Morphokinetic parameters of early embryo development via time lapse monitoring and their effect on embryo selection and ICSI outcomes: a prospective cohort study

PURPOSE: To compare the outcomes of embryos selected via time lapse monitoring (TLM) versus those selected with conventional methods of selection in subfertile women undergoing ICSI. METHODS: The study population (239 women) was classified into two groups, based on the monitoring method used: Group 1 (TLM) and Group 2 (conventional monitoring). Groups were compared according to the clinical and ICSI cycle characteristics and reproductive outcomes, while transfers were performed at day 2 or 3. Subgroup analyses were performed, in women of both groups according to age and clinical parameters, and in embryos of Group 1 based on their cellular events. RESULTS: There was a statistically significant difference between the two study groups with regard to the outcome parameters, favoring Group 1 and especially in women >40 years of age. No differences were found in subgroup analyses in participants of both groups, regarding the stimulation protocol used, number of the oocytes retrieved and type of subfertility, while in Group 1 the percentages of "in range" cellular events were higher in certain divisions in ages 35-40, non-smokers, and the GnRH-agonist group, and in embryos that resulted in pregnancy. CONCLUSION: Morphokinetic parameters of early embryo development via TLM are related to the characteristics of subfertile patients and associated with ICSI outcomes

Invisibility in PT-symmetric complex crystals

Bragg scattering in sinusoidal PT-symmetric complex crystals of finite thickness is theoretically investigated by the derivation of exact analytical expressions for reflection and transmission coefficients in terms of modified Bessel functions of first kind. The analytical results indicate that unidirectional invisibility, recently predicted for such crystals by coupled-mode theory [Z. Lin et al., Phys. Rev. Lett. 106, 213901 (2011)], breaks down for crystals containing a large number of unit cells. In particular, for a given modulation depth in a shallow sinusoidal potential, three regimes are encountered as the crystal thickness is increased. At short lengths the crystal is reflectionless and invisible when probed from one side (unidirectional invisibility), whereas at intermediate lengths the crystal remains reflectionless but not invisible; for longer crystals both unidirectional reflectionless and invisibility properties are broken.Comment: 18 page

Analytical performance specifications for 25-hydroxyvitamin d examinations

Currently the 25-hydroxy vitamin D (25(OH)D) concentration is thought to be the best estimate of the vitamin D status of an individual. Unfortunately, its measurement remains complex, despite recent technological advances. We evaluated the biological variation (BV) of 25(OH)D in order to set analytical performance specifications (APS) for measurement uncertainty (MU). Six European laboratories recruited 91 healthy participants. The 25(OH)D concentrations in K3-EDTA plasma were examined weekly for up to 10 weeks in duplicate on a Lumipulse G1200 (Fujirebio, Tokyo, Japan). The linear regression of the mean 25(OH)D concentrations at each blood collection showed that participants were not in a steady state. The dissection of the 10-sample collection into two subsets, namely collections 1–5 and 6–10, did not allow for correction of the lack of homogene-ity: estimates of the within-subject BV ranged from 5.8% to 7.1% and the between-subject BV ranged from 25.0% to 39.2%. Methods that would differentiate a difference induced by 25(OH)D supple-mentation at p < 0.05 should have MU < 13.6%, while at p < 0.01, the MU should be <9.6%. The development of APS using BV assumes a steady state of patients. The findings in this study suggest that patients are not in steady state. Therefore, APS that are based on MU appear to be more appro-priate

On the rocking behavior of rigid objects

A novel formulation for the rocking motion of a rigid block on a rigid foundation is presented in this work. The traditional piecewise equations are replaced by a single ordinary differential equation. In addition, damping effects are no longer introduced by means of a coefficient of restitution but understood as the presence of impulsive forces. The agreement with the classical formalism is very good for both free rocking regime and harmonic forcing excitation

Reduced cardiovascular morbidity in patients with hemophilia:results of a 5-year multinational prospective study

Hemophilia is a congenital bleeding disorder caused by low levels of clotting factor VIII or IX. The life expectancy of people with hemophilia (PWH) has increased with the availability of clotting factor concentrates. At the same time, the incidence of cardiovascular disease (CVD) has increased; in retrospective studies, there are conflicting data regarding if, despite this increase, the incidence is still lower than in the general population. We prospectively compared the incidence of CVD in PWH vs the predicted incidence. This prospective, multicenter, observational study included adult PWH (aged &gt;30 years) from The Netherlands and United Kingdom. They were followed up for a 5-year period, and CVD incidence was compared with a predicted event rate based on the QRISK2-2011 CVD risk model. The primary end point was the observed fatal and nonfatal CVD incidence after 5 years compared with the estimated events and in relation to severity of hemophilia. The study included 709 patients, of whom 687 (96.9%) completed 5 years' follow-up or reached an end point. For 108 patients, the QRISK score could not be calculated at inclusion. For the remaining 579, fewer CVD events were observed than predicted: 9 vs 24 (relative risk, 0.38; 95% confidence interval, 0.18-0.80; P 5 .01), corresponding with an absolute risk reduction of 2.4%. Severe hemophilia treated on demand had the highest risk reduction. There was no statistically significant relation between severity of hemophilia and incidence of CVD. In hemophilia, a lower-than-predicted CVD incidence was found, supporting the theory that hemophilia protects against CVD. The study is registered at www.clinicaltrials.gov as #NCT01303900.</p

Analytical performance specifications for the measurement uncertainty of 24,25-dihydroxyvitamin D examinations

Objectives: The exploration of the metabolites in the degradation pathways of vitamin D (VTD) has gained importance in recent years and simultaneous quantitation of twenty-five-hydroxy vitamin D (25(OH)D) mass concentration together with 24,25-dihydroxyvitamin D (24,25(OH)2D) has been proposed as a newer approach to define VTD deficiency. Yet, no data are available on 24,25(OH)2D biological variation (BV). In this study, we evaluated 24,25(OH)2D's BV on the European Biological Variation Study (EuBIVAS) cohort samples to determine if analytical performance specifications (APS) for 24,25(OH)2D could be generated. Methods: Six European laboratories recruited 91 healthy participants. 25(OH)D and 24,25(OH)2D concentrations in K3-EDTA plasma were examined weekly for up to 10 weeks in duplicate with a validated LC-MS/MS method. The Vitamin D Metabolite Ratio (24,25(OH)2D divided by 25(OH)D × 100) was also calculated at each time point. Results: Linear regression of the mean 24,25(OH)2D concentrations at each blood collection showed participants were not in steady state. Variations of 24,25(OH)2D over time were significantly positively associated with the slopes of 25(OH)D concentrations over time and the concentration of 25(OH)D of the participant at inclusion, and negatively associated with body mass index (BMI), but not with age, gender, or location of the participant. The variation of the 24,25(OH)2D concentration in participants over a 10 weeks period was 34.6%. Methods that would detect a significant change linked to the natural production of 24,25(OH)2D over this period at p&lt;0.05 would need a relative measurement uncertainty (u%)&lt;14.9% while at p&lt;0.01, relative measurement uncertainty should be &lt;10.5%. Conclusions: We have defined for the first time APS for 24,25(OH)2D examinations. According to the growing interest in this metabolite, several laboratories and manufacturers might aim to develop specific methods for its determination. The results presented in this paper are thus necessary prerequisites for the validation of such methods.</p

The relationship of the neo-angiogenic marker, endoglin, with response to neoadjuvant chemotherapy in breast cancer

Endoglin (CD105) is upregulated in endothelial cells of tissues undergoing neovascularisation. A greater number of CD105-positive vessels predicts poor survival in breast cancer. We examine whether CD105 expression predicts response to neoadjuvant chemotherapy. Fifty-seven women (median age 50 years, range 29–70) received neoadjuvant chemotherapy for operable breast cancer. Immunohistochemical staining using monoclonal antibodies to CD105 and CD34 was performed on pretreatment biopsies and post-treatment surgical specimens. Individual microvessels were counted in 10 random fields at × 200 magnification. Median counts were correlated with clinical and pathological response using the Mann–Whitney U-test. Forty-five out of fifty-seven patients (79%) responded clinically, 22 (39%) responded pathologically. On pretreatment biopsies, clinical responders had significantly lower median CD105-positive vessel counts than nonresponders (median counts 5 and 9.3/high-power field (hpf), median difference=4.0/hpf, 95% CI 0.5–8.0/hpf, P=0.02). For pathological responders and nonresponders, median counts were 4.8 and 5.5/hpf (median difference –0.5/hpf, 95% CI=−2.5–2.0/hpf, P=0.77). CD34 expression (total microvessel density) did not correlate with response. Pretreatment CD105 expression predicts for clinical response to chemotherapy, with a lower initial count being favourable. Patients with high baseline new vessel counts or increased counts after conventional therapy may benefit from additional antiangiogenic therapy

The nonlinear Schroedinger equation for the delta-comb potential: quasi-classical chaos and bifurcations of periodic stationary solutions

The nonlinear Schroedinger equation is studied for a periodic sequence of delta-potentials (a delta-comb) or narrow Gaussian potentials. For the delta-comb the time-independent nonlinear Schroedinger equation can be solved analytically in terms of Jacobi elliptic functions and thus provides useful insight into the features of nonlinear stationary states of periodic potentials. Phenomena well-known from classical chaos are found, such as a bifurcation of periodic stationary states and a transition to spatial chaos. The relation of new features of nonlinear Bloch bands, such as looped and period doubled bands, are analyzed in detail. An analytic expression for the critical nonlinearity for the emergence of looped bands is derived. The results for the delta-comb are generalized to a more realistic potential consisting of a periodic sequence of narrow Gaussian peaks and the dynamical stability of periodic solutions in a Gaussian comb is discussed.Comment: Enhanced and revised version, to appear in J. Nonlin. Math. Phy