Bcl-xL Is Essential for the Survival and Function of Differentiated Neurons in the Cortex That Control Complex Behaviors

Apoptosis plays an essential role during brain development, yet the precise mechanism by which this pathway is regulated in the brain remains unknown. In particular, mammalian cells are known to express multiple anti-apoptotic Bcl-2 family proteins. However, the cells of the developing brain could also exist in a primed state in which the loss of a single anti-apoptotic Bcl-2 family protein is sufficient to trigger apoptosis. Here, we examined the critical role of Bcl-xL, an anti-apoptotic protein, during brain development. Using conditional knock-out mice in which Bcl-xL is deleted in neural progenitor cells (Bcl-xLEmx1–Cre), we show that the loss of Bcl-xL is not sufficient to trigger apoptosis in these proliferating progenitors. In contrast, specific populations of postmitotic neurons derived from these progenitors, including upper layer cortical neurons and the CA1–CA3 regions of the hippocampus, were acutely dependent on Bcl-xL. Consistent with this finding, deletion of Bcl-xL selectively in the postmitotic neurons in the brain (Bcl-xLNex–Cre) also resulted in similar patterns of apoptosis. This Bcl-xL deficiency-induced neuronal death was a consequence of activation of the apoptotic pathway, because the cell death was rescued with codeletion of the proapoptotic proteins Bax and Bak. Importantly, the loss of these Bcl-xL-dependent neurons led to severe neurobehavioral abnormalities, including deficits in motor learning, hyperactivity, and increased risk-taking and self-injurious behaviors. Together, our results identify a population of neurons in the developing brain that are acutely dependent on Bcl-xL during the peak period of synaptic connectivity that are important for the establishment of higher-order complex behaviors

UTM UAS Service Supplier Development: Sprint 2 Toward Technical Capability Level 4

NASA's UAS Traffic Management (UTM) Project has been tasked with developing concepts and initial implementations for integrating and managing small unmanned aircraft systems (UAS) into the low altitude airspace. To accomplish this task, the UTM Project planned a phased approach based on four Technical Capability Levels (TCLs). As of this writing, TCL4 is currently in development for a late Spring 2019 flight demonstration. This TCL is focused on operations in an urban environment and includes the handling of high density environments, large-scale off-nominal conditions, vehicle-to-vehicle communications, detect-and-avoid technologies, communication requirements, public safety operations, airspace restrictions, and other related goals. Through research and testing to date, NASA has developed an architecture for UTM that depends on commercial entities collaboratively providing services that are traditionally provided by the Air Navigation Service Provider (ANSP) in manned aviation. A key component of this architecture is the UAS Service Supplier (USS), which acts as a communications bridge between UAS operators and the ANSP when necessary. In addition, the collection of USSs form a USS Network to collaboratively manage the airspace through the sharing of data and the adherence to a standard or set of standards required to participate in this USS Network. This document provides a record of the second of four planned steps in the development of interoperable USSs that will ultimately support TCL4 flight testing and formalization of the overall UTM concept. To develop these USSs and their underlying specifications, NASA has planned a series of "Sprints" to work with industry partners in implementing the features and develop proposed specifications for USSs in order to to participate in TCL4. This report describes Sprint Two. In this Sprint, there was a major theme with four goals. The theme was the development and testing of a new USS discovery system, to better enable USSs to find and communicate with each other. The goals supporting this theme were: participants needed to implement and exercise the discovery service for USS-USS communications; USSs needed to demonstrate strategic deconfliction through operation sharing; the systems were to use discovery to aid in handling off-nominal operations; and finally, there was an investigation of an initial off-nominal reporting capability

UTM UAS Serivce Supplier Development: Sprint 1 Toward Technical Capability Level 4

NASA's UAS Traffic Management (UTM) Project has been tasked with developing concepts and initial implementations for integrating and managing small unmanned aircraft systems (UAS) into the low altitude airspace. To accomplish this task, the Project planned a phased approach based on four Technical Capability Levels (TCLs). As of this writing, TCL4 is currently in development for a late Spring 2019 flight demonstration. This TCL is focused on operations in an urban environment and includes the handling of high density and large-scale off-nominal conditions, vehicle-to-vehicle communications, detect-and-avoid technologies, communication requirements, public safety operations, airspace restrictions, and other related goals. Through research and testing to date, NASA has developed an architecture for UTM that depends on commercial entities collaboratively providing services that are traditionally provided by the Air Navigation Service Provider(ANSP) in manned aviation. A key component of this architecture is the UAS Service Supplier (USS), which acts as a communications bridge between UAS operators and the ANSP when necessary. In addition, the collection of USSs form a USS Network to collaboratively manage the airspace through the sharing of data and the adherence to a standard or set of standards required to participate in this USS Network. This document provides a record of the first step in the development of interoperable USSs that will ultimately support TCL4 flight testing and formalization of the overall UTM concept. To develop these USSs and the underlying specifications for them, NASA has planned a series of "Sprints" to work with industry partners in implementing the features and proposed specifications for USSs to participate in TCL4. This report describes Sprint One. In this Sprint, the focus was on establishing a baseline for the Application Programming Interfaces (APIs) and their associated data models. In addition, the concept of UAS Volume Reservations (UVR) (areas that impose restrictions on sUAS that are allowed to operate) was tested. NASA provided the specifications and iterated on them with partners while implementers developed to those specifications. NASA then tested each partner's implementation to ensure compatibility with all other implementers. This process helped all stakeholders gain confidence that the foundation for future Sprints was solid

Admission and Discharge Practices Among Assisted Living Communities: the Role of State Regulations and Organizational Characteristics

A better understanding of factors associated with assisted living admission and discharge practices can help identify communities that are more likely to allow residents to age in place. This study examined how state regulations and assisted living organizational characteristics relate to community admission and discharge practices for bathing, getting out of bed, and feeding

An Exploratory Model of the Relationships Between Cancer-Related Trauma Outcomes on Quality of Life in Non-Hodgkin Lymphoma Survivors

Given that more than one-third of some cohorts of cancer survivors exhibit post-traumatic stress disorder (PTSD) symptomatology, this study examines how trauma outcomes might relate to quality of life (QOL). Eight hundred thirty survivors of adult lymphoma were assessed for PTSD, post-traumatic growth (PTG) and QOL. Structural equation modeling revealed that QOL was best explained by the model in which stressors (e.g., co-morbidities) were mediated by PTSD and PTG. Trauma outcomes mediated the relationship between specific stressors and QOL. These findings support using PTSD and PTG as a diagnostic framework in understanding symptomatology in survivors

Post-Traumatic Stress Outcomes in Non-Hodgkin's Lymphoma Survivors

A large body of evidence suggests that being diagnosed with and treated for cancer adversely affects functioning and quality of life, yet less is known about longer term outcomes. Therefore, this study aims to estimate the prevalence of post-traumatic stress disorder (PTSD) symptoms in survivors of adult non-Hodgkin’s lymphoma (NHL) who are at least 2 years postdiagnosis and identify the risk factors associated with PTSD symptoms, with a focus on those that are amenable for screening and modifiable

A National Typology of Health Service Regulation in Assisted Living

Background and Objectives State regulating agencies use 350 different licenses and certifications to govern assisted living (AL), resulting in significant variation in regulations governing health services, the scope of practice, and capacity. This lack of standardization makes it difficult to compare and contrast AL operations and residents’ outcomes across similarly regulated communities. Research Design and Methods We used qualitative and quantitative methods to empirically develop and describe a typology of state AL regulations that captures inter and intra-state variation. Based on the rules governing health services, we created regulatory specificity scores for five thematic dimensions: medication administration, third-party care, skilled nursing, medication review, and licensed nurse staffing. With these scores, we conducted a K-means cluster analysis to identify groups of AL license types. To differentiate the regulatory types, we calculated standardized mean differences across structure, process, outcome, and resident characteristics of the AL communities licensed under each type. Results We identified six types of AL differentiated by the regulatory provisions governing health services: Housing, Holistic, Hybrid, Hospitality, Healthcare, and Health Support. The types align with previous work and reflect tangible differences in resident characteristics, health service structures, processes, and outcomes. Discussion and Implications This typology effectively captures differences across regulated dimensions and can inform and support quality of care. Researchers, policymakers, and consumers may benefit from using this typology and acknowledging these differences in AL licensure when designing research studies, developing policies, and selecting an AL community

Prevalence and molecular characterization of Clostridium difficile isolated from feedlot beef cattle upon arrival and mid-feeding period

<p>Abstract</p> <p>Background</p> <p>The presence of indistinguishable strains of <it>Clostridium difficile </it>in humans, food animals and food, as well as the apparent emergence of the food-animal-associated ribotype 078/toxinotype V as a cause of community-associated <it>C. difficile </it>infection have created concerns about the potential for foodborne infection. While studies have reported <it>C. difficile </it>in calves, studies of cattle closer to the age of harvest are required. Four commercial feedlots in Alberta (Canada) were enrolled for this study. Fecal samples were collected at the time of arrival and after acclimation (< 62, 62-71 or > 71 days on feed). Selective culture for <it>Clostridium difficile </it>was performed, and isolates were characterized by ribotyping and pulsed-field gel electrophoresis. A logistic regression model was built to investigate the effect of exposure to antimicrobial drugs on the presence of <it>C. difficile</it>.</p> <p>Results</p> <p><it>Clostridium difficile </it>was isolated from 18 of 539 animals at the time of feedlot arrival (CI = 2.3-6.1) and from 18 of 335 cattle at mid-feeding period (CI = 2.9-13.1). Overall, there was no significant difference in the prevalence of <it>C. difficile </it>shedding on arrival versus mid-feeding period (<it>P </it>= 0.47). No association between shedding of the bacterium and antimicrobial administration was found (<it>P </it>= 0.33). All the isolates recovered were ribotype 078, a toxinotype V strain with genes encoding toxins A, B and CDT. In addition, all strains were classified as NAP7 by pulsed field gel electrophoresis (PFGE) and had the characteristic 39 base pairs deletion and upstream truncating mutation on the <it>tcd</it>C gene.</p> <p>Conclusions</p> <p>It is apparent that <it>C. difficile </it>is carried in the intestinal tracts of a small percentage of feedlot cattle arriving and later in the feeding period and that ribotype 078/NAP7 is the dominant strain in these animals. Herd management practices associated with <it>C. difficile </it>shedding were not identified, however further studies of the potential role of antimicrobials on <it>C. difficile </it>acquisition and shedding are required.</p

Cooperative learning in the first year of undergraduate medical education

<p>Abstract</p> <p>Background</p> <p>Despite extensive research data indicating that cooperative learning promotes higher achievement, the creation of positive relationships, and greater psychological health for students at all levels in their education, cooperative learning as a teaching strategy is still underutilized in undergraduate medical education.</p> <p>Methods</p> <p>A cooperative learning task was introduced as part of the mandatory first Year undergraduate Pathology course. The task was to create an 8.5" × 11" poster summary of pre-assigned content in self-chosen groups of four or five students. On the designated "Poster Day," the posters were displayed and evaluated by the students using a group product evaluation. Students also completed an individual group process reflection survey. An objective evaluation of their understanding was gauged at the midterm examination by specific content-related questions.</p> <p>Results</p> <p>Majority (91–96%) of students judged the group products to be relevant, effective, easy-to-understand, and clearly communicated. The majority of the students (90–100%) agreed that their group process skills of time management, task collaboration, decision-making and task execution were effective in completing this exercise. This activity created a dynamic learning environment as was reflected in the students' positive, professional discussion, and evaluation of their posters. The content-related questions on the midterm examination were answered correctly by 70–92% of the students. This was a mutually enriching experience for the instructor and students.</p> <p>Conclusion</p> <p>These findings demonstrate that cooperative learning as a teaching strategy can be effectively incorporated to address both content <it>and </it>interpersonal skill development in the early years of undergraduate medical education.</p

Post-Traumatic Stress Symptoms in Long-Term Non-Hodgkin's Lymphoma Survivors: Does Time Heal?

Little is known about the trajectory of post-traumatic stress disorder (PTSD) symptoms in cancer survivors, despite the fact that such knowledge can guide treatment. Therefore, this study examined changes in PTSD symptoms among long-term survivors of non-Hodgkin's lymphoma (NHL) and identified demographic, clinical, and psychosocial predictors and correlates of PTSD symptomatology