Preimplantation Genetic Testing for Aneuploidy in In Vitro Fertilization Using Comprehensive Chromosome Screening: A Systematic Review and Meta-Analysis.

The utility of pre-implantation genetic testing (PGT-A) is controversial, with older meta-analyses demonstrating improved pregnancy outcomes, while newer trials have not shown benefit. Therefore, we performed a meta-analysis which aimed to evaluate the benefits of PGT-A using comprehensive chromosome screening (CCS) and its effects on in vitro fertilization (IVF) outcomes among randomized controlled trials (RCTs). We conducted a systematic search to identify RCTs comparing women undergoing PGT-A with CSS with women not undergoing PGT-A, from inception to December 2020. Random effects meta-analysis was utilized to calculate average odds ratios (OR) for clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR), and miscarriage rate (MR). The heterogeneity of exposure was assessed using Forest plots and I2 statistics. Publication bias was evaluated using Egger's test. Among 1251 citations, seven RCTs met the inclusion criteria. Biopsies of embryos were carried out at various developmental stages, including polar body, day 3, and day 5-6 of culture. Data was analyzed as all studies and blastocyst only. Meta-analysis failed to show improvement in OPRs using PGT-A in the all ages, <35 years old and ≥35 years old age groups. There was also no significant difference in CPRs in any group. The MR decreased with the use of PGT-A (among all biopsy types and among blastocyst biopsies) in the all-ages group, but not when stratifying according to patient age <35 and ≥35 years old. More data regarding the risks and advantages of PGT-A are needed to make a final decision on the value of this intervention in clinical practice. The exact magnitude of the benefit of PGT-A selection cannot be correctly determined until multiple standardized protocol IVF PGT-A trials are conducted.

A switch in jaw form-function coupling during the evolution of mammals.

The evolutionary shift from a single-element ear, multi-element jaw to a multi-element ear, single-element jaw during the transition to crown mammals marks one of the most dramatic structural transformations in vertebrates. Research on this transformation has focused on mammalian middle-ear evolution, but a mandible comprising only the dentary is equally emblematic of this evolutionary radiation. Here, we show that the remarkably diverse jaw shapes of crown mammals are coupled with surprisingly stereotyped jaw stiffness. This strength-based morphofunctional regime has a genetic basis and allowed mammalian jaws to effectively resist deformation as they radiated into highly disparate forms with markedly distinct diets. The main functional consequences for the mandible of decoupling hearing and mastication were a trade-off between higher jaw stiffness versus decreased mechanical efficiency and speed compared with non-mammals. This fundamental and consequential shift in jaw form-function underpins the ecological and taxonomic diversification of crown mammals. This article is part of the theme issue 'The mammalian skull: development, structure and function'.

The developing bird pelvis passes through ancestral dinosaurian conditions.

Living birds (Aves) have bodies substantially modified from the ancestral reptilian condition. The avian pelvis in particular experienced major changes during the transition from early archosaurs to living birds1,2. This stepwise transformation is well documented by an excellent fossil record2-4; however, the ontogenetic alterations that underly it are less well understood. We used embryological imaging techniques to examine the morphogenesis of avian pelvic tissues in three dimensions, allowing direct comparison with the fossil record. Many ancestral dinosaurian features2 (for example, a forward-facing pubis, short ilium and pubic 'boot') are transiently present in the early morphogenesis of birds and arrive at their typical 'avian' form after transitioning through a prenatal developmental sequence that mirrors the phylogenetic sequence of character acquisition. We demonstrate quantitatively that avian pelvic ontogeny parallels the non-avian dinosaur-to-bird transition and provide evidence for phenotypic covariance within the pelvis that is conserved across Archosauria. The presence of ancestral states in avian embryos may stem from this conserved covariant relationship. In sum, our data provide evidence that the avian pelvis, whose early development has been little studied5-7, evolved through terminal addition-a mechanism8-10 whereby new apomorphic states are added to the end of a developmental sequence, resulting in expression8,11 of ancestral character states earlier in that sequence. The phenotypic integration we detected suggests a previously unrecognized mechanism for terminal addition and hints that retention of ancestral states in development is common during evolutionary transitions.

Unveiling the third dimension in morphometry with automated quantitative volumetric computations.

As computed tomography and related technologies have become mainstream tools across a broad range of scientific applications, each new generation of instrumentation produces larger volumes of more-complex 3D data. Lagging behind are step-wise improvements in computational methods to rapidly analyze these new large, complex datasets. Here we describe novel computational methods to capture and quantify volumetric information, and to efficiently characterize and compare shape volumes. It is based on innovative theoretical and computational reformulation of volumetric computing. It consists of two theoretical constructs and their numerical implementation: the spherical wave decomposition (SWD), that provides fast, accurate automated characterization of shapes embedded within complex 3D datasets; and symplectomorphic registration with phase space regularization by entropy spectrum pathways (SYMREG), that is a non-linear volumetric registration method that allows homologous structures to be correctly warped to each other or a common template for comparison. Together, these constitute the Shape Analysis for Phenomics from Imaging Data (SAPID) method. We demonstrate its ability to automatically provide rapid quantitative segmentation and characterization of single unique datasets, and both inter-and intra-specific comparative analyses. We go beyond pairwise comparisons and analyze collections of samples from 3D data repositories, highlighting the magnified potential our method has when applied to data collections. We discuss the potential of SAPID in the broader context of generating normative morphologies required for meaningfully quantifying and comparing variations in complex 3D anatomical structures and systems.

The anatomy and palaeobiology of the early armoured dinosaur Scutellosaurus lawleri (Ornithischia: Thyreophora) from the Kayenta Formation (Lower Jurassic) of Arizona.

The armoured dinosaurs, Thyreophora, were a diverse clade of ornithischians known from the Early Jurassic to the end of the Cretaceous. During the Middle and Late Jurassic, the thyreophorans radiated to evolve large body size, quadrupedality, and complex chewing mechanisms, and members of the group include some of the most iconic dinosaurs, including the plated Stegosaurus and the club-tailed Ankylosaurus; however, the early stages of thyreophoran evolution are poorly understood due to a paucity of relatively complete remains from early diverging thyreophoran taxa. Scutellosaurus lawleri is generally reconstructed as the earliest-diverging thyreophoran and is known from over 70 specimens from the Lower Jurassic Kayenta Formation of Arizona, USA. Whereas Scutellosaurus lawleri is pivotal to our understanding of character-state changes at the base of Thyreophora that can shed light on the early evolution of the armoured dinosaurs, the taxon has received limited study. Herein, we provide a detailed account of the osteology of Scutellosaurus lawleri, figuring many elements for the first time. Scutellosaurus lawleri was the only definitive bipedal thyreophoran. Histological studies indicate that it grew slowly throughout its life, possessing lamellar-zonal tissue that was a consequence neither of its small size nor phylogenetic position, but may instead be autapomorphic, and supporting other studies that suggest thyreophorans had lower basal metabolic rates than other ornithischian dinosaurs. Faunal diversity of the Kayenta Formation in comparison with other well-known Early Jurassic-aged dinosaur-bearing formations indicates that there was considerable spatial and/or environmental variation in Early Jurassic dinosaur faunas.

An Evolutionary Microcircuit Approach to the Neural Basis of High Dimensional Sensory Processing in Olfaction.

Odor stimuli consist of thousands of possible molecules, each molecule with many different properties, each property a dimension of the stimulus. Processing these high dimensional stimuli would appear to require many stages in the brain to reach odor perception, yet, in mammals, after the sensory receptors this is accomplished through only two regions, the olfactory bulb and olfactory cortex. We take a first step toward a fundamental understanding by identifying the sequence of local operations carried out by microcircuits in the pathway. Parallel research provided strong evidence that processed odor information is spatial representations of odor molecules that constitute odor images in the olfactory bulb and odor objects in olfactory cortex. Paleontology provides a unique advantage with evolutionary insights providing evidence that the basic architecture of the olfactory pathway almost from the start ∼330 million years ago (mya) has included an overwhelming input from olfactory sensory neurons combined with a large olfactory bulb and olfactory cortex to process that input, driven by olfactory receptor gene duplications. We identify a sequence of over 20 microcircuits that are involved, and expand on results of research on several microcircuits that give the best insights thus far into the nature of the high dimensional processing.

Global elongation and high shape flexibility as an evolutionary hypothesis of accommodating mammalian brains into skulls.

Little is known about how the large brains of mammals are accommodated into the dazzling diversity of their skulls. It has been suggested that brain shape is influenced by relative brain size, that it evolves or develops according to extrinsic or intrinsic mechanical constraints, and that its shape can provide insights into its proportions and function. Here, we characterize the shape variation among 84 marsupial cranial endocasts of 57 species including fossils, using three-dimensional geometric morphometrics and virtual dissections. Statistical shape analysis revealed four main patterns: over half of endocast shape variation ranges from elongate and straight to globular and inclined; little allometric variation with respect to centroid size, and none for relative volume; no association between locomotion and endocast shape; limited association between endocast shape and previously published histological cortex volumes. Fossil species tend to have smaller cerebral hemispheres. We find divergent endocast shapes in closely related species and within species, and diverse morphologies superimposed over the main variation. An evolutionarily and individually malleable brain with a fundamental tendency to arrange into a spectrum of elongate-to-globular shapes-possibly mostly independent of brain function-may explain the accommodation of brains within the enormous diversity of mammalian skull form.

A practical clinical guide to counselling on and managing contraception, pre-conception planning, and menopause for women living with HIV.

Background: Women represent one quarter of the population living with HIV in Canada and are an increasingly important sector of the HIV community. While some women's health issues such as cervical cancer screening and management are well addressed in HIV management guidelines, others are not. These include sexual and reproductive health factors such as contraception, pre-conception planning, and menopause. Existing literature has shown that while women living with HIV in Canada receive good HIV care based on HIV care cascade indicators, their women's health and sexual and reproductive health care needs are not being met. Methods: In this article, we present a clinical guide for clinicians providing care for women living with HIV on three key women's health topics that are under-discussed during HIV care visits: (1) contraception, (2) pre-conception planning, and (3) menopause. Results: We have summarized the most pertinent clinical factors on each topic to support straightforward counselling and present important considerations in the context of HIV-related diseases and treatment. Finally, when relevant, we have provided practical stepwise approaches for addressing each of these women's health care topics when seeing a patient during a visit. Conclusions: It is important that HIV specialists stay well-versed in the complex clinical interactions between HIV treatment and management of women's health issues.

Historique: Les femmes forment le quart de la population qui vit avec le VIH au Canada et un segment croissant de la communauté du VIH. Certains problèmes de santé des femmes, comme le dépistage et la prise en charge du cancer du col de l'utérus, sont bien couverts dans les directives sur la prise en charge du VIH, mais d'autres non. Des facteurs liés à la santé sexuelle et reproductive, tels que la contraception, la planification avant la conception et la ménopause, en font partie. Les publications scientifiques ont démontré que les femmes qui vivent avec le VIH au Canada reçoivent de bons soins du VIH en fonction des indicateurs de soins du VIH ventilés en cascade, mais que leurs besoins en matière de santé des femmes, de santé sexuelle et de santé reproductive ne sont pas respectés. Méthodologie: Dans le présent article, les auteurs proposent un guide clinique à l'intention des cliniciens qui soignent des femmes atteintes du VIH, à l'égard de trois sujets en santé des femmes qui ne sont pas assez abordés pendant les rendez-vous sur les soins du VIH : 1) la contraception, 2) la planification avant la conception et 3) la ménopause. Résultats: Les auteurs ont résumé les facteurs cliniques les plus appropriés relatifs à chaque sujet pour favoriser un counseling franc et présentent des points de vue importants dans le contexte des maladies et des traitements liés au VIH. Enfin, lorsque c'est approprié, ils ont fourni une démarche pratique graduelle pour aborder chacun de ces sujets en santé des femmes lors d'un rendez-vous. Conclusions: Il est important que les spécialistes du VIH demeurent bien informés des interactions cliniques complexes entre le traitement du VIH et la prise en charge des problèmes de santé des femmes.

Thromboelastography to Detect Hypercoagulability and Reduced Fibrinolysis in Coronavirus Disease 2019 Acute Respiratory Distress Syndrome Patients.

OBJECTIVES: Microvascular thrombosis contributes to acute respiratory distress syndrome pathophysiology and has been demonstrated in coronavirus disease 2019-associated acute respiratory distress syndrome. Clinical laboratory measurements of coagulation and disseminated intravascular coagulation, such as coagulation factor function, platelet count, and fibrinogen, may not fully reflect the extent of microvascular thrombosis present in these patients. We investigated thromboelastography in patients with coronavirus disease 2019-associated acute respiratory distress syndrome with the objective of characterizing suspected coagulopathy and impaired fibrinolysis. DESIGN: Retrospective observational cohort study. SETTING: Single-center academic medical center. PATIENTS: Ten patients with polymerase chain reaction-confirmed coronavirus disease 2019 disease complicated by acute respiratory distress syndrome. INTERVENTIONS: Measurement of thromboelastography (n = 10) and thrombolysis with alteplase (n = 4). MEASUREMENTS AND MAIN RESULTS: Hypercoagulability and decreased or absent fibrinolysis were demonstrated by thromboelastography. Thrombocytopenia and hypofibrinogenemia were not observed, while seven of 10 patients had elevated d-dimer values. For patients who received thrombolytic therapy, repeat thromboelastography demonstrated improvements in coagulation index and lysis at 30 minutes reflecting reduced hypercoagulability and increased fibrinolysis. One major bleeding complication was detected following thrombolysis. Eight of 10 patients survived and were successfully extubated, and six of 10 have since been discharged. CONCLUSIONS: In coronavirus disease 2019 patients with acute respiratory distress syndrome in whom thromboelastography was performed, hypercoagulability and impaired fibrinolysis were observed. In the context of autopsy studies demonstrating pulmonary microvascular thromboses in coronavirus disease 2019 patients, noninvasive detection of hypercoagulability and deficient fibrinolysis in coronavirus disease 2019 acute respiratory distress syndrome using thromboelastography could improve understanding and management of coronavirus disease 2019.

Atherosclerotic cardiovascular disease in women with endometriosis: a systematic review of risk factors and prospects for early surveillance.

Endometriosis and atherosclerotic cardiovascular disease (ASCVD) share similar pathogenic mechanisms. Hence, this systematic review evaluates the association between endometriosis and lifetime ASCVD risk including co-prevalence with dyslipidaemia, atherosclerosis and non-invasive markers of endothelial dysfunction. The electronic databases Embase, PubMed, MEDLINE, Cochrane Register of Trials and ClinicalTrials.gov were systematically searched for relevant articles. Two prospective cohort studies demonstrated an increased lifetime ASCVD risk after controlling for demographic and lifestyle confounders in women with endometriosis, as measured by higher incidence of myocardial infarction (relative risk [RR] 1.52), angiography-confirmed angina (RR 1.91), or requiring coronary artery bypass graft surgery (RR 1.35). Among 10 studies that included 407 patients with surgically proven endometriosis and 557 controls, RR of developing hypercholesterolemia and hypertension were 1.25 and 1.14, respectively, while higher serum lipoprotein a and lower paraoxonase 1 levels were found in women with endometriosis that was negatively correlated with stage of disease (r = -0.74, P < 0.0001). Hence, currently available evidence suggests that women with endometriosis are at higher lifetime risk of developing ASCVD than women without endometriosis. However, robust causal evidence is still lacking and future studies are needed to determine whether women with endometriosis represent a high-risk population for lifelong ASCVD risk.

First record of a basal mammaliamorph from the early Late Triassic Ischigualasto Formation of Argentina.

We describe a new probainognathian cynodont, Pseudotherium argentinus, from the early Late Triassic Ischigualasto Formation of Argentina. Pseudotherium adds to a growing assemblage of small Triassic cynodonts that offers new insight into events leading up to the origin of crown Mammalia and the successively more inclusive Mammaliaformes and Mammaliamorpha. Using high-resolution X-ray computed tomography, we illustrate and describe the holotype and only known specimen, which consists of a well-preserved isolated skull. It preserves apomorphic features of the orbit and braincase. Prefrontal and vestigial postorbital bones are present, despite the absence of an ossified postorbital bar. As in Brasilitherium riograndensis, thin turbinal-like bones are present in the nasopharyngeal passage, and we discuss impediments to establishing their identity and function. Compared to more basal cynodonts, the cochlea is elongated but uncoiled and in this and other features it resembles basal mammaliamorphs. Our analysis found weak support for Pseudotherium as the sister taxon of Tritylodontidae. However, a broader assessment of its relationships in light of additional character data from the literature and unpublished computed tomography data suggest that it may be more realistic to view the relationships of Pseudotherium as an unresolved polytomy with tritylodontids, and the taxa referred to as tritheledontids and brasilodontids (groups of variable membership and questionable monophyly). Thus, Pseudotherium may lie just inside or just outside of Mammaliamorpha, and there is also weak character support for its sister taxon relationship with Brasilitherium. Our results amplify previous conclusions that phylogenetic relationships in this adaptive radiation of small cynodonts will remain somewhat uncertain until more complete specimens are recovered, and until high-resolution CT scans of existing specimens become available to the larger community. Toward that goal, we make the CT dataset for the holotype of Pseudotherium argentinus publically available under a Creative Commons license at www.DigiMorph.org.

N° 311 - Prise en charge de la ménopause (Résumé/Déclarations Sommaires et Recommandations).

OBJECTIF: Offrir, aux fournisseurs de soins de santé, une mise à jour de la directive clinique quant à la prise en charge de la ménopause chez les femmes asymptomatiques en santé, ainsi que chez les femmes qui présentent des symptômes vasomoteurs ou urogénitaux; cette mise à jour se penche également sur les facteurs associés à la maladie cardiovasculaire, au cancer du sein, à l'urogynécologie et à la sexualité. ISSUES: Les interventions quant au mode de vie, les médicaments d'ordonnance et les traitements de médecine complémentaire et parallèle sont présentés en fonction de leur efficacité dans la prise en charge des symptômes ménopausiques. Des stratégies de counseling et thérapeutiques en ce qui concerne les préoccupations en matière de sexualité au cours de la périménopause et de la postménopause sont passées en revue. Des approches quant à l'identification et à l'évaluation des femmes exposées à un risque élevé d'ostéoporose (ainsi que des options en matière de prévention et de traitement) sont présentées dans la directive clinique sur l'ostéoporose qui accompagne les présentes. RéSULTATS: La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans PubMed et The Cochrane Library, en août et en septembre 2012, au moyen d'un vocabulaire contrôlé (p. ex. « hormone replacement therapy ¼, « menopause ¼, « cardiovascular diseases ¼ et « sexual function ¼) et de mots clés (p. ex. « HRT ¼, « perimenopause ¼, « heart disease ¼ et « sexuality ¼). Les résultats ont été restreints aux directives cliniques, aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles. Les résultats ont également été restreints aux documents publiés, en anglais ou en français, à partir de 2009. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'au 5 janvier 2013. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques, auprès de sociétés de spécialité médicale nationales et internationales, et dans des collections de directives cliniques. VALEURS: La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (Tableau 1).

Link between Endometriosis, Atherosclerotic Cardiovascular Disease, and the Health of Women Midlife.

Endometriosis and atherosclerotic cardiovascular disease (ASCVD) are both essentially diseases of inflammation. It is well established that inflammation is the leading mechanism in the initiation and maintenance of vascular injury and in the development and progression of atherosclerosis. Thus, if women with endometriosis do indeed have increased general inflammation, they are at increased risk of developing microvascular dysfunction and atherosclerosis. Currently available evidence suggests that young female patients with proven endometriosis may be at a higher lifetime risk of developing cardiovascular disease; this may be unrecognized due to the relatively young age of women found to have endometriosis. Other mechanisms proposed to explain the link between endometriosis and ASCVD include similarities in the genetic underpinnings of each condition, including microRNA dysfunction and the association between endometriosis and early menopause, a risk for developing ASCVD. Although physicians today primarily focus on traditional risk factors when evaluating an individual female patient's risk of developing ASCVD, we believe that a history of endometriosis should be included as a possible risk factor and needs further exploration. A better understanding of the mechanisms linking endometriosis with ASCVD will hopefully guide the implementation of new therapies to mitigate the increased cardiovascular disease burden that patients with endometriosis might face.

Anatomy and systematics of the sauropodomorph Sarahsaurus aurifontanalis from the Early Jurassic Kayenta Formation.

Sarahsaurus aurifontanalis, from the Kayenta Formation of Arizona, is one of only three sauropodomorph dinosaurs known from the Early Jurassic of North America. It joins Anchisaurus polyzelus, from the older Portland Formation of the Hartford Basin, and Seitaad reussi, from the younger Navajo Sandstone of Utah, in representing the oldest North American sauropodomorphs. If it is true that sauropodomorphs were absent from North America during the Late Triassic, the relationship among these three dinosaurs offers a test of the mechanisms that drove recovery in North American biodiversity following the end-Triassic extinction event. Here we provide the first thorough description of Sarahsaurus aurifontanalis based on completed preparation and computed tomographic imaging of the holotype and referred specimens. With new anatomical data, our phylogenetic analysis supports the conclusion that Sarahsaurus aurifontanalis is nested within the primarily Gondwanan clade Massospondylidae, while agreeing with previous analyses that the three North American sauropodomorphs do not themselves form an exclusive clade. A revised diagnosis and more thorough understanding of the anatomy of Sarahsaurus aurifontanalis support the view that independent dispersal events were at least partly responsible for the recovery in North American vertebrate diversity following a major extinction event.