Meiosis reveals the early steps in the evolution of a neo-XY sex chromosome pair in the African pygmy mouse Mus minutoides.

Sex chromosomes of eutherian mammals are highly different in size and gene content, and share only a small region of homology (pseudoautosomal region, PAR). They are thought to have evolved through an addition-attrition cycle involving the addition of autosomal segments to sex chromosomes and their subsequent differentiation. The events that drive this process are difficult to investigate because sex chromosomes in almost all mammals are at a very advanced stage of differentiation. Here, we have taken advantage of a recent translocation of an autosome to both sex chromosomes in the African pygmy mouse Mus minutoides, which has restored a large segment of homology (neo-PAR). By studying meiotic sex chromosome behavior and identifying fully sex-linked genetic markers in the neo-PAR, we demonstrate that this region shows unequivocal signs of early sex-differentiation. First, synapsis and resolution of DNA damage intermediates are delayed in the neo-PAR during meiosis. Second, recombination is suppressed or largely reduced in a large portion of the neo-PAR. However, the inactivation process that characterizes sex chromosomes during meiosis does not extend to this region. Finally, the sex chromosomes show a dual mechanism of association at metaphase-I that involves the formation of a chiasma in the neo-PAR and the preservation of an ancestral achiasmate mode of association in the non-homologous segments. We show that the study of meiosis is crucial to apprehend the onset of sex chromosome differentiation, as it introduces structural and functional constrains to sex chromosome evolution. Synapsis and DNA repair dynamics are the first processes affected in the incipient differentiation of X and Y chromosomes, and they may be involved in accelerating their evolution. This provides one of the very first reports of early steps in neo-sex chromosome differentiation in mammals, and for the first time a cellular framework for the addition-attrition model of sex chromosome evolution.

Bypassing Mendel's First Law: Transmission Ratio Distortion in Mammals.

Mendel's law of segregation states that the two alleles at a diploid locus should be transmitted equally to the progeny. A genetic segregation distortion, also referred to as transmission ratio distortion (TRD), is a statistically significant deviation from this rule. TRD has been observed in several mammal species and may be due to different biological mechanisms occurring at diverse time points ranging from gamete formation to lethality at post-natal stages. In this review, we describe examples of TRD and their possible mechanisms in mammals based on current knowledge. We first focus on the differences between TRD in male and female gametogenesis in the house mouse, in which some of the most well studied TRD systems have been characterized. We then describe known TRD in other mammals, with a special focus on the farmed species and in the peculiar common shrew species. Finally, we discuss TRD in human diseases. Thus far, to our knowledge, this is the first time that such description is proposed. This review will help better comprehend the processes involved in TRD. A better understanding of these molecular mechanisms will imply a better comprehension of their impact on fertility and on genome evolution. In turn, this should allow for better genetic counseling and lead to better care for human families.

How to Use Microhistory Methodology in Mental Health Research.

Incorporating anthropological principles, microhistory is a research methodology useful for exploring the interplay between ordinary people and social abstractions such as, the market, social systems, and governments. In this paper, the background and characteristics of microhistory are described, and a novel six-stage approach for conducting microhistories in mental healthcare is introduced. Each stage of the process is illustrated using sections from a microhistory focussed on the earliest recorded case comparison between British colonial mental healthcare and Aboriginal Australian traditional healing. Microhistory provides a way to uncover new insights about past mental healthcare, which may contribute to re-conceptualisations of modern-day beliefs and practices.

Outcomes by cannulation methods for venovenous extracorporeal membrane oxygenation during COVID-19: A multicenter retrospective study.

In a multicenter, retrospective analysis of 435 patients with refractory COVID-19 placed on V-V ECMO, cannulation by a single, dual-lumen catheter with directed outflow to the pulmonary artery was associated with lower inpatient mortality.

Aboriginal Australian mental health during the first 100 years of colonization, 1788-1888: a historical review of nineteenth-century documents.

Past histories charting interactions between British healthcare and Aboriginal Australians have tended to be dominated by broad histological themes such as invasion and colonization. While such descriptions have been vital to modernization and truth telling in Australian historical discourse, this paper investigates the nineteenth century through the modern cultural lens of mental health. We reviewed primary documents, including colonial diaries, church sermons, newspaper articles, medical and burial records, letters, government documents, conference speeches and anthropological journals. Findings revealed six overlapping fields which applied British ideas about mental health to Aboriginal Australians during the nineteenth century. They included military invasion, religion, law, psychological systems, lunatic asylums, and anthropology.

Gambling Interventions in Indigenous Communities, from Theory to Practice: A Rapid Qualitative Review of the Literature.

Indigenous populations globally experience problem gambling at higher rates than mainstream communities, often leading to adverse outcomes in social, cultural, and health domains (The term 'indigenous' within this paper refers to all first nations people from the specified countries. When capitalised, this refers to Australian Indigenous people specifically.). Problem gambling in indigenous communities has been linked to relative poverty and social disadvantage. The sweeping impacts of problem gambling for indigenous communities are holistic in nature and are felt throughout many aspects of the community, including the local economy, education, employment, and cultural kinship obligations. The social links inherent in many gambling activities in addition to the motivations of players and complex socio-cultural milieu can make it very difficult to renounce the practice. This paper aims to evaluate the indigenous gambling literature to discern appropriate and effective principles to guide intervention development in the context of problem gambling pertaining to the Australian Indigenous population. A rapid review will be undertaken to gather, analyse, and interpret appropriate theoretical and empirical literature relating to gambling interventions for indigenous populations. Papers from Canada, Australia, New Zealand, and U.S.A (CANZUS) will be considered in the review and thematic analysis will be undertaken to ascertain a broad understanding of effective and appropriate problem gambling intervention principles applicable to these population groups. Despite the relative dearth of empirical evidence within this field, approaches to problem gambling intervention within indigenous populations must be culturally-centred and underpinned by a public health framework that considers the broad socio-politico-cultural context of the whole community. The importance of community-control, collaboration, community capacity building, workforce competence, a holistic approach, and gambling regulation cannot be overstated. The available literature focusses on an alternative approach to addressing problem gambling in indigenous communities, with much of the findings highlighting key indigenist principles within a context-based method of engagement and intervention, including addressing the social, political, and cultural determinants of problem gambling at a community-level.

Survivorship and Radiological Analysis of a Monoblock, Hydroxyapatite-Coated Titanium Stem in Revision Hip Arthroplasty.

BACKGROUND: We evaluated the survivorship, incidence of complications, radiological subsidence, proximal stress shielding, and patient-reported outcomes of a conservative, monoblock, hydroxyapatite-coated femoral stem. METHODS: This retrospective cohort study reports on 254 revision hip arthroplasties between January 2006 and June 2016. The mean age of patients was 71 years. The mean length of follow-up was 62 months (range 12-152). RESULTS: There were 13 stem re-revisions: infection (4), periprosthetic fracture (4), aseptic stem loosening (3), stem fracture (1), and extended trochanteric osteotomy nonunion (1). Kaplan-Meier aseptic stem survivorship was 97.33% (confidence interval 94-100) at 6 years. There were 29 intraoperative fractures. There were 6 cases of subsidence greater than 10 mm; however, none required revision. Ninety-six percent of cases showed no proximal stress shielding. Thigh pain was reported in 3% of cases. CONCLUSION: This study confirms that this stem provides good survivorship at 6 years, acceptable complication rates, adequate proximal bone loading, low incidences of thigh pain, and reliable clinical performance in revision hip arthroplasty. KEY MESSAGE: A monoblock, fully hydroxyapatite-coated titanium stem is reliable in revision arthroplasty with mild-moderate femur deficiencies.

Impact of deleterious mutations, sexually antagonistic selection, and mode of recombination suppression on transitions between male and female heterogamety.

Deleterious mutations accumulating on non-recombining Y chromosomes can drive XY to XY turnovers, as they allow to replace the old mutation-loaded Y by a new mutation-free one. The same process is thought to prevent XY to ZW turnovers, because the latter requires fixation of the ancestral Y, assuming dominance of the emergent feminizing mutation. Using individual-based simulations, we explored whether and how an epistatically dominant W allele can spread in a young XY system that gradually accumulates deleterious mutations. We also investigated how sexually antagonistic (SA) polymorphism on the ancestral sex chromosomes and the mechanism controlling X-Y recombination suppression affect these transitions. In contrast with XY to XY turnovers, XY to ZW turnovers cannot be favored by Y chromosome mutation load. If the arrest of X-Y recombination depends on genotypic sex, transitions are strongly hindered by deleterious mutations, and totally suppressed by very small SA cost, because deleterious mutations and female-detrimental SA alleles would have to fix with the Y. If, however, the arrest of X-Y recombination depends on phenotypic sex, X and Y recombine in XY ZW females, allowing for the purge of Y-linked deleterious mutations and loss of the SA polymorphism, causing XY to ZW turnovers to occur at the same rate as in the absence of deleterious and sex-antagonistic mutations. We generalize our results to other types of turnovers (e.g., triggered by non-dominant sex-determining mutations) and discuss their empirical relevance.

Sex chromosome turnovers and genetic drift: a simulation study.

The recent advances of new genomic technologies have enabled the identification and characterization of sex chromosomes in an increasing number of nonmodel species, revealing that many plants and animals undergo frequent sex chromosome turnovers. What evolutionary forces drive these turnovers remains poorly understood, but it was recently proposed that drift might play a more important role than generally assumed. We analysed the dynamics of different types of turnovers using individual-based simulations and show that when mediated by genetic drift, turnovers are usually easier to achieve than substitutions at neutral markers, but that their dynamics and relative likelihoods vary with the type of the resident and emergent sex chromosome system (XY and/or ZW) and the dominance relationships among the sex-determining factors. Focusing on turnovers driven by epistatically dominant mutations, we find that drift-mediated turnovers that preserve the heterogamety pattern are 2-4× more likely than those along which the heterogametic sex changes. This ratio nevertheless decreases along with effective population size and can even reverse in case of extreme polygyny. This can be attributed to a 'drift-induced' selective force, known to influence transitions between male and female heterogamety, but which according to our study does not affect turnovers that preserve the heterogametic sex.

Stoichiometric distribution models: ecological stoichiometry at the landscape extent.

Human activities are altering the fundamental geography of biogeochemicals. Yet we lack an understanding of how the spatial patterns in organismal stoichiometry affect biogeochemical processes and the tools to predict the impacts of global changes on biogeochemical processes. In this contribution we develop stoichiometric distribution models (StDMs), which allow us to map spatial structure in resource elemental composition across a landscape and evaluate spatial responses of consumers. We parameterise StDMs for a consumer-resource (moose-white birch) system and demonstrate that we can develop predictive models of resource stoichiometry across a landscape and that such models could improve our predictions of consumer space use. With results from our study system application, we argue that explicit consideration of the spatial patterns in organismal elemental composition may uncover emergent individual, population, community and ecosystem properties that are not revealed at the local extents routinely used in ecological stoichiometry. We discuss perspectives for further developments and application of StDMs to advance three emerging frameworks for spatial ecosystem ecology in an era of global change; meta-ecosystem theory, macroecological stoichiometry and remotely sensed biogeochemistry. Progress on these emerging frameworks will allow for the integration of ecological stoichiometry and individual space use and fitness.

Hormone profiles of the African pygmy mouse Mus minutoides, a species with XY female sex reversal.

In mammals, most sex differences in phenotype are controlled by gonadal hormones, but recent work on transgenic mice has shown that sex chromosomes can have a direct influence on sex-specific behaviors. In this study, we take advantage of the naturally occurring sex reversal in a mouse species, Mus minutoides, to investigate for the first time the relationship between sex chromosomes, hormones, and behaviors in a wild species. In this model, a feminizing variant of the X chromosome, named X*, produces three types of females with different sex chromosome complements (XX, XX*, and X*Y), associated with alternative behavioral phenotypes, while all males are XY. We thus compared the levels of three major circulating steroid hormones (testosterone, corticosterone, and estradiol) in the four sex genotypes to disentangle the influence of sex chromosomes and sex hormones on behavior. First, we did not find any difference in testosterone levels in the three female genotypes, although X*Y females are notoriously more aggressive. Second, in agreement with their lower anxiety-related behaviors, X*Y females and XY males display lower baseline corticosterone concentration than XX and XX* females. Instead of a direct hormonal influence, this result rather suggests that sex chromosomes may have an impact on the baseline corticosterone level, which in turn may influence behaviors. Third, estradiol concentrations do not explain the enhanced reproductive performance and maternal care behavior of the X*Y females compared to the XX and XX* females. Overall, this study highlights that most of the behaviors varying along with sex chromosome complement of this species are more likely driven by genetic factors rather than steroid hormone concentrations.

Successful treatment of early bioprosthetic mitral valve fusion in a patient on VA ECMO with balloon valvuloplasty via direct cannulation of pulmonary vein.

We present a case of a 57-year-old male who underwent bioprosthetic mitral valve replacement (MVR) and developed postoperative cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation (VA ECMO) and Impella 5.5 (Abiomed) hemodynamic support.

Using a Handful of Transcriptomes to Detect Sex-Linked Markers and Develop Molecular Sexing Assays in a Species with Homomorphic Sex Chromosomes.

To understand the biology of a species, it is often crucial to be able to differentiate males and females. However, many species lack easily identifiable sexually dimorphic traits. In those that possess sex chromosomes, molecular sexing offers a good alternative, and molecular sexing assays can be developed through the comparison of male and female genomic sequences. However, in many nonmodel species, sex chromosomes are poorly differentiated, and identifying sex-linked sequences and developing sexing assays can be challenging. In this study, we highlight a simple transcriptome-based procedure for the detection of sex-linked markers suitable for the development of sexing assays that circumvents limitations of more commonly used approaches. We apply it to the spotted snow skink Carinascincus ocellatus, a viviparous lizard with homomorphic XY chromosomes that has environmentally induced sex reversal. With transcriptomes from three males and three females alone, we identify thousands of putative Y-linked sequences. We confirm linkage through alignment of assembled transcripts to a distantly related lizard genome and readily design multiple single locus polymerase chain reaction primers to sex C. ocellatus and related species. Our approach also facilitates valuable comparisons of sex determining systems on a broad taxonomic scale.

Hip offset and leg-length restoration in revision hip arthroplasty with a monoblock, hydroxyapatite-coated stem.

AIMS: Restoration of normal hip biomechanics in arthroplasty surgery is important in order to achieve good muscle function and joint stability. METHODS: In this retrospective cohort study, we examined the postoperative radiographs of 131 femoral revision arthroplasty procedures using a monoblock, fully hydroxyapatite (HA)-coated titanium stem. Femoral offset, modified-global offset and leg length were measured of the operated and contralateral hips. RESULTS: Femoral offset was restored to ±10 mm in 108 cases (82%), modified-global offset was restored ±10 mm in 93 cases (71%) and leg length was restored to ±10 mm in 102 cases (81%). There were 4 dislocations with a mean follow-up period of 38 months. CONCLUSIONS: Restoration of hip biomechanics is achievable with a monoblock stem and thus is a viable option in revision hip arthroplasty.

Evaluation of the usability, content, readability and cultural appropriateness of online alcohol and other drugs resources for Aboriginal and Torres Strait Islander Peoples in New South Wales, Australia.

OBJECTIVES: This study aimed to analyse the usability, content, readability and cultural appropriateness of alcohol and other drugs (AODs) resources for Aboriginal and Torres Strait Islander Peoples in New South Wales (NSW), Australia. OUTCOME MEASURES: The content of 30 AOD resources for Aboriginal and Torres Strait Islander Peoples was analysed according to the following criteria: general characteristics; elements of graphical design and written communication; thoroughness and content; readability (Flesch-Kincaid grade level (FKGL), Gunning Fog index (Fog), Simplified Measure of Gobbledygook and Flesch Reading Ease); and cultural appropriateness. RESULTS: Most resources displayed good usability, depicted by the use of headings and subheadings (n=27), superior writing style (n=19), relevant visuals (n=19) and use of colour support (n=30). However, some resources used at least one professional jargon (n=13), and many did not provide any peer-reviewed references (n=22). During content analysis, 12 resources were categorised into the alcohol group and 18 resources in the other drugs group. Impact of alcohol during pregnancy and breast feeding (n=12) was the most common included topics in the resources related to alcohol, while the physical impact of drugs (n=15) was the most discussed topics among the other drugs group. Based on the FKGL readability score, 83% of resources met the recommended reading grade level of 6-8 by NSW Health. Many resources (n=21) met at least half of the cultural appropriateness elements of interest. However, less than one-third were developed in collaboration with the local community (n=9), used local terms (n=5), targeted the local community (n=3), included an Aboriginal voice (n=2) and addressed the underlying cause (n=1). CONCLUSIONS: Many AOD resources are developed specifically for Aboriginal and Torres Strait Islander Peoples, but their usability, content and readability differed, and they were not culturally appropriate for all communities. Development of a standardised protocol for resource development is suggested.

Is there a sex difference in mortality rates in paediatric intensive care units?: a systematic review.

Introduction: Mortality rates in infancy and childhood are lower in females than males. However, for children admitted to Paediatric Intensive Care Units (PICU), mortality has been reported to be lower in males, although males have higher admission rates. This female mortality excess for the subgroup of children admitted in intensive care is not well understood. To address this, we carried out a systematic literature review to summarise the available evidence. Our review studies the differences in mortality between males and females aged 0 to <18 years, while in a PICU, to examine whether there was a clear difference (in either direction) in PICU mortality between the two sexes, and, if present, to describe the magnitude and direction of this difference. Methods: Any studies that directly or indirectly reported the rates of mortality in children admitted to intensive care by sex were eligible for inclusion. The search strings were based on terms related to the population (those admitted into a paediatric intensive care unit), the exposure (sex), and the outcome (mortality). We used the search databases MEDLINE, Embase, and Web of Science as these cover relevant clinical publications. We assessed the reliability of included studies using a modified version of the risk of bias in observational studies of exposures (ROBINS-E) tool. We considered estimating a pooled effect if there were at least three studies with similar populations, periods of follow-up while in PICU, and adjustment variables. Results: We identified 124 studies of which 114 reported counts of deaths by males and females which gave a population of 278,274 children for analysis, involving 121,800 (44%) females and 156,474 males (56%). The number of deaths and mortality rate for females were 5,614 (4.61%), and for males 6,828 (4.36%). In the pooled analysis, the odds ratio of female to male mortality was 1.06 [1.01 to 1.11] for the fixed effect model, and 1.10 [1.00 to 1.21] for the random effects model. Discussion: Overall, males have a higher admission rate to PCU, and potentially lower overall mortality in PICU than females. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=203009, identifier (CRD42020203009).

Cultural Proficiency in First Nations Health Research: A Mixed-Methods, Cross-Cultural Evaluation of a Novel Resource.

Recent efforts have illustrated the efficacy of culturally proficient approaches to research, underpinned by robust partnerships between researchers and First Nations peoples and communities. This article seeks to determine differences in approaches to First Nations research engagement perceptions between First Nations and non-First Nations researchers, as well as whether participation in a cultural proficiency workshop improved the perceived cultural proficiency of non-First Nations health researchers. Also, whether a set of novel cultural proficiency resources, designed in the Sydney region could be applied broadly across First Nations contexts within Australia. The evaluation adopted a mixed-methods, cross-cultural (First Nations and non-First Nations) design to appraise the novel cultural proficiency resources, identifying participant perceptions to First Nations research engagement, as well as views regarding the feasibility of universal application of the resources. A quantitative pre- and post-workshop evaluation was also undertaken to measure differences in self-reported cultural proficiency. Qualitative data underwent thematic analysis and quantitative data were analysed applying t-tests. Both qualitative and quantitative evaluation showed minimal variation between the cultural groups regarding research engagement perceptions, based on viewing of the online resources. A statistically significant increase in self-reported cultural proficiency was found in non-First Nations workshop participants. Cultural proficiency education and training programs that promote an immersive, interactive, and ongoing framework can build the perceived cultural proficiency of non-First Nations health researchers, however First Nations expertise must validate this perceived cultural proficiency to be beneficial in practice. Based on the research findings, applying the underlying ethical principles of First Nations research with a local, context-centred approach allows for the broad application of cultural proficiency research education and training programs within Australia.

Multiple sex chromosome drivers in a mammal with three sex chromosomes.

Eukaryotes with separate males and females display a great diversity in the way they determine sex, but it is still unclear what evolutionary forces cause transitions between sex-determining systems. Rather that the lack of hypotheses, the problem is the scarcity of adequate biological systems to test them. Here, we take advantage of the recent evolution of a feminizing X chromosome (called X∗) in the African pygmy mouse Mus minutoides to investigate one of the evolutionary forces hypothesized to cause such transitions, namely sex chromosome drive (i.e., biased transmission of sex chromosomes to the next generation). Through extensive molecular sexing of pups at weaning, we reveal the existence of a remarkable male sex chromosome drive system in this species, whereby direction and strength of drive are conditional upon the genotype of males' partners: males transmit their Y at a rate close to 80% when mating with XX or XX∗ females and only 36% when mating with X∗Y females. Using mathematical modeling, we explore the joint evolution of these unusual sex-determining and drive systems, revealing that different sequences of events could have led to the evolution of this bizarre system and that the "conditional" nature of sex chromosome drive plays a crucial role in the short- and long-term maintenance of the three sex chromosomes.