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Objectives: We sought to determine:1) whether normal D-dimer enzyme-linked immunosorbent assay (ELISA) assays predicted the absence of pulmonary embolism (PE) in the high-volume emergency department (ED) of the Brigham and Women's Hospital, and 2) whether ED physicians accepted normal D-dimer levels as confirmation of no PE without further diagnostic testing such as lung scanning, chest computed tomography (CT) scanning, or pulmonary angiography.Background: Although the plasma D-dimer ELISA is a sensitive screening test for excluding acute PE, this laboratory marker has not been widely integrated into clinical algorithms such as creatine kinase-MB fraction or troponin testing for acute myocardial infarction.Methods: We mandated that ED physicians order D-dimer ELISA tests on all patients suspected of acute PE. We reviewed the clinical record of each ED patient initially evaluated for suspected PE during the year 2000. We determined whether additional imaging tests for PE were obtained and whether the final diagnosis was PE.Results: Of 1,106 D-dimer assays, 559 were elevated and 547 were normal. Only 2 of 547 had PE despite a normal D-dimer. The sensitivity of the D-dimer ELISA for acute PE was 96.4% (95% confidence interval [CI]: 87.5% to 99.6%), and the negative predictive value was 99.6% (95% CI: 98.7% to >99.9%). Nevertheless, 24% of patients with normal D-dimers had additional imaging tests for PE.Conclusions: The D-dimer ELISA has a high negative predictive value for excluding PE. By paying more attention to normal D-dimer results, fewer chest CT scans and lung scans will be required, and improvements may be realized in diagnostic efficiency and cost reduction. [ABSTRACT FROM AUTHOR]

Since α6β1 integrin has been shown to function as a sperm adhesion receptor in the mouse, we investigated the potential role of β1 integrin in the gamete fusion process in humans. The expression of β1 integrin was morphologically analysed by indirect immunofluorescence and confocal microscopy. A homogeneous and intense staining was detected at the plasma membrane, and in some subcortical vesicles of germinal vesicle stage oocytes (GV). β1 almost disappeared from oolemma and cytoplasm of metaphase I (MI) oocytes, but was re-expressed as asymmetrical patches at the plasma membrane of metaphase II stage oocytes (MII). A functional fusion assay based on Hoechst or calcein-AM dye transfer from one gamete to the other showed that maturing oocytes were able to fuse with an increasing number of spermatozoa (11-22 from GV to MII respectively), and that fused spermatozoa co-localized with β1 integrin patches. Human gamete fusion was only partially inhibited either by RGD-containing peptide (GRGDTP), or by blocking anti-human ν1 integrin monoclonal antibody (DE9), with a maximum of 50% inhibition. Despite the combined addition of GRGDTP and blocking mouse anti-human β1 integrin DE9 in the assay, a complete inhibition of fusion could not be achieved. A mouse polyclonal antibody raised against human oocyte membranes was more potent in inhibiting the fusion. Since β1 integrin expression at the plasma membrane was not correlated to oocyte fusibility, and since it was only partially inhibited by DE9 and/or RGD peptide, we suggest that human gamete fusion can bypass the β1 requirement. β1 integrin certainly participates in human gamete fusion by acting in co-operation with multiple integrin/disintegrin couples or another cofactor, not yet identified. [ABSTRACT FROM PUBLISHER]

We report one case of a de-novo complex chromosomal rearrangement (CCR), t(1;5;13)ins(14;13), in an abnormal 19-month-old boy. Clinical features associated were a mild facial dysmorphy and a psychomotor retardation. Parental ages were, respectively, 29 years for the mother and 60 years for the father. We point out the usefulness of fluorescence in-situ hybridization in elucidating CCRs, and discuss the possible correlation between the existence of a chromosomal aberration and advanced paternal age. [ABSTRACT FROM PUBLISHER]

Assisted reproductive technologies have offered new ways and pathways to conceive a child. However, very few is known about insights into the complexities and challenges faced by trans fathers in contemporary parenthood journeys. This qualitative study explores the experiences of transgender and cisgender fathers who conceived children through donor sperm insemination (DSI) and natural conception (NC). The study will examine the recognition and challenges associated with paternal experiences. Seventy-nine interviews (one per child) were conducted with 16 transgender fathers who conceived trough DSI, 15 infertile cisgender fathers who conceived trough DSI, and 17 cisgender fathers who conceived through NC. The study employed thematic analysis and the Five-Minute Speech Sample to assess family dynamics. Results indicate that in the Trans-DSI group, fatherhood was often defined within the social role of masculinity, with some expressing ' intranquility ' (i.e., feelings of unease or insecurity). The Cis-DSI group showed more tranquility but faced challenges regarding biological filiation. The NC group exhibited diverse experiences. Findings suggest that fathers' self-confidence, especially for transgender and non-biologically related fathers, can be challenged. Recognizing these challenges can guide better support for families navigating diverse parenthood journeys., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nicolas Mendes reports financial support was provided by Pfizer Foundation. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The stem cell niche plays a crucial role in the decision to either self-renew or differentiate. Recent observations lead to the hypothesis that O 2 supply by blood and local O 2 tension could be key components of the testicular niche of spermatogonial stem cells (SSCs). In this study, we investigated the impact of different hypoxic conditions (3.5%, 1%, and 0.1% O 2 tension) on murine and human SSCs in culture. We observed a deleterious effect of severe hypoxia (1% O 2 and 0.1% O 2 ) on the capacity of murine SSCs to form germ cell clusters when plated at low density. Severe effects on SSCs proliferation occur at an O 2 tension ≤1% and hypoxia was shown to induce a slight differentiation bias under 1% and 0.1% O 2 conditions. Exposure to hypoxia did not appear to change the mitochondrial mass and the potential of membrane of mitochondria in SSCs, but induced the generation of mitochondrial ROS at 3.5% and 1% O 2 . In 3.5% O 2 conditions, the capacity of SSCs to form colonies was maintained at the level of 21% O 2 at low cell density, but it was impossible to amplify and maintain stem cell number in high cell density culture. In addition, we observed that 3.5% hypoxia did not improve the maintenance and propagation of human SSCs. Finally, our data tend to show that the transcription factors HIF-1α and HIF-2α are not involved in the SSCs cell autonomous response to hypoxia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gille, Givelet, Pehlic, Lapoujade, Lassalle, Barroca, Bemelmans, Borderie, Moison, Livera, Gauthier, Boussin, Thiounn, Allemand, Peyssonnaux, Wolf, Barraud-Lange, Riou and Fouchet.)

In the framework of the Laser Lightning Rod project, whose aim is to show that laser-induced filaments can guide lightning discharges over considerable distances, we study over a distance of 140 m the filaments created by a laser system with J-range pulses of 1 ps duration at 1 kHz repetition rate. We investigate the spatial evolution of the multiple filamentation regime using the fundamental beam at 1030 nm or using combination with the second and third harmonics. The measurements were made using both a collimated beam and a loosely focused beam., (© 2023. The Author(s).)

Proton transfer is one of the most fundamental events in aqueous-phase chemistry and an emblematic case of coupled ultrafast electronic and structural dynamics 1,2 . Disentangling electronic and nuclear dynamics on the femtosecond timescales remains a formidable challenge, especially in the liquid phase, the natural environment of biochemical processes. Here we exploit the unique features of table-top water-window X-ray absorption spectroscopy 3-6 to reveal femtosecond proton-transfer dynamics in ionized urea dimers in aqueous solution. Harnessing the element specificity and the site selectivity of X-ray absorption spectroscopy with the aid of ab initio quantum-mechanical and molecular-mechanics calculations, we show how, in addition to the proton transfer, the subsequent rearrangement of the urea dimer and the associated change of the electronic structure can be identified with site selectivity. These results establish the considerable potential of flat-jet, table-top X-ray absorption spectroscopy 7,8 in elucidating solution-phase ultrafast dynamics in biomolecular systems., (© 2023. The Author(s).)

Background: The exposure to plastic derivatives during human life is deleterious. Infants conceived using ART (IVF or ICSI) have twice as many risks of major birth defects compared to naturally conceived infants. Could plastic ware used during ART trigger defects in the fetal development?, Methods: Three groups of blastocysts were transferred to pseudopregnant mice. One was obtained after IVF and embryo development in plastic ware, the second in glass ware. The third, was obtained in vivo by natural mating. On day 16.5 of pregnancy, females were sacrificed and fetal organs collected for gene expression analysis. Fetal sex was determined by RT-PCR. RNA was extracted from a pool of five placental or brain samples coming from at least two litters from the same group and analyzed by hybridisation onto the mouse Affymetrix 430.2.0 GeneChips, confirmed by RT-qPCR for 22 genes., Findings: This study highlights a major impact of plastic ware on placental gene expression (1121 significantly deregulated genes), while glassware was much closer to in vivo offspring (only 200 significantly deregulated genes). Gene Ontology indicated that the modified placental genes were mostly involved in stress, inflammation and detoxification. A sex specific analysis revealed in addition a more drastic effect on female than male placentas. In the brains, whatever the comparison, less than 50 genes were found deregulated., Interpretation: Embryos incubated in plastic ware resulted in pregnancy with massive alterations of placental gene expression profile in concerted biological functions. There were no obvious effects on the brains. Besides other effects, this suggests that plastic ware in ART could be a cause of the increased level of pregnancy disorders observed recurrently in ART pregnancies., Funding: This study was funded by two grants from the Agence de la Biomedecine in 2017 and 2019., Competing Interests: Declaration of interests None declared., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Researchers and clinicians have traditionally relied on elastic caps with markings to reposition the transcranial magnetic stimulation (TMS) coil between trains and sessions. Newer neuronavigation technology co-registers the patient's head and structural magnetic resonance imaging (MRI) scan, providing the researcher with real-time feedback about how to adjust the coil to be on-target. However, there has been no head to head comparison of accuracy and precision across treatment sessions., Objective: /Hypothesis: In this two-part study, we compared elastic cap and neuronavigation targeting methodologies on distance, angle, and electric field (E-field) magnitude values., Methods: In 42 participants receiving up to 50 total accelerated rTMS sessions in 5 days, we compared cap and neuronavigation targeting approaches in 3408 distance and 6816 angle measurements. In Experiment 1, TMS administrators saved an on-target neuronavigation location at Beam F3, which served as the landmark for all other measurements. Next, the operators placed the TMS coil based on cap markings or neuronavigation software to measure the distance and angle differences from the on-target sample. In Experiment 2, we saved each XYZ coordinate of the TMS coil from cap and neuronavigation targeting in 12 participants to compare the E-field magnitude differences at the cortical prefrontal target in 1106 cap and neuronavigation models., Results: Cap targeting was significantly off-target for distance, placing the coil an average of 10.66 mm off-target (Standard error of the mean; SEM = 0.19 mm) compared to 0.3 mm (SEM = 0.03 mm) for neuronavigation (p < 0.0001). Cap targeting also significantly deviated for angles off-target, averaging 7.79 roll/pitch degrees (SEM = 1.07°) off-target and 5.99 yaw degrees (SEM = 0.12°) off-target; in comparison, neuronavigation targeting positioned the coil 0.34 roll/pitch degrees (SEM = 0.01°) and 0.22 yaw (SEM = 0.004°) off-target (both p < 0.0001). Further analyses revealed that there were significant inter-operator differences on distance and angle positioning for F3 (all p < 0.05), but not neuronavigation. Lastly, cap targeting resulted in significantly lower E-fields at the intended prefrontal cortical target, with equivalent E-fields as 110.7% motor threshold (MT; range = 58.3-127.4%) stimulation vs. 119.9% MT (range = 115-123.3%) from neuronavigated targeting with 120% MT stimulation applied (p < 0.001)., Conclusions: Cap-based targeting is an inherent source of target variability compared to neuronavigation. Additionally, cap-based coil placement is more prone to differences across operators. Off-target coil placement secondary to cap-based measurements results in significantly lower amounts of stimulation reaching the cortical target, with some individuals receiving only 48.6% of the intended on-target E-field. Neuronavigation technology enables more precise and accurate TMS positioning, resulting in the intended stimulation intensities at the targeted cortical level., Competing Interests: Declaration of competing interest We confirm that there are no known conflicts of interest associated with this publication and there was no financial support for this work that could have influenced its outcome., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Meiotic maturation is a crucial step of oocyte formation, allowing its potential fertilization and embryo development. Elucidating this process is important for both fundamental research and assisted reproductive technology. However, few computational tools based on non-invasive measurements are available to characterize oocyte meiotic maturation. Here, we develop a computational framework to phenotype oocytes based on images acquired in transmitted light. We trained neural networks to segment the contour of oocytes and their zona pellucida using oocytes from diverse species. We defined a comprehensive set of morphological features to describe an oocyte. These steps were implemented in an open-source Fiji plugin. We present a feature-based machine learning pipeline to recognize oocyte populations and determine morphological differences between them. We first demonstrate its potential to screen oocytes from different strains and automatically identify their morphological characteristics. Its second application is to predict and characterize the maturation potential of oocytes. We identify the texture of the zona pellucida and cytoplasmic particle size as features to assess mouse oocyte maturation potential and tested whether these features were applicable to the developmental potential of human oocytes. This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Palcewska et al. first demonstrated near infrared (NIR) visual response in human volunteers upon two-photon absorption (TPA), in a seminal work of 2014, and assessed the process in terms of wavelength- and power-dependence on murine ex-vivo retinas. In the present study, ex-vivo electroretinography (ERG) is further developed to perform a complete characterization of the effect of NIR pulse duration, energy, and focal spot size on the response. The same set of measurements is successively tested on living mice. We discuss how the nonlinear intensity dependence of the photon absorption process is transferred to the amplitude of the visual response acquired by ERG. Finally, we show that the manipulation of the spectral phase of NIR pulses can be translated to predictable change in the two-photon induced response under physiological excitation conditions., Competing Interests: The authors declare no conflicts of interest., (Copyright 2022 Geoffrey Gaulier, Quentin Dietschi, Aleksa Djorovic, Luca La Volpe, Tania Rodrigues, Luigi Bonacina, Ivan Rodriguez, Jean-Pierre Wolf. License: This work is licensed under a Creative Commons Attribution 4.0 International License.)

Male infertility is responsible for approximately half of all cases of reproductive issues. Spermatogenesis originates in a small pool of spermatogonial stem cells (SSCs), which are of interest for therapy of infertility but remain not well defined in humans. Using multiparametric analysis of the side population (SP) phenotype and the α-6 integrin, THY1, and β-2 microglobulin cell markers, we identified a population of human primitive undifferentiated spermatogonia with the phenotype β-2 microglobulin (β-2M) - SPα-6 + THY1 + , which is highly enriched in stem cells. By analyzing the expression signatures of this SSC-enriched population along with other germinal progenitors, we established an exhaustive transcriptome of human spermatogenesis. Transcriptome profiling of the human β-2M - SPα-6 + THY1 + population and comparison with the profile of mouse undifferentiated spermatogonia provide insights into the molecular networks and key transcriptional regulators regulating human SSCs, including the basic-helix-loop-helix (bHLH) transcriptional repressor HES1, which we show to be implicated in maintenance of SSCs in vitro., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Alcohol use disorder (AUD) is associated with elevated brain response to cues. Recent studies have suggested that theta burst stimulation (TBS) to the medial prefrontal cortex (MPFC) can decrease reactivity to cues in a transdiagnostic manner. The goal of this clinical trial was to evaluate the effect of continuous TBS as a tool to decrease drinking behavior and brain reactivity to alcohol cues among individuals with AUD., Methods: A total of 50 individuals with AUD were recruited from an intensive outpatient treatment program. Using a randomized, double-blind, sham-controlled design, participants received 10 sessions of continuous TBS (left frontal pole, 1 session/10 days, 110% resting motor threshold, 3600 pulse/session, cue provocation before and during session). Brain reactivity to alcohol cues was acquired at four time points: at baseline and after all TBS sessions (1 month, 2 months, and 3 months)., Results: Overall, 80% of the participants completed all TBS sessions. Individuals who received real TBS were 2.71 times more likely to remain enrolled in the study after 3 months and 3.09 times more likely to remain sober 3 months after treatment initiation. Real TBS also led to a significantly greater reduction in brain reactivity to alcohol cues, specifically a reduction in MPFC-striatum and MPFC-insula connectivity 2 and 3 months after TBS treatment., Conclusions: Ten days of MPFC TBS is well tolerated, reduces drinking, and decreases brain reactivity to alcohol cues for up to 3 months after treatment initiation. These results pave a critical next step in the path toward developing transcranial magnetic stimulation as an intervention for AUD and disorders associated with elevated cue reactivity., (© 2022 The Authors.)

Sub- μ m thin samples are essential for spectroscopic purposes. The development of flat micro-jets enabled novel spectroscopic and scattering methods for investigating molecular systems in the liquid phase. However, the temperature of these ultra-thin liquid sheets in vacuum has not been systematically investigated. Here, we present a comprehensive temperature characterization using optical Raman spectroscopy of sub-micron flatjets produced by two different methods: colliding of two cylindrical jets and a cylindrical jet compressed by a high pressure gas. Our results reveal the dependence of the cooling rate on the material properties and the source characteristics, i.e., nozzle-orifice size, flow rate, and pressure. We show that materials with higher vapor pressures exhibit faster cooling rates, which is illustrated by comparing the temperature profiles of water and ethanol flatjets. In a sub- μ m liquid sheet, the temperature of the water sample reaches around 268 K and the ethanol around 253 K close to the flatjet's terminus., (© 2022 Author(s).)

Cyclic fertilin peptide (cFEE: phenylalanine, glutamic acid; glutamic acid) improves gamete interaction in humans. We investigate whether it could be via improvement of sperm movement parameters and their mitochondrial ATP production. Sperm movement parameters were studied using computer-assisted sperm analysis (CASA) in sperm samples from 38 patients with normal sperm in medium supplemented with cyclic fertilin against a control group. Sperm mitochondrial functions were studied using donor's sperm, incubated or not with cFEE. It was evaluated by the measurement of their ATP production using bioluminescence, their respiration by high resolution oxygraphy, and of mitochondrial membrane potential (MMP) using potentiometric dyes and flow cytometry. cFEE significantly improved sperm movement parameters and percentage of hyperactivated sperm. Impact of inhibitors showed OXPHOS as the predominant energy source for sperm movement. However, cFEE had no significant impact on any of the analyzed mitochondrial bioenergetic parameters, suggesting that it could act via a more efficient use of its energy resources.

Vision is usually assumed to be sensitive to the light intensity and spectrum but not to its spectral phase. However, experiments performed on retinal proteins in solution showed that the first step of vision consists in an ultrafast photoisomerization that can be coherently controlled by shaping the phase of femtosecond laser pulses, especially in the multiphoton interaction regime. The link between these experiments in solution and the biological process allowing vision was not demonstrated. Here, we measure the electric signals fired from the retina of living mice upon femtosecond multipulse and single-pulse light stimulation. Our results show that the electrophysiological signaling is sensitive to the manipulation of the light excitation on a femtosecond time scale. The mechanism relies on multiple interactions with the light pulses close to the conical intersection, like pump-dump (photoisomerization interruption) and pump-repump (reverse isomerization) processes. This interpretation is supported both experimentally and by dynamics simulations., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background: Across Ohio, parental substance abuse has contributed to a marked increase in the number of children in foster care. Children exposed to parental substance use have a higher likelihood of physical abuse and neglect, and consequently a variety of physical, psychological and cognitive problems. The Enhancing Permanency in Children and Families (EPIC) program is a collaborative effort between the Ohio State University College of Social Work, two county offices of the Ohio Department of Job and Family Services, two juvenile courts and local behavioral health agencies. The goal of EPIC is to use three evidence-based and evidence-informed practices to reduce abusive and neglectful parenting, reduce addiction severity in parents, and improve permanency outcomes for families involved with the child welfare system due to substance abuse., Methods: EPIC is a quasi-experimental study. Under the program, child welfare-involved adults who screen positive for substances are matched with a peer recovery supporter. Participants are also incentivized to participate in family treatment drug court, medications for opioid use disorders and home-based parenting supports. Participating adults (N = 250) are matched with comparison groups from counties participating in a separate intervention (Ohio START) and to those receiving treatment as usual, resulting in a final sample of 750 adults. Primary outcomes including addiction severity, child trauma symptoms, resilience, and attachment are assessed at baseline and at program completion. Additional outcomes include timely access to treatment services, length of placement in out-of-home care and recidivism into the child welfare system., Discussion: This intervention formalizes cross-system collaboration between child welfare, behavioral health and juvenile courts to support families affected by addiction. The use of three evidence-based or evidence-informed strategies presents the opportunity to determine specific strategies that are most effective for reducing addiction severity. Lastly, the intervention combines several sources of funding to bolster sustainability beyond the life of the Regional Partnership Grant (RPG)., Trial Registration: NCT04700696 . Registered January 7, 2021-retrospectively registered.

Medical advances in assisted reproductive technology have created new ways for transgender persons to become parents outside the context of adoption. The limited empirical data does not support the idea that trans-parenthood negatively impacts children's development. However, the question has led to lively societal debates making the need for evidence-based studies urgent. We aimed to compare cognitive development, mental health, gender identity, quality of life and family dynamics using standardized instruments and experimental protocols in 32 children who were conceived by donor sperm insemination (DSI) in French couples with a cisgender woman and a transgender man, the transition occurring before conception. We constituted two control groups matched for age, gender and family status. We found no significant difference between groups regarding cognitive development, mental health, and gender identity, meaning that neither the transgender fatherhood nor the use of DSI had any impact on these characteristics. The results of the descriptive analysis showed positive psycho-emotional development. Additionally, when we asked raters to differentiate the family drawings of the group of children of trans-fathers from those who were naturally conceived, no rater was able to differentiate the groups above chance levels, meaning that what children expressed through family drawing did not indicate cues related to trans-fatherhood. However, when we assessed mothers and fathers with the Five-Minute Speech Sample, we found that the emotions expressed by transgender fathers were higher than those of cisgender fathers who conceived by sex or by DSI. We conclude that the first empirical data regarding child development in the context of trans-parenthood are reassuring. We believe that this research will also improve transgender couple care and that of their children in a society where access to care remains difficult in this population. However, further research is needed with adolescents and young adults., Competing Interests: The authors have read the journal’s policy and have the following potential competing interests: AC has received funding for this project from the Pfizer France Foundation and the Centre d’Activités de Recherche en Psychiatrie Infanto-Juvénile (CARPIJ). Pfizer is a commercial funder. This does not alter our adherence to PLOS ONE policies on sharing data and materials. None of the authors have any commercial relationship with Pfizer, and there are no patents, products in development or marketed products associated with this research to declare.

We have previously shown, using antibodies, that the sperm alpha6beta1 integrin is involved in mouse gamete fusion in vitro. Here we report the conditional knockdown of the sperm Itgb1 gene. It induced a drastic failure of sperm fusogenic ability with sperm accumulation in the perivitelline space of in vitro inseminated oocytes deleted or not for the Itgb1 gene. These data demonstrate that sperm, but not oocyte, beta1 integrin subunit is involved in gamete adhesion/fusion. Curiously, knockdown males were fertile in vivo probably because of the incomplete Cre-mediated deletion of the sperm Itgb1 floxed gene. Indeed, this was shown by Western blot analysis and confirmed by both the viability and litter size of pups obtained by mating partially sperm Itgb1 deleted males with females producing completely deleted Itgb1 oocytes. Because of the total peri-implantation lethality of Itgb1 deletion in mice, we assume that sperm that escaped the Itgb1 excision seemed to be preferentially used to fertilize in vivo. Here, we showed for the first time that the deletion, even partial, of the sperm Itgb1 gene makes the sperm unable to normally fertilize oocytes. However, to elucidate the question of the essentiality of its role during fertilization, further investigations using a mouse expressing a recombinase more effective in male germ cells are necessary.

We present space and time resolved measurements of the air hydrodynamics induced by femtosecond laser pulse excitation of the air gap between two electrodes at high potential difference. We explore both plasma-based and plasma-free gap excitation. The former uses the plasma left in the wake of femtosecond filamentation, while the latter exploits air heating by multiple-pulse resonant excitation of quantum molecular wavepackets. We find that the cumulative electrode-driven air density depression channel plays the dominant role in the gap evolution leading to breakdown. Femtosecond laser heating serves mainly to initiate the depression channel; the presence of filament plasma only augments the early heating.

Objective: In 2018, the Association of College & Research Libraries (ACRL) Health Sciences Interest Group convened a working group to update the 2013 Information Literacy Competency Standards for Nursing to be a companion document to the 2016 Framework for Information Literacy in Higher Education. To create this companion document, the working group first needed to understand how nursing faculty approached information literacy (IL) instruction., Methods: The working group designed a survey that assessed how nursing faculty utilized IL principles in coursework and instruction. The survey consisted of nineteen mixed methods questions and was distributed to nursing faculty at eight institutions across the United States., Results: Most (79%) faculty indicated that they use a variety of methods to teach IL principles in their courses. While only 12% of faculty incorporated a version of the ACRL IL competencies in course design, they were much more likely to integrate nursing educational association standards. Faculty perceptions of the relevance of IL skills increased as the education level being taught increased., Conclusion: The integration of IL instruction into nursing education has mostly been achieved through using standards from nursing educational associations. Understanding these standards and understanding how faculty perceptions of the relevance of IL skills change with educational levels will guide the development of a companion document that librarians can use to collaborate with nurse educators to integrate IL instruction throughout nursing curriculums at course and program levels., (Copyright © 2020 Bethany S. McGowan, Laureen P. Cantwell, Jamie L. Conklin, Rebecca Raszewski, Julie Planchon Wolf, Maribeth Slebodnik, Sandy McCarthy, Shannon Johnson.)

High intensity laser filamentation in air has recently demonstrated that, through plasma generation and its associated shockwave, fog can be cleared around the beam, leaving an optically transparent path to transmit light. However, for practical applications like free-space optical communication (FSO), channels of multi-centimeter diameters over kilometer ranges are required, which is extremely challenging for a plasma based method. Here we report a radically different approach, based on quantum control. We demonstrate that fog clearing can also be achieved by producing molecular quantum wakes in air, and that neither plasma generation nor filamentation are required. The effect is clearly associated with the rephasing time of the rotational wave packet in N 2 .Pump excitation provided in the form of resonant trains of 8 pulses separated by the revival time are able to transmit optical data through fog with initial extinction as much as -6 dB.

Three genes are known to be essential for gamete adhesion/fusion (Cd9, Izumo1 and Juno). Here, we confirmed that Spaca6 null males are infertile and showed that their sperm accumulate in the perivitelline space but are unable to fuse with oocyte. Like IZUMO1, SPACA6 which is expressed by human sperm, is remained on the equatorial segment after acrosomal reaction and is involved in human fertilization since an anti-SPACA6 antibody inhibited it. Despite the similarity of the phenotypes caused by Spaca6 and Izumo1 knockouts, these are not redundant and the essential relocation of IZUMO1 is not affected by the lack of SPACA6. We propose a model in which IZUMO1 and SPACA6 would be part of a molecular complex necessary for gamete fusion and that their concomitant presence would be required for the recruitment of another essential molecular actor, such as a fusogen, for the fusion to take place.

In humans, structural or functional defects of the sperm flagellum induce asthenozoospermia, which accounts for the main sperm defect encountered in infertile men. Herein we focused on morphological abnormalities of the sperm flagellum (MMAF), a phenotype also termed "short tails," which constitutes one of the most severe sperm morphological defects resulting in asthenozoospermia. In previous work based on whole-exome sequencing of a cohort of 167 MMAF-affected individuals, we identified bi-allelic loss-of-function mutations in more than 30% of the tested subjects. In this study, we further analyzed this cohort and identified five individuals with homozygous truncating variants in TTC29, a gene preferentially and highly expressed in the testis, and encoding a tetratricopeptide repeat-containing protein related to the intraflagellar transport (IFT). One individual carried a frameshift variant, another one carried a homozygous stop-gain variant, and three carried the same splicing variant affecting a consensus donor site. The deleterious effect of this last variant was confirmed on the corresponding transcript and protein product. In addition, we produced and analyzed TTC29 loss-of-function models in the flagellated protist T. brucei and in M. musculus. Both models confirmed the importance of TTC29 for flagellar beating. We showed that in T. brucei the TPR structural motifs, highly conserved between the studied orthologs, are critical for TTC29 axonemal localization and flagellar beating. Overall our work demonstrates that TTC29 is a conserved axonemal protein required for flagellar structure and beating and that TTC29 mutations are a cause of male sterility due to MMAF., (Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Ongoing progress in genomic technologies offers exciting tools that can help to resolve transcriptome and genome-wide DNA modifications at single-cell resolution. These methods can be used to characterize individual cells within complex tissue organizations and to highlight various molecular interactions. Here, we will discuss recent advances in the definition of spermatogonial stem cells (SSC) and their progenitors in humans using the single-cell transcriptome sequencing (scRNAseq) approach. Exploration of gene expression patterns allows one to investigate stem cell heterogeneity. It leads to tracing the spermatogenic developmental process and its underlying biology, which is highly influenced by the microenvironment. scRNAseq already represents a new diagnostic tool for the personalized investigation of male infertility. One may hope that a better understanding of SSC biology could facilitate the use of these cells in the context of fertility preservation of prepubertal children, as a key component of regenerative medicine.

Synthetic peptides mimicking the binding site of fertilin β to its receptor, integrin α6β1, were shown to inhibit sperm-egg fusion when added to in vitro media. In contrast, the synthetic cyclic hexapeptide, cyclo(Cys 1 -Ser 2 -Phe 3 -Glu 4 -Glu 5 -Cys 6 ), named as cFEE, proved to stimulate gamete fusion. Owing to its biological specificity, this hexapeptide could help improve the in vitro fertilization pregnancy rate in human. In an attempt to establish the structure-activity relationship of cFEE, its structural dynamics was herein analyzed by means of ultraviolet circular dichroism (UV-CD) and Raman scattering. The low concentration CD profile in water, containing mainly a deep minimum at ∼202 nm, is consistent with a rather unordered chain. However, an ordering trend of the peptide loop has been observed in a less polar solvent such as methanol, where the UV-CD signal shape is formed by a double negative marker at ∼202/215 nm, indicating the presence of a type-II' β-turn. Raman spectra recorded in aqueous samples upon a 100-fold concentration increase, still showed an important population (∼30%) of the disordered structure. The structural flexibility of the disulfide bridge was confirmed by the Raman markers arising from the Cys 1 -Cys 6 disulfide bond-stretch motions. Density functional theory calculations highlighted the formation of the type-II' β-turn on the four central residues of cFEE (i.e., -Ser 2 -Phe 3 -Glu 4 -Glu 5 -) either with a left- or with a right-handed disulfide. The structure with a left-handed S-S bond, however, appears to be more stable., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Study Question: How efficacious is transplantation of ovarian cortex previously exposed to chemotherapy?, Summary Answer: Prior exposure to chemotherapy did not disrupt the function of cryopreserved ovarian tissue after transplantation., What Is Known Already: Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) is an efficacious technique for restoration of female fertility. At least 130 children have been born following this procedure. To date, little is known about the efficacy of OTT in patients exposed to cancer chemotherapy prior to OTC., Study Design, Size, Duration: This study evaluates the recovery of ovarian function and fertility in 31 consecutive patients who had received OTT, between 2005 and 2015., Participants/materials, Setting, Methods: Thirty one patients, wanting children, were transplanted with autologous ovarian cortex, among which 22 patients (71%) had been exposed to chemotherapy before OTC. Recovery of ovarian function was considered total once menstruation occurred. Ovarian function recovery (OFR), ovarian graft survival, and incidence of pregnancy were related to previous chemotherapy exposure, type of chemotherapy and graft characteristics (number of grafted fragments and follicular density)., Main Results and Role of Chance: The amount of ovarian tissue collected was the only parameter to show any significant change between patients with versus without previous chemotherapy. At 1 year after OTT, the cumulative incidence of OFR was 83% (93% in patients exposed to chemotherapy and 67% in others (P = 0.14)). A low follicular density (<0.3 foll/mm2) in the transplant and a low number of grafted fragments (<16) were significantly associated with a delayed OFR. Graft survival at 2 years after OTT was 77%. It was significantly lower in patients exposed to bifunctional alkylating agents before ovarian cryopreservation and in patients with a low follicular density. The proportion of women who succeeded in having at least one live birth was 23% in the total population, 0% (0/9) in the group 'no previous chemotherapy', and 32% (7/22) in the group 'previous chemotherapy'. The cumulative incidence of pregnancy (Kaplan-Meier) at 3 years after OTT was 36% overall and 49% in case of previous chemotherapy, with no difference related to previous chemotherapy exposure. In total there were 13 pregnancies and 8 births in 7 patients., Limitations, Reasons for Caution: The pathology in the two groups of patients was not comparable. In the group of patients who had chemotherapy before OTC, there were 95% of hematological malignancies. In the group of patients who did not have chemotherapy before OTC only 1 out of 9 patients had a malignant hematological disease while 44% had some pathology affecting the ovaries. Few women are available for study and only large changes are likely to have statistical significance., Wider Implications of the Findings: These results suggest that prior cancer chemotherapy should no longer be considered a limitation to cryopreservation of ovarian tissue and current recommendations in this regard should be revised., Study Funding/competing Interest(s): This study was supported by the Agence de la Biomédecine (France's biomedical office). There are no competing interests to report., Trial Registration Number: NCT02184806., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We study the use of frequency upconversion schemes of near-IR picosecond laser pulses and compare their ability to guide and trigger electric discharges through filamentation in air. Upconversion, such as Second Harmonic Generation, is favorable for triggering electric discharges for given amount of available laser energy, even taking into account the losses inherent to frequency conversion. We focus on the practical question of optimizing the use of energy from a given available laser system and the potential advantage to use frequency conversion schemes.

Study Question: Did the revised Alpha/ESHRE consensus (Vienna, 2017) bring a real answer on managing oocytes with aggregates of smooth endoplasmic reticulum (SERa)?, Summary Answer: According to the currently available literature, a case by case approach on the time of injecting/inseminating SERa+ oocytes may be not helpful for embryologists making a decision, so we suggest fertilizing both SERa+ and SERa- oocytes and prioritizing embryos derived from SERa- oocytes., What Is Known Already?: In 2011, the Istanbul consensus recommended not to inject/inseminate SER+ oocytes due to adverse foetal outcomes reported in literature. At the end of 2017, a panel of experts reconsidered this recommendation and advised a case by case approach. Hence, with a lack of clear recommendations, in-vitro fertilization practitioners still have heterogeneous attitudes when managing SERa+ oocytes. In this context of controversy, an updated review could be helpful in (i) forming a common language for managing cases of SERa+ oocytes and (ii) offering the most ethical practice and best care for patients seeking infertility treatment or fertility preservation., Study Design, Size, Duration: This review (with a last literature search on 1 June 2018) evaluated the effect of the SER dysmorphism on embryological and neonatal outcomes., Participants/materials, Setting, Methods: Studies were considered for inclusion if they were prospective or retrospective cohort or case-control studies. Electronic searches of the Pubmed and Embase databases were done using the keyword combination: smooth endoplasmic reticulum, SER, oocyte and zygote. Abstracts and articles written in English and limited to humans were included., Main Results and the Role of Chance: The search returned a total of 726 studies among which 21 met the inclusion criteria. The literature does not unanimously support a negative association between SERa and embryogenesis, implantation or assisted reproductive therapy outcomes. The reviewed studies reported 112 neonatal outcomes after transfers where at least one embryo originated from oocyte affected by SERa. They included 101 healthy babies, three live births with malformations, three neonatal deaths, one stillbirth and four medical interruptions of pregnancy. After transfer of embryos exclusively derived from SERa+ oocytes, a total of 48 healthy newborns were reported along with four babies with perinatal complications (including one ventricular septal defect), one stillbirth, one neonatal death and one pregnancy termination for multiple malformations., Limitations, Reasons for Caution: As with any review, this review was limited by the quality of the included studies especially in terms of possible methodological limitations, the limited sample size and the retrospective aspect of the studies. Among the 21 selected studies, seven were abstracts and two were case reports. Of the remaining 14 studies, only three were prospective. The tools used in identifying SERa+ oocytes may have varied from one study to another and a consequent misclassification cannot be excluded. Considering the poor resolution of light microscopy in detecting SER aggregates, we are not sure that apparently SERa- oocytes do not really exhibit such a dysmorphism if they were analysed under electronic microscopy or a time lapse system., Wider Implications of the Findings: In the light of the existing data and the lack of a real link between fertilizing SERa+ oocytes and the occurrence of embryo aneuploidy/malformations, we think that discarding SERa+ oocytes may be not the most ethical approach even in patients with large cohorts on the day of oocyte retrieval. Avoiding the wastage of oocytes and embryos with respect to medical ethics remains a constant concern in daily IVF practice. Thus, we recommend that all mature oocytes could be fertilized and embryos originating from SERa- oocytes would be preferably transferred, even if they come from a cohort with SERa+ oocytes. The remaining embryos derived from SERa+ oocytes could be considered with a lower priority for transfer after obtaining consent from the couple if a strict follow-up of the pregnancy and the baby is performed., Study Funding/competing Interest(s): We have no conflict of interest to declare and no funding was received., Registration Number: N/A., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Study Question: Is JUNO protein present at the surface membrane of human oocytes and involved in the fertilisation process?, Summary Answer: JUNO protein is expressed on the plasma membrane of human oocytes and its inhibition by a monoclonal antibody completely blocks gamete fusion., What Is Known Already: Fusion of gamete membranes is the culminating event of the fertilisation process, but its molecular mechanisms are poorly understood. Until now, three molecules have been shown to be essential: CD9 tetraspanin in the oocyte, Izumo1 protein on the sperm and Juno, its corresponding receptor on the oocyte. Oocyte CD9 and sperm IZUMO1 have been identified in human gametes and their interaction is also well-conserved among several mammalian species. The presence of JUNO on human oocytes, however, has not yet been reported, nor has its role in fertilisation been investigated., Study Design, Size, Duration: We selected an anti-human JUNO antibody in order to investigate the presence of JUNO on the oocyte membrane surface and studied its potential involvement in gamete membrane interaction during fertilisation., Participants/materials, Setting, Methods: Monoclonal antibodies against human JUNO (anti-hJUNO mAb) were produced by immunisation of mice with HEK cells transfected with the putative human JUNO sequence (HEK-hJUNO). These antibodies were used for immunostaining experiments and in vitro fertilisation assays with human gametes (GERMETHEQUE Biobank)., Main Results and the Role of Chance: Three hybridoma supernatants, verified by immunostaining, revealed specifically HEK-hJUNO cells. The three purified monoclonal antibodies, FJ2E4 (IgG1), FJ8E8 (IgG1) and FJ4F5 (IgG2a), recognised the soluble recombinant human JUNO protein and, in a western blot of HEK-hJUNO extracts, a protein with an expected MW of 25 kDa. In addition, soluble recombinant human IZUMO protein inhibited the binding of anti-hJUNO mAbs to cells expressing hJUNO. Using these anti-hJUNO mAbs in immunostaining, we identified the presence of JUNO protein at the plasma membrane of human oocytes. Furthermore, we revealed a progressive expression of JUNO according to oocyte maturity. Finally, we showed that human zona-free oocytes, inseminated in the presence of anti-hJUNO mAb, were not fertilised by human sperm. These results suggest that, as seen in the mouse, JUNO is indeed involved in human gamete membrane fusion during fertilisation., Large-Scale Data: N/A., Limitations, Reasons for Caution: In accordance with French bioethics laws, functional tests were performed using zona-free oocytes, which of course does not fully encompass all normal in vivo physiological conditions. However, these in vitro tests do provide direct information regarding sperm-oocyte membrane interactions., Wider Implications of the Findings: Mechanisms of gamete fusion appear to be homologous between mice and humans. However, some differences do exist and analysing the human mechanisms is essential. In fact, this is the first report describing the presence of JUNO on human oocytes and its involvement in human fertilisation. This discovery allows further examination of the understanding of molecular mechanisms that drive gamete fusion: a crucial challenge at a time when infertility affects 16% of reproductively active couples., Study Funding/competing Interests: This work was supported by the Agence Nationale pour la Recherche, Grant no. ANR-13-BVS5-0004, and by Association Institut du Cancer et d'Immunogénétique (ICIG). There are no competing interests.

Parental alcohol use and alcohol outlet densities in residential areas are related to risk for child maltreatment. However, some parents spend significant time outside of their residential neighborhood. Thus, we may not be accurately assessing how alcohol environments are related to risks for problematic parenting. Here, we examine how residential environments and activity spaces are related to outlet density and whether drinking events in our sample of parents differ by location (e.g., routine vs. rare locations) and whether their children are present. We conducted semi-structured interviews with 60 parents living in four cities in the San Francisco Bay area who provided information on where they spent time, where they drank, and whether children were present. We constructed measures of activity spaces (e.g., convex hull polygons) and activity patterns (e.g., shortest network distance) and calculated outlet density in each. Density of alcohol outlets for residential Census tract was not related to density of the activity space and activity pattern measures. Alcohol use occurred more frequently (regardless of whether their children were present) inside activity spaces operationalized as convex hull polygons or two standard deviational ellipses. Measures that capture larger activity space areas (e.g., convex hull polygons, two standard deviational ellipses) may better model where people spend time, regardless of whether the location is routine or rare. By continuing to use activity spaces to explore relationships between outlet densities, drinking behaviors, and problems, we can start to ascertain those mechanisms by which outlets may affect local problems.

Purpose: This study was designed to evaluate patient management and quality of information given by French oncologists to cancer women concerning fertility issues and possibilities of fertility preservation., Methods: An online survey was sent to 1161 physicians in all major cancer centers throughout France between May 2012 and January 2013., Results: A total of 102 responses were received and analyzed. Only 46% of all physicians surveyed reported discussing infertility risks with patients of reproductive age and 22% referred them to a fertility center before beginning treatments. Only 14% of practitioners considered themselves knowledgeable in FP techniques and ovarian transposition was the most frequently mentioned technique in consultation., Conclusion: This study is at the best of our knowledge the first nationwide survey to assess the state of the art in oncofertility management. It highlights inadequate management of fertility preservation for female patients in France. Physicians reported lacking knowledge and tools that would allow them to provide patients with appropriate information. A better collaboration between cancer and fertility centers needs to be organized in France as already organized in other countries.

We present a 0.2 TW sub-two-cycle 1.8 µm carrier-envelope-phase stable source based on two-stage pulse compression by filamentation for driving high-order harmonic generation extending beyond the oxygen K absorption edge. The 1 kHz repetition rate, high temporal resolution enabled by the short 11.8 fs driving pulse duration, and bright high-order harmonics generated in helium make this an attractive source for solid-state and molecular-dynamics studies.

Motile cilia and sperm flagella share an extremely conserved microtubule-based cytoskeleton, called the axoneme, which sustains beating and motility of both organelles. Ultra-structural and/or functional defects of this axoneme are well-known to cause primary ciliary dyskinesia (PCD), a disorder characterized by recurrent respiratory tract infections, chronic otitis media, situs inversus, male infertility and in most severe cases, hydrocephalus. Only recently, mutations in genes encoding axonemal proteins with preferential expression in the testis were identified in isolated male infertility; in those cases, individuals displayed severe asthenozoospermia due to Multiple Morphological Abnormalities of the sperm Flagella (MMAF) but not PCD features. In this study, we performed genetic investigation of two siblings presenting MMAF without any respiratory PCD features, and we report the identification of the c.2018T > G (p.Leu673Pro) transversion in AK7, encoding an adenylate kinase, expressed in ciliated tissues and testis. By performing transcript and protein analyses of biological samples from individual carrying the transversion, we demonstrate that this mutation leads to the loss of AK7 protein in sperm cells but not in respiratory ciliated cells, although both cell types carry the mutated transcript and no tissue-specific isoforms were detected. This work therefore, supports the notion that proteins shared by both cilia and sperm flagella may have specific properties and/or function in each organelle, in line with the differences in their mode of assembly and organization. Overall, this work identifies a novel genetic cause of asthenozoospermia due to MMAF and suggests that in humans, more deleterious mutations of AK7 might induce PCD.

Study Question: The aim of this study was to evaluate the live birth rate (LBR) after frozen-thawed Day 5 (D5) and Day 6 (D6) blastocyst transfers., Summary Answer: LBR following frozen-thawed blastocyst transfer is significantly lower with D6 than with D5 blastocyst regardless of embryo quality., What Is Known Already: During fresh embryo transfer cycles, pregnancy rates (PR) are significantly higher when transferring blastocysts expanded on D5 compared with slow developing blastocysts (D6). In programmed thawed blastocyst transfer (TBT) cycles, the same clinical outcomes should be expected when transferring D5 or D6 blastocysts because of endometrial/embryonic synchronization due to hormonal priming of endometrial receptivity. However, the impact of delayed blastocyst expansion at D6 on clinical outcomes remains unclear. Some reports have shown higher PRs after D5 TBT compared with those of D6, while others have shown equivalent TBT outcomes after D5 and D6 cryopreserved blastocysts transfers., Study, Design, Size, Duration: This retrospective cohort follow-up study included 1347 single autologous frozen-thawed blastocyst transfers performed between January 2012 and December 2015 at a tertiary care university hospital., Participants/materials, Setting, Methods: All of the patients scheduled for TBT were allocated to two groups according to the day of blastocyst expansion: on D5 (n = 994) or on D6 (n = 353). The primary outcome was LBR per embryo transfer in the first blastocyst thawing cycle. Secondary outcomes were clinical pregnancy rate (cPR), early miscarriage rate and neonatal outcomes following TBT for the two groups. Statistical analyses were conducted using univariate and multivariate logistic regression model., Main Results and the Role of Chance: The LBR was significantly increased in the D5 group compared to the D6 group [294/994 (29.6%) versus 60/353 (17.0%); P < 0.001]. The cPR was also higher when blastocysts were vitrified on D5 compared with those vitrified on D6 [429/994 (43.2%) versus 95/353 (26.9%); P < 0.001]. No significant differences were found between groups in terms of early miscarriage rate (P = 0.862). More good-quality embryos (defined as an B3-B4 or B5 embryo ≥BB according to the grading scale proposed by Gardner) were transferred in the D5 group than in the D6 group [807 (81.2%) versus 214 (60.6%); P < 0.001]. However, a comparison of TBT cycles with equal embryo quality (good versus low) also supported the superiority of D5 blastocysts. Concerning neonatal outcomes, the D5 group infants had a lower mean birth weight compared to those of the D6 group (P = 0.001). In addition, a significantly shorter gestational age at birth is reported in the D5 blastocyst group as compared to the D6 group (P = 0.004). After multivariate logistic regression taking into account potential confounders such as the women's age, number of previous IVF/ICSI procedures, the day of the blastocyst vitrification (D5 or D6) and embryo quality, blastocyst expansion at D6 was independently associated with a significant decrease in LBR compared to D5 expanded-blastocysts (OR 0.52; 95% CI 0.38-0.72; P < 0.001)., Limitations, Reasons for Caution: The poor predictive value of the morphological approach in embryo selection could constitute a limitation in this study. However, blastocyst quality was evaluated similarly in both groups., Wider Implications of the Findings: The LBR following frozen-thawed blastocyst transfer was significantly lower with D6 than with D5 blastocysts, regardless of their quality. These results could affect cryopreservation procedures as they suggest that the use of D5-expanded blastocysts for TBT may be preferred in order to shorten the time of conceiving., Study Funding/competing Interest(s): No specific funding was obtained for this study. None of the authors have any competing interests to declare., Trial Registration Number: Not applicable.

Spermatogenesis defects concern millions of men worldwide, yet the vast majority remains undiagnosed. Here we report men with primary infertility due to multiple morphological abnormalities of the sperm flagella with severe disorganization of the sperm axoneme, a microtubule-based structure highly conserved throughout evolution. Whole-exome sequencing was performed on 78 patients allowing the identification of 22 men with bi-allelic mutations in DNAH1 (n = 6), CFAP43 (n = 10), and CFAP44 (n = 6). CRISPR/Cas9 created homozygous CFAP43/44 male mice that were infertile and presented severe flagellar defects confirming the human genetic results. Immunoelectron and stimulated-emission-depletion microscopy performed on CFAP43 and CFAP44 orthologs in Trypanosoma brucei evidenced that both proteins are located between the doublet microtubules 5 and 6 and the paraflagellar rod. Overall, we demonstrate that CFAP43 and CFAP44 have a similar structure with a unique axonemal localization and are necessary to produce functional flagella in species ranging from Trypanosoma to human.

Purpose: The aims of this study were to investigate the possible benefits of extending the culture of poor-quality day-2 embryos (PQE) versus good-quality embryos (GQE) and to identify factors associated with pregnancy and live birth when transferring frozen-thawed blastocysts originating from GQE and PQE., Methods: This is a retrospective cohort follow-up study performed between November 2012 and February 2015 at the IVF Laboratory Unit of Cochin University Hospital (Paris, France) including 3108 day-2 supernumerary embryos resulting from 1237 IVF/ICSI cycles., Results: Total blastulation rate was 67.2% from GQE and 48.7% from PQE. Percentage of good-quality blastocysts was 60.7 and 47.9% respectively including 14.7 and 7.3% top-quality blastocysts. A total of 150 blastocysts originating from GQE and 729 from PQE were frozen, and then, 37 and 164 were thawed and transferred respectively resulting in 19 (51.4%) and 61 (37.9%) clinical pregnancies with 13 (35.1%) deliveries from GQE and 32 (19.9%) from PQE (p = 0.046) without any difference in neonatal outcomes. Quality of blastocysts that resulted in live birth was similar in the two groups. Women < 35 years old and day-5 blastocyst expansion were predictive of pregnancy and live birth., Conclusions: (i) PQE are able to reach the blastocyst stage, to implant, and to give healthy babies and (ii) women age and day of blastocyst expansion are predictive of pregnancy and live birth.

Today, thanks to biomedical technologies advances, some persons with fertility issues can conceive. Transgender persons benefit also from these advances and can not only actualize their self-identified sexual identities but also experience parenthood. Based on clinical multidisciplinary seminars that gathered child psychiatrists and psychoanalysts interested in the fields of assisted reproduction technology (ART) and gender dysphoria, philosophers interested in bioethics, biologists interested in ART, and endocrinologists interested in pubertal suppression, we explore how new biotechnical advances, whether in gender transition or procreation, could create new ways to conceive a child possible. After reviewing the various medical/surgical techniques for physical gender transition and the current ART options, we discuss how these new ways for persons to self-actualize and to experience parenthood can not only improve the condition of transgender persons (and the human condition as a whole through greater equity) but also introduce some elements of change in the habitual patterns of thinking especially in France. Finally, we discuss the ethical issues that accompany the arrival of these children and provide creative solutions to help society handle, accept, and support the advances made in this area.