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Retention in care is a major challenge for pregnant and postpartum women living with HIV (PPHIV) in the prevention of mother-to-child HIV transmission (PMTCT) continuum. However, the factors influencing retention from the perspectives of women who have become lost to follow-up (LTFU) are not well described. We explored these factors within an enhanced sub-cohort of the East Africa International Epidemiology Databases to Evaluate AIDS Consortium. From 2018–2019, a purposeful sample of PPHIV ≥18 years of age were recruited from five maternal and child health clinics providing integrated PMTCT services in Kenya. Women retained in care were recruited at the facility; women who had become LTFU (last visit >90 days) were recruited through community tracking. Interview transcripts were analyzed thematically using a social-ecological framework. Forty-one PPHIV were interviewed. The median age was 27 years, 71% were pregnant, and 39% had become LTFU. In the individual domain, prior PMTCT experience and desires to safeguard infants’ health enhanced retention but were offset by perceived lack of value in PMTCT services following infants’ immunizations. In the peer/family domain, male-partner financial and motivational support enhanced retention. In the community/society domain, some women perceived social pressure to attend clinic while others perceived pressure to utilize traditional birth attendants. In the healthcare environment, long queues and negative provider attitudes were prominent barriers. HIV-related stigma and fear of disclosure crossed multiple domains, particularly for LTFU women, and were driven by perceptions of HIV as a fatal disease and fear of partner abandonment and abuse. Both retained and LTFU women perceived that integrated HIV services increased the risk of disclosure. Retention was influenced by multiple factors for PPHIV. Stigma and fear of disclosure were prominent barriers for LTFU women. Multicomponent interventions and refining the structure and efficiency of PMTCT services may enhance retention for PPHIV.

Standard setters and investors have expressed concern about the substantial amount of repetition of information found within firms' 10-K disclosures. Ostensibly, such repetition is the result of overlapping disclosure requirements that solicit similar information in separate sections of the 10-K. Our evidence, however, suggests that repetition of information within the 10-K is also a strategic response to managers' reporting incentives. We find evidence that, on average, discretionary repetition of information within the 10-K is driven by both litigation concerns and by managers' incentives to report information more opaquely when earnings performance is poor. We find no evidence that repetition of information within the 10-K is associated with improved price discovery following the 10-K filing date, but that repetition is in some cases associated with slower price discovery. Overall, our results suggest that current overlap in disclosure requirements allows managers to repeat information in ways that serve their strategic reporting purposes but that do not result in increased clarity for investors. JEL Classifications: D8; G38; M4

Current theories of psychosis highlight the role of abnormal learning signals, i.e., prediction errors (PEs) and uncertainty, in the formation of delusional beliefs. We employed computational analyses of behaviour and functional magnetic resonance imaging (fMRI) to examine whether such abnormalities are evident in clinical high risk (CHR) individuals. Non-medicated CHR individuals (n = 13) and control participants (n = 13) performed a probabilistic learning paradigm during fMRI data acquisition. We used a hierarchical Bayesian model to infer subject-specific computations from behaviour – with a focus on PEs and uncertainty (or its inverse, precision) at different levels, including environmental ‘volatility’ – and used these computational quantities for analyses of fMRI data. Computational modelling of CHR individuals’ behaviour indicated volatility estimates converged to significantly higher levels than in controls. Model-based fMRI demonstrated increased activity in prefrontal and insular regions of CHR individuals in response to precision-weighted low-level outcome PEs, while activations of prefrontal, orbitofrontal and anterior insula cortex by higher-level PEs (that serve to update volatility estimates) were reduced. Additionally, prefrontal cortical activity in response to outcome PEs in CHR was negatively associated with clinical measures of global functioning. Our results suggest a multi-faceted learning abnormality in CHR individuals under conditions of environmental uncertainty, comprising higher levels of volatility estimates combined with reduced cortical activation, and abnormally high activations in prefrontal and insular areas by precision-weighted outcome PEs. This atypical representation of high- and low-level learning signals might reflect a predisposition to delusion formation., NeuroImage: Clinical, 26, ISSN:2213-1582

Although estrus detection makes a relevant contribution to the reproductive performance of dairy cattle, studies on the economic evaluation of automatic estrus detection systems are rare. The objective of the present study is to provide an economic evaluation of activity meters used for estrus detection. The effect of different estrus detection rates on gross margins was modeled with SimHerd (SimHerd A/S, Viborg, Denmark). The analysis considers all costs associated with the investment in activity meters. The economic evaluation was carried out through simulation of Simmental herds with yearly milk yields of 7,000 or 9,000 kg and Holstein Friesian herds with yearly milk yields of 9,000 or 11,000 kg, each with herd sizes of 70 or 210 cows. Furthermore, we distinguished between 2 investment scenarios. In scenario 1, only cows are equipped with activity meters for estrus detection, whereas scenario 2 assumes that cows and heifers are equipped with activity meters. Because existing empirical information for some variables shows significant variability (estrus detection rates, time for estrus detection), they were modeled with distributions using the Monte Carlo method in @RISK (Palisade Corporation, Ithaca, NY), allowing us to model a probability distribution of net returns (NR) of investment in activity meters for estrus detection. The simulation results show that the average NR of investment in activity meters for estrus detection over all scenarios ranges from +€7 to +€40 per cow per year for the Simmental breed, and from +€19 to +€46 per cow per year for the Holstein Friesian breed. Generally, the NR depends on the milk production level assumed. For the Simmental breed, depending on the scenario, the simulation results show a 54 to 200% larger average NR of investment in activity meters for estrus detection with a milk yield of 9,000 kg/yr compared with 7,000 kg/yr. For the Holstein Friesian breed, the effect of the modeled milk yield on the NR is much less pronounced. Average NR of investment in activity meters are greater for larger herd sizes because of cost degression effects. An additional equipping of heifers has, on average, a positive effect on the economics of activity meters for estrus detection because of the resulting reduction in the age at first calving. Considering all scenarios, the probability of a positive NR of investment in activity meters ranges between 74 and 98% for the Simmental breed and between 85 and 99% for the Holstein Friesian breed.

Since access to HIV testing, counselling, and drug therapy has improved so dramatically, scholars have investigated ways this 'scale-up' has interacted with HIV/AIDS-related stigma in sub-Saharan Africa. Drawing on data collected during ethnographic research in a trading centre in western Kenya, this paper critically analyses two violent and localised case studies of panic over the ill health of particular community residents as a nuanced lens through which to explore the dynamic interplay of gender politics and processes of HIV/AIDS-related stigma in the aftershocks of the AIDS crisis. Gaining theoretical momentum from literatures focusing on stigma, gender, witchcraft, gossip, and accusation, we argue that the cases highlight collective anxieties, as well as local critiques of shifting gender roles and the strain of globalisation and legacies of uneven development on myriad forms of relationships. We further contend that these heightened moments of panic and accusation were deployments of power that ultimately sharpened local gender politics and conflicts on the ground in ways that complicated the social solidarity necessary to tackle social and health inequalities. The paper highlights one community's challenge to eradicate the stigma associated with HIV/AIDS during a period of increased access to HIV services.

The reprogramming process that leads to induced pluripotent stem cells (iPSCs) may benefit from adding oocyte factors to Yamanaka's reprogramming cocktail (OCT4, SOX2, KLF4, with or without MYC; OSK(M)). We previously searched for such facilitators of reprogramming (the reprogrammome) by applying label-free LC-MS/MS analysis to mouse oocytes, producing a catalog of 28 candidates that are (i) able to robustly access the cell nucleus and (ii) shared between mature mouse oocytes and pluripotent embryonic stem cells. In the present study, we hypothesized that our 28 reprogrammome candidates would also be (iii) abundant in mature oocytes, (iv) depleted after the oocyte-to-embryo transition, and (v) able to potentiate or replace the OSKM factors. Using LC-MS/MS and isotopic labeling methods, we found that the abundance profiles of the 28 proteins were below those of known oocyte-specific and housekeeping proteins. Of the 28 proteins, only arginine methyltransferase 7 (PRMT7) changed substantially during mouse embryogenesis and promoted the conversion of mouse fibroblasts into iPSCs. Specifically, PRMT7 replaced SOX2 in a factor-substitution assay, yielding iPSCs. These findings exemplify how proteomics can be used to prioritize the functional analysis of reprogrammome candidates. The LC-MS/MS data are available via ProteomeXchange with identifier PXD003093.

Background: Thoracentesis and video-assisted thoracic surgery procedures can result in haemorrhage as a consequence of severing the collateral branches of the posterior intercostal artery. These branches have been shown to be most common in the 5th intercostal space (ICS). Tortuosity has been shown to be especially prevalent nearer to midline. A group of investigators have recommended the 4th and 7th ICS, 120 mm lateral to midline as a safe zone, least likely to hit branches when cutting into the ICS. The present study aimed to investigate that safe zone as a better entry points for procedures. In addition, investigation of the least safe 5th ICS was also performed. Materials and methods: A total of 56 embalmed human cadavers were selected for the study. With the cadavers laid prone, 2 cm incisions were made at the 4th, 5th and 7th ICS, 120 mm lateral to midline bilaterally. The cadavers were then placed supine and the incisions were dissected. Careful attention was paid to identify if any collateral branches were cut. Results: After thorough dissection of the 4th, 5th and 7th ICS incision sites, it was shown that damage to the 5th intercostal was seen most frequently. Conclusions: Based on this cadaveric study, a 2 cm incision at the 4th, 5th and 7th ICS 120 mm lateral from midline resulted in the most damage at the level of the 5th ICS. The 4th ICS had the least damage seen. Therefore, it is recommended that insertion should be placed at the level of the 4th ICS bilaterally.

Objective The aim of this study was to provide descriptive characteristics of companies accredited as part of the HealthLead Workplace Accreditation and to assess congruence between data reported via online organizational self-assessment and third-party onsite audit. Methods Synthesized organizational level data collected through the HealthLead accreditation process (N = 22). Online self-assessment and onsite third-party audit data were compared using paired t-tests. Results Statistical tests revealed significantly higher onsite audit scores than organizational self-assessment scores. Descriptive analyses demonstrated that Outcomes Reporting was the lowest scoring area among all companies. Companies also varied widely in levels of Leadership Support for wellness. Conclusions Gaps observed between organizational self-assessment and onsite audit scores were relatively stable across the sample, indicating that observed differences may be process related. Organizations awarded accreditation show a wide variation in Leadership Support, and Outcomes Reporting appears to be low across the sample.

Summary Cardiac induction requires stepwise integration of BMP and WNT pathway activity. Human embryonic stem cells (hESCs) are developmentally and clinically relevant for studying the poorly understood molecular mechanisms downstream of these cascades. We show that BMP and WNT signaling drive cardiac specification by removing sequential roadblocks that otherwise redirect hESC differentiation toward competing fates, rather than activating a cardiac program per se. First, BMP and WNT signals pattern mesendoderm through cooperative repression of SOX2, a potent mesoderm antagonist. BMP signaling promotes miRNA-877 maturation to induce SOX2 mRNA degradation, while WNT-driven EOMES induction transcriptionally represses SOX2. Following mesoderm formation, cardiac differentiation requires inhibition of WNT activity. We found that WNT inhibition serves to restrict expression of anti-cardiac regulators MSX1 and CDX2/1. Conversely, their simultaneous disruption partially abrogates the requirement for WNT inactivation. These results suggest that human cardiac induction depends on multi-stage repression of alternate lineages, with implications for deriving expandable cardiac stem cells.

ZusammenfassungDie Ptosis im Rahmen der chronisch progressiven externen Ophthalmoplegie (CPEO) ist häufig das erste Symptom einer sehr seltenen systemischen Muskelerkrankung. In der Progression über viele Jahre treten oft später Einschränkungen der Augenmotilität auf, die den Verdacht auf CPEO begründen. Man beobachtet in den Jahren der Frühphase eine einfache erworbene Ptosis, die mit Levatorchirurgie korrigiert werden kann. Wegen der außerordentlichen Seltenheit der CPEO (

International audience; Iron(i) species are debated as key intermediates during the C-halide activation step in Kumuda type C-C cross-coupling catalysis. However, there is only limited knowledge on the reactivity of isolable iron(i) complexes towards organohalides. Using the known two-coordinate iron(i) complex K{18c6}[FeI(N(SiMe3)2)2] we disclose its proficiency to rapidly cleave different types of carbon halide bonds including even C-F bonds. Mechanistic studies indicate stepwise one-electron processes with the involvement of organoradicals.

Background Knee varus alignment may increase loading in the medial tibiofemoral compartment, which can increase strain on the articular cartilage. Knee valgus unloader braces seek to reduce loading through the medial femoral compartment, but their effects on cartilage characteristics during dynamic tasks have not been evaluated. Objective To determine the effects of a knee valgus unloader brace on medial femoral articular cartilage deformation following a single 5000-step walking protocol in individuals with varus-knee alignment. Methods Twenty-four healthy individuals (63% female, BMI = 22 ± 3 kg/m2, age = 21 ± 3 years) completed two testing sessions (braced and unbraced) separated by one week. During both sessions, femoral cartilage ultrasound images were acquired prior to and following a 5000-step treadmill walking protocol at self-selected speed. Percent change scores in medial cartilage cross-sectional area (MCCA) were calculated and used as the primary outcome, and compared between the braced and unbraced conditions. Results There was no difference in percent change of MCCA between conditions (braced = − 2.77%, unbraced = − 3.15%, p = 0.699). Individuals whose cartilage deformed more than a previously established minimal detectable change (MDC ≥ 1.58 mm2) deformed less during the braced condition (braced = − 2.94%, unbraced = − 6.34%, p = 0.028), compared to individuals who did not deform greater than the MDC (n = 15, braced = − 2.67%, unbraced = − 1.23%, p = 0.210). Conclusions There was no significant difference in MCCA percent change between the braced and unbraced conditions across the entire cohort; yet a valgus unloader braces may serve as a potential intervention strategy for reducing articular cartilage deformation in certain varus-aligned individuals who normally undergo measurable deformation during walking.

Bats are amazing animals. They are among the best flyers of the natural world and are able to maneuver in the dark to intersect small flying insects. Bats consume large quantities of insects, and this helps hold down the populations of pests that could otherwise destroy agricultural crops and forests. Bats also pollinate many species of plants that provide us with food and medicine. Most people in the United States view bats as pests, and this view has undoubtedly contributed to precipitous declines for some species. However, in much of Europe, bats are protected and measures are taken to incorporate bat housing into buildings and bat-friendly habitat into neighborhoods. Many bat species in the United States also take advantage of human structures. With good design, bat housing could be incorporated into buildings and other structures and could provide support for U.S. bat populations. This publication provides an overview of resources available to help people who want to support bats with their existing structures and/or new building projects.

Purpose Aberrant walking biomechanics after anterior cruciate ligament reconstruction (ACLR) are hypothesized to be associated with deleterious changes in knee cartilage. T1ρ magnetic resonance imaging (MRI) is sensitive to decreased proteoglycan density of cartilage. Our purpose was to determine associations between T1ρ MRI interlimb ratios (ILR) and walking biomechanics 6 months after ACLR. Methods Walking biomechanics (peak vertical ground reaction force (vGRF), vGRF loading rate, knee extension moment, knee abduction moment) were extracted from the first 50% of stance phase in 29 individuals with unilateral ACLR. T1ρ MRI ILR (ACLR limb/uninjured limb) was calculated for regions of interest in both medial and lateral femoral (LFC) and medial and lateral tibial condyles. Separate, stepwise linear regressions were used to determine associations between biomechanical outcomes and T1ρ MRI ILR after accounting for walking speed and meniscal/chondral injury (P ≤ 0.05). Results Lesser peak vGRF in the ACLR limb was associated with greater T1ρ MRI ILR for the LFC (posterior ΔR = 0.14, P = 0.05; central ΔR = 0.15, P = 0.05) and medial femoral condyle (central ΔR = 0.24, P = 0.01). Lesser peak vGRF loading rate in the ACLR limb (ΔR = 0.21, P = 0.02) and the uninjured limb (ΔR = 0.27, P = 0.01) was associated with greater T1ρ MRI ILR for the anterior LFC. Lesser knee abduction moment for the injured limb was associated with greater T1ρ MRI ILR for the anterior LFC (ΔR = 0.16, P = 0.04) as well as the posterior medial tibial condyle (ΔR = 0.13, P = 0.04). Conclusion Associations between outcomes related to lesser mechanical loading during walking and greater T1ρ MRI ILR were found 6 months after ACLR. Although preliminary, our results suggest that underloading of the ACLR limb at 6 months after ACLR may be associated with lesser proteoglycan density in the ACLR limb compared with the uninjured limb.

The extracellular matrix (ECM) is an important constituent for a variety of tissues including vascular tissue in which the ECM maintains aortic wall integrity. An important component of vascular tissue ECM is type I collagen. Type I collagen is normally a molecule composed of three collagen chains of which two are the same chain [proa1(I)] and one is distinctly different [proa2(I)]. The focus of this dissertation is to examine the role of the proa2(I) chain in determining thoracic aorta integrity and how the thoracic aortic integrity changes with age. To assess the role of proa2(I) chains we used a mouse model, termed 'oim', that produces only proa1(I) chains and evaluated thoracic aortas of our mouse model at 3, 8, and 18 months old of age. We evaluated thoracic aortic strength, stiffness, ECM content, ECM gene expression, and collagen crosslinking at each age point. Oim mice exhibited reduced aortic strength and stiffness at each age group and exhibited increased aortic strength and stiffness at 18 months of age compared to 3 months of age. Oim mice also exhibited reduced aortic collagen content, while other aortic ECM components were unchanged. However, aortic collagen content was significantly increased at 8 and 18 months of age as compared to 3 months of age. Aortic ECM gene expression demonstrated reduced expression at 18 months of age as compared to 3 months of age. In addition, oim aortas demonstrated increased collagen crosslinks at each age group, while the ratio of collagen crosslinking remained the same at each age group. Our results demonstrate that proa2(I) collagen is central for proper aortic strength and stiffness even in the presence of increased collagen crosslinking and increasing collagen content of homotrimeric type I collagen with age. This study suggests that fibrils composed of homotrimeric type I collagen are inherently weaker than fibrils composed of heterotrimeric type I collagen.

Posttransplant cyclophosphamide (PTCy) has been found to be effective in ameliorating acute graft-versus-host disease (GVHD) in patients following allogeneic hematopoietic stem cell transplantation (aHSCT). Adoptive transfer of high numbers of donor Tregs in experimental aHSCT has shown promise as a therapeutic modality for GVHD regulation. We recently described a strategy for in vivo Treg expansion targeting two receptors: TNFRSF25 and CD25. To date, there have been no direct comparisons between the use of PTCy and Tregs regarding outcome and immune reconstitution within identical groups of transplanted mice. Here, we assessed these two strategies and found both decreased clinical GVHD and improved survival long term. However, recipients transplanted with Treg-expanded donor cells (TrED) exhibited less weight loss early after HSCT. Additionally, TrED recipients demonstrated less thymic damage, significantly more recent thymic emigrants, and more rapid lymphoid engraftment. Three months after HSCT, PTCy-treated and TrED recipients showed tolerance to F1 skin allografts and comparable immune function. Overall, TrED was found superior to PTCy with regard to weight loss early after transplant and initial lymphoid engraftment. Based on these findings, we speculate that morbidity and mortality after transplant could be diminished following TrED transplant into aHSCT recipients, and, therefore, that TrED could provide a promising clinical strategy for GVHD prophylaxis.

The association between lower-extremity loading and clinically relevant knee symptoms at different time points after anterior cruciate ligament reconstruction (ACLR) is unclear. Vertical ground reaction force (vGRF) from walking was compared between individuals with and without clinically relevant knee symptoms in three cohorts:12 months post-ACLR, 12-24 months post-ACLR, and24 months post-ACLR.One hundred twenty-eight individuals with unilateral ACLR were classified as symptomatic or asymptomatic, based on previously defined cutoff values for the Knee Osteoarthritis and Injury Outcome Score (12 months post-ACLR [symptomatic n = 28, asymptomatic n = 24]; 12-24 months post-ACLR [symptomatic n = 15, asymptomatic n = 15], and24 months post-ACLR [symptomatic, n = 13; asymptomatic, n = 33]). Vertical ground reaction force exerted on the ACLR limb was collected during walking gait, and functional analyses of variance were used to evaluate the effects of symptoms and time post-ACLR on vGRF throughout stance phase (α = 0.05).Symptomatic individuals,12 months post-ACLR, demonstrated less vGRF during both vGRF peaks (i.e., weight acceptance and propulsion) and greater vGRF during midstance, compared to asymptomatic individuals. Vertical ground reaction force characteristics were not different between symptomatic and asymptomatic individuals for most of stance in individuals between 12 and 24 months post-ACLR. Symptomatic individuals who were24 months post-ACLR, exhibited greater vGRF during both peaks, but lesser vGRF during midstance, compared to asymptomatic individuals.Relative to asymptomatic individuals, symptomatic individuals are more likely to underload the ACLR limb early after ACLR (i.e.,12 months) during both vGRF peaks, but overload the ACLR limb, during both vGRF peaks, at later time points (i.e.,24 months). We propose these differences in lower-extremity loading during walking might have implications for long-term knee health, and should be considered when designing therapeutic interventions for individuals with an ACLR.

Objective To determine whether walking speed, collected at 6 and 12 months following anterior cruciate ligament reconstruction (ACLR), is associated with inter-extremity differences in proteoglycan density, measured via T1ρ magnetic resonance imaging, in tibiofemoral articular cartilage 12 months following ACLR. Methods Twenty-one individuals with a unilateral patellar-tendon autograft ACLR (10 women and 11 men, mean ± SD age 23.9 ± 2.7 years, mean ± SD body mass index 23.9 ± 2.7 kg/m2 ) were recruited for participation in this study. Walking speed was collected using 3-dimensional motion capture at 6 and 12 months following ACLR. The articular cartilage of the medial femoral condyle (MFC) and lateral femoral condyle and medial and lateral tibial condyles was manually segmented and subsectioned into 3 regions of interest (anterior, central, and posterior) based on the location of the meniscus in the sagittal plane. Inter-extremity mean T1ρ relaxation time ratios (T1ρ ACLR extremity / T1ρ contralateral extremity) were calculated and used for analysis. Pearson product-moment correlations were used to determine associations between walking speed and inter-extremity differences in T1ρ relaxation time ratios. Results Slower walking speed 6 months post-ACLR was significantly associated with higher T1ρ relaxation time ratios in the MFC of the ACLR extremity 12 months following ACLR (posterior MFC, r = -0.51, P = 0.02; central MFC, r = -0.47, P = 0.04). Similarly, slower walking speed at 12 months post-ACLR was significantly associated with higher T1ρ relaxation time ratios in the posterior MFC ACLR extremity (r = -0.47, P = 0.04) 12 months following ACLR. Conclusion Slower walking speed at 6 and 12 months following ACLR may be associated with early proteoglycan density changes in medial femoral compartment cartilage health in the first 12 months following ACLR.

Control of alkalinity, dissolved carbon dioxide (dCO 2 ), and pH are critical in marine recirculating aquaculture systems (RAS) in order to maintain health and maximize growth. A small-scale prototype aragonite sand filled fluidized bed reactor was tested under varying conditions of alkalinity and dCO 2 to develop and model the response of dCO 2 across the reactor. A large-scale reactor was then incorporated into an operating marine recirculating aquaculture system to observe the reactor as the system moved toward equilibrium. The relationship between alkalinity dCO 2 , and pH across the reactor are described by multiple regression equations. The change in dCO 2 across the small-scale reactor indicated a strong likelihood that an equilibrium alkalinity would be maintained by using a fluidized bed aragonite reactor. The large-scale reactor verified this observation and established equilibrium at an alkalinity of approximately 135 mg/L as CaCO 3 , dCO 2 of 9 mg/L, and a pH of 7.0 within 4 days that was stable during a 14 day test period. The fluidized bed aragonite reactor has the potential to simplify alkalinity and pH control, and aid in dCO 2 control in RAS design and operation. Aragonite sand, purchased in bulk, is less expensive than sodium bicarbonate and could reduce overall operating production costs.

SYNOPSIS This study provides evidence on relative magnitudes of factors that appear to drive 10-K length. We employ statistical analysis and text analysis software to partition 10-K length into the portions explained by each of three fundamental determinants: (1) firms' operating complexity, (2) disclosure redundancy, and (3) residual disclosure. Our primary analyses shed light on the relative magnitudes of each of these components and on the extent to which each varies across firms. Disclosure redundancy and operating complexity explain roughly equal amounts of variation in 10-K length within our sample. However, 10-K length unexplained by redundancy or firms' operating complexity (residual disclosure) accounts for the largest degree of variation in 10-K length. Our results are consistent with the notion that a substantial amount of disclosure volume contained in 10-K reports is attributable to managerial discretion in how firms respond to mandatory disclosure requirements. Our study expands prior literature that has focused largely on the consequences of 10-K length and provides important insights for policy makers and regulators seeking to improve disclosure requirements. Data Availability: Data available upon request.

Ptosis is often the first symptom of chronic progressive external ophthalmoplegia (CPEO), a rare muscle disorder. As the disease progresses, it can lead to ocular motility defects. Ptosis is present in the early stages of the disease and can be corrected by levator surgery. Due to the rarity of CPEO ( 1% of ptosis patients), further diagnostic steps with muscle biopsy and genetic analysis of mitochondrial DNA are usually not considered in the early phase. Intraoperative abnormal observations during ptosis surgery and postoperative motility problems are signs of CPEO. If CPEO is confirmed, alternative surgical methods can correct the ptosis, like frontalis suspension.Die Ptosis im Rahmen der chronisch progressiven externen Ophthalmoplegie (CPEO) ist häufig das erste Symptom einer sehr seltenen systemischen Muskelerkrankung. In der Progression über viele Jahre treten oft später Einschränkungen der Augenmotilität auf, die den Verdacht auf CPEO begründen. Man beobachtet in den Jahren der Frühphase eine einfache erworbene Ptosis, die mit Levatorchirurgie korrigiert werden kann. Wegen der außerordentlichen Seltenheit der CPEO ( 1% der Ptosisformen) werden aufwendige Muskelbiopsien oder genetische Analysen der mitochondrialen DNA zunächst nicht primär in Erwägung gezogen. Intraoperative Beobachtungen während der Ptosischirurgie und postoperative Motilitätsprobleme erwecken jedoch schon in der Frühphase den Verdacht auf CPEO und begründen diese speziellen Untersuchungen. Nach Bestätigung einer CPEO können alternative Operationsverfahren, z. B. Frontalissuspension, eingesetzt werden.

Master cell fate determinants are thought to induce specific cell lineages in gastrulation by orchestrating entire gene programs. The T-box transcription factor EOMES (eomesodermin) is crucially required for the development of the heart—yet it is equally important for endoderm specification suggesting that it may act in a context-dependent manner. Here, we define an unrecognized interplay between EOMES and the WNT signaling pathway in controlling cardiac induction by using loss and gain-of-function approaches in human embryonic stem cells. Dose-dependent EOMES induction alone can fully replace a cocktail of signaling molecules otherwise essential for the specification of cardiogenic mesoderm. Highly efficient cardiomyocyte programming by EOMES mechanistically involves autocrine activation of canonical WNT signaling via the WNT3 ligand, which necessitates a shutdown of this axis at a subsequent stage. Our findings provide insights into human germ layer induction and bear biotechnological potential for the robust production of cardiomyocytes from engineered stem cells., The T-box transcription factor eomesodermin (EOMES) acts both in endoderm specification as well as heart development, suggesting context-specific function. Here, the authors show that dose-controlled EOMES induction is sufficient for cardiogenic programming of human pluripotent stem cells.

Through critical reflection on the conspiracy theories told about the origins of HIV by American Indians, we learned that many community members refused the universalized aspects of AIDS prevention, education, and intervention. We found that standard HIV/AIDS-related prevention and treatment programs tend to universalize experiences with and responses to the AIDS epidemic and ignore – or push to the margin – alternative framings and understandings of this disease. Inspired by American Indians’ refusal to synthesize (in the Hegelian dialectical sense) their own experience into national and international AIDS knowledges, in this article we seek to engage with such marginal understandings, as well as their interactions with universal, individual, and community notions of care, AIDS, and health causality. The use of non-standard theories of the origins of AIDS by American Indians, we argue, disrupts the logic that attempts to universalize AIDS and community experiences. By making AIDS a ‘White Man’s disease’, Natives bring the epidemic in line with a history of social and health neglect by the settler state, and refuse to collapse their own, marginalized experiences and understandings of HIV/AIDS into dominant knowledges of the disease.

Background Aberrant walking-gait and jump-landing biomechanics may influence the development of post-traumatic osteoarthritis and increase the risk of a second anterior cruciate ligament injury, respectively. It remains unknown if individuals who demonstrate altered walking-gait biomechanics demonstrate similar altered biomechanics during jump-landing. Our aim was to determine associations in peak knee biomechanics and limb-symmetry indices between walking-gait and jump-landing tasks in individuals with a unilateral anterior cruciate ligament reconstruction. Methods Thirty-five individuals (74% women, 22.1 [3.4] years old, 25 [3.89] kg/m2) with an anterior cruciate ligament reconstruction performed 5-trials of self-selected walking-gait and jump-landing. Peak kinetics and kinematics were extracted from the first 50% of stance phase during walking-gait and first 100 ms following ground contact for jump-landing. Pearson product-moment (r) and Spearman's Rho (ρ) analyses were used to evaluate relationships between outcome measures. Significance was set a priori (P ≤ 0.05). Findings All associations between walking-gait and jump-landing for the involved limb, along with the majority of associations for limb-symmetry indices and the uninvolved limb, were negligible and non-statistically significant. There were weak significant associations for instantaneous loading rate (ρ = 0.39, P = 0.02) and peak knee abduction angle (ρ = 0.36, p = 0.03) uninvolved limb, as well as peak abduction displacement limb-symmetry indices (ρ= − 0.39, p = 0.02) between walking-gait and jump-landing. Interpretation No systematic associations were found between walking-gait and jump-landing biomechanics for either limb or limb-symmetry indices in people with unilateral anterior cruciate ligament reconstruction. Individuals with an anterior cruciate ligament reconstruction who demonstrate high-involved limb loading or asymmetries during jump-landing may not demonstrate similar biomechanics during walking-gait.