Development of automated annotation software for human embryo morphokinetics.

STUDY QUESTION: Is it possible to develop an automated annotation tool for human embryo development in time-lapse devices based on image analysis? SUMMARY ANSWER: We developed and validated an automated software for the annotation of human embryo morphokinetic parameters, having a good concordance with expert manual annotation on 701 time-lapse videos. WHAT IS KNOWN ALREADY: Morphokinetic parameters obtained with time-lapse devices are increasingly used for the assessment of human embryo quality. However, their annotation is time-consuming and can be slightly operator-dependent, highlighting the need to develop fully automated approaches. STUDY DESIGN, SIZE, DURATION: This monocentric study was conducted on 701 videos originating from 584 couples undergoing IVF with embryo culture in a time-lapse device. The only selection criterion was that the duration of the video must be over 60 h. PARTICIPANTS/MATERIALS, SETTING, METHODS: An automated morphokinetic annotation tool was developed based on gray level coefficient of variation and detection of the thickness of the zona pellucida. The detection of cellular events obtained with the automated tool was compared with those obtained manually by trained experts in clinical settings. MAIN RESULTS AND THE ROLE OF CHANCE: Although some differences were found when embryos were considered individually, we found an overall concordance between automated and manual annotation of human embryo morphokinetics from fertilization to expanded blastocyst stage (r2 = 0.92). LIMITATIONS, REASONS FOR CAUTION: These results should undergo multicentric external evaluation in order to test the overall performance of the annotation tool. Getting access to the export of 3D videos would enhance the quality of the correlation with the same algorithm and its extension to the 3D regions of interest. A technical limitation of our work lies within the duration of the video. The more embryo stages the video contains, the more information the script has to identify them correctly. WIDER IMPLICATIONS OF THE FINDINGS: Our system paves the way for high-throughput analysis of multicentric morphokinetic databases, providing new insights into the clinical value of morphokinetics as a predictor of embryo quality and implantation. STUDY FUNDING/COMPETING INTEREST(S): This study was partly funded by Finox-Gedeon Richter Forward Grant 2016 and NeXT (ANR-16-IDEX-0007). We have no conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Multidisciplinary decision-making regarding chemotherapy for lung cancer patients-An age-based comparison.

Optimising decision-making in elderly patients is becoming increasingly urgent. We analysed treatment decisions and course of therapy for patients with lung cancer in different age categories: <65, 65-75, and 75 years and older. About 349 patients with lung cancer (median age 67.8 years), discussed at the multidisciplinary team meeting in the Diakonessenhuis Utrecht, the Netherlands, were reviewed. Multidisciplinary decision-making and subsequent clinical course were extracted from medical files. We found that 39% of eligible patients older than 75 years of age started treatment with chemotherapy compared to 80% of the younger patients (<65 and 65-75). When patients did receive chemotherapy, primary and secondary treatment adaptations were effectuated in 58%: for patients aged <65 in 49%, for patients aged 65-75 and >75 years in 66%. For 44% of all patients treated with chemotherapy, unplanned hospital admissions were required: in 42% for the patients <65, in 52% for those aged 65-75 and in 27% for >75 years. The decision-making process and course of treatment for lung cancer vary per age category. In particular, patients between 65 and 75 years of age might be more frail than initially thought. Age and frailty are important characteristics that need more attention.

Chemotherapy and healthcare utilisation near the end of life in patients with cancer.

The quality of medical care delivered to patients with cancer near the end of life is a significant issue. Previous studies have defined several areas suggestive of aggressive cancer treatment as potentially representing poor quality care. The primary objective of current analysis was to examine chemotherapy and healthcare utilisation in the last 3 months of life among patients with cancer that received palliative chemotherapy. Patients were selected from the hospital administration database of the Diakonessenhuis Utrecht, the Netherlands. Data were extracted from the medical files. A total of 604 patients were included for analysis (median age: 64 years). For 300 patients (50%) chemotherapy was given in the last 3 months (CT+). For 76% (n = 229) of CT+ patients unplanned hospital admissions were made in these last 3 months, compared to 44% (n = 133) of CT- patients (p < .001). Visits to the emergency room in last 3 months were made by 67% (n = 202) of CT+ patients compared to 43% (n = 132) of CT- patients (p < .001). Healthcare consumption was significantly higher in patients who received chemotherapy in the last 3 months of life. Being able to inform our patients about these aspects of treatment can help to optimise both the quality of life and the quality of dying in patients with cancer.

Sperm cryopreservation and assisted reproductive technology outcome in patients with spinal cord injury.

This study aimed to describe spinal cord injured patients' semen characteristics before and after cryopreservation, and assisted reproductive technology cycles outcome compared to the infertile population. Data about sperm analysis and assisted reproductive technology (ART) cycles outcomes for 78 men with spinal cord injury referred for sperm cryopreservation between 1998 and 2013 were retrospectively analysed and compared with a reference group consisting of every Intra Cytoplasmic Sperm Injection (ICSI) cycle performed in our in vitro fertilization unit over the 2009-2014 period. Semen was collected by penile vibratory stimulation (PVS), electroejaculation or via testis biopsies. Fresh and frozen semen parameters and ART outcomes with frozen-thawed sperm were measured. Patients were divided into three groups according to the sperm retrieval methods: 37 electroejaculations, 37 PVSs and four surgical sperm retrievals. Low ejaculate volume was observed in 33% of the patients, and oligozoospermia in 37% of the patients. Specimens from 77 of the patients contained motile sperm and were therefore frozen for future use. There was no statistical difference for any of the fresh semen parameters between all groups. Twenty of them underwent ICSI leading to five live births, while four underwent intrauterine insemination. ART with frozen-thawed spermatozoa can provide men with SCI with comparable results as in the infertile population.

Diagnosing eosinophilic asthma using a multivariate prediction model based on blood granulocyte responsiveness.

BACKGROUND: The identification of inflammatory asthma phenotypes, using sputum analysis, has proven its value in diagnosis and disease monitoring. However due to technical limitations of sputum analysis, there is a strong need for fast and noninvasive diagnostics. This study included the activation state of eosinophils and neutrophils in peripheral blood to phenotype and monitor asthma. OBJECTIVES: To (i) construct a multivariable model using the activation state of blood granulocytes, (ii) compare its diagnostic value with sputum eosinophilia as gold standard and (iii) validate the model in an independent patient cohort. METHODS: Clinical parameters, activation of blood granulocytes and sputum characteristics were assessed in 115 adult patients with asthma (training cohort/Utrecht) and 34 patients (validation cohort/Oxford). RESULTS: The combination of blood eosinophil count, fractional exhaled nitric oxide, Asthma Control Questionnaire, medication use, nasal polyposis, aspirin sensitivity and neutrophil/eosinophil responsiveness upon stimulation with formyl-methionyl-leucyl phenylalanine was found to identify sputum eosinophilia with 90.5% sensitivity and 91.5% specificity in the training cohort and with 77% sensitivity and 71% specificity in the validation cohort (relatively high percentage on oral corticosteroids [OCS]). CONCLUSIONS: The proposed prediction model identifies eosinophilic asthma without the need for sputum induction. The model forms a noninvasive and externally validated test to assess eosinophilic asthma in patients not on OCS.

Effectiveness of a brief school-based intervention on depression, anxiety, hyperactivity, and delinquency: a cluster randomized controlled trial.

Problematic substance use and mental health problems often co-occur in adolescents. Effective school-based interventions that are brief and target multiple problems are promising in the field of health promotion. Preventure is a brief, school-based, selective preventive intervention, tailored to four personality profiles. Preventure has already proved effective on alcohol outcomes. Previous trials also reveal effects on several mental health outcomes, yet the evidence for these outcomes is limited. This study presents the results of the Dutch Preventure Trial, on a range of mental health outcomes. In a cluster RCT, including 699 high risk students (mean age 14 years), the intervention effects on mental health problems at 2, 6, and 12 months post intervention were tested in the total high risk population and in four specific personality groups. No significant intervention effects were found on 22 from the 24 tests. A positive intervention effect on anxiety was found in the anxiety sensitivity personality group at 12-month follow-up, and a negative intervention effect on depression was found at 12-month follow-up in the negative thinking group. In post hoc growth curve analyses these effects were not found. This study found no convincing evidence for the effectiveness of Preventure in The Netherlands on mental health problems. This finding is not in line with the results of an earlier effectiveness study in the UK. This highlights the need for more research into the knowledge transfer model of interventions, to ensure that interventions are effective in a variety of circumstances.

CT screening for pulmonary pathology in common variable immunodeficiency disorders and the correlation with clinical and immunological parameters.

BACKGROUND: Pulmonary disease is common in patients with common variable immunodeficiency disorders (CVID) and involves infections, chronic airway disease and interstitial lung disease. Chronic pulmonary disease is associated with excess morbidity and early mortality and therefore early detection and monitoring of progression is essential. METHODS AND PURPOSE: Thin slice CT scan and pulmonary function were used to determine the prevalence and spectrum of chronic (pre-clinical) pulmonary disease in adult CVID patients regardless of symptoms. CT Scans were scored for airway abnormalities (AD) and interstitial lung disease (ILD). Other CVID related complications and B and T lymphocyte subsets were analyzed to identify patients at risk for pulmonary disease. RESULTS: Significant pulmonary abnormalities were detected in 24 of the 47 patients (51%) consisting of AD in 30% and ILD in 34% of cases. In only 7 (29%) of these 24 patients pulmonary function test proved abnormal. The presence of AD was correlated to (recurrent) lower respiratory tract infections despite IgG therapy. The presence of ILD was correlated to autoimmune disease and a reduction in the numbers of CD4 + T cells, naïve CD4 + T cells, naïve CD8 + T cells and memory B cells and lower IgG through levels over time. CONCLUSION: Preclinical signs of AD and ILD are common in CVID patients despite Ig therapy and do not correlate to pulmonary function testing. Patients at risk for ILD might be identified by the presence of autoimmunity or a deranged T cell pattern. Larger studies are needed to confirm these findings and to determine thresholds for the T lymphocyte subsets.

Double-blind prospective study comparing two automated sperm analyzers versus manual semen assessment.

PURPOSE: Despite controversy regarding its clinical value, male fertility investigation mainly relies on semen analysis. Even though reference guidelines are available, manual sperm analysis still suffers from analytical variability, thus questioning the interest of automated sperm analysis systems. The aim of this study is to compared automated computerized semen analysis systems (SQA-V GOLD and CASA CEROS) to the conventional manual method in terms of accuracy and precision. METHODS: We included 250 men in this double-blind prospective study. The SQA-V GOLD (Medical Electronic Systems) and CEROS, CASA system (Hamilton Thorne) were compared to the standard manual assessment based on the WHO 5th Edition. The main outcome measures were sperm concentration, total sperm number, total motility, progressive motility, non-progressive motility, morphology, motile sperm concentration (MSC) and progressively motile sperm concentration (PMSC) with the three methods. RESULTS: Statistical analysis of the test results from the automated systems and the manual method demonstrated no significant differences for most of the semen parameters. The Spearman coefficients of rank correlation (rho) for CASA and the SQA-V GOLD automated systems vs. the manual method were: Sperm concentration (0.95 and 0.95), total sperm number (0.95 and 0.95), MSC (0.94 and 0.96) and PMSC (0.94 and 0.93) correspondingly. Concerning sperm morphology, both automated systems demonstrated high specificity (Sp) and negative predictive values (NPV), despite significantly different medians (CASA: 83.7 % for Sp and 95.2 % for NPV, SQA-V: 97.9 % for Sp and 92.5 %). The highest precision (lowest 95 % confidence interval for duplicate tests) for all semen variables was found in the SQA-V GOLD. CONCLUSIONS: The advantages of using automated semen analysers are: Standardization, speed (lower turnaround time), precision, reduced potential for human error, automated data recording and less need for highly skilled professionals to run the systems. The disadvantages of using automated systems are: notably the problem with testing some atypical samples and the inability to perform an assessment of morphology abnormalities. Based on the results of this study, the SQA-V Gold demonstrated better agreement vs. the manual method. In conclusion, automated semen analyzers can be used for routine semen analysis providing rapid clinically acceptable results with higher precision, and positively impacting laboratory standardization.

Diabetes before and after lung transplantation in patients with cystic fibrosis and other lung diseases.

AIMS: The aims of the study are to investigate the prevalence of diabetes in patients with cystic fibrosis compared with patients without cystic fibrosis, and its impact on the outcome after lung transplantation. METHODS: Data were reviewed from 77 lung transplantation recipients in our centre between 2001 and 2010; 43 patients had cystic fibrosis and 34 patients had other lung diseases (no cystic fibrosis). To define diabetes, we used the American Diabetes Association definition. RESULTS: Before lung transplantation, diabetes was diagnosed in 63% of patients with cystic fibrosis and 6% of patients without cystic fibrosis (P<0.001). In both groups, approximately 60% of the patients at risk developed new-onset diabetes after transplantation. The mortality in patients with cystic fibrosis was higher in patients with diabetes diagnosed before lung transplantation compared with those without (44 vs. 6%, P=0.04). Diabetes remained an independent factor in multivariate analyses. CONCLUSIONS: Diabetes diagnosed before lung transplantation has a negative effect on survival after lung transplantation in patients with cystic fibrosis. Pre-existing diabetes is common in patients with cystic fibrosis, in contrast to patients without cystic fibrosis. Development of new-onset diabetes after transplantation is similar in both groups.

The relationship between lung function impairment and quantitative computed tomography in chronic obstructive pulmonary disease.

OBJECTIVES: To determine the relationship between lung function impairment and quantitative computed tomography (CT) measurements of air trapping and emphysema in a population of current and former heavy smokers with and without airflow limitation. METHODS: In 248 subjects (50 normal smokers; 50 mild obstruction; 50 moderate obstruction; 50 severe obstruction; 48 very severe obstruction) CT emphysema and CT air trapping were quantified on paired inspiratory and end-expiratory CT examinations using several available quantification methods. CT measurements were related to lung function (FEV(1), FEV(1)/FVC, RV/TLC, Kco) by univariate and multivariate linear regression analysis. RESULTS: Quantitative CT measurements of emphysema and air trapping were strongly correlated to airflow limitation (univariate r-squared up to 0.72, p < 0.001). In multivariate analysis, the combination of CT emphysema and CT air trapping explained 68-83% of the variability in airflow limitation in subjects covering the total range of airflow limitation (p < 0.001). CONCLUSIONS: The combination of quantitative CT air trapping and emphysema measurements is strongly associated with lung function impairment in current and former heavy smokers with a wide range of airflow limitation.

Quantitative computed tomography in COPD: possibilities and limitations.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that is characterized by chronic airflow limitation. Unraveling of this heterogeneity is challenging but important, because it might enable more accurate diagnosis and treatment. Because spirometry cannot distinguish between the different contributing pathways of airflow limitation, and visual scoring is time-consuming and prone to observer variability, other techniques are sought to start this phenotyping process. Quantitative computed tomography (CT) is a promising technique, because current CT technology is able to quantify emphysema, air trapping, and large airway wall dimensions. This review focuses on CT quantification techniques of COPD disease components and their current status and role in phenotyping COPD.

Steroids induce a disequilibrium of secreted interleukin-1 receptor antagonist and interleukin-1ß synthesis by human neutrophils.

Chronic obstructive pulmonary disease (COPD) is characterised by neutrophilic inflammation in the airways and these neutrophils contribute to the production of inflammatory mediators. Dampening the production of proinflammatory mediators might be an important strategy to treat COPD and glucocorticosteroids are known to do so via inhibition of nuclear factor-κB. However, this pathway is important for the control of pro- and anti-inflammatory genes. We studied the effects of dexamethasone on production and secretion of pro-inflammatory interleukin (IL)-1ß and anti-inflammatory secreted IL-1 receptor antagonist (sIL-1Ra) by human neutrophils activated with tumor necrosis factor (TNF)-α. In vitro, TNF-α-stimulated neutrophils produced significant amounts of IL-1ß and sIL-1Ra; this production was inhibited by dexamethasone. However, synthesis and secretion of sIL-1Ra was inhibited at lower concentrations dexamethasone compared to IL-1ß, which changed the IL-1ß:sIL-1Ra ratio significantly. This altered ratio resulted in a more pro-inflammatory condition, as visualised by increased intercellular adhesion molecule-1 expression on human endothelial cells. In vivo, moderate-to-severe COPD patients using inhaled glucocorticosteroids have decreased plasma sIL-Ra levels compared with mild-to-moderate patients not on glucocorticosteroid treatment. In conclusion, dexamethasone induces a pro-inflammatory shift in the IL-1ß:sIL-1Ra cytokine balance in neutrophils in vitro, which might contribute to a lack of endogenous anti-inflammatory signals to dampen inflammation in vivo.

Association of the transfer coefficient of the lung for carbon monoxide with emphysema progression in male smokers.

A decreased transfer coefficient of the lung for carbon monoxide (K(CO)) is associated with emphysema. We evaluated whether in heavy smokers, baseline K(CO) was associated with the progression of computed tomography (CT)-detected emphysema, and the progression of airflow limitation. Heavy smokers, mean ± sd 41.3 ± 18.7 pack-yrs, participating in a lung cancer screening trial underwent diffusion testing and CT scanning of the lungs. CT scanning was repeated after median (25th-75th percentile) 2.8 (2.7-3.0) yrs and emphysema was assessed by lung densitometry using the 15th percentile. The association between K(CO) at baseline with progression of emphysema and lung function decline was assessed by multiple linear regression, correcting for baseline CT-quantified emphysema severity and forced expiratory volume in 1 s (FEV1/forced vital capacity (FVC), age, height, body mass index, pack-yrs and smoking status (current or former smoker). 522 participants aged 60.1 ± 5.4 yrs were included. Mean ± sd 15th percentile was -938 ± 19, absolute FEV1/FVC was 71.6 ± 9% and K(CO) was 1.23 ± 0.25, which is 81.8 ± 16.5% of predicted. By interpolation, a one sd (0.25) lower K(CO) value at baseline predicted a 1.6 HU lower 15th percentile and a 0.78% lower FEV1/FVC after follow-up (p < 0.001). A lower baseline K(CO) value is independently associated with a more rapid progression of emphysema and airflow limitation in heavy smokers.

The impact of using different symptom-based exacerbation algorithms in patients with COPD.

Not all exacerbations are captured by reliance on healthcare contacts. Symptom-based exacerbation definitions have shown to provide more adequate measures of exacerbation rates, severity and duration. However, no consensus has been reached on what is the most useful method and algorithm to identify these events. This article provides an overview of the existing symptom-based definitions and tests the hypothesis that differences in exacerbation characteristics depend on the algorithms used. We systematically reviewed symptom-based methods and algorithms used in the literature, and quantified the impact of the four most referenced algorithms on exacerbation-related outcome using an existing chronic obstructive pulmonary disease (COPD) cohort (n = 137). We identified 51 studies meeting our criteria using 14 widely varying symptom algorithms to define onset, severity and recovery. The most (71%) frequently referenced algorithm (modified Anthonisen) identified an incidence rate of 1.7 episodes·patient-yr⁻¹ (95% CI 1.4-2.1), while for requiring only one major or two major symptoms this was 1.9 episodes·patient-yr⁻¹ (95% CI 1.6-2.3) and 1.5 episodes·patient-yr⁻¹ (95% CI 0.6-1.0), respectively. Studies were generally lacking methods to enhance validity and accuracy of symptom recording. This review revealed large inconsistencies in definitions, methods and accuracy to define symptom-based COPD exacerbations. We demonstrated that minor changes in symptom criteria substantially affect incidence rates, clustering type and classification of exacerbations.

Pneumoconiosis and emphysema in construction workers: results of HRCT and lung function findings.

OBJECTIVES: To evaluate the prevalence of HRCT findings in construction workers previously surveyed by chest radiographs classified according to ILO guidelines. To examine the association between HRCT findings and exposure to quartz containing dust, and lung function. METHODS: The study comprised a questionnaire, dynamic and static lung function measurements, single-breath CO diffusion capacity, chest radiographs and HRCT in 79 individuals. Certified 'B' readers coded radiographs according to the ILO classification. HRCT scans were read according to an international classification system. A qualitative exposure index for cumulative respiratory quartz on a 10-point scale was used. RESULTS: Agreement between HRCT readers was good (κ>0.60), except for irregular opacities (κ=0.23). In ILO category 0/0, 8% HRCT round, 22% irregular and/or linear opacities and 41% HRCT emphysema was found. HRCT round opacities was associated with high cumulative quartz exposure (OR 7.1; 95% CI 1.3 to 37.8). Emphysema was associated with smoking (OR 10.1; 95% CI 1.2 to 84.2) and showed a reduction in T(L,CO,sb). HRCT round opacities was not associated with lung function. Current smoking was negatively associated with FEV1/FVC ratio and positively with RV/TLC ratio, and showed a reduction in T(L,CO,sb) (13.4%), adjusted for different HRCT findings. CONCLUSIONS: Low grade silicosis cannot be excluded in workers with normal chest radiographs (ILO 0/0). In relatively highly exposed construction workers, a sevenfold increased risk of simple (nodular) silicosis was found. Emphysema on HRCT was associated with current or former smokers, but not with exposure, and contributed to reduced diffusion capacity. Airflow limitation was mainly determined by current smoking and was not associated with simple (nodular) silicosis.

Neurobehavioral effects of acute exposure to isoparaffinic and cycloparaffinic hydrocarbons.

This article reports neurobehavioral tests in rats with C5-C11 isoparaffinic and cycloparaffinic hydrocarbons. Testing, conducted shortly after exposure, evaluated the effects in several domains including clinical effects, motor activity, functional observations, and visual discrimination performance. Isopentane and cyclopentane did not produce any evidence of acute central nervous system (CNS) effects at levels up to 20 000 mg/m(3). A C(6)/C(7) mixed cycloparaffinic solvent produced minor, reversible changes in latency to response in visual discrimination testing at 14 000 mg/m(3); the no-effect level was 4200 mg/m(3). A C(8) isoparaffin produced no effects at 14 000 mg/m(3), the highest level tested. A C(9)/C(11) isoparaffinic solvent produced minor acute CNS effects at 5000 mg/m(3), with 1500 mg/m(3) as the no-effect level. A C(10) cycloparaffinic solvent did not produce any statistically significant CNS effects at 5000 mg/m(3). These studies were designed to provide data that may be useful in setting occupational exposure limits for C5-C11 isoparaffinic and cycloparaffinic hydrocarbons.

Neurobehavioral effects of acute exposure to normal (n-) paraffins.

This article reports the results of neurobehavioral tests on C(5)-C(10) normal paraffinic constituents (n-paraffins). Shortly after exposure, effects were evaluated in several domains including clinical effects, motor activity, functional observations, and visual discrimination performance. The representative C(5) n-paraffin, n-pentane, did not produce any evidence of acute central nervous system (CNS) effects at levels up to 20 000 mg/m(3). Similarly, there was no compelling evidence that n-octane (C(8)) produced CNS effects at 14 000 mg/m(3), the highest concentration tested. n-decane (C(10)) produced minor, reversible acute CNS effects at 5000 mg/m(3), with 1500 mg/m(3) as the no-effect level. Consistent with literature data, there seemed to be a relationship between increasing molecular weight up to C(10) and acute CNS effects. However, the CNS effects were reversible. Repeated exposures did not provide evidence of metabolic induction.

[Pre-implantation genetic testing: Comparison between cleavage stage and blastocyst biopsy]. / Le diagnostic préimplantatoire : comparaison des stratégies de biopsie embryonnaire au stade clivé et au stade blastocyste.

OBJECTIVES: Preimplantation genetic testing (PGT) refers to the set of techniques for testing whether embryos obtained through in vitro fertilization have genetic defect. There is a lack of global standardization regarding practices between countries or even from one center to another. In ours, biopsies are preferably performed on day 3 embryos, but also at the blastocyst stage on day 5. The blastocyst biopsy often requires systematic freezing of the embryos before obtaining the genetic results, whereas day 3 biopsy allows fresh embryo transfer of the healthy or balanced embryo after getting the genetic results. We wanted to compare the chances of success for couples performing PGT in our center according to the day of the biopsy. METHODS: For this, we carried out a retrospective monocentric study including all PGT cycles performed between 2016 and 2019 divided into two groups: day 3 or day 5 biopsy. RESULTS: There was no significant difference in terms of live birth rate (P=0.7375) after fresh embryo transfers, as well for pregnancy rates, clinical pregnancy rates, implantation rates and miscarriage rates. On the other hand, we observed higher live birth rates after frozen-thawed embryo transfer when the biopsy was performed on day 5 rather on day 3 (P=0.0001). We also wanted to assess what was the most efficient biopsy strategy in our laboratory. Our rates of useful embryos were similar regardless of the day of the biopsy (34% in D3 and 37.7% in D5, P=0.244). No statistical difference was found in the number of unnecessarily biopsied embryos in the two groups. But still, the percentage of embryos biopsied on D5 and immediately frozen was 42.8% (118 blastocysts), while no embryo biopsied on D3 led to this case. CONCLUSION: Therefore, our results are in favor of generalization of the D5 biopsy as the international standard. However, the organizational, financial and logistical implications that this technic would impose make it unsystematic in our center.

Real-time feedback control of the impurity emission front in tokamak divertor plasmas.

In magnetic confinement thermonuclear fusion the exhaust of heat and particles from the core remains a major challenge. Heat and particles leaving the core are transported via open magnetic field lines to a region of the reactor wall, called the divertor. Unabated, the heat and particle fluxes may become intolerable and damage the divertor. Controlled 'plasma detachment', a regime characterized by both a large reduction in plasma pressure and temperature at the divertor target, is required to reduce fluxes onto the divertor. Here we report a systematic approach towards achieving this critical need through feedback control of impurity emission front locations and its experimental demonstration. Our approach comprises a combination of real-time plasma diagnostic utilization, dynamic characterization of the plasma in proximity to the divertor, and efficient, reliable offline feedback controller design.

Prolonged protection of the new inhaled corticosteroid fluticasone furoate against AMP hyperresponsiveness in patients with asthma.

INTRODUCTION: Single-dose inhaled corticosteroids (ICS) induce direct anti-inflammatory effects in asthma thereby improving airway hyperresponsiveness (AHR). A novel enhanced-affinity ICS, fluticasone furoate (FF), demonstrated a prolonged duration of action in vitro. The aim of this study was to evaluate the efficacy and duration of action of a single dose of FF by studying protection against AHR to adenosine 5'-monophosphate (AMP) and effects on exhaled nitric oxide (eNO). METHODS: A randomized, double-blind, placebo-controlled, 6-way crossover study (FFA10026) was performed in 24 patients with allergic asthma (mean age 32.8 years, FEV(1) ≥ 70% predicted and PC(20) AMP ≤ 50 mg/ml). Each subject received a single dose of FF 1000 µg, fluticasone proprionate (FP) 1000 µg, or placebo at 2 (FF only), 14 or 26 h prior to AMP challenge and eNO measurement. RESULTS: FF significantly improved PC(20) AMP compared to placebo, the difference in doubling concentrations being 2.18 (95% confidence interval: 1.13-3.23), 1.54 (0.48-2.59), and 1.30 (0.26-2.34) at 2, 14 and 26 h. FP improved PC(20) AMP significantly at 14 h compared to placebo, but not at the 26-hour time point, the difference in doubling concentrations being 1.72 (0.70-2.75) and 0.33 (-0.69-1.34). There was no significant effect on eNO after either FF or FP at all time points. FF was well tolerated and there were no serious adverse events. CONCLUSION: The new inhaled corticosteroid FF, but not FP, demonstrates prolonged protection up to 26 h against AHR to AMP in asthma patients.