Variability in tracheal mucociliary transport is not controlled by beating cilia in lambs in vivo during ventilation with humidified and nonhumidified air.

Mucociliary transport in the respiratory epithelium depends on beating of cilia to move a mucus layer containing trapped inhaled particles toward the mouth. Little is known about the relationship between cilia beat frequency (CBF) and mucus transport velocity (MTV) in vivo under normal physiological conditions and when inspired air is dry or not fully humidified. This study was designed to use video-microscopy to simultaneously measure CBF and MTV in the tracheal epithelium through an implanted optical window in mechanically ventilated lambs. The inspired air in 6 animals was heated to body temperature and fully saturated with water for 4 hours as a baseline. In another series of experiments, 5 lambs were ventilated with air at different temperatures and humidities and the mucosal surface temperature was monitored with infrared macro-imaging. In the baseline experiments, during ventilation with fully humidified air at body temperature, CBF remained constant, mean 13.9 ± 1.6 Hz but MTV varied considerably between 0.1 and 26.1 mm/min with mean 11.0 ± 3.9 mm/min, resulting in a maximum mucus displacement of 34.2 µm/cilia beat. Fully humidified air at body temperature prevented fluctuations in the surface temperature during breathing indicating a thermodynamic balance in the airways. When lambs were ventilated with dryer air, the mucosal surface temperature and MTV dropped without a significant change in CBF. When inspired air was dry, mainly latent heat (92%) was transferred to air in the trachea, reducing the surface temperature by 5 °C. Reduced humidity of the inspired air lowered the surface temperature and reduced MTV in the epithelium during ventilation.

Editor's Choice - Nationwide Analysis of Patients Undergoing Iliac Artery Aneurysm Repair in the Netherlands.

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests. RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively). CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.

Lung function parameters in omalizumab responder patients: An interesting tool?

BACKGROUND: Omalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and nonresponder patients remain inconclusive. The objective of this real-life study was to compare the changes in forced expiratory volume in 1 second (FEV1) of omalizumab responders and nonresponders at 6 months. METHODS: A multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity (FVC), pre- and postbronchodilator FEV1, residual volume (RV), and total lung capacity (TLC) were determined at baseline and at 6 months. Omalizumab response was assessed at the 6-month visit. In the omalizumab responder patients, lung function parameters were also obtained at 12, 18, and 24 months. RESULTS: Mean prebronchodilator FEV1 showed improvement in responders at 6 months, while a decrease was observed in nonresponders (+0.2±0.4 L and -0.1±0.4 L, respectively, P<.01). After an improvement at 6 months, pre- and postbronchodilator FEV1 remained stable at 12, 18, and 24 months. The FEV1/FVC remained unchanged over time, but the proportion of patients with an FEV1/FVC ratio <0.7 decreased at 6, 12, 18, and 24 months (55.2%, 54.0%, 54.0%, and 44.8%, respectively, P<.05). Mean RV values decreased at 6 months but increased at 12 months and 24 months (P<.05). Residual volume/total lung capacity (RV/TLC) ratio decreased at 6 months and remained unchanged at 24 months. CONCLUSION: After omalizumab initiation, FEV1 improved at 6 months in responder patients and then remained stable for 2 years. RV and RV/TLC improved at 6 months.

Longitudinal stability of asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study.

BACKGROUND: Asthma is a biologically heterogeneous disease and development of novel therapeutics requires understanding of pathophysiologic phenotypes. There is uncertainty regarding the stability of clinical characteristics and biomarkers in asthma over time. This report presents the longitudinal stability over 12 months of clinical characteristics and clinically accessible biomarkers from ADEPT. METHODS: Mild, moderate, and severe asthma subjects were assessed at 5 visits over 12 months. Assessments included patient questionnaires, spirometry, bronchodilator reversibility, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum. RESULTS: Mild (n = 52), moderate (n = 55), and severe (n = 51) asthma cohorts were enrolled from North America and Western Europe. For all clinical characteristics and biomarkers, group mean data showed no significant change from visit to visit. However, individual data showed considerable variability. FEV1/FVC ratio showed excellent reproducibility while pre-bronchodilator FEV1 and FVC were only moderately reproducible. Of note bronchodilator FEV1 reversibility showed low reproducibility, with the nonreversible phenotype much more reproducible than the reversible phenotype. The 7-item asthma control questionnaire (ACQ7) demonstrated moderate reproducibility for the combined asthma cohorts, but the uncontrolled asthma phenotype (ACQ7 > 1.5) was inconstant in mild and moderate asthma but stable in severe asthma. FENO demonstrated good reproducibility, with the FENO-low phenotype (FENO < 35 ppb) more stable than the FENO-high phenotype (FENO ≥ 35 ppb). Induced sputum inflammatory phenotypes showed marked variability across the 3 sputum samples taken over 6 months. CONCLUSIONS: The ADEPT cohort showed group stability, individual stability in some parameters e.g. low FEV1/FVC ratio, and low FENO, but marked individual variability in other clinical characteristics and biomarkers e.g. type-2 biomarkers over 12 months. This variability is possibly related to seasonal variations in climate and allergen exposure, medication changes and acute exacerbations. The implications for patient selection strategies based on clinical biomarkers may be considerable.

Asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) longitudinal profiling study.

BACKGROUND: Asthma is a heterogeneous disease and development of novel therapeutics requires an understanding of pathophysiologic phenotypes. The purpose of the ADEPT study was to correlate clinical features and biomarkers with molecular characteristics, by profiling asthma (NCT01274507). This report presents for the first time the study design, and characteristics of the recruited subjects. METHODS: Patients with a range of asthma severity and healthy non-atopic controls were enrolled. The asthmatic subjects were followed for 12 months. Assessments included history, patient questionnaires, spirometry, airway hyper-responsiveness to methacholine, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum, blood, and bronchoscopy samples. All subjects underwent sputum induction and 30 subjects/cohort had bronchoscopy. RESULTS: Mild (n = 52), moderate (n = 55), severe (n = 51) asthma cohorts and 30 healthy controls were enrolled from North America and Western Europe. Airflow obstruction, bronchodilator response and airways hyperresponsiveness increased with asthma severity, and severe asthma subjects had reduced forced vital capacity. Asthma control questionnaire-7 (ACQ7) scores worsened with asthma severity. In the asthmatics, mean values for all clinical and biomarker characteristics were stable over 12 months although individual variability was evident. FENO and blood eosinophils did not differ by asthma severity. Induced sputum eosinophils but not neutrophils were lower in mild compared to the moderate and severe asthma cohorts. CONCLUSIONS: The ADEPT study successfully enrolled asthmatics across a spectrum of severity and non-atopic controls. Clinical characteristics were related to asthma severity and in general asthma characteristics e.g. lung function, were stable over 12 months. Use of the ADEPT data should prove useful in defining biological phenotypes to facilitate personalized therapeutic approaches.

Cumulative incidence of graft infection after primary prosthetic aortic reconstruction in the endovascular era.

OBJECTIVE: The introduction of endovascular techniques has had a major impact on the case mix of patients that undergo open aortic reconstruction. Hypothetically, this may also have increased the incidence of aortic graft infection (AGI). The aim of this study was to report on the short and mid-term incidence of AGI after primary open prosthetic aortic reconstruction in the endovascular era. METHODS: From 2000 to 2010, all 514 patients in a tertiary referral university hospital, undergoing primary open prosthetic aortic reconstruction for aneurysmal or occlusive aortic disease with at least one aortic anastomosis were included. Data were obtained by retrospectively analyzing the medical records, by contacting patients or their general practitioner by telephone, and by merging the dataset with the national Cause of Death Register. AGI was defined as proven by cultures or clinically in combination with positive imaging results. The 30 day, 1 year, and 2 year incidence rates were computed using life table analysis and expressed as percentages with 95% confidence intervals (CI). RESULTS: AGI was diagnosed in 23 of the 514 included patients. 56% of the patients underwent elective surgery and 86% underwent surgery for an abdominal aortic aneurysm. The 30 day incidence was 1.6% (95% CI 0.4-2.8%), 1 year incidence was 3.6% (95% CI 1.7-5.5%), and 2 year incidence for AGI was 4.5% (95% CI 2.4-6.6%). The total number of person years (1058) yielded an AGI rate of 2.2 per 100 person years. CONCLUSION: The 2 year cumulative incidence of AGI following primary, open aortic procedures with at least one aortic anastomosis is considerable, at around 1 in 20.

Differential FDG-PET Uptake Patterns in Uninfected and Infected Central Prosthetic Vascular Grafts.

OBJECTIVE: (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning has been suggested as a means to detect vascular graft infections. However, little is known about the typical FDG uptake patterns associated with synthetic vascular graft implantation. The aim of the present study was to compare uninfected and infected central vascular grafts in terms of various parameters used to interpret PET images. METHODS: From 2007 through 2013, patients in whom a FDG-PET scan was performed for any indication after open or endovascular central arterial prosthetic reconstruction were identified. Graft infection was defined as the presence of clinical or biochemical signs of graft infection with positive cultures or based on a combination of clinical, biochemical, and imaging parameters (other than PET scan data). All other grafts were deemed uninfected. PET images were analyzed using maximum systemic uptake value (SUVmax), tissue to background ratio (TBR), visual grading scale (VGS), and focality of FDG uptake (focal or homogenous). RESULTS: Twenty-seven uninfected and 32 infected grafts were identified. Median SUVmax was 3.3 (interquartile range [IQR] 2.0-4.2) for the uninfected grafts and 5.7 for the infected grafts (IQR 2.2-7.8). Mean TBR was 2.0 (IQR 1.4-2.5) and 3.2 (IQR 1.5-3.5), respectively. On VGS, 44% of the uninfected and 72% of the infected grafts were judged as a high probability for infection. Homogenous FDG uptake was noted in 74% of the uninfected and 31% of the infected grafts. Uptake patterns of uninfected and infected grafts showed a large overlap for all parameters. CONCLUSION: The patterns of FDG uptake for uninfected vascular grafts largely overlap with those of infected vascular grafts. This questions the value of these individual FDG-PET-CT parameters in identifying infected grafts.

Candidate epitopes for measurement of hCG and related molecules: the second ISOBM TD-7 workshop.

Participants of the Second International Workshop (WS) on human chorionic gonadotropin (hCG) of the International Society of Oncology and Biomarkers Tissue Differentiation 7 (ISOBM TD-7) have characterized in detail a panel of 69 antibodies (Abs) directed against hCG and hCG-related variants that were submitted by eight companies and research groups. Specificities of the Abs were determined using the First WHO International Reference Reagents for six hCG variants, i.e., hCG, hCGn, hCGß, hCGßn, hCGßcf, and hCGα, which are calibrated in SI units, and hLH. Molecular epitope localizations were assigned to the ISOBM-mAbs by comparing ISOBM-Ab specificity, sandwich compatibility, and mutual inhibition profiles, to those of 17 reference monoclonal (m)Abs of known molecular epitope specificities. It appeared that 48 Abs recognized hCGß-, 8 hCGα-, and 13 αß-heterodimer-specific epitopes. Twenty-seven mAbs were of pan hCG specificity, two thereof with no (<0.1%; epitope ß1), 12 with low (<1.0%; epitopes ß2/4), and 13 with high (>>1%; epitopes ß3/5) hLH cross-reactivity. The majority of hCGß epitopes recognized were located in two major antigenic domains, one on the peptide chain of the tips of ß-sheet loops 1 and 3 (epitopes ß2-6; 27 mAbs) and the second around the cystine knot (e.g., epitopes ß1, ß7, and ß10; 9 mAbs). Four mAbs recognized epitopes on hCGßcf-only (e.g., epitopes ß11 and ß13) and six mAbs epitopes on the remote hCGß-carboxyl-terminal peptide (epitopes ß8 and ß9 corresponding to amino acids 135-144 and 111-116, respectively). For routine diagnostic measurements, methods are used that either detect hCG-only, hCGß-only, or hCG together with hCGß or hCG together with hCGß and hCGßcf. Sandwich assays that measure hCG plus hCGß and eventually hCGßcf should recognize the protein backbone of the analytes preferably on an equimolar basis, should not cross-react with hLH and not be susceptible to blunting of signal by nonmeasured variants like hCGßcf. Such assays can be constructed using pairs of mAbs directed against the cystine knot-associated epitope ß1 (Asp10, Asp60, and Gln89) in combination with epitopes ß2 or ß4 located at the top of ß-sheet loops 1 + 3 of hCGß involving aa hCGß20-25 + 68-77. In summary, the results of the First and Second ISOBM TD-7 WSs on hCG provide the basis for harmonization of specificities and epitopes of mAbs to be used in multifunctional and selective diagnostic hCG methods for different clinical purposes.

Localized argyria caused by metallic silver aortic grafts: a unique adverse effect.

INTRODUCTION: Silver-coated grafts are designed to prevent vascular graft infections. Silver is a safe element but toxic effects have been reported. We describe two cases of possible localized argyria after silver graft implantation. REPORT: Two patients presented with perigraft groin collections after implantation of silver grafts. During reoperation, an ashen-grey necrotic substance was seen surrounding the grafts. The grafts were explanted and lower limb perfusion restored. Cultures were negative and both patients had uneventful recoveries. DISCUSSION: Our cases are highly suggestive of a possible unique adverse effect: a combination of localized silver toxicity and neutrophilic mediated tissue destruction.

Seminal plasma enhances and accelerates progesterone-induced decidualisation of human endometrial stromal cells.

In preparation for embryo implantation, endometrial stromal cells (ESC) undergo differentiation, termed decidualisation. Enhancing endometrial decidualisation may overcome reduced endometrial receptivity, a major limiting factor in natural and assisted reproduction. To determine whether seminal plasma (SP) influences decidualisation, primary human ESC were treated with progesterone (P4, 50 ng mL(-1)) in the presence or absence of dialysed SP (0.5%) for 24 h or for up to 27 days to investigate immediate early effects or the effects of prolonged exposure, respectively. Combined SP and P4 treatment induced ESC morphological differentiation. Relative to control, P4 alone, and SP alone combined treatment with SP and P4 for 27 days significantly upregulated mRNA levels of the decidua-specific markers prolactin (PRL) and insulin-like growth factor binding protein 1 (IGFBP1). Consistently, PRL protein secretion was significantly increased over the course of 27 days combined SP and P4 treatment relative to control, P4 alone and SP alone. Likewise, IGFBP1 secretion was significantly greater relative to control and P4 alone over the course of 27 days. Thus, SP enhances and accelerates P4-mediated decidualisation of human ESC and may enhance endometrial receptivity.

[CD8+ T cells and fibrocytes: dangerous interplay in the distal bronchi of patients with chronic obstructive pulmonary disease?] / Lymphocytes T CD8+ et fibrocytes : un jeu dangereux dans les bronches distales des patients atteints de bronchopneumopathie chronique obstructive ?

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by chronic inflammation and bronchial remodeling, resulting in airflow limitation. Several studies indicate a detrimental role of CD8+ T cells in the evolution of the disease, however the mechanisms of CD8+T cell activation in the lungs of COPD patients are still not understood. Fibrocytes, whose density is associated with bronchial remodeling and bronchial obstruction, have immunomodulatory properties. We will describe how interactions between CD8+T cells and fibrocytes may be involved in disease initiation and progression.

[Take-home messages from the COPD 2021 biennial of the French Society of Respiratory Diseases. Understanding to so as to better innovate]. / Principaux messages de la première Biennale BPCO 2021 de la SPLF. Mieux comprendre pour innover.

INTRODUCTION: The first COPD biennial organized by the French Society of Respiratory Diseases (SPLF) took place on 17 December 2021. STATE OF THE ART: The objective of the biennial was to discuss current knowledge regarding COPD pathophysiology, current treatments, research development, and future therapeutic approaches. PERSPECTIVES: The different lecturers laid emphasis on the complexity of pathophysiologic mechanisms including bronchial, bronchiolar and parenchymal alterations, and also dwelt on the role of microbiota composition in COPD pathenogenesis. They pointed out that addition to inhaled treatments, ventilatory support and endoscopic approaches have been increasingly optimized. The development of new therapeutic pathways such as biotherapy and cell therapy (stem cells…) call for further exploration. CONCLUSIONS: The dynamism of COPD research was repeatedly underlined, and needs to be further reinforced, the objective being to "understand so as to better innovate" so as to develop effective new strategies for treatment and management of COPD.

A Bayesian threshold-linear model evaluation of perinatal mortality, dystocia, birth weight, and gestation length in a Holstein herd.

The objective of this research was to estimate genetic parameters for a multiple-trait evaluation of dystocia (DYS), perinatal mortality (PM), birth weight (BWT), and gestation length (GL) in Holsteins. The data included 5,712 calving records collected between 1968 and 2005 from the Iowa State University dairy breeding herd in Ankeny. The incidence of PM was 8.8% and that of DYS 28.8%; mean BWT was 40.5 kg, and GL was 279 d. A threshold-linear animal model included the effects of year, season, sex of calf, parity, sire group, direct genetic, maternal genetic, and maternal permanent environment. Direct heritabilities for DYS, PM, BWT, and GL were 0.11 (0.04), 0.13 (0.05), 0.26 (0.04), and 0.51 (0.05), respectively. Maternal heritabilities were 0.14 (0.04), 0.15 (0.03), 0.08 (0.01), and 0.08 (0.02), for DYS, PM, BWT, and GL, respectively. The heritabilities are the posterior means of the Gibbs samples with their standard deviations in parentheses. The direct genetic correlation between PM and DYS was estimated at 0.67 (0.19), whereas the maternal genetic correlation was 0.45 (0.16). Direct and maternal PM and DYS are partially controlled by the same genes. Selection on only calving ease is not sufficient to control PM. With moderate genetic correlations between all 4 traits, BWT and GL should be included with DYS and PM in an evaluation of calving performance.

Aberrant CREB1 activation in prostate cancer disrupts normal prostate luminal cell differentiation.

The molecular mechanisms of luminal cell differentiation are not understood well enough to determine how differentiation goes awry during oncogenesis. Using RNA-Seq analysis, we discovered that CREB1 plays a central role in maintaining new luminal cell survival and that oncogenesis dramatically changes the CREB1-induced transcriptome. CREB1 is active in luminal cells, but not basal cells. We identified ING4 and its E3 ligase, JFK, as CREB1 transcriptional targets in luminal cells. During luminal cell differentiation, transient induction of ING4 expression is followed by a peak in CREB1 activity, while JFK increases concomitantly with CREB1 activation. Transient expression of ING4 is required for luminal cell induction; however, failure to properly down-regulate ING4 leads to luminal cell death. Consequently, blocking CREB1 increased ING4 expression, suppressed JFK, and led to luminal cell death. Thus, CREB1 is responsible for the suppression of ING4 required for luminal cell survival and maintenance. Oncogenic transformation by suppressing PTEN resulted in constitutive activation of CREB1. However, the tumor cells could no longer fully differentiate into luminal cells, failed to express ING4, and displayed a unique CREB1 transcriptome. Blocking CREB1 in tumorigenic cells suppressed tumor growth in vivo, rescued ING4 expression, and restored luminal cell formation, but ultimately induced luminal cell death. IHC of primary prostate tumors demonstrated a strong correlation between loss of ING4 and loss of PTEN. This is the first study to define a molecular mechanism whereby oncogenic loss of PTEN, leading to aberrant CREB1 activation, suppresses ING4 expression causing disruption of luminal cell differentiation.

Pathophysiology of bronchial smooth muscle remodelling in asthma.

Whereas the role of bronchial smooth muscle remains controversial in healthy subjects its role is well established in asthmatics. Bronchial smooth muscle contraction induces airway narrowing. The smooth muscle also contributes to bronchial inflammation by secreting a range of inflammatory mediators, recruiting and activating inflammatory cells, such as mast cells or T-lymphocytes. In addition, bronchial smooth muscle mass is significantly increased in asthma. Such an increase has been related to a deposition of extracellular matrix proteins, and an increase in both cell size and number. However, the mechanisms of this smooth muscle remodelling are complex and not completely understood. The article will review recent data regarding the pathophysiology of bronchial smooth muscle remodelling in asthma.

Mast cell adhesion to bronchial smooth muscle in asthma specifically depends on CD51 and CD44 variant 6.

BACKGROUND: Mast cells infiltrate the bronchial smooth muscle (BSM) in asthmatic patients, but the mechanism of mast cell adhesion is still unknown. The adhesion molecules CD44 (i.e. hyaluronate receptor) and CD51 (i.e. vitronectin receptor) are widely expressed and bind to many extracellular matrix (ECM) proteins. The aims of the study are (i) to identify the role of ECM in mast cell adhesion to BSM and (ii) to examine the role of CD51 and CD44 in this adhesion. METHODS: Human lung mast cells, human mast cell line (HMC-1), and BSM cells from control donors or asthmatic patients were cultured in the presence/absence of various cytokines. Mast cell-BSM interaction was assessed using (3)H-thymidine-pulsed mast cells, confocal immunofluorescence, or electron microscopy. Adhesion molecules expression and collagen production on both cell types were evaluated by quantitative RT-PCR, western blot, and flow cytometry. RESULTS: Mast cell adhesion to BSM cells mostly involved type I collagen of the ECM. Such an adhesion was increased in normal BSM cells under inflammatory condition, whereas it was maximal in asthmatic BSM cells. Blockade of either CD51 or CD44 significantly decreased mast cell adhesion to BSM. At the molecular level, protein and the transcriptional expression of type I collagen, CD51 or CD44 remained unchanged in asthmatic BSM cells or in mast cells/BSM cells under inflammatory conditions, whereas that of CD44 variant isoform 6 (v6) was increased. CONCLUSIONS: Mast cell-BSM cell adhesion involved collagen, CD44, and CD51, particularly under inflammatory conditions. CD44v6 expression is increased in asthmatic BSM cells.

Validation of whole genome linkage-linkage disequilibrium and association results, and identification of markers to predict genetic merit for twinning.

A previous genome-wide search with a moderate density 10K marker set identified many marker associations with twinning rate, either through single-marker analysis or combined linkage-linkage disequilibrium (LLD; haplotype) analysis. The objective of the current study was to validate putative marker associations using an independent set of phenotypic data. Holstein bulls (n = 921) from 100 paternal half-sib families were genotyped. Twinning rate predicted transmitting abilities were calculated using calving records from 1994 to 1998 (Data I) and 1999 to 2006 (Data II), and the underlying liability scores from threshold model analysis were used as the trait in marker association analyses. The previous analysis used 201 bulls with daughter records in Data I. In the current analysis, this was increased to 434, providing a revised estimate of effect and significance. Bulls with daughter records in Data II totaled 851, and analysis of this data provided the validation of results from analysis of Data I. Single nucleotide polymorphisms (SNPs) were selected to validate previously significant single-marker associations and LLD results. Bulls were genotyped for a total of 306 markers. Nine of 13 LLD regions located on chromosomes 1, 2, 3, 6, 9, 22, 23(2) and 26 were validated, showing significant results for both Data I and II. Association analysis revealed 55 of 174 markers validated, equating to a single-marker validation rate of 31%. Stepwise backward elimination and cross-validation analyses identified 18 SNPs for use in a final reduced marker panel explaining 34% of the genetic variation, and to allow prediction of genetic merit for twinning rate.

Validation of the Simulator for Testing and Rating Endovascular SkillS (STRESS)-machine in a setting of competence testing.

AIM: Endovascular skills are an integral part of modern-day vascular surgery. The STRESS machine has been developed to test these skills in vascular surgeons. This study aims to define an optimal pass/fail cutoff value for the STRESS test score. METHODS: The STRESS machine consists of a dry glass model of the abdominal aorta and its tributaries with various stenotic lesions, elongations, and tortuosities. A camera and computer software are used to simulate plain fluoroscopy-mode. The test subjects are given two assignments after which two reviewers use a combination of the ICEPS and MRS to produce the final total score; 43 subjects were tested. According to previous endovascular experience, subjects were classified into four groups: novice-low (no experience, less than 11 performed procedures, less than 50 assisted procedures), novice-high (11-25 performed procedures, more than 50 assisted procedures), intermediate (1-10 performed and >11-25 assisted procedures, 11-25 performed and >1-10 assisted procedures or 25-50 performed procedures) and advanced (more than 50 performed procedures). RESULTS: Test-score and noted experience showed a correlation of 0.794. All intermediate and advanced test subjects scored more than 50 points compared to 4 out of 15 novices. CONCLUSION: We demonstrated that it is possible to determine an optimal cut-off value for competence testing with the STRESS machine.