3D Winding Number: Theory and Application to Medical Imaging

We develop a new formulation, mathematically elegant, to detect critical points of 3D scalar images. It is based on a topological number, which is the generalization to three dimensions of the 2D winding number. We illustrate our method by considering three different biomedical applications, namely, detection and counting of ovarian follicles and neuronal cells and estimation of cardiac motion from tagged MR images. Qualitative and quantitative evaluation emphasizes the reliability of the results

Genomics of sex allocation in the parasitoid wasp Nasonia vitripennis

This research was funded by the Netherlands Genomics Initiative (Zenith 93511041) and the by the Natural Environment Research Council (NE/J024481/1).Background Whilst adaptive facultative sex allocation has been widely studied at the phenotypic level across a broad range of organisms, we still know remarkably little about its genetic architecture. Here, we explore the genome-wide basis of sex ratio variation in the parasitoid wasp Nasonia vitripennis, perhaps the best studied organism in terms of sex allocation, and well known for its response to local mate competition. Results We performed a genome-wide association study (GWAS) for single foundress sex ratios using iso-female lines derived from the recently developed outbred N. vitripennis laboratory strain HVRx. The iso-female lines capture a sample of the genetic variation in HVRx and we present them as the first iteration of the Nasonia vitripennis Genome Reference Panel (NVGRP 1.0). This panel provides an assessment of the standing genetic variation for sex ratio in the study population. Using the NVGRP, we discovered a cluster of 18 linked SNPs, encompassing 9 annotated loci associated with sex ratio variation. Furthermore, we found evidence that sex ratio has a shared genetic basis with clutch size on three different chromosomes. Conclusions Our approach provides a thorough description of the quantitative genetic basis of sex ratio variation in Nasonia at the genome level and reveals a number of inter-related candidate loci underlying sex allocation regulation.Publisher PDFPeer reviewe

Constraints on Natal Kicks in Galactic Double Neutron Star Systems

Since the discovery of the first double neutron star (DNS) system in 1975 by Hulse and Taylor, there are currently 8 confirmed DNS in our galaxy. For every system, the masses of both neutron stars, the orbital semi- major axis and eccentricity are measured, and proper motion is known for half of the systems. Using the orbital parameters and kinematic information, if available, as constraints for all system, we investigate the immediate progenitor mass of the second-born neutron star and the magnitude of the supernova kick it received at birth, with the primary goal to understand the core collapse mechanism leading to neutron star formation. Compared to earlier studies, we use a novel method to address the uncertainty related to the unknown radial velocity of the observed systems. For PSR B1534+12 and PSR B1913+16, the kick magnitudes are 150 - 270 km/s and 190 - 450 km/s (with 95% confidence) respectively, and the progenitor masses of the 2nd born neutron stars are 1.3 - 3.4 Msun and 1.4 - 5.0 Msun (95%), respectively. These suggest that the 2nd born neutron star was formed by an iron core collapse supernova in both systems. For PSR J0737-3039, on the other hand, the kick magnitude is only 5 - 120 km/s (95%), and the progenitor mass of the 2nd born neutron star is 1.3 - 1.9 Msun (95%). Because of the relatively low progenitor mass and kick magnitude, the formation of the 2nd born neutron star in PSR J0737-3039 is potentially connected to an electron capture supernova of a massive O - Ne - Mg white dwarf. For the remaining 5 Galactic DNS, the kick magnitude ranges from several tens to several hundreds of km/s, and the progenitor mass of the 2nd formed neutron star can be as low as ~1.5 Msun, or as high as ~8 Msun. Therefore in these systems, it is not clear which type of supernova is more likely to form the 2nd neutron star.Comment: 13 pages, 16 figures, accepted for publication in Ap

Clinimetric evaluation of methods to measure muscle functioning in patients with non-specific neck pain: a systematic review

Contains fulltext : 69123.pdf (publisher's version ) (Open Access)BACKGROUND: Neck pain is a significant health problem in modern society. There is evidence to suggest that neck muscle strength is reduced in patients with neck pain. This article provides a critical analysis of the research literature on the clinimetric properties of tests to measure neck muscle strength or endurance in patients with non-specific neck pain, which can be used in daily practice. METHODS: A computerised literature search was performed in the Medline, CINAHL and Embase databases from 1980 to January 2007. Two reviewers independently assessed the clinimetric properties of identified measurement methods, using a checklist of generally accepted criteria for reproducibility (inter- and intra-observer reliability and agreement), construct validity, responsiveness and feasibility. RESULTS: The search identified a total of 16 studies. The instruments or tests included were: muscle endurance tests for short neck flexors, craniocervical flexion test with an inflatable pressure biofeedback unit, manual muscle testing of neck musculature, dynamometry and functional lifting tests (the cervical progressive iso-inertial lifting evaluation (PILE) test and the timed weighted overhead test). All the articles included report information on the reproducibility of the tests. Acceptable intra- and inter-observer reliability was demonstrated for t enduranctest for short neck flexors and the cervical PILE test. Construct validity and responsiveness have hardly been documented for tests on muscle functioning. CONCLUSION: The endurance test of the short neck flexors and the cervical PILE test can be regarded as appropriate instruments for measuring different aspects of neck muscle function in patients with non-specific neck pain. Common methodological flaws in the studies were their small sample size and an inappropriate description of the study design

Human precision-cut cystic duct and gallbladder slices: a novel method for studying cholangiopathies

Background and aimsPrecision-cut tissue slices (PCTS) are widely used as an ex vivo culture tissue culture technique to study pathogeneses of diseases and drug activities in organs in vitro. A novel application of the PCTS model may be in the field of translational research into cholangiopathies such as biliary atresia. Therefore, the aim of this study was to apply the precision-cut slice technique to human bile duct and gallbladder tissue.MethodsCystic duct and gallbladder tissue derived from patients undergoing a cholecystectomy were collected, preserved and used for preparation of precision-cut cystic duct slices (PCCDS) and precision-cut gallbladder slices (PCGS). The PCCDS and PCGS were prepared using a mechanical tissue slicer and subsequently incubated for 24 and 48 h respectively in William's Medium E (WME) culture medium. Viability was assessed based on ATP/protein content and tissue morphology [hematoxylin and eosin (H&E) staining].ResultsIt was shown that viability, assessed by the ATP/protein content and morphology, of the PCCDS (n = 8) and PCGS (n = 8) could be maintained over the 24 and 48 h incubation period respectively. ATP/protein content of the PCCDS increased significantly from 0.58 ± 0.13 pmol/µg at 0 h to 2.4 ± 0.29 pmol/µg after 24 h incubation (P = .0003). A similar significant increase from 0.94 ± 0.22 pmol/µg at 0 h to 3.7 ± 0.41 pmol/µg after 24 h (P = .0005) and 4.2 ± 0.47 pmol/µg after 48 h (P = .0002) was observed in the PCGS. Morphological assessment of the PCCDS and PCGS showed viable tissue at 0 h and after 24 and 48 h incubation respectively.ConclusionThis study is the first to report on the use of the PCTS model for human gallbladder and cystic duct tissue. PCCDS and PCGS remain viable for an incubation period of at least 24 h, which makes them suitable for research purposes in the field of cholangiopathies, including biliary atresia

Analysis of rare variants in the C3 gene in patients with age-related macular degeneration

Age-related macular degeneration (AMD) is a progressive retinal disorder affecting over 33 million people worldwide. Genome-wide association studies (GWASs) for AMD identified common variants at 19 loci accounting for 15-65% of the heritability and it has been hypothesized that the missing heritability may be attributed to rare variants with large effect sizes. Common variants in the complement component 3 (C3) gene have been associated with AMD and recently a rare C3 variant (Lys155Gln) was identified which exerts a large effect on AMD susceptibility independent of the common variants. To explore whether additional rare variants in the C3 gene are associated with AMD, we sequenced all coding exons in 84 unrelated AMD cases. Subsequently, we genotyped all identified variants in 1474 AMD cases and 2258 controls. Additionally, because of the known genetic overlap between AMD and atypical hemolytic uremic syndrome (aHUS), we genotyped two recurrent aHUS-associated C3 mutations in the entire cohort. Overall, we identified three rare variants (Lys65Gln (P = 0.04), Arg735Trp (OR = 17.4, 95% CI = 2.2-136; P = 0.0003), and Ser1619Arg (OR = 5.2, 95% CI = 1.0-25; P = 0.05) at the C3 locus that are associated with AMD in our EUGENDA cohort. However, the Arg735Trp and Ser1619Arg variants were not found to be associated with AMD in the Rotterdam Study. The Lys65Gln variant was only identified in patients from Nijmegen, the Netherlands, and thus may represent a region-specific AMD risk variant

Prevalence of complaints of arm, neck and shoulder among computer office workers and psychometric evaluation of a risk factor questionnaire

<p>Abstract</p> <p>Background</p> <p>Complaints of Arm Neck and Shoulder (CANS) represent a wide range of complaints, which can differ in severity from mild, periodic symptoms to severe, chronic and debilitating conditions. They are thought to be associated with both physical and psychosocial risk factors. The measurement and identification of the various risk factors for these complaints is an important step towards recognizing (a) high risk subgroups that are relevant in profiling CANS; and (b) also for developing targeted and effective intervention plans for treatment. The purpose of the present study was to investigate the prevalence of CANS in a Dutch population of computer workers and to develop a questionnaire aimed at measuring workplace physical and psychosocial risk factors for the presence of these complaints.</p> <p>Methods</p> <p>To examine potential workplace risk factors for the presence of CANS, the Maastricht Upper Extremity Questionnaire (MUEQ), a structured questionnaire, was developed and tested among 264 computer office workers of a branch office of the national social security institution in the Netherlands. The MUEQ holds 95 items covering demographic characteristics, in addition to seven main domains assessing potential risk factors with regard to (1) work station, (2) posture during work, (3) quality of break time, (4) job demands, (5) job control, and (6) social support. The MUEQ further contained some additional questions about the quality of the work environment and the presence of complaints in the neck, shoulder, upper and lower arm, elbow, hand and wrist. The prevalence rates of CANS in the past year were computed. Further, we investigated the psychometric properties of the MUEQ (i.e. factor structure and reliability).</p> <p>Results</p> <p>The one-year prevalence rate of CANS indicated that 54% of the respondents reported at least one complaint in the arm, neck and/or shoulder. The highest prevalence rates were found for neck and shoulder symptoms (33% and 31% respectively), followed by hand and upper arm complaints (11% to 12%) and elbow, lower arm and wrist complaints (6% to 7%). The psychometric properties of the MUEQ were assessed using exploratory factor analysis which resulted in the identification of 12 factors. The calculation of internal consistency and cross validation provided evidence of reliability and lack of redundancy of items.</p> <p>Conclusion</p> <p>Neck and shoulder complaints are more frequently reported among Dutch computer workers than arm, elbow and hand complaints. The results further indicate that the MUEQ has satisfactory reliability and internal consistency when used to document CANS among computer workers in the Netherlands.</p

Chronic non-specific abdominal complaints in general practice: a prospective study on management, patient health status and course of complaints

BACKGROUND: While in general practice chronic non-specific abdominal complaints are common, there is insufficient data on the clinical course and the management of these complaints. Aim of this study was to present a primary care based profile of these chronic complaints including health care involvement, health status and clinical course. METHODS: Thirty general practitioners (GPs) and patients from their practices participated in a prospective follow-up study. All patients and GPs were asked to complete questionnaires at baseline and at 6, 12 and 18 months of follow-up. The GPs provided information on diagnostic and therapeutic management and on referral concerning 619 patients with chronic non-specific abdominal complaints, while 291 patients provided information about health status and clinical course of the complaints. RESULTS: When asked after 18 months of follow-up, 51,7% of the patients reported an equal or worsened severity of complaints. General health perception was impaired and patients had high scores on SCL-anxiety and SCL-depression scales. Diagnostic tests other than physical examination and laboratory tests were not frequently used. Medication was the most frequent type of treatment. The persistence of chronic non-specific abdominal complaints was quite stable. CONCLUSION: Once non-specific chronic abdominal complaints have become labelled as chronic by the attending physician, little improvement can be expected. The impact on patients' physiological and psychological well-being is large. GPs use a variety of diagnostic and therapeutic strategies. Research into the evidence base of currently applied management strategies is recommended