LSH versus LH. This multi-centre retrospective cohort study (Canadian Task Force classification II-2) was conducted in multi-centres (two teaching hospitals and one university medical centre) in the Netherlands, all experienced in minimally invasive gynaecology. In a multi-centre retrospective cohort study we compared the long-term outcomes of laparoscopic subtotal hysterectomy and laparoscopic total hysterectomy (including laparoscopic assisted vaginal hysterectomy, laparoscopic hysterectomy and total laparoscopic hysterectomy). All laparoscopic hysterectomies from the last 10 years (January 1998 till December 2007) were included. Patient characteristics, intra- and postoperative complications, operating time and duration of hospital stay were recorded. The minimum follow-up was 6 months. A total of 390 cases of laparoscopic hysterectomies were included in the analysis: 192 laparoscopic subtotal hysterectomies and 198 laparoscopic total hysterectomies. Patient characteristics such as age and parity were equal in the groups. The overall number of short-term and long-term complications was comparable in both groups: 17% and 15%. Short-term complications (bleeding, fever) were 3% in the LSH group and 12% in the LH group. Long-term complications were (tubal prolapse and cervical stump reoperations) 15% in the LSH group and 3% in the LH group. Laparoscopic subtotal hysterectomy as compared with the different types of laparoscopic total hysterectomy is associated with more long-term postoperative complications, whereas laparoscopic total hysterectomy is associated with more short-term complications

Technique of anterior colporrhaphy: a Dutch evaluation

Contains fulltext : 96395.pdf (publisher's version ) (Closed access)INTRODUCTION AND HYPOTHESIS: To evaluate the variation in techniques of anterior colporrhaphy among members of the Dutch Urogynecologic Society. METHODS: A questionnaire evaluating the technique of anterior colporrhaphy, preoperative and postoperative care, and use of the POP-Q score was sent out by e-mail. RESULTS: One hundred thirty-three completed questionnaires were received. The response rate was 65%. There are large variations in incisions, use of hydrodissection, method of plication, and excision of redundant vaginal epithelium. The urinary catheter was generally removed on day 2 after surgery and the vaginal pack on day 1. Less than half of the respondents used the POP-Q score routinely. CONCLUSIONS: Dutch gynecologists use a variety of surgical techniques to operate on a cystocele. This suggests that there is no widely accepted opinion on the best surgical approach. The lack of differentiation between central and lateral defects is striking and in contrast with the, mostly, American literature

Prediction model and prognostic index to estimate clinically relevant pelvic organ prolapse in a general female population

Introduction and hypothesis: Estimation on prevalence and distribution of pelvic organ prolapse (POP) signs in a general female population is difficult. We therefore developed and validated

Molecular landscape of pelvic organ prolapse provides insights into disease etiology

Pelvic organ prolapse (POP) represents a major health care burden in women, but its underlying pathophysiological mechanisms have not been elucidated. We first used a case-control design to perform an exome chip study in 526 women with POP and 960 control women to identify single nucleotide variants (SNVs) associated with the disease. We then integrated the functional interactions between the POP candidate proteins derived from the exome chip study and other POP candidate molecules into a molecular landscape. We found significant associations between POP and SNVs in 54 genes. The proteins encoded by 26 of these genes fit into the molecular landscape, together with 43 other POP candidate molecules. The POP landscape is located in and around epithelial cells and fibroblasts of the urogenital tract and harbors four interacting biological processes—epithelial-mesenchymal transition, immune response, modulation of the extracellular matrix, and fibroblast function—that are regulated by sex hormones and TGFB1. Our findings were corroborated by enrichment analyses of differential gene expression data from an independent POP cohort. Lastly, based on the landscape and using vaginal fibroblasts from women with POP, we predicted and showed that metformin alters gene expression in these fibroblasts in a beneficial direction. In conclusion, our integrated molecular landscape of POP provides insights into the biological processes underlying the disease and clues towards novel treatments.Development and application of statistical models for medical scientific researc

Protocol for Translabial 3D-Ultrasonography for diagnosing levator defects (TRUDIL): a multicentre cohort study for estimating the diagnostic accuracy of translabial 3D-ultrasonography of the pelvic floor as compared to MR imaging

Contains fulltext : 96237.pdf (publisher's version ) (Open Access)BACKGROUND: Pelvic organ prolapse (POP) is a condition affecting more than half of the women above age 40. The estimated lifetime risk of needing surgical management for POP is 11%. In patients undergoing POP surgery of the anterior vaginal wall, the re-operation rate is 30%. The recurrence risk is especially high in women with a levator ani defect. Such defect is present if there is a partially or completely detachment of the levator ani from the inferior ramus of the symphysis. Detecting levator ani defects is relevant for counseling, and probably also for treatment. Levator ani defects can be imaged with MRI and also with Translabial 3D ultrasonography of the pelvic floor. The primary aim of this study is to assess the diagnostic accuracy of translabial 3D ultrasonography for diagnosing levator defects in women with POP with Magnetic Resonance Imaging as the reference standard. Secondary goals of this study include quantification of the inter-observer agreement about levator ani defects and determining the association between levator defects and recurrent POP after anterior repair. In addition, the cost-effectiveness of adding translabial ultrasonography to the diagnostic work-up in patients with POP will be estimated in a decision analytic model. METHODS/DESIGN: A multicentre cohort study will be performed in nine Dutch hospitals. 140 consecutive women with a POPQ stage 2 or more anterior vaginal wall prolapse, who are indicated for anterior colporapphy will be included. Patients undergoing additional prolapse procedures will also be included. Prior to surgery, patients will undergo MR imaging and translabial 3D ultrasound examination of the pelvic floor. Patients will be asked to complete validated disease specific quality of life questionnaires before surgery and at six and twelve months after surgery. Pelvic examination will be performed at the same time points. Assuming a sensitivity and specificity of 90% of 3D ultrasound for diagnosing levator defects in a population of 120 women with POP, with a prior probability of levator ani defects of 40%, we will be able to estimate predictive values with good accuracy (i.e. confidence limits of at most 10% below or above the point estimates of positive and negative predictive values).Anticipating 3% unclassifiable diagnostic images because of technical reasons, and a further safety margin of 10% we plan to recruit 140 patients. TRIAL REGISTRATION: Nederlands trial register NTR2220

Effectiveness of a multidisciplinary care program on recovery and return to work of patients after gynaecological surgery; design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Return to work after gynaecological surgery takes much longer than expected, irrespective of the level of invasiveness. In order to empower patients in recovery and return to work, a multidisciplinary care program consisting of an e-health intervention and integrated care management including participatory workplace intervention was developed.</p> <p>Methods/Design</p> <p>We designed a randomized controlled trial to assess the effect of the multidisciplinary care program on full sustainable return to work in patients after gynaecological surgery, compared to usual clinical care. Two hundred twelve women (18-65 years old) undergoing hysterectomy and/or laparoscopic adnexal surgery on benign indication in one of the 7 participating (university) hospitals in the Netherlands are expected to take part in this study at baseline. The primary outcome measure is sick leave duration until full sustainable return to work and is measured by a monthly calendar of sickness absence during 26 weeks after surgery. Secondary outcome measures are the effect of the care program on general recovery, quality of life, pain intensity and complications, and are assessed using questionnaires at baseline, 2, 6, 12 and 26 weeks after surgery.</p> <p>Discussion</p> <p>The discrepancy between expected physical recovery and actual return to work after gynaecological surgery contributes to the relevance of this study. There is strong evidence that long periods of sick leave can result in work disability, poorer general health and increased risk of mental health problems. We expect that this multidisciplinary care program will improve peri-operative care, contribute to a faster return to work of patients after gynaecological surgery and, as a consequence, will reduce societal costs considerably.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2087">NTR2087</a></p

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways