Disentangling genetic, plastic and social learning drivers of sex-specific foraging behaviour in Trinidadian guppies (Poecilia reticulata).

Evolutionary biologists have long been interested in parsing out the roles of genetics, plasticity and their interaction on adaptive trait divergence. Since males and females often have different ecological and reproductive roles, separating how their traits are shaped by interactions between their genes and environment is necessary and important. Here, we disentangle the sex-specific effects of genetic divergence, developmental plasticity, social learning and contextual plasticity on foraging behaviour in Trinidadian guppies (Poecilia reticulata) adapted to high- or low-predation habitats. We reared second-generation siblings from both predation regimes with or without predator chemical cues, and with adult conspecifics from either high- or low-predation habitats. We then quantified their foraging behaviour in water with and without predator chemical cues. We found that high-predation guppies forage more efficiently than low-predation guppies, but this behavioural difference is context-dependent and shaped by different mechanisms in males and females. Higher foraging efficiency in high-predation females is largely genetically determined, and to a smaller extent socially learned from conspecifics. However, in high-predation males, higher foraging efficiency is plastically induced by predator cues during development. Our study demonstrates sex-specific differences in genetic versus plastic responses in foraging behaviour, a trait of significance in organismal fitness and ecosystem dynamics.

POSTOPERATIVE CASTING OF BELOW-KNEE AMPUTATION REDUCES STUMP COMPLICATIONS.

INTRODUCTION: Against the technological advances in limb salvage, below-the-knee amputation (BKA) remains a common procedure. Although most elective BKA is classified as clean operation, the reported stump complication rate is much higher than predicted. Postoperative casting (PC) may reduce the number of these complications. The aim of this study was to compare the efficacy of elastic bandage with knee immobilizer (EBKI) and PC in BKA stump complications. METHODS: Retrospective cohort comparison design identified patients who underwent BKA between 2000-2023 for uncorrectable lower extremity ischemia, or excessive tissue loss secondary to non-correctable critical limb ischemia (CLI), excessive tissue loss secondary to CLI, infection, severe neuropathy, or the combination of these and stratified them into 2 cohorts based on their postoperative stump dressing: EBKI and PC. BKAs that were done for trauma or neoplastic process were excluded. The primary outcome measures: wound healing in 6 weeks and length of stay (LOS). SECONDARY OUTCOME MEASURES: stump injury, infection, dehiscence, necrosis, number of higher-level amputations, knee contracture and post BKA mobility with SIGAM score. RESULTS: 116 patients with 122 limbs (52 EBKI, 70 PC) were found who met inclusion criteria and analyzed. The groups were comparable in demographics and comorbidities and pre-operative variables, including mobility. The primary wound healing at 6 weeks was higher (p=0.007), wound dehiscence (p=0.01) and length of stay (p=0.006) was lower in the PC group compared to EBKI group. The PC group achieved higher SIGAM mobility score and lower number of contractures developed compared to the EBKI group. CONCLUSIONS: Applying and maintaining PC to the BKA stump during the first month of healing reduced the incidence of stump complications, shortened the LOS and improved post rehabilitation mobility results. We found no effect of PC on postoperative infections, stump necrosis and higher-level amputations.

Maximizing Reflexive HCV RNA Testing of HCV Antibody-Reactive Samples Within United States Public Health Laboratories.

Hepatitis C virus (HCV) infection can cause significant morbidity and mortality if left untreated and diagnosis is the first step in any treatment regimen. In the United States, a two-step algorithm is recommended for detection of current HCV infection. The algorithm consists of an HCV antibody screening test followed by a supplemental test for HCV RNA if the HCV antibody test is reactive. To assess HCV testing practices and identify associated challenges, the Association of Public Health Laboratories (APHL) conducted a survey on HCV diagnostics practices of US public health laboratories. Additionally, APHL and the Centers for Disease Control and Prevention's (CDC) Division of Viral Hepatitis (DVH) convened a two-day meeting of HCV subject matter experts (SMEs) to identify opportunities for improvement in diagnosis of current HCV infection. Automatic reflexive HCV RNA testing of HCV antibody-reactive specimens was identified as a high priority target area by HCV SMEs and as a gap in laboratory practice by the APHL survey, which found that only 54% of respondent laboratories always automatically reflexed or referred an Ab-reactive specimen to an HCV RNA test. To facilitate accurate diagnosis and ensure that patients are not lost to follow up, laboratories and public health programs should work to ensure that the entire HCV testing algorithm (i.e., antibody and nucleic acid testing) can be completed with a sample(s) collected during a single patient visit.

Adherence to Extended Venous Thromboembolism Prophylaxis and Outcomes After Complex Gastrointestinal Oncologic Surgery.

BACKGROUND: Clinical guidelines recommend extended venous thromboembolism (VTE) prophylaxis for cancer patients after major gastrointestinal (GI) operations. However, adherence to the guidelines has been low, and the clinical outcomes not well defined. METHODS: This study retrospectively analyzed a random 10 % sample of the 2009-2022 IQVIA LifeLink PharMetrics Plus database, an administrative claims database representative of the commercially insured population of the United States. The study selected cancer patients undergoing major pancreas, liver, gastric, or esophageal surgery. The primary outcomes were 90-day post-discharge VTE and bleeding. RESULTS: The study identified 2296 unique eligible operations. During the index hospitalization, 52 patients (2.2 %) experienced VTE, 74 patients (3.2 %) had postoperative bleeding, and 140 patients (6.1 %) had a hospital stay of at least 28 days. The remaining 2069 operations comprised 833 pancreatectomies, 664 hepatectomies, 295 gastrectomies, and 277 esophagectomies. The median age of the patients was 49 years, and 44 % were female. Extended VTE prophylaxis prescriptions were filled for 176 patients (10.4 % for pancreas, 8.1 % for liver, 5.8 % for gastric cancer, and 6.5 % for esophageal cancer), and the most used agent was enoxaparin (96 % of the patients). After discharge, VTE occurred for 5.2 % and bleeding for 5.2 % of the patients. The findings showed no association of extended VTE prophylaxis with post-discharge VTE (odds ratio [OR], 1.54; 95 % confidence interval [CI], 0.81-2.96) or bleeding (OR, 0.72, 95 % CI, 0.32-1.61). CONCLUSIONS: The majority of the cancer patients undergoing complex GI surgery did not receive extended VTE prophylaxis according to the current guidelines, and their VTE rate was not higher than for the patients who received it.

Evolutionary divergence of developmental plasticity and learning of mating tactics in Trinidadian guppies.

Behavioural plasticity is a major driver in the early stages of adaptation, but its effects in mediating evolution remain elusive because behavioural plasticity itself can evolve. In this study, we investigated how male Trinidadian guppies (Poecilia reticulata) adapted to different predation regimes diverged in behavioural plasticity of their mating tactic. We reared F2 juveniles of high- or low-predation population origins with different combinations of social and predator cues and assayed their mating behaviour upon sexual maturity. High-predation males learned their mating tactic from conspecific adults as juveniles, while low-predation males did not. High-predation males increased courtship when exposed to chemical predator cues during development; low-predation males decreased courtship in response to immediate chemical predator cues, but only when they were not exposed to such cues during development. Behavioural changes induced by predator cues were associated with developmental plasticity in brain morphology, but changes acquired through social learning were not. We thus show that guppy populations diverged in their response to social and ecological cues during development, and correlational evidence suggests that different cues can shape the same behaviour via different neural mechanisms. Our study demonstrates that behavioural plasticity, both environmentally induced and socially learnt, evolves rapidly and shapes adaptation when organisms colonize ecologically divergent habitats.

La plasticidad conductual es un factor importante en las primeras fases de adaptación, pero se conocen poco sus efectos sobre la evolución porque la plasticidad conductual en sí puede evolucionar. En este estudio, investigamos cómo los machos del guppy de Trinidad (Poecilia reticulata) adaptados a regímenes de depredación diferentes, han divergido en la plasticidad de su táctica de apareamiento. Criamos juveniles provenientes de poblaciones de alta y baja depredación hasta segunda generación (F2) bajo diferentes combinaciones de señales sociales y de depredación, y evaluamos su comportamiento de apareamiento al llegar a la madurez sexual. Los machos de alta depredación aprendieron su táctica de apareamiento de sus conespecíficos adultos, mientras que los machos de baja depredación no. Los machos de alta depredación aumentaron su cortejo al ser expuestos a señales de depredadores durante su desarrollo; mientras que los machos de baja depredación redujeron su cortejo en respuesta a señales inmediatas de depredadores, pero tan solo cuando no fueron expuestos a tales señales durante el desarrollo. Los cambios conductuales observados inducidos por las señales de depredación están asociados con una plasticidad en el desarrollo de la morfología cerebral, pero los cambios adquiridos por aprendizaje social no. En conclusión, demostramos que las poblaciones de guppy han divergido en su respuesta a señales sociales y ecológicas durante su desarrollo, y mostramos evidencia correlativa que sugiere que diferentes tipos de señales pueden influenciar el mismo comportamiento via mecanismos neuronales diferentes. Nuestro estudio muestra que la plasticidad conductual, tanto inducida por el medio ambiente combo aprendida socialmente, evoluciona rápidamente e influencia la adaptación durante la colonización de hábitats ecológicamente divergentes.

Effects of Probiotics on Colitis-Induced Exacerbation of Alzheimer's Disease in AppNL-G-F Mice.

Alzheimer's disease (AD) is characterized by progressive cognitive decline and is a leading cause of death in the United States. Neuroinflammation has been implicated in the progression of AD, and several recent studies suggest that peripheral immune dysfunction may influence the disease. Continuing evidence indicates that intestinal dysbiosis is an attribute of AD, and inflammatory bowel disease (IBD) has been shown to aggravate cognitive impairment. Previously, we separately demonstrated that an IBD-like condition exacerbates AD-related changes in the brains of the AppNL-G-F mouse model of AD, while probiotic intervention has an attenuating effect. In this study, we investigated the combination of a dietary probiotic and an IBD-like condition for effects on the brains of mice. Male C57BL/6 wild type (WT) and AppNL-G-F mice were randomly divided into four groups: vehicle control, oral probiotic, dextran sulfate sodium (DSS), and DSS given with probiotics. As anticipated, probiotic treatment attenuated the DSS-induced colitis disease activity index in WT and AppNL-G-F mice. Although probiotic feeding significantly attenuated the DSS-mediated increase in WT colonic lipocalin levels, it was less protective in the AppNL-G-F DSS-treated group. In parallel with the intestinal changes, combined probiotic and DSS treatment increased microglial, neutrophil elastase, and 5hmC immunoreactivity while decreasing c-Fos staining compared to DSS treatment alone in the brains of WT mice. Although less abundant, probiotic combined with DSS treatment demonstrated a few similar changes in AppNL-G-F brains with increased microglial and decreased c-Fos immunoreactivity in addition to a slight increase in Aß plaque staining. Both probiotic and DSS treatment also altered the levels of several cytokines in WT and AppNL-G-F brains, with a unique increase in the levels of TNFα and IL-2 being observed in only AppNL-G-F mice following combined DSS and probiotic treatment. Our data indicate that, while dietary probiotic intervention provides protection against the colitis-like condition, it also influences numerous glial, cytokine, and neuronal changes in the brain that may regulate brain function and the progression of AD.

Positionality, intersectionality, power dynamics in community participatory research to define public safety in Black communities.

Community-based participatory research (CBPR) is necessary for shifting knowledge and empowering community members to establish ownership over research. It was used in this current project to study safety in predominately Black communities. Findings illustrate how the embodiment of power was a present theme and impacted the partnerships among the academics and community, as well as defining "who" could speak on the issues the project was attempting to address. This paper builds upon previous research in CBPR findings to illustrate how community leaders can shape the research, the importance of defining community, and the need to bring to the forefront issues of intersectionality and positionality. In doing so, it attempts to reshape existing CBPR models to better account for the fluid, interactive relationships among the academics, community researchers, and the community leader and expand upon the role of intersectionality in these relationships.

Students' preferences for returning to colleges and universities during the COVID-19 pandemic: A discrete choice experiment.

Importance: When an emerging infectious disease outbreak occurs, such as COVID-19, institutions of higher education (IHEs) must weigh decisions about how to operate their campuses. These decisions entail whether campuses should remain open, how courses should be delivered (in-person, online, or a mixture of the two), and what safety plans should be enacted for those on campus. These issues have weighed heavily on campus administrators during the on-going COVID-19 pandemic. However, there is still limited knowledge about how such decisions affect students' enrollment decisions and campus safety in practice when considering compliance. Objectives: To assess 1) students' willingness to comply with health protocols and contrast their perception of their classmates' compliance, 2) whether students prefer in-person or online learning during a pandemic, and 3) the importance weights of different aspects of campus operations (i.e., modes of course delivery and safety plans) for students when they decide to enroll or defer. Design setting and participants: An internet-based survey of college students took place from June 25, 2020 to July 10, 2020. Participants included 398 industrial engineering students at the Georgia Institute of Technology, a medium-size public university in Atlanta, Georgia. The survey included a discrete choice experiment with questions that asked students to choose whether to enroll or defer when presented with hypothetical scenarios related to Fall 2020 modes of course delivery and aspects of campus safety. The survey also asked students about expected compliance with health protocols, whether they preferred in-person or online courses, and sociodemographic information. Main outcomes and measures: We examine students' willingness to comply with potential health protocols. We estimated logistic regression models to infer significant factors that lead to a student's choice between in-person and online learning. Additionally, we estimated discrete choice models to infer the importance of different modes of course delivery and safety measures to students when deciding to enroll or defer. Results: The survey response rate was 20.8%. A latent class model showed three classes of students: those who were "low-concern" (comprising a 29% expected share of the sample), those who were "moderate-concern" (54%) and those who were "high-concern" (17%). We found that scenarios that offered an on-campus experience with large classes delivered online and small classes delivered in-person, strict safety protocols in terms of mask-wearing, testing, and residence halls, and lenient safety protocols in terms of social gatherings were broadly the scenarios with the highest expected enrollment probabilities. The decision to enroll or defer for all students was largely determined by the mode of delivery for courses and the safety measures on campus around COVID-19 testing and mask-wearing. A logistic regression model showed that a higher perceived risk of infection of COVID-19, a more suitable home environment, being older, and being less risk-seeking were significant factors for a person to choose online learning. Students stated for themselves and their classmates that they would comply with some but not all health protocols against COVID-19, especially those limiting social gatherings. Conclusions and relevance: The majority of students indicated a preference to enroll during the COVID-19 pandemic so long as sufficient safety measures were put in place and all classes were not entirely in-person. As IHEs consider different options for campus operations during pandemics, they should consider the heterogeneous preferences among their students. Offering flexibility in course modes may be a way to appeal to many students who vary in terms of their concern about the pandemic. At the same time, since students overall preferred some safety measures placed around mask-wearing and COVID-19 testing on campus, IHEs may want to recommend or require wearing masks and doing some surveillance tests for all students, faculty, and staff. Students were expecting themselves and their fellow classmates to comply with some but not all health protocols, which may help IHEs identify protocols that need more education and awareness, like limits on social gatherings and the practice of social distancing at social gatherings.

A Cross-Language Comparison of Sentence Recognition Using American English and Mandarin Chinese HINT and AzBio Sentences.

OBJECTIVES: The aim of this study was to perform a cross-language comparison of two commonly used sentence-recognition materials (i.e., Hearing in Noise Test [HINT] and AzBio) in American English (AE) and Mandarin Chinese (MC). DESIGNS: Sixty normal-hearing, native English-speaking and 60 normal-hearing, native Chinese-speaking young adults were recruited to participate in three experiments. In each experiment, the subjects were tested in their native language. In experiments I and II, noise and tone vocoders were used to process the HINT and AzBio sentences, respectively. The number of channels varied from 1 to 9, with an envelope cutoff frequency of 160 Hz. In experiment III, the AE AzBio and the MC HINT sentences were tested in speech-shaped noise at various signal to noise ratios (i.e., -20, -15, -10, -5, and 0 dB). The performance-intensity functions of sentence recognition using the two sets of sentence materials were compared. RESULTS: Results of experiments I and II using vocoder processing indicated that the AE and MC versions of HINT and AzBio sentences differed in level of difficulty. The AE version yielded higher recognition performance than the MC version for both HINT and AzBio sentences. The type of vocoder processing (i.e., tone and noise vocoders) produced little differences in sentence-recognition performance in both languages. Incidentally, the AE AzBio sentences and the MC HINT sentences had similar recognition performance under vocoder processing. Such similarity was further confirmed under noise conditions in experiment III, where the performance-intensity functions of the two sets of sentences were closely matched. CONCLUSIONS: The HINT and AzBio sentence materials developed in AE and MC differ in level of difficulty. The AE AzBio and the MC HINT sentence materials are similar in level of difficulty. In cross-language comparative research, the MC HINT and the AE AzBio sentences should be chosen for the respective language as the target sentence-recognition test materials.

Pilot Study of Telehealth Evaluations in Patients Undergoing Hematopoietic Cell Transplantation.

Telehealth involves the use of telecommunication and information technology for the delivery of clinical care and may be a mechanism to alleviate the burden of visits faced by patients undergoing hematopoietic cell transplantation (HCT). Few studies have evaluated the feasibility and acceptability of telehealth visits in the care of HCT patients. We conducted 27 telehealth visits with 25 patients undergoing HCT using a videoconferencing system that allows for real-time, 2-way interactions and administered satisfaction surveys to patients and providers. Of the 25 patients included in the study, 20 (80%) and 5 (20%) were undergoing autologous and allogeneic HCT, respectively. The telehealth visits were distributed as follows: 3 inpatient visits upon admission for HCT; 11 inpatient visits between 2 and 14 days post-HCT; 4 inpatient visits prior to discharge after HCT; 8 outpatient, post-HCT follow-up visits; and 1 handoff to a community oncologist. Out of a total of 54 provider assessments, 7 providers (13%) were unable to complete some part of the physical examination, but no provider reported being unable to manage patients' symptoms through telehealth. Eighty-one percent of patients were either satisfied or very satisfied with the telemedicine session. Overall satisfaction was higher among patients than providers (mean scores 4.12 versus 2.64; scale 1 to 5, with 1 = very poor to 5 = excellent). Technological barriers resulting in delays and suboptimal physical examination were largely responsible for provider dissatisfaction. The use of telehealth to deliver comprehensive follow-up care to HCT patients is feasible across different HCT types but is dependent upon quality of data streaming and videoconferencing technologies.

Preliminary assessment of aneuploidy rates between the polar, mid and mural trophectoderm.

The objective of this study is to compare aneuploidy rates between three distinct areas of the human trophectoderm: mural, polar and a region in between these two locations termed the 'mid' trophectoderm. This is a cohort study on in vitro fertilization (IVF) patients undergoing comprehensive chromosome screening at the blastocyst stage at a private IVF clinic. All embryos underwent assisted hatching on day 3 with blastocyst biopsy and comprehensive chromosome screening. Biopsied blastocysts were divided into three groups depending on which area (polar, mid, or mural) of the trophectoderm was protruding from the zona pellucida and biopsied. Aneuploidy rates were significantly higher with cells from the polar region of the trophectoderm (56.2%) compared with cells removed from the mural region of the trophectoderm (30.0%; P = 0.0243). A comparison of all three areas combined also showed a decreasing trend, but this did not reach clinical significance, polar (56.2%), mid (47.4%) and mural trophectoderm (30.0%; P = 0.1859). The non-concordance demonstrated between polar and mural trophectoderm can be attributed to biological occurrences including chromosomal mosaicism or procedural differences between embryologists.

The predictive power of intelligence: Miranda abilities of individuals with intellectual disability.

OBJECTIVE: The Miranda v. Arizona (1966) decision was intended to protect individuals' rights in custodial situations. The purpose of this paper was to evaluate Miranda abilities of individuals with intellectual disability and evaluate the utility of intelligence in predicting these abilities. Additionally, we aimed to provide an updated resource for forensic examiners regarding the performance of individuals with intellectual disability on the Standardized Assessment of Miranda Abilities (SAMA). HYPOTHESES: We hypothesized that IQ, particularly verbal intelligence and working memory, would significantly predict abilities related to recall, vocabulary, knowledge, and acquiescence in a sample with intellectual disability. METHOD: Sixty-two individuals diagnosed with intellectual disability completed the Wechsler Adult Intelligence Scale-4th ed. (WAIS-IV), the SAMA, and a background questionnaire. RESULTS: Participants demonstrated significantly worse Miranda abilities when compared to the normative sample of the SAMA apart from acquiescence, which they demonstrated at significantly higher rates. Participants exhibited limited existing knowledge of Miranda rights and showed minimal improvement following exposure to a Miranda warning. Verbal abilities were a significant predictor of recall and vocabulary abilities with large effect sizes on average (i.e., ds > 1). IQ was not predictive of misconceptions about Miranda or acquiescence. CONCLUSIONS: Verbal intelligence was an important contributor to understanding Miranda. This study provided data related to performance on the SAMA by a sample of individuals with intellectual disability. It may serve as a reference for evaluators, legal professionals, and law enforcement officers when working with justice-involved persons with suspected intellectual disability. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

The cold truth about postcardiac arrest targeted temperature management: 33°C vs. 36°C.

This article provides nurses with up-to-date evidence to empower them in contributing to the 33°C versus 36°C discussion in postcardiac arrest targeted temperature management (TTM). Presented in debate format, this article addresses the pros and cons of various target temperatures, examines the evidence around TTM, and applies it to clinical scenarios.

Intratumoral delivery of an HPV vaccine elicits a broad anti-tumor immune response that translates into a potent anti-tumor effect in a preclinical murine HPV model.

Therapeutic cancer vaccines have met limited clinical success. In the setting of cancer, the immune system is either tolerized and/or has a limited tumor-specific T cell repertoire. In this study, we explore whether intratumoral (IT) vaccination with an HPV vaccine can elicit quantitative and qualitative differences in immune response as compared to intramuscular (IM) vaccination to overcome immune resistance in established tumors. We report that IT administration of an HPV-16 E7 peptide vaccine formulated with polyinosinic-polycytidylic acid [poly(I:C)] generated an enhanced antitumor effect relative to IM delivery. The elicited anti-tumor effect with IT vaccination was consistent among the vaccinated groups and across various C57BL/6 substrains. IT vaccination resulted in an increased frequency of PD-1hi TILs, which represented both vaccine-targeted and non-vaccine-targeted tumor-specific CD8+ T cells. Overall, the CD8+/Treg ratio was increased within the tumor microenvironment using IT vaccination. We also assessed transcriptional changes in several immune-related genes in the tumor microenvironment of the various treated groups, and our data suggest that IT vaccination leads to upregulation of a broad complement of immunomodulatory genes, including upregulation of interferon gamma (IFNγ) and antigen presentation and processing machine (APM) components. IT vaccine delivery is superior to traditional IM vaccination routes with the potential to improve tumor immunogenicity, which has potential clinical application in the setting of accessible lesions such as head and neck squamous cell carcinomas (HNSCCs).

Experimental Effects of Acute Exercise in Attenuating Memory Interference: Considerations by Biological Sex.

Background and Objectives: The objective of this experiment was to evaluate the effects of acute exercise on memory interference and determine if this potential relationship is moderated by sex. Materials and Methods: A randomized controlled experiment was conducted (N = 40), involving young adult males (n = 20) and females (n = 20) completing two counterbalanced visits (exercise and no exercise). The exercise visit involved an acute (15 min), moderate-intensity bout of treadmill exercise, while the control visit involved a time-matched seated task. Memory interference, including both proactive interference and retroactive interference, involved the completion of a multi-trial memory task. Results: In a factorial ANOVA with the outcome being List B, there was a main effect for condition (F(1,38) = 5.75, P = 0.02, n2p = 0.13), but there was no main effect for sex (F(1,38) = 1.39, P = 0.24, n2p = 0.04) or sex by condition interaction (F(1,38) = 1.44, P = 0.23, n2p = 0.04). Conclusion: In conclusion, acute moderate-intensity exercise was effective in attenuating a proactive memory interference effect. This effect was not moderated by biological sex.

Does Yik Yak Promote Risky Health Behavior on College Campuses?

This study offers an analysis of how healthy and risky behaviors are discussed on an emerging social media platform. We sought to understand what behaviors are communicated and if they are encouraged or discouraged. We completed a content analysis of messages (n = 3,776) posted to Yik Yak captured three times a day on 4 days of the week across two separate weeks. We analyzed messages to determine the category of the behavior, an appraisal of the behavior, and normative voting feedback. Our results show that risky behaviors were discussed with greater frequency and received more user votes than healthy behaviors. Exposure to these messages could influence other students' perceptions of norms associated with these risky behaviors. We suggest further research to determine how Yik Yak may affect normative perceptions on college campuses.

Reproductive Decision-Making in Women with BRCA1/2 Mutations.

Expanded genetic testing of BRCA mutations has led to identification of more reproductive-aged women who test positive for the mutation which might impact attitudes and decisions about relationships, childbearing and the use of preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND). A cross-sectional survey was administered to 1081 self-reported BRCA carriers to investigate how knowledge of BRCA status influences these issues. The mean age at BRCA test disclosure was 44 years and 36 % reported a personal history of cancer. Of 163 women who were unpartnered, 21.5 % felt more pressure to get married. Of 284 women whose families were not complete, 41 % reported that carrier status impacted their decision to have biological children. Women with a history of cancer were more likely to report that knowledge of BRCA+ status impacted their decision to have a child (OR 1.8, 95 % CI 1-3.2). Fifty-nine percent thought PGD should be offered to mutation carriers and 55.5 % thought PND should be offered. In conclusion, knowledge of BRCA status impacts attitudes regarding relationships and childbearing, and most carriers believe that PGD and PND should be offered to other carriers. This study suggests that BRCA carriers desire and would benefit from reproductive counseling after test disclosure.

Technique to 'Map' Chromosomal Mosaicism at the Blastocyst Stage.

The purpose of this study was to identify a technique that allows for comprehensive chromosome screening (CCS) of individual cells within human blastocysts along with the approximation of their location in the trophectoderm relative to the inner cell mass (ICM). This proof-of-concept study will allow for a greater understanding of chromosomal mosaicism at the blastocyst stage and the mechanisms by which mosaicism arises. One blastocyst was held by a holding pipette and the ICM was removed. While still being held, the blastocyst was further biopsied into quadrants. To separate the individual cells from the biopsied sections, the sections were placed in calcium/magnesium-free medium with serum for 20 min. A holding pipette was used to aspirate the sections until individual cells were isolated. Individual cells from each section were placed into PCR tubes and prepped for aCGH. A total of 18 cells were used for analysis, of which 15 (83.3%) amplified and provided a result and 3 (16.7%) did not. Fifteen cells were isolated from the trophectoderm; 13 (86.7%) provided an aCGH result, while 2 (13.3%) did not amplify. Twelve cells were euploid (46,XY), while 1 was complex abnormal (44,XY), presenting with monosomy 7, 10, 11, 13, and 19, and trisomy 14, 15, and 21. A total of 3 cells were isolated from the ICM; 2 were euploid (46,XY) and 1 did not amplify. Here, we expand on a previously published technique which disassociates biopsied sections of the blastocyst into individual cells. Since the blastocyst sections were biopsied in regard to the position of the ICM, it was possible to reconstruct a virtual image of the blastocyst while presenting each cell's individual CCS results.

Differential Effects of Left Ventricular Pacing Sites on Regional Contraction Patterns and Global Performance.

OBJECTIVE: To define the differential effect of site-specific ventricular counterpacing efficacy during cardiac resynchronization therapy (CRT) to identify the most informative imaging views to quantify it. Cross-sectional and long-axis views commonly are used to assess left ventricular (LV) contractility. DESIGN: The effects of LV apical (LVa) and free-wall (LVfw) pacing during CRT on long- and short-axis contraction, cardiac output, and stroke work were assessed in an open-chested acute canine model to determine whether LVa and LVfw would induce earlier apical than basilar LV radial contraction and earlier free-wall than septal contraction, respectively. Apical (CRTa) and free-wall (CRTfw) using right ventricular (RV) pacing-induced dyssynchrony also were examined. SETTING: University large animal research laboratory. PARTICIPANTS: Ten acutely anesthetized and instrumented open-chested purpose-bred dogs. INTERVENTIONS: RV pacing served as the model of cardiac dyssynchrony. Selective LVfw and LVa pacing alone or with RV (CRTfw and CRTa, respectively) were studied relative to right atrial pacing (RA) as the control. MEASUREMENTS AND MAIN RESULTS: Two pairs of 3 ultrasonic crystals were place along the LV longitudinal axis-apex and mid-to-base pairs along septal and free wall lines. Conductance catheter-defined longitudinal LV segmental volumes and pressure-volume data were collected. RV decreased cardiac output and stroke work compared with RA (2.0±0.3 v 1.4±0.1 L/min; 137±22 v 60±14 mJ; p<0.05, respectively). LVfw but not LVa decreased stroke work (130±35 mJ), and CRTa but not CRTfw improved both (2.1±0.2 L/min; 113±13 mJ; p<0.01 v RV pacing). No difference in time to minimal length free wall-to-septal crystal was seen with pacing. Both LVa and CRTa displayed increased apical-to-basilar shortening delay compared with RA, RV, and LVfw (42±47, 9±105, and 1±46 msec, respectively; p<0.05). No matching regional LV volume changes were seen during LVa. CONCLUSIONS: LV functional analysis from only a cross-sectional plane may be insufficient to characterize improved LV contraction synchrony during multisite CRT.