Supercritical-Carbon Dioxide-Assisted Cyclic Deposition of Metal Oxide and Metal Thin Films

Thin films of aluminum oxide and palladium were deposited on silicon at low temperatures (70-120 °C) by a cyclic adsorption/reaction processes using supercritical CO2 solvent. Precursors included Al(hfac)3, Al(acac)3, and Pd(hfac)2, and aqueous H2O2, tert-butyl peracetate, and H2 were used as the oxidants or reductants. For the precursors studied, growth proceeds through a multilayer precursor adsorption in each deposition cycle, and film thickness increased linearly with the number of growth cycles

Thermal Analysis of Adsorbed Poly(Methyl Methacrylate) on Silica

Modulated differential scanning calorimetry has been used to quantify the glass transitions of small, adsorbed amounts of poly (methyl methacrylate) (PMMA) on silica. While a relatively narrow, single glass transition was found for bulk PMMA, broader two-component transitions were found for the adsorbed polymer. a two-state model based on loosely bound polymer (glass transition similar to bulk) and more tightly bound polymer (glass transition centered around 156°C) was used to interpret the thermograms. on the basis of this model, the amount of tightly bound polymer was found to be approximately 1.3 mg/m 2, corresponding to a 1.1 nm thick layer. the change in heat capacity for the tightly bound polymer at the glass transition temperature was estimated to be about 16% of that of the bulk polymer. © 2006 American Chemical Society

Increased risk for other cancers in individuals with Ewing sarcoma and their relatives.

BackgroundThere are few reports of the association of other cancers with Ewing sarcoma in patients and their relatives. We use a resource combining statewide genealogy and cancer reporting to provide unbiased risks.MethodsUsing a combined genealogy of 2.3 million Utah individuals and the Utah Cancer Registry (UCR), relative risks (RRs) for cancers of other sites were estimated in 143 Ewing sarcoma patients using a Cox proportional hazards model with matched controls; however, risks in relatives were estimated using internal cohort-specific cancer rates in first-, second-, and third-degree relatives.ResultsCancers of three sites (breast, brain, complex genotype/karyotype sarcoma) were observed in excess in Ewing sarcoma patients. No Ewing sarcoma patients were identified among first-, second-, or third-degree relatives of Ewing sarcoma patients. Significantly increased risk for brain, lung/bronchus, female genital, and prostate cancer was observed in first-degree relatives. Significantly increased risks were observed in second-degree relatives for breast cancer, nonmelanoma eye cancer, malignant peripheral nerve sheath cancer, non-Hodgkin lymphoma, and translocation sarcomas. Significantly increased risks for stomach cancer, prostate cancer, and acute lymphocytic leukemia were observed in third-degree relatives.ConclusionsThis analysis of risk for cancer among Ewing sarcoma patients and their relatives indicates evidence for some increased cancer predisposition in this population which can be used to individualize consideration of potential treatment of patients and screening of patients and relatives

Caloric Restriction Alters Postprandial Responses of Essential Brain Metabolites in Young Adult Mice

Caloric restriction (CR) has been shown to extend longevity and protect brain function in aging. However, the effects of CR in young adult mice remain largely unexplored. In addition to the fundamental, long-term changes, recent studies demonstrate that CR has a significant impact on transient, postprandial metabolic flexibility and turnover compared to control groups. The goal of this study was to identify the brain metabolic changes at a transient (2 h) and steady (6 h) postprandial state in young mice (5–6 months of age) fed with CR or ad libitum (AL; free eating). Using metabolomics profiling, we show that CR mice had significantly higher levels of neurotransmitters (e.g., glutamate, N-acetylglutamate), neuronal integrity markers (e.g., NAA and NAAG), essential fatty acids (e.g., DHA and DPA), and biochemicals associated carnitine metabolism (related to reduced oxidative stress and inflammation) in the cerebral cortex and hippocampus at 2-h. These biochemicals remained at high levels at the 6-h postprandial time-point. The AL mice did not show the similar increases in essential fatty acid and carnitine metabolism until the 6-h time-point, and failed to show increases in neurotransmitters and neuronal integrity markers at any time-point. On the other hand, metabolites related to glucose utilization—glycolysis and pentose phosphate pathway (PPP)—were low in the CR mice throughout the 6-h period and significantly increased at the 6-h time-point in the AL mice. Our findings suggest that CR induces distinct postprandial responses in metabolites that are essential to maintain brain functions. CR mice produced higher levels of essential brain metabolites in a shorter period after a meal and sustained the levels for an extended period, while maintaining a lower level of glucose utilization. These early brain metabolism changes in the CR mice might play a critical role for neuroprotection in aging. Understanding the interplay between dietary intervention and postprandial metabolic responses from an early age may have profound implications for impeding brain aging and reducing risk for neurodegenerative disorders

Associations of walkability, regional and transit accessibility around home and workplace with active and sedentary travel

Few studies have simultaneously examined whether the neighborhood built environment near work is independently associated with active versus sedentary travel. We investigate the associations of objectively assessed built environment and regional/transit accessibility around home and work locations with active (walking, biking) and sedentary (auto-use) transportation while controlling for attitudinal predispositions, perceptions, and demographic factors. Baseline data from 2012 to 2013 on a sample of 648 participants in the Rails & Health study based in Portland, Oregon were analyzed. Data about active and sedentary travel outcomes, attitudes, perceptions, and demographics were derived from a survey. Road network buffers (with a 1 km range) around each of the home and work locations were used to create detailed measures of walkability, natural environment, regional and transit accessibility. Log-linear and log-linear Tobit regression models tested associations of home and worksite neighborhood features with weekly amount of walking, biking, and auto use. Significant differences in walkability, regional accessibility, and natural environment between home and workplaces were observed. Independent of walkability around home, a one-unit increase in walkability index around work was correlated with a 2.8% [90% CI: 0.5% - 4.9%] and 2.7% [90% CI: 0.5% - 4.8%] higher weekly duration of biking and walking, respectively. Greater walkability around workplace was associated with lower time spent in automobiles. Greater regional and transit accessibility around work was correlated with higher walking/biking and lower automobile travel. The study highlights the important role of more walkable, connected, denser, and diverse workplace environments in enhancing public health

LEAD 2.0: An Interprofessional Leadership Curriculum

Purpose: To develop knowledge, skills, and attitudes about leadership for graduate medical education trainees, junior nurses, and allied health trainees. Background: Many graduate medical education (GME) trainees, junior nurses, and allied health professionals complete training with exceptional clinical skills, but are not equipped to assume leadership roles or work well within teams. The goal of LEAD 2.0 is fill the gap for those assuming leadership positions, and to enhance the leadership skills of all trainees. Intervention: Walter Reed National Military Medical Center’s Department of GME developed an interprofessional leadership curriculum called LEAD 2.0 in 2016. The curriculum of LEAD 2.0 was derived from a systematic review of existing leadership curricula as well as a local needs assessment focusing on content, format, barriers, and logistics. The curriculum is composed of 8 core topics, each with well-defined goals and objectives: leadership fundamentals (leadership styles, definitions, etc.), mentoring and coaching, emotional intelligence, conflict resolution, feedback, managing effectively, building an effective team, and implementing change). Teaching methods are interactive and based on the Kolb Learning Cycle and Adult Learning Theory. LEAD 2.0 sessions are 1.5 hours long and occur monthly. Preliminary Results: Four sessions have been completed with 106 interprofessionals attending at least one session. Survey results suggest that sessions are useful and leading to changes in leadership behaviors among participants. Ninety percent (18/20) of those attending Leadership 101 (n=53) who responded to a post-class survey said the session was useful and 95% (19/20) said they were inspired to learn more about leadership. Recommendations: 1. Participants want materials that allow for interactive teaching sessions to include personal leadership inventories and case studies. 2. Speakers should be a mix of local speakers and outside experts if possible. 3. Logistics and timing should be coordinated with all stakeholders well in advance to allow for maximal participation. Learning Objectives: Determine the key elements of a successful interprofessional leadership curriculum. Demonstrate potential teaching strategies for leadership development. Recognize optimal methods for evaluating a leadership curriculum

Genetic basis of thermal nociceptive sensitivity and brain weight in a BALB/c reduced complexity cross

Thermal nociception involves the transmission of temperature-related noxious information from the periphery to the CNS and is a heritable trait that could predict transition to persistent pain. Rodent forward genetics complement human studies by controlling genetic complexity and environmental factors, analysis of end point tissue, and validation of variants on appropriate genetic backgrounds. Reduced complexity crosses between nearly identical inbred substrains with robust trait differences can greatly facilitate unbiased discovery of novel genes and variants. We found BALB/cByJ mice showed enhanced sensitivity on the 53.5°C hot plate and mechanical stimulation in the von Frey test compared to BALB/cJ mice and replicated decreased gross brain weight in BALB/cByJ versus BALB/cJ. We then identified a quantitative trait locus (QTL) on chromosome 13 for hot plate sensitivity (LOD = 10.7; p < 0.001; peak = 56 Mb) and a QTL for brain weight on chromosome 5 (LOD = 8.7; p < 0.001). Expression QTL mapping of brain tissues identified H2afy (56.07 Mb) as the top transcript with the strongest association at the hot plate locus (FDR = 0.0002) and spliceome analysis identified differential exon usage within H2afy associated with the same locus. Whole brain proteomics further supported decreased H2AFY expression could underlie enhanced hot plate sensitivity, and identified ACADS as a candidate for reduced brain weight. To summarize, a BALB/c reduced complexity cross combined with multiple-omics approaches facilitated identification of candidate genes underlying thermal nociception and brain weight. These substrains provide a powerful, reciprocal platform for future validation of candidate variants

Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals.

Innovative new crystallographic methods are facilitating structural studies from ever smaller crystals of biological macromolecules. In particular, serial X-ray crystallography and microcrystal electron diffraction (MicroED) have emerged as useful methods for obtaining structural information from crystals on the nanometre to micrometre scale. Despite the utility of these methods, their implementation can often be difficult, as they present many challenges that are not encountered in traditional macromolecular crystallography experiments. Here, XFEL serial crystallography experiments and MicroED experiments using batch-grown microcrystals of the enzyme cyclophilin A are described. The results provide a roadmap for researchers hoping to design macromolecular microcrystallography experiments, and they highlight the strengths and weaknesses of the two methods. Specifically, we focus on how the different physical conditions imposed by the sample-preparation and delivery methods required for each type of experiment affect the crystal structure of the enzyme

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

The Project ENABLE Cornerstone Randomized Controlled Trial: Study Protocol for a Lay Navigator-led, Early Palliative Care Coaching Intervention for African American and Rural-dwelling Advanced Cancer Family Caregivers

Background: Family caregivers play a vital, yet stressful role in managing the healthcare needs and optimizing the quality of life of patients with advanced cancer, from the time they are newly diagnosed until end of life. While early telehealth palliative care has been found to effectively support family caregivers, little work has focused on historically under-resourced populations, particularly African American and rural-dwelling individuals. To address this need, we developed and are currently testing Project ENABLE (Educate, Nurture, Advise, Before Life Ends) Cornerstone, a lay navigator-led, early palliative care coaching intervention for family caregivers of African American and rural-dwelling patients with newly diagnosed advanced cancer.Methods: This is a 2-site, single-blind, hybrid type I implementation-effectiveness trial of the Cornerstone intervention versus usual care. Cornerstone is a multicomponent intervention based on Pearlin’s Stress-Health Process Model where African American and/or rural-dwelling family caregivers of patients with newly diagnosed advanced cancer (target sample size = 294 dyads) are paired with a lay navigator coach and receive a series of six, brief 20–60-min telehealth sessions focused on stress management and coping, caregiving skills, getting help, self-care, and preparing for the future/advance care planning. Subsequent to core sessions, caregivers receive monthly follow-up indefinitely until the patient’s death. Caregiver and patient outcomes are collected at baseline and every 12 weeks until the patient’s death (primary outcome: caregiver distress at 24 weeks; secondary outcomes: caregiver: quality of life and burden; patient: distress, quality of life, and healthcare utilization). Implementation costs and the intervention cost effectiveness are also being evaluated.Discussion: Should this intervention demonstrate efficacy, it would yield an implementation-ready model of early palliative care support for under-resourced family caregivers. A key design principle that has centrally informed the Cornerstone intervention is that every caregiving situation is unique and each caregiver faces distinct challenges that cannot be addressed using a one-size-fits all approach. Hence, Cornerstone employs culturally savvy lay navigator coaches who are trained to establish a strong, therapeutic alliance with participants and tailor their coaching to a diverse range of individual circumstances