Exploration of the hereditary cause of sex ratio distortion in horses

Even sex ratios are seen as evolutionarily stable and are maintained by a selection against a skewed sex ratio. However, sometimes sex ratios at birth are skewed towards one sex. Reasons for this phenomenon are often unknown. The aim of this project was to explore distorted sex ratios in Icelandic horses, Standardbred trotters, and Coldblooded trotters, to estimate the heritability of distorted sex ratios in Icelandic horses and explore families with distorted sex ratios, and set the outline for future research. To investigate the aims, datasets were extracted from the Icelandic studbook, WorldFengur, and the online studbook information for Standardbreds and Coldblooded trotters from the Swedish Trotting association. The datasets included 509 008 Icelandic horses (born between 1860-2020), 504 Standardbred stallions, and 125 Coldblooded trotter stallions (both born between 1990-2020). In the breeds, individuals with skewing sex ratios among their offspring (skewing horses) were identified using chi-square tests. For Icelandic horses the heritability was estimated with a parent-offspring regression, using the proportion of male offspring of fathers and sons. Families were identified using the hundred most skewing Icelandic stallions and as preparation for future research a new protocol for real-time PCR (qPCR) analysis was developed and tested, to identify sex ratios in horse semen. The proportion of males registered in the complete Icelandic horse dataset was 43.7%, whereas it was 49.0% for the last 10-year period studied. For Standardbreds and Coldblooded trotter stallions, the proportion of male offspring was 48.9% and 50.5%, respectively. Multiple skewing horses were identified in all breeds, 16.0% in Icelandic stallions, 5.8% in Icelandic mares, 11.5% in Standardbred stallions, and 6.4% in Coldblooded trotter stallions. In Icelandic horses and Standardbreds, female skewing was more common than male skewing. The heritability of the proportion of male offspring in Icelandic horses was estimated at 0.29 (SE: 0.08), but the sensitivity of this estimate to the number of offspring of father and sons required was high. Five female-skewing families were identified containing between 31 and 513 significantly skewing horses. Lastly, qPCR experimentation was performed using four primers. The Y-primer did not result in an amplification product, however the X and two autosomal controls were successful and usable on purified (without somatic cells) and raw horse semen. The difference between sex ratio and proportion of female-skewing horses in Icelandic horses and Standardbreds might be explained by incomplete recordings especially in the past, and the existence of meat horses in the Icelandic horse pedigree. These meat horses cause incomplete registration of offspring, most often males. However, the extent of this bias to the analyses is still unknown. In further analyses, meat horses need to be excluded and some more data editing performed. The heritability estimates may be improved by using a better fitting model. In future, it would be interesting to investigate sex ratios in horse semen, to compare female-skewing and male-skewing stallions to a control, to investigate where in development skewing of sex ratios start. Lastly, whole genome sequencing of skewing individuals can give us more information on the genetic cause, with the aim to identify genetic elements causing distorted sex ratios

Plasticity of plasma membrane compartmentalization during plant immune responses

Plasma membranes require high levels of plasticity to modulate the perception and transduction of extracellular and intracellular signals. Dynamic lateral assembly of protein complexes combined with an independent compositional lipid patterning in both membrane leaflets provide cells the opportunity to decorate this interface with specific proteins in an organized but dynamic manner. Such ability to dynamically reorganize the protein content of the plasma membrane is essential for the regulation of processes such as polarity of transport, development, and microbial infection. While the plant cell wall represents the first physical and mostly unspecific barrier for invading microbes, the plasma membrane is at the forefront of microbial recognition and initiation of defense responses. Accumulating evidence indicating dynamic compartmentalization of plasma membranes in response to environmental cues has increased the interest in the compositional heterogeneity of this bilayer. Here, we elucidate the recruitment of specific proteins into defined membrane structures that ensure functional compartmentalization of the bilayer during infection processes

A Well Place to Be: The Intersection of Canadian School-Based Mental Health Policy with Student and Teacher Resiliency

This policy analysis identifies and critiques dominant narratives in the school-based mental health (SBMH) movement in Canada, with an eye to the ideas and resources being mobilized. The policy narratives were identified as SBMH problems and solutions, represented by the websites and links to other resources of the ministries and departments of education in Canada. There are three areas under-represented in the policy narratives that deserve more nuanced attention in SBMH initiatives; these are (a) to work with educators to develop communities of practice on school mental health around the notion of resiliency, (b) to consider the structural and material factors that affect people’s ability to be resilient at school, and (c) to extend the current focus on promoting student wellness to include teacher wellness. We ground these recommendations by contrasting the policy narratives with the story of our work with educators on a website about resiliency through the lenses of positive psychological health and a sociomaterial perspective on resources. We suggest that a sociomaterial approach to SBMH initiatives, using conceptual tools from implementation science and workplace psychological health, may help both students and teachers develop resiliency

Systematic Advance Care Planning and Potentially Avoidable Hospitalizations of Nursing Facility Residents

BACKGROUND/OBJECTIVES The Optimizing Patient Transfers, Impacting Medical Quality, Improving Symptoms: Transforming Institutional Care (OPTIMISTIC) project is a successful, multicomponent demonstration project to reduce potentially avoidable hospitalizations of long‐stay nursing facility residents. Systematic advance care planning (ACP) is a core component of the intervention, based on research suggesting ACP is associated with decreased hospitalizations of nursing facility residents. The purpose of this study was to describe associations between ACP documentation resulting from the OPTIMISTIC intervention and hospitalizations. DESIGN Specially trained project nurses were embedded in 19 nursing facilities and systematically engaged in ACP as part of a larger demonstration project. PARTICIPANTS Residents (n = 1482) enrolled in the demonstration project for a minimum of 30 days between January 1, 2015, and June 30, 2016. MEASUREMENTS ACP status: (1) Physician Orders for Scope of Treatment (POST) comfort measures or do not hospitalize (DNH) orders; (2) ACP orders with no hospitalization limit (eg, code status only); and (3) no ACP (potentially avoidable and all‐cause hospitalizations per 1000 resident days). RESULTS Residents with POST comfort measures/DNH orders (33.2% or n = 493) were less likely than residents with no ACP (14.7% or n = 218) to experience a potentially avoidable hospitalization (P = .001) or all‐cause hospitalization (P = .001). These differences became statistically nonsignificant after adjusting for age, functional status, and cognitive functioning. CONCLUSION In this successful multicomponent demonstration project to reduce potentially avoidable hospitalizations, ACP outcomes were not associated with hospitalization rates of nursing facility residents after adjusting for resident characteristics. These findings highlight the challenge of measuring the contributions of individual components of complex, multicomponent interventions. Associations between lower hospitalization rates and ACP completion may be influenced by contextual factors, such as clinical expertise and resources to manage acute conditions leading to hospitalization, in addition to interventions to increase ACP

Advance Care Planning as a Shared Endeavor: Completion of ACP Documents in a Multidisciplinary Cancer Program

Objective—We examined the roles of oncology providers in advance care planning (ACP) delivery in the context of a multidisciplinary cancer program. Methods—Semi-structured interviews were conducted with 200 women with recurrent and/or metastatic breast or gynecologic cancer. Participants were asked to name providers they deemed important in their cancer care and whether they had discussed and/or completed ACP documentation. Evidence of ACP documentation was obtained from chart reviews. Results—Fifty percent of participants self-reported completing an advance directive (AD) and 48.5% had named a healthcare power of attorney (HPA), 38.5% had completed both, and 39.0% had completed neither document. Among women who self-reported completion of the documents, only 24.0% and 14.4% of women respectively had documentation of an AD and HPA in their chart. Completion of an AD was associated with number (adjusted odds ratio [AOR] = 1.49) and percentage (AOR = 6.58) of providers with whom the participant had a conversation about end-of-life decisions. Participants who named a social worker or nurse practitioner were more likely to report having completed an AD. Participants who named at least one provider in common (e.g., named the same oncologist) were more likely to have comparable behaviors related to naming a HPA (AOR = 1.13, p = 0.011) and completion of an AD (AOR = 1.06, p = 0.114). Conclusions—Despite the important role of physicians in facilitating ACP discussions, involvement of other staff was associated with a greater likelihood of completion of ACP documentation. Patients may benefit from opportunities to discuss ACP with multiple members of their cancer care team

Paleo-denudation rates suggest variations in runoff drove aggradation during last glacial cycle, Crete, Greece

Fluvial aggradation and incision are often linked to Quaternary climate cycles, but it usually remains unclear whether variations in runoff or sediment supply or both drive channel response to climate variability. Here we quantify sediment supply with paleo-denudation rates and provide geochronological constraints on aggradation and incision from the Sfakia and Elafonisi alluvial-fan sequences in Crete, Greece. We report seven optically stimulated luminescence and ten radiocarbon ages, eight 10Be and eight 36Cl denudation rates from modern channel and terrace sediments. For five samples, 10Be and 36Cl were measured on the same sample by measuring 10Be on chert and 36Cl on calcite. Results indicate relatively steady denudation rates throughout the past 80 kyr, but the aggradation and incision history indicates a link with climate shifts. At the Elafonisi fan, we identify four periods of aggradation coinciding with Marine Isotope Stages (MIS) 2, 4, 5a/b, and likely 6, and three periods of incision coinciding with MIS 1, 3, and likely 5e. At the Sfakia fan, rapid aggradation occurred during MIS 2 and 4, followed by incision during MIS 1. Nearby climate and vegetation records show that MIS 2, 4, and 6 stadials were characterized by cold and dry climates with sparse vegetation, whereas forest cover and more humid conditions prevailed during MIS 1, 3, and 5. Our data thus suggest that past changes in climate had little effect on landscape-wide denudation rates but exerted a strong control on the aggradation–incision behaviour of alluvial channels on Crete. During glacial stages, we attribute aggradation to hillslope sediment release promoted by reduced vegetation cover and decreased runoff; conversely, incision occurred during relatively warm and wet stages due to increased runoff. In this landscape, past hydroclimate variations outcompeted changes in sediment supply as the primary driver of alluvial deposition and incision

Pharmacokinetics of oral micronized β-estradiol in postmenopausal women receiving maintenance hemodialysis

BACKGROUND: Although 11% of postmenopausal women with end-stage renal disease (ESRD) are prescribed hormone replacement therapy (HRT), the appropriate use remains poorly explored. Although there remains controversy surrounding the benefits of HRT, it may be of particular interest in this population, which has a high risk of bone loss and a fourfold increase in fracture risk compared to the general population. However, the appropriate dose of estrogen for use in postmenopausal women with ESRD is not known. The objective of this study was to evaluate the steady-state pharmacokinetics of oral micronized beta-estradiol in postmenopausal women with ESRD compared with postmenopausal women with normal renal function in order to determine equivalent dosing. METHODS: Six postmenopausal women with ESRD receiving maintenance hemodialysis and 6 healthy postmenopausal controls received 14 days of micronized beta-estradiol (1.0 mg for control, 0.5 mg for ESRD). Blood, urine, and dialysate samples were obtained during a dosage interval on day 14. Estradiol, estrone, albumin, and sex-hormone binding globulin (SHBG) concentrations were determined. Free estradiol concentrations were calculated using a previously described method. RESULTS: Women with ESRD had significantly lower serum albumin (610 +/- 31 micromol/L vs. 684 +/- 83 micromol/L) and SHBG (78 +/- 17 vs. 118 +/- 13 nmol/L) than control subjects. Total clearance of estradiol was not significantly different. Due to difference in binding, free estradiol concentrations were significant higher in ESRD women (53.2 +/- 17.7 pg/mL) than control women (43.5 +/- 8.7 pg/mL), despite receiving 50% of the dose. There was no significant difference in estrone concentrations. Clearance of both estradiol and estrone in the dialysate was minimal. CONCLUSION: Women with ESRD should receive approximately 50% of the dose typically prescribed to women without ESRD