Early pregnancy complications after frozen-thawed embryo transfer in different cycle regimens: A retrospective cohort study.

OBJECTIVE Frozen-thawed embryo transfers (FET) are a key component of assisted reproductive technologies (ART) and various cycle regimens are used worldwide because of insufficient evidence to favour particular transfer schedules. In this study, we investigated the associations between different cycle regimens and early pregnancy complications as well as live birth rates (LBR) per pregnancy after FET. STUDY DESIGN We conducted a retrospective cohort study analysing a total of 7342 pregnancies after FET registered in the Swiss IVF Registry from 2014 to 2019. Women were divided into three groups according to the different cycle regimens: Natural Cycles (NC-FET, n = 998), low-dose Stimulation Cycles (SC-FET, n = 984) and Hormone Replacement Cycles (HRC-FET, n = 5360) leading to pregnancy. Outcomes included early pregnancy complications such as bleeding, miscarriages and ectopic pregnancies. Additionally, we evaluated LBR per pregnancy. Incidences were compared using Fisher's exact or Chi-square tests. Mean values were compared using t-tests. Multivariate mixed model analysis was performed with early pregnancy complications as outcome. RESULTS The incidence of bleeding in the first trimester (NC: 3.5 %, SC: 4.3 %, HRC: 8.4 %; p < 0.001) and miscarriage < 12 weeks (NC: 19.0 %, SC: 19.7 %, HRC: 29.1 %; p < 0.001) was highest in HRC-FET. Multivariate analysis revealed almost doubled adjusted odds ratios of bleeding in the first trimester (aOR 1.92; 95 % CI 1.30-2.81) and miscarriage < 12 weeks (aOR 1.82; 95 % CI 1.51-2.19) in HRC-FET vs NC-FET. There were comparable odds ratios in HRC-FET vs SC-FET. No differences were observed in the outcomes between SC-FET and NC-FET. Highest proportion of LBR per pregnancy (NC: 78.0 %, SC: 77.2 %, HRC: 68.2 %%; p < 0.001) was reported in NC-FET. CONCLUSIONS This is the latest large European register study evaluating early pregnancy complications and LBR per pregnancy after FET between all three different cycle regimens. Miscarriage rate was highest in HRC-FET which can be translated into lower LBR. Therefore, HRC-FET should be avoided and replaced by SC-FET or NC-FET to achieve better pregnancy outcomes

Implication of the Autologous Immune System in BCR-ABL Transcript Variations in Chronic Myelogenous Leukemia Patients Treated with Imatinib.

International audienceImatinib and other tyrosine kinase inhibitors (TKI) have improved treatment of chronic myelogenous leukemia (CML); however, most patients are not cured. Deeper mechanistic understanding may improve TKI combination therapies to better control the residual leukemic cell population. In analyzing our patients' data, we found that many patients who otherwise responded well to imatinib therapy still showed variations in their BCR-ABL transcripts. To investigate this phenomenon, we applied a mathematical model that integrates CML and an autologous immune response to the patients' data. We define an immune window or a range of leukemic loads for which the autologous immune system induces an improved response. Our modeling results suggest that, at diagnosis, a patient's leukemic load is able to partially or fully suppress the autologous immune response developed in a majority of patients, toward the CML clone(s). Imatinib therapy drives the leukemic population into the "immune window," allowing the patient's autologous immune cells to expand and eventually mount an efficient recognition of the residual leukemic burden. This response drives the leukemic load below this immune window, allowing the leukemic population to partially recover until another weaker immune response is initiated. Thus, the autologous immune response may explain the oscillations in BCR-ABL transcripts regularly observed in patients on imatinib

PHANGS-JWST First Results: A Global and Moderately Resolved View of Mid-Infrared and CO Line Emission from Galaxies at the Start of the JWST Era

We explore the relationship between mid-infrared (mid-IR) and CO rotational line emission from massive star-forming galaxies, which is one of the tightest scalings in the local universe. We assemble a large set of unresolved and moderately ($\sim 1$ kpc) spatially resolved measurements of CO (1-0) and CO (2-1) intensity, $I_{\rm CO}$, and mid-IR intensity, $I_{\rm MIR}$, at 8, 12, 22, and 24$\mu$m. The $I_{\rm CO}$ vs. $I_{\rm MIR}$ relationship is reasonably described by a power law with slopes $0.7{-}1.2$ and normalization $I_{\rm CO} \sim 1$ K km s$^{-1}$ at $I_{\rm MIR} \sim 1$ MJy sr$^{-1}$. Both the slopes and intercepts vary systematically with choice of line and band. The comparison between the relations measured for CO~(1-0) and CO (2-1) allow us to infer that $R_{21} \propto I_{\rm MIR}^{0.2}$, in good agreement with other work. The $8\mu$m and $12\mu$m bands, with strong PAH features, show steeper CO vs. mid-IR slopes than the $22\mu$m and $24\mu$m, consistent with PAH emission arising not just from CO-bright gas but also from atomic or CO-dark gas. The CO-to-mid-IR ratio correlates with global galaxy stellar mass ($M_\star$) and anti-correlates with SFR/$M_\star$. At $\sim 1$ kpc resolution, the first four PHANGS-JWST targets show CO to mid-IR relationships that are quantitatively similar to our larger literature sample, including showing the steep CO-to-mid-IR slopes for the JWST PAH-tracing bands, although we caution that these initial data have a small sample size and span a limited range of intensities.Comment: 29 pages, 13 figures, key quantitative results in Table 3, Accepted as part of a PHANGS-JWST Focus Issue to appear in Ap

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Typage, compilation, et cryptographie pour la programmation repartie securisée

Mes travaux s'articulent principalement autour de trois axes concernant la programmation sécurisée, plus particulièrement dans le cadre d'applications distribuées. Ainsi, nous considérons plusieurs participants ne se faisant pas mutuellement confiance et ayant des niveaux de sécurité différents. On s'intéresse alors au garanties restantes lorsque certains de ces participants sont compromis. Par exemple, lors d'une opération de commerce électronique, le client, le serveur, et la banque ne se font pas mutuellement confiance et font encore moins confiance aux machines intermédiaires du réseau; on veut pourtant qu'une transaction sécurisée puisse avoir lieuWe are more and more dependent on our computing infrastructure, and yet its security is challenged every day. From a research viewpoint, a lot of progress in security has been made, using in particular formal methods and programming language techniques. This has lead us to a first few small, exemplary verified systems and protocols. In spite of these results, it is still hard to gain strong confidence that a program is correct and secure, and most of the software that we depend upon offers very few guarantees. In this thesis, we focus on language-based security by construction. We take as input the specification of a distributed computation involving multiple participants, together with its expected security properties. We then verify that this specification is sound, using static verification techniques such as type systems, and we then automatically generate a program for each participant. During this compilation process, we select adequate cryptographic and hardware mechanisms, such that the compiled programs correctly implement the computation with the required security propertiesPALAISEAU-Polytechnique (914772301) / SudocSudocFranceF

Synthesis of hafnium germanate (HfGeO4) particles: Impact of crystallization route on X/UV conversion properties

International audienceThe crystallization route - calcination or hydrothermal ripening - of an amorphous hafnium and germanium oxide coprecipitate determines the X/UV conversion properties of the resulting hafnium germanate (HfGeO4). The calcination of the amorphous precipitate leads to micrometric aggregated particles exhibiting strong X/UV conversion whereas its hydrothermal crystallization resulted in well individualized nanoparticles with no X/UV conversion property. To explain these phenomena, the crystalline structure and chemical composition of the final products were investigated with X-ray diffraction (XRD) and inductively coupled plasma-mass spectrometry (ICP-MS). The key result is that germanium is partially solubilized from the amorphous precursor in hydrothermal conditions, resulting in the crystallization of a Ge deficient hafnium germanate possessing no X/UV conversion properties

Synthesis of hafnium germanate (HfGeO4) by co-precipitation routes

International audienc

Hormone replacement cycles are associated with a higher risk of hypertensive disorders: retrospective cohort study in singleton and twin pregnancies.

OBJECTIVE To elaborate the associations of different cycle regimens (natural cycle = NC, stimulated cycle = SC, hormone replacement cycle = HRC) on maternal and neonatal adverse pregnancy outcomes after frozen-thawed embryo transfers (FET). DESIGN Population-based registry study. SETTING Swiss IVF Registry. POPULATION OR SAMPLE Singleton (n = 4636) and twin life births (n = 544) after NC-FET (n = 776), SC-FET (n = 758) or HRC-FET (n = 3646) registered from 2014 to 2019. METHODS Fifteen pregnancy pathologies were modelized for singleton and twin pregnancies using mixed models adjusted for cycle regimen, delivery, fertilization technique, chronic anovulation, age of mother and centre. MAIN OUTCOME MEASURES Maternal (vaginal bleeding, isolated arterial hypertension and preeclampsia) and neonatal (gestational age, birthweight, mode of delivery) adverse pregnancy outcomes. RESULTS In singleton pregnancies, the incidences of bleeding in first trimester, isolated hypertension and preeclampsia were highest in HRC-FET with doubled odds of bleeding in first trimester (adjusted odds ratio = aOR 2.23; 95% CI 1.33-3.75), isolated hypertension (aOR 2.50; 95% CI 1.02-6.12) and preeclampsia (aOR 2.16; 95% CI 1.13-4.12) in HRC-FET vs. NC-FET and with doubled respectively sixfold odds of bleeding (aOR 2.08; 95% CI 1.03-4.21) and preeclampsia (6.02; 95% CI 1.38-26.24) in HRC-FET vs. SC-FET. In twin pregnancies, the incidence of preeclampsia was highest in HRC-FET with numerically higher odds of preeclampsia in HRC-FET vs. NC-FET and vs. SC-FET. CONCLUSIONS Our data implied the highest maternal risks of hypertensive disorders in HRC-FET, therefore clinicians should prefer SC-FET or NC-FET if medically possible

The Perinuclear ER Scales Nuclear Size Independently of Cell Size in Early Embryos

International audienc

Strong instrumental variables biased propensity scores in comparative effectiveness research: A case study in oncology

International audienceBackground and Objectives: Some medications require specific medical procedures in the weeks before their start. Such procedures may meet the definition of instrumental variables (IVs). We examined how they may influence treatment effect estimation in propensity score (PS)-adjusted comparative studies, and how to remedy. Study Design and Setting: Different covariate assessment periods (CAPs) did and did not include the month preceding treatment start were used to compute PS in the French claims database (Syt eme National des Donn ees de Sant e-SNDS), and 1:1 match patients with metastatic castration resistant prostate cancer initiating abiraterone acetate or docetaxel. The 36-month survival was assessed. Results: Among 1, 213 docetaxel and 2, 442 abiraterone initiators, the PS distribution resulting from the CAP [-12; 0 months] distinctly separated populations (c 5 0.93; 273 matched pairs). The CAPs [-12;-1 months] identified 765 pairs (c 5 0.81). Strong docetaxel treatment predictors during the month before treatment start were implantable delivery systems (1% vs. 59%), which fulfilled IV conditions. The 36-month survival was not meaningfully different under the [-12; 0 months] CAP but differed by 10% points (38% vs. 28%) after excluding month À1. Conclusion: In the setting of highly predictive pretreatment procedures, excluding the immediate pre-exposure time from the CAP will reduce the risk of including potential IVs in PS models and may reduce bias