cssi/SciSciGPT-SciSciNet huggingface dataset:
Defining the temporal course of murine neurofibromatosis-1 optic gliomagenesis reveals a therapeutic window to attenuate retinal dysfunction.

Background Optic gliomas arising in the neurofibromatosis type 1 (NF1) cancer predisposition syndrome cause reduced visual acuity in 30%-50% of affected children. Since human specimens are rare, genetically engineered mouse (GEM) models have been successfully employed for preclinical therapeutic discovery and validation. However, the sequence of cellular and molecular events that culminate in retinal dysfunction and vision loss has not been fully defined relevant to potential neuroprotective treatment strategies. Methods Nf1flox/mut GFAP-Cre (FMC) mice and age-matched Nf1flox/flox (FF) controls were euthanized at defined intervals from 2 weeks to 24 weeks of age. Optic nerve volumes were measured, and optic nerves/retinae analyzed by immunohistochemistry. Optical coherence tomography (OCT) was performed on anesthetized mice. FMC mice were treated with lovastatin from 12 to 16 weeks of age. Results The earliest event in tumorigenesis was a persistent elevation in proliferation (4 wk), which preceded sustained microglia numbers and incremental increases in S100+ glial cells. Microglia activation, as evidenced by increased interleukin (IL)-1β expression and morphologic changes, coincided with axonal injury and retinal ganglion cell (RGC) apoptosis (6 wk). RGC loss and retinal nerve fiber layer (RNFL) thinning then ensued (9 wk), as revealed by direct measurements and live-animal OCT. Lovastatin administration at 12 weeks prevented further RGC loss and RNFL thinning both immediately and 8 weeks after treatment completion. Conclusion By defining the chronology of the cellular and molecular events associated with optic glioma pathogenesis, we demonstrate critical periods for neuroprotective intervention and visual preservation, as well as establish OCT as an accurate biomarker of RGC loss.
Effect of trihalomethanes (chloroform and bromoform) on human haematological count.

With the increasing concerns about the harmful effects of disinfection products the process of chlorination is becoming questionable. Bromoform and chloroform are among the most frequently occurring disinfection by-products. Haematological parameters are an important indicator of human well-being which is why the prime objective of the current study was to conduct a dose–response assessment to investigate the effects of trihalomethanes on human haematological count. Blood samples of healthy subjects were exposed to different concentrations (10, 30 and 50 μg/mL) of chloroform and bromoform in vitro to analyse how these compounds affected the haematological count with increasing dose concentrations . Headspace gas chromatography analysis was also conducted on samples to assess the difference between measured and spiked values of doses. The results indicated that the damage caused by bromoform was statistically more significant as compared to chloroform. Haemoglobin (HGB) and mean corpuscular haemoglobin concentration levels lowered as they were significantly affected ( p p p p > 0.05).
The potential relaxation instability in a helicon plasma

High positive grid biasing ( >10Te) in a large-scale helicon plasma at the University of New Mexico has led to the excitation of large fluctuations (>50%) in ion saturation current and floating potential at a low frequency (100–300 Hz). These fluctuations have been identified as an instability and have been studied under a variety of conditions, including variations in the bias voltage, magnetic field strength, and the length of the plasma column. A series of measurements with Langmuir probes has been used to analyze the characteristics of the fluctuations. The instability has been found to travel predominately along the axis with a speed of 1–3cs, where cs is the ion sound speed. The frequency of the mode is found to be dependent on the bias voltage. Increasing the grid bias leads to an increase in the frequency until a second critical voltage causes the fluctuations to disappear. The magnetic field and plasma length are found to affect the amplitude of the mode and the voltage range over which it exists. This mode has been identified as the potential relaxation instability.
Th17 Cells in Parkinson's Disease: The Bane of the Midbrain.

Emerging data implicate potential roles for T cells in Parkinson's disease (PD); however, direct evidence for human T cells in PD-associated neurodegeneration has been lacking. In this issue of Cell Stem Cell, Sommer et al. (2018) demonstrate that IL-17-producing T cells from sporadic PD patients promote cell death of patient iPSC-derived midbrain neurons.
Anatomy of Olivocochlear Neurons

Hair cell receptors for the hearing and balance organs, and the lateral line, are unique among the senses by receiving an efferent innervation of the periphery. Olivocochlear (OC) neurons supply this efferent innervation, and they are the most peripheral of the many descending neural systems of the central auditory pathway (see Schofield, Chap. 9). OC neurons are named by their origins in the superior olivary complex and terminations in the cochlea (Fig. 2.1). In the cochlea, they innervate the hair cells and auditory-nerve fibers. This chapter mainly covers the new ground on OC anatomy in mammals since Warr’s (1992) comprehensive chapter on this topic about 15 years ago. Since that time, there is even stronger evidence for the separate innervation of the periphery by the two major groups of OC neurons. It is also now clear that both of these groups consist of distinct subgroups. There is additional information on the reflex pathways leading up to OC neurons that enables their response to sound. Overall, this anatomy may help to define the functions that OC neurons perform in the sense of hearing.
The Battle for Leyte Gulf: Symbolic Mathematics

On October 20, 1944, the United States began its invasion of the Philippines. The ensuing seven-week Battle for Leyte Gulf was the largest naval engagement in history. The United States committed 216 combat ships to the battle, but the Japanese could muster only 64. Knowing that the U.S. had superior naval power in the theater, the Japanese fleet split into three forces and employed a series of feints. The plan was to use one of the forces to draw the bulk of the U.S. fleet out of position. On October 24 this strategy worked when the U.S. Third Fleet was drawn away.
Phenotypes of Recurrent Wheezing in Preschool Children: Identification by Latent Class Analysis and Utility in Prediction of Future Exacerbation.

Background Recurrent preschool wheezing is a heterogeneous disorder with significant morbidity, yet little is known about phenotypic determinants and their impact on clinical outcomes. Objective Latent class analysis (LCA) was used to identify latent classes of recurrent preschool wheeze and their association with future exacerbations and inhaled corticosteroid (ICS) treatment response. Methods Data from 5 clinical trials of 1708 children aged 12 to 71 months with recurrent wheezing were merged. LCA was performed on 10 demographic, exposure, and sensitization variables to determine the optimal number of latent classes. The primary outcome was the annualized rate of wheezing exacerbations requiring systemic corticosteroids during the study intervention period; the secondary outcome was the time to first exacerbation. Exploratory analyses examined the effect of daily ICS treatment on exacerbation outcomes. Results Four latent classes of recurrent wheezing were identified; these were not distinguished by current symptoms or historical exacerbations but differed with regard to allergen sensitization and/or exposures. Annualized exacerbation rates (mean ± SEM/year) were 0.65 ± 0.06 for class 1 ("minimal sensitization"), 0.93 ± 0.10 for class 2 ("sensitization with indoor pet exposure"), 0.60 ± 0.07 for class 3 ("sensitization with tobacco smoke exposure"), and 0.81 ± 0.10 for class 4 ("multiple sensitization and eczema") (P Conclusions Sensitization and exposure assessments are useful in the prediction of future exacerbation and may identify children most likely to respond favorably to daily ICS treatment.
Video Game User Experience: To VR, or Not to VR?

Virtual reality (VR) has become an alternative medium for entertainment purposes, ranging from watching a movie to playing video games. Given the increasing use of VR for video gaming, the current study investigated whether VR gaming might affect the video gaming user experience (UX). We compared three different gaming platforms, namely desktop computer, Oculus Rift, and HTC Vive, in terms of gaming UX satisfaction. A total of 48 participants were randomly assigned to one of the three gaming platforms. Participants played a first-person shooter video game for ten minutes and provided game UX satisfaction ratings. Results revealed no statistically significant differences across the three platforms in video game UX satisfaction levels. Participants, however, rated desktop gaming as significantly more usable, when compared to the two VR conditions. In addition, sense of presence was a strong predictor of game UX satisfaction. Taken together, these results indicate that VR gaming may not always be a better alternative to traditional desktop gaming in terms of video game UX satisfaction, while at the same time providing further support for the putative role sense of presence plays in game satisfaction.
Bilateral central retinal artery occlusion from catastrophic antiphospholipid syndrome.

A 23-year-old woman with history of systemic lupus erythematous presented with dizziness and headache and was admitted for the stroke workup. During her stay, she had sudden painless loss of vision in her right eye consistent with central retinal artery occlusion (CRAO). Ocular massage and paracentesis were attempted without success to resume the flow. She was started on oral high-dose steroids (1 mg/kg) for lupus flare and therapeutic anticoagulation for antiphospholipid syndrome (positive for anticardiolipin and beta-2 microglobulin antibodies). On day 4, she started having painful bluish discoloration of her left index finger and right fifth toe, and on day 5 she had acute onset of left blurry vision with findings consistent with CRAO. She fulfilled the criteria of catastrophic antiphospholipid syndrome and was started on intravenous pulse steroids, plasmapheresis and higher international normalised ratio goal of 3–3.5 with improvement in her left eye vision from 20/200 to 20/20 on near card test by the end of treatment.
Before You Were Born I Consecrated You (Jeremiah 1:5, NRSV): Spiritual Resilience and Resistance Within Transgender Families and Communities

Transgender individuals remain highly stigmatized and discriminated against within our society. While DSM understandings of gender dysphoria contribute to this stigma, much remains rooted in religious interpretations that view transgender identities as sinful. These beliefs and related experiences of rejection and discrimination place transgender people at high risk for both self-harm and violence from others. Socially just clinical practice with trans individuals, couples, and families must incorporate two processes: (1) an exploration of ways faith and religion may contribute to experiences of loss, pain, internalized oppression, or trauma, and (2) the development of resilience strategies that facilitate a positive sense of self, spirituality, hope, and resistance. Using an extended case example, I will demonstrate these two processes while providing specific clinical interventions for increasing resilience and resistance in the transgender community.
Presentation and eustachian tube function test results in children evaluated at a specialty clinic

OBJECTIVES/HYPOTHESIS Interest in eustachian tube (ET) dysfunction (ETD) has increased with the recent Food and Drug Administration approval of a new device for balloon dilation of the ET (BDET) in adults. However, children have been receiving BDET treatment with ET-specific or sinus balloons around the world and off-label in the United States for years. It is important, therefore, to understand the manifestations of and methods to verify ETD in children. STUDY DESIGN Retrospective cross-sectional study. METHODS This is a retrospective study of clinical presentations and results of ET function (ETF) tests in children referred to the ETD clinic. An otorhinolaryngology exam, nasopharyngeal videoendoscopy of the ET orifices during swallow and maneuvers, and ETF tests, including inflation deflation, forced response test, and pressure chamber tests, were performed as applicable. RESULTS Data for 30 children aged 6.2 to 17.3 years (mean = 12.9 ± 2.8 years) were analyzed. Of 60 ears, 19 (31.7%) had an intact tympanic membrane (TM), 16 (26.7%) had a patent and two had a blocked ventilation tube, and 23 (38.3%) had a TM perforation. Endoscopy of the nasopharynx revealed a large amount of secretions in 19/45 (42.2%); ET orifices and mucosal inflammation in 22/45 (48.8%); a large amount of adenoid tissue in the fossa of Rosenmuller was noted in 21/45 (46.7%). ETF tests revealed abnormal active function in 43/54 ears (79.6%) and abnormal passive function in 40/54 ears (74.1%). CONCLUSIONS ETD in children is often associated with residual or regrowth of adenoids and inflammation. Caution should be taken assigning a uniform phenotype and treatment prior to thorough evaluation and testing. LEVEL OF EVIDENCE 4 Laryngoscope, 129:1218-1228, 2019.
Transformation Politics: The Debate Between Václav Havel and Václav Klaus on the Free Market and Civil Society

In 1994 then-Prime Minister Vaclav Klaus and playwright-President Vaclav Havel engaged in a spirited debate over proposed changes to the Czech constitution that would have decentralized power and strengthened the authority of local governments. Although few commentators at the time grasped the significance of the exchange, the dispute became the basis of a long-standing feud between the Czech leaders. "Regionalism," as the controversy was characterized in the press, went to the heart of the difficulties that postcommunist countries have faced as they began establishing free market economic systems and building the social structures neces sary to support democracy. Even beyond the immediate political and economic issues involved in the Czech Republic, the discus sion raised questions concerning the nature of human beings and the most fitting way to organize social life in the post-Cold War era.1
2011 Texas Estate Planning Legislative Update

This article reviews the legislation enacted by the 2011 Texas Legislature relating to the Texas law of intestacy, wills, estate administration, trusts, and other estate planning matters.
Accuracy of Dopamine Transporter Imaging with 123I-Ioflupane in Hispanic and Non-Hispanic Patients

Racial and ethnic disparities in the prevalence of neurodegenerative diseases exist. This study examined the agreement between gold standard diagnosis and visual assessment of dopamine transporter (DaT) imaging in Hispanic and non-Hispanic patients being evaluated for Parkinsonian syndromes (PS). Methods: A retrospective review of DaT imaging and demographic data was performed with institutional review board approval. Documented interpretation by visual assessment was used to classify scans as normal or abnormal. The gold standard for the final diagnosis of PS was determined by a neurologist after 2 or more years of clinical follow-up. Data were analyzed with a z-test for uncorrelated samples. Results: In 30 Hispanic patients, DaT imaging was abnormal in 17, normal in 12, and nondiagnostic in 1. Of those with abnormal imaging, PS was confirmed in 16 of 17. Of those with normal imaging, no PS was confirmed in any patient. Sensitivity was 100%, and specificity was 92%. The single patient with nondiagnostic imaging was excluded. Of 77 non-Hispanic patients, visual assessment of DaT imaging was abnormal in 51. Of those with abnormal imaging, PS was confirmed in 48 of 51. Of those with normal imaging, no PS was confirmed in 22 of 26. Sensitivity was 92%, and specificity was 88%. There was no statistically significant difference (z = 0.34) in the rates of agreement between the gold standard and DaT imaging in Hispanic versus non-Hispanic patients. The study sample size afforded a power of 0.60. Conclusion: No significant difference was found in the accuracy of DaT imaging between Hispanic and non-Hispanic patients. Accuracy was high for both groups.
Fraternity Chapter Masculine Norm Climates as Predictors of Social Dominance Hazing Motivations

Relying on data collected from a college social fraternity (n = 2,678) represented at 76 institutions, the study utilized hierarchical linear modeling to explore if collective fraternity chapter tr...
Electrical Insulation Packaging for a 20 kV High Density Wide Bandgap Power Module

In this paper, we introduce a new substrate design "protruding stacked substrate" that in combination with applying nonlinear field dependent conductivity (FDC) materials to high electric stress regions can thoroughly address the electrical field enhancement issue within a 20-kV high-density wide bandgap (WBG) module.
Zimbabwe's AIDS action programme for schools: a case study.

In October 1991 in Zimbabwe UNICEF-Harare proposed an AIDS education program for schools. The Ministry of Education and Culture began such a program in January 1992. The AIDS Action Programme for Schools includes development of syllabi; development pretesting and distribution of core and supplementary materials; training education officials and teachers; and a research monitoring and evaluation component. Between August 1993 and December 1994 140 district workshops were held to develop the district level training capacity. A key lesson learned for training was the need for integration of participatory methods and core materials (e.g. live teaching sessions with pupils). In February 1994 AIDS education was introduced into 27 colleges under the Ministry of Higher Education (MHE). A lack of ability at the MHE head office prevented preservice training from succeeding. Three baseline surveys were conducted on the knowledge attitudes and practices of pupils toward AIDS. By July 1995 89% of primary school heads and 90% of the teachers had used the AIDS textbooks in class. Yet only about 33% of teachers used the materials prescribed in the teachers book. About 33% of teachers had received training in AIDS education. AIDS education was integrated into other subjects rather than being a separate subject. Participatory methods and life skills were poorly understood. Some teachers were embarrassed to address sexual issues. AIDS education materials have been introduced into more than 6000 schools. AIDS program managers are willing to assess their problems and make corrections as necessary. Key lessons learned are described: school-based AIDS education is both necessary and feasible; a key to success is willingness to learn and to adapt; one must start quickly but plan properly; orientation training and supervision of writers are important; and detailed planning and careful monitoring are needed for teacher training. Another essential component is effective research monitoring and evaluation.
Prognostic value of diffusion-weighted MRI for post-cardiac arrest coma

Objective To validate quantitative diffusion-weighted imaging (DWI) MRI thresholds that correlate with poor outcome in comatose cardiac arrest survivors, we conducted a clinician-blinded study and prospectively obtained MRIs from comatose patients after cardiac arrest. Methods Consecutive comatose post-cardiac arrest adult patients were prospectively enrolled. MRIs obtained within 7 days after arrest were evaluated. The clinical team was blinded to the DWI MRI results and followed a prescribed prognostication algorithm. Apparent diffusion coefficient (ADC) values and thresholds differentiating good and poor outcome were analyzed. Poor outcome was defined as a Glasgow Outcome Scale score of ≤2 at 6 months after arrest. Results Ninety-seven patients were included, and 75 patients (77%) had MRIs. In 51 patients with MRI completed by postarrest day 7, the prespecified threshold of >10% of brain tissue with an ADC Conclusions This prospective, clinician-blinded study validates previous research showing that an ADC 10% of brain tissue in an MRI obtained by postarrest day 7 is highly specific for poor outcome in comatose patients after cardiac arrest.
β-catenin and PD-L1 expression in mismatch repair deficient endometrial carcinomas.

Introduction Predictors of non-response in mismatch repair deficiency cancers are poorly understood. Upregulation of the canonical Wnt pathway has been associated with decreased immune cell infiltration in many cancer types. The relationship between Wnt/β-catenin pathway activation and the programmed death-ligand 1 axis in endometrial cancer remains poorly characterized. This study evaluates β-catenin expression in a well characterized cohort of endometrial cancers by mismatch repair status and programmed death-ligand 1 expression. Methods Whole sections of formalin-fixed, paraffin embedded tissue from 23 Lynch syndrome-associated carcinomas, 20 mutL homolog-1 (MLH1) promoter hypermethylated carcinomas, and 19 mismatch repair intact carcinomas were evaluated. Immunohistochemistry staining for β-catenin and programmed death-ligand 1 was performed on all cases. Programmed death-ligand 1 expression was scored in both the tumor and the peri-tumoral immune compartment. Tumor staining was classified as positive when membranous (programmed death-ligand 1) staining was present in ≥1% of tumor cells. Immune stromal staining was scored as positive when ≥5% of peritumoral and intratumoral immune cells (including lymphocytes and macrophages) showed reactivity. Results Six tumors (6/62, 9.7%) demonstrated nuclear expression of β-catenin (4 were Lynch syndrome-associated, 1 was MLH1 methylated, 1 was mismatch repair intact). The majority of tumors with nuclear β-catenin expression demonstrated concomitant tumoral programmed death-ligand 1 expression (5/6, 83.3%) and were more likely to demonstrate tumoral programmed death-ligand 1 expression compared to tumors without nuclear β-catenin expression (83.3% vs 39.3%, p=0.04). Both tumoral and immune cell expression of programmed death-ligand 1 was statistically significantly associated with mismatch repair deficient tumors. Discussion Tumors demonstrating nuclear β-catenin expression were more likely to express tumoral programmed death-ligand 1 staining than tumors without nuclear β-catenin expression. Nuclear β-catenin expression could be a potential predictive biomarker for non-response to immune checkpoint inhibition in mismatch repair deficient tumors. Nuclear β-catenin expression status should be considered as a translational endpoint in future clinical trials of immune checkpoint inhibition in endometrial cancer.
Associations Between Hormonal Biomarkers and Preterm Infant Health and Development During the First 2 Years After Birth.

Background:Testosterone levels have been used to examine infant boys’ vulnerability to health and developmental problems, following the general theories of gender differences and the theory of extr...
E-097 Technical outcomes of mechanical thrombectomy using the sofia plus aspiration catheter

Introduction The Sofia Plus aspiration catheter (Microvention; Tustin, CA) is a recently introduced 0.070-inch inner diameter catheter designed to provide distal intracranial access and engage thrombus to facilitate thrombectomy for acute ischemic stroke. Methods This single-center retrospective study assessed technical outcomes of mechanical thrombectomy using the Sofia Plus aspiration catheter. Utilizing a prospective database of all acute stroke interventions at our institution, cases utilizing SOFIA Plus on the first pass were identified. Patient characteristics, procedural details, and radiographic outcomes were analyzed. Results Sofia Plus was utilized as a first pass aspiration catheter in 138 cases. Patients presented with a median NIHSS of 17 (IQR 10–22), ASPECT of 10 (IQR 8–10), and had target occlusions involving the ICA (n=30), M1 (n=73), M2 (n=22), or basilar artery (n=13). The aspiration catheter was used for first-pass direct aspiration alone in 86 patients (62%), and in conjunction with a stent retriever in 52 patients (38%). A recanalization grade of TICI 2b or better was achieved in 118 patients (86%), which was accomplished with a single pass in 88 (64%). Median time from groin puncture to recanalization was 44 minutes (IQR 30–68). Comparison of direct aspiration alone versus with stent retrievers demonstrated no difference in recanalization grade (p=0.64) or rates of first-pass recanalization (p=0.28), but direct aspiration was associated with faster recanalization (41 vs 53 minutes, p=0.02). There were two cases of vessel perforation (both involving stent retrievers), and two additional patients had symptomatic ICH on follow-up CT. Conclusions Our experience demonstrates that the SOFIA Plus aspiration can facilitate safe and effective revascularization for acute ischemic stroke, either using a direct aspiration technique or in conjunction with a stent-retriever. However, reperfusion was achieved faster with direct aspiration alone. Disclosures A. Witek: None. T. Patterson: None. L. Sheikhi: None. M. Bain: 2; C; Medtronic PLC, Stryker Corp. M. Hussain: 2; C; Johnson & Johnson. G. Toth: None.
Reforming Canada’s war prerogative

In Canada, the power to declare war and deploy the military is sourced in the royal prerogative. In this paper, I argue that it is time to place the war prerogative on statutory footing. The deploy...
Secondary Surgery and Residual Dysplasia Following Late Closed or Open Reduction of Developmental Dysplasia of the Hip.

Background Outcomes studies following successful closed reduction of late-detected developmental dysplasia of the hip (DDH) reveal high rates of secondary reconstructive surgery with limited comparative data demonstrating lower rates of residual dysplasia with open reduction. The purpose of this study was to compare long-term outcomes, with regard to radiographic evidence of residual dysplasia and secondary reconstructive procedures, between late closed and late open reduction for DDH in patients 6 to 24 months of age at reduction. Methods We identified all patients between 6 and 24 months of age who underwent closed or open reduction for DDH between 1980 and 2008 and were followed until at least 10 years of age. Outcomes included radiographic measurement of acetabular dysplasia after triradiate cartilage closure, development of osteonecrosis, and the need for secondary procedures for residual dysplasia. Results One hundred and four hips underwent index closed reduction and 54 hips underwent index open reduction. There was no significant difference in the age at reduction (p = 0.07). Among the 116 hips for which initial anteroposterior pelvic radiographs were available, most closed reductions (55%) were performed in International Hip Dysplasia Institute (IHDI) grade-III hips whereas most open reductions (71%) were performed in IHDI grade-IV hips. Analysis of the hips that did not undergo a secondary procedure showed that those with an index open reduction had a greater lateral center-edge angle (mean and standard deviation, 27.2° ± 10.0° versus 22.4° ± 6.8° in the closed reduction cohort; p = 0.02), lower femoral head extrusion index (22.2% ± 8.9% versus 26.0% ± 6.2%; p = 0.04), and lower Sharp angle (43.3° ± 6.0° versus 46.6° ± 3.1°; p = 0.002) at triradiate closure. There was no difference in the prevalence of osteonecrosis (Bucholz-Ogden grades II, III, and IV) between the closed and open reduction cohorts (22% versus 19%, respectively; p = 0.60). Secondary procedures were performed more frequently after closed reduction than after open reduction (47% versus 30%, respectively; p = 0.03). Conclusions In patients with late reduction of DDH, closed reduction was associated with increased residual dysplasia and it was associated with a higher rate of secondary surgery in those >12 months old despite a decreased severity of displacement based on the IHDI classification. Additional, prospective studies with assessment of functional outcomes are needed to validate these findings. Level of evidence Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Subcutaneous tiletamine-zolazepam immobilization and effect of flumazenil reversal in African pygmy hedgehogs (Atelerix albiventris)

ABSTRACT African pygmy hedgehogs (Atelerix albiventris) are popular zoological companion animals that routinely require chemical immobilization for veterinary care. The objective of this randomized, blinded, cross-over study was to evaluate the efficacy of low and high dosages of subcutaneous (SC) tiletamine-zolazepam for sedation and the efficacy of flumazenil for recovery in African pygmy hedgehogs. Twelve adult hedgehogs (7 males, 5 females) were administered tiletamine-zolazepam at 10 mg/kg (T10) or 30 mg/kg (T30) SC. Physiologic variables, reflexes and behaviors were monitored to evaluate quality of immobilization. Forty-five minutes after tiletamine-zolazepam injection, hedgehogs were administered flumazenil or an equivalent volume of saline SC. Baseline daily food intake was measured and then recorded daily for 6 days following sedation trials. Median (interquartile range [IQR]) time to onset of first effects for T10 and T30 was 2.9 minutes (2.5–5.3 minutes) and 2 minutes (1.4–2.9 minutes), respectively. Eighty-three percent of T10 and 100% of T30 hedgehogs lost righting reflex. The median (IQR) duration righting reflex was lost for T10 was 32.5 minutes (23.8–37.5 minutes) and it was lost for 47.5 minutes (36.25–63.75 minutes) for T30. Jaw tone was reduced in the majority of animals for both dosages but never lost. Heart and respiratory rate for both treatments remained within normal limits. Hedgehogs became rapidly hypothermic after induction. Flumazenil administration did not have a statistically significant effect on recovery time, but mean recovery times were 18 minutes faster for T10 hedgehogs administered flumazenil. There were no statistically significant differences in food intake within or between dosages of tiletamine-zolazepam at any time point for hedgehogs administered saline or flumazenil; however, mean food intake over the 6 days following T10 administration was 16 g/kg more for hedgehogs administered flumazenil. SC tiletamine-zolazepam at 10 and 30 mg/kg produces dose-dependent heavy sedation to light anesthesia in hedgehogs. Subjectively, while both dosages provided a sufficient depth of immobilization to permit a physical examination and noninvasive procedures like blood collection or diagnostic imaging, some jaw tone was maintained precluding endotracheal intubation. T30 provided a deeper level of immobilization than T10 but longer recovery times. Flumazenil administration did not have a statistically significant effect on recovery but recovery times were noticeably faster following SC flumazenil in hedgehogs sedated with T10. For hedgehogs immobilized with T10, mean food intake was greater when flumazenil was administered. Tiletamine-zolazepam provides an injectable option for immobilization of hedgehogs.
27363 Forging Collaboration and the Scalable Dissemination of Biomedical Research Commercialization Education

ABSTRACT IMPACT: A robust and collaborative network of expertise and services is essential for successful research commercialization, including timely and scalable educational support for CTSA institutions and individual faculty investigators with biomedical innovations. OBJECTIVES/GOALS: Leverage expertise at the University of Michigan (UM) by creating collaborative and scalable interactive online courses to instruct and prepare internal and external faculty to navigate critical stages of life science academic research commercialization. METHODS/STUDY POPULATION: UM’s Fast Forward Medical Innovation created two online courses with the UM Office of Technology Transfer and the Michigan Institute for Clinical & Health Research (MICHR). Collaborative planning committees, with content and educational experts, set course goals and learning objectives based on audience needs (e.g. preparation for consultations, commercialization concepts, etc.). Draft content was developed, peer reviewed, and revised before Articulate Storyline was used to convert didactic content to active learning content (e.g. interactive slides, scenarios, quizzes, and forms). Pilot testing was conducted prior to the launch to faculty investigators throughout the UM network. RESULTS/ANTICIPATED RESULTS: Intellectual Property in the Academic Setting launched via the FFMI website and newsletter in July 2020 and has had 66 learners to date. Medical Device Regulations launched in October 2020 and has 22 learners. OTT and MICHR have successfully integrated the courses into their consultation process by requesting review from faculty investigators. We suspect that this will lead to more in-depth and meaningful conversation. Additionally, these courses have been integrated into an FFMI commercialization course to instruct on critical concepts. Evaluation and refinement for both use cases will ensue, as well as inform future collaborative courses. DISCUSSION/SIGNIFICANCE OF FINDINGS: Early results suggest that the courses are advantageous and can serve as a model for future collaborations. The opportunity to disseminate the courses across the CTSA network, as well as collaborate with other institutions, to scale localized expertise to a broader network is promising.
Trans‐ovo permethrin exposure affects growth, brain morphology and cardiac development in quail

Permethrin is a commonly used, highly effective pesticide in poultry agriculture, and has recently been trialed in conservation efforts to protect Galapagos finch hatchlings from an invasive ectoparasite. Although permethrin is considered safe for adults, pesticides can have health consequences when animals are exposed during early life stages. The few studies that have examined permethrin's effects in embryonic chicks and rats have shown hydrocephaly, anencephaly, reduced cellular energy conversion, and disruption of developing heart muscle. To test whether trans-ovo exposure of permethrin affects early development in birds, we exposed Japanese quail (Coturnix japonica) eggs to cotton treated with 1% permethrin that was incorporated into nests in two amounts (0.2, 0.8 g), each with a paired untreated cotton control group. When measured on incubation Day 15, we found permethrin-treated developing birds were smaller and showed signs of microcephaly, although mortality rates were the same. Despite no difference in heart mass, ventricular tissue was less compact, cardiac arteries were reduced and heart rates were slower in permethrin-treated birds. Differences in heart development were also observed at 5 days of incubation, indicating that abnormalities are present from early in cardiac development. Future studies are needed to examine permethrin's effects on developmental pathways and to determine if these effects persist after hatching to affect offspring health. This study provides evidence that permethrin can cross the eggshell to cause non-lethal but adverse effects on embryonic development, and studies should look beyond hatching when monitoring the efficacy of permethrin on wild bird populations.
First results of a randomized phase IB study comparing nivolumab/ipilimumab with or without CBM-588 in patients with metastatic renal cell carcinoma.

4513Background: Recent evidence suggests that the gut microbiome is a potent mediator of immune checkpoint inhibitor (ICI) activity in metastatic renal cell carcinoma (mRCC), with both specific bac...
Tree root mounds and their role in transporting soil on forested landscapes

The growth and decay of tree roots can stir and transport soil. This is one process that contributes to the mass-movement of soil on hillslope. To explore the efficiency of this process, we document the mounding of soil beside Ponderosa and Lodgepole pine trees in the forests that dominate the mid-elevations of Colorado's Boulder Creek watershed. Mounds are best expressed around Ponderosa pines, reaching vertical displacements above the far-field slopes of order 10–20 cm, fading into the slope by roughly 100 cm distance from the trunks with common diameters of 30 cm. Positive mounding occurs on all sides of trees on slopes, indicating that the mounding is not attributable to deflection of a creeping flow of soil around the tree, but rather to the insertion of root volume on all sides in the subsurface. Mounding is commonly asymmetric even on cross-slope profiles. Significant variation in the mound sizes results in no clear relationship between tree diameter and root volume displaced. These observations motivated the development of a discrete element model of tree root growth using the LIGGGHTS model, in which grains we specified to be ‘root cells’ were allowed to enlarge within the simulated granular matrix. Mounding could be reproduced, with the majority of the vertical displacement of the surface being attributable to reduction of the bulk density due to dilation of the granular matrix during root enlargement. Finally, we develop a previous analysis of the role of roots in transporting soil during growth and decay cycles. We find that even in shallow soils, the root-cycle can drive significant soil transport down forested montane slopes. Copyright © 2013 John Wiley & Sons, Ltd.
Testing Copula Functions as a Method to Derive Bivariate Weibull Distributions

This paper presents copula functions as a method to derive bivariate distributions. Copula functions allow for the construction of previously unknown bivariate distributions based on known marginals. This paper uses Weibull marginals to construct six bivariate Weibull distributions suitable for survival analysis. The paper tests the performance of these distributions with a simulation experiment. The results from the experiment show that all bivariate distributions perform as well or better than the marginal distribution. Furthermore, some bivariate distributions perform better than others. However, performance is not the only element to consider in the selection of a distribution. The structure of dependence between marginals and estimation complexity are also key criteria for the selection of the right copula.
A useful method for producing competitive ad hoc task results

This paper reports the final results of our experiments involving the 2009 INEX Ad-Hoc Track and describes the methodology upon which our current, 2010 experiments are built. In 2009, our INEX investigations centered on indentifying a methodology for producing what we have referred to as improved focused elements--i.e., elements which when evaluated are competitive with others in the upper ranges of the official rankings. Our 2009 INEX paper [5] describes our approach to producing such elements, which is based on the combination of traditional document retrieval (to identify the document set of interest to the query) with our method of dynamic element retrieval (to generate and retrieve the elements of the document(s) so identified) and the subsequent application of a specific focusing technique for the Focused and Relevant-in-Context tasks (to select the focused elements). The system is based on the Vector Space Model [10]; basic functions are performed using the Smart experimental retrieval system [9]. In this paper, we report the final results of these experiments, applied to the INEX 2009 Thorough, Focused and Relevant-in-Context tasks. Results show that this approach produces highly ranked results for all three of these Ad Hoc tasks. Significance tests, applied to these results as compared to the top-ranked runs, show in which cases statistically significant results are obtained. Our 2010 work is ongoing at present.
Unanticipated Influence of Coordination Mechanisms on Physician Workstyles and ED Operational Efficiency

The coordination of activities in a work context has been examined by many disciplines and in recent years the role of information systems and other artifacts has become increasingly prominent. The emergency department (ED) of a hospital in a large US city is used to study how information systems and other coordinating mechanisms affect how physicians choose to perform their work and how such choices can impact the operational performance of the ED as a whole. The study used direct observation of the work performed in the ED, interviews of physicians, nurses and other ED staff members, and the analysis of historical performance data. The key findings were that the workstyles adopted by physicians were shaped by incidental characteristics of coordination mechanisms. Some workstyles appear to have adverse, albeit unintended, effects on aspects of the department's operational performance.
Study of the Effects of Pressure-Induced Viscmity Changes on the Fluid Flow Characteristics in a Circular Tube

6 = fj. = v = p = Nomenclature fluid compressibility factor, in./lb length of pressure release tube, in. fluid pressure, lb/in. pressure in pressure pot at time equal to zero, lb/in. atmospheric pressure, lb/in. volume rate of fluid flow, in./sec radial and longitudinal coordinates, in. internal radius of the pressure release tube, in. event time, msec volume of fluid in reservoir, in. volume of fluid that exits the reservoir during depressurization, in. longitudinal velocity of fluid within bore of pressure release tube, in./sec time constant, msec coefficient of viscosity of fluid, lb-sec/in. kinematic viscosity of fluid, in./sec mass density of fluid, slugs/in.
The Cerebral Cortex of Reptiles

Reptiles and mammals are the two groups of vertebrates with well-developed cerebral cortices. Ray-finned fishes have forebrains that develop by an eversion of the rostral neural tube that reduces the roof of the telencephalon to a thin membrane (Nieuwenhuys, 1982; Northcutt and Davis, 1983). They have olfactory cortices on the ventrolateral walls of their cerebral hemispheres (e.g., Braford and Northcutt, 1974), but the eversion process seemingly precludes the formation of a cortical roof to the telencephalon. Cartilaginous fishes (such as sharks), fleshy-finned fishes (lungfishes and coelacanths), amphibians, reptiles, birds, and mammals all have forebrains that develop via a fundamentally different process. This involves an evagination of the rostral neural tube resulting in paired lateral ventricles, interventricular foramina, and a neuronal roof to the telencephalon that can form an extensive cerebral cortex. However, the telencephalic roof of sharks forms a solid mass of neurons lacking the lamination usually associated with the cerebral cortex (Smeets et al., 1983). Although amphibians (Northcutt and Kicliter, 1980) and lungfishes (Northcutt, 1986) have laminated cortices, they show little migration of neurons away from the ependyma. Birds have a small cerebral cortex, ostensibly resulting from a secondary reduction of the reptilian pattern (Benowitz, 1980). It is only in reptiles and mammals that the telencephalic roof develops into extensive and multilayered cortices.
Level set methods in image science

In this article, we discuss the question "what level set methods can do for image science". We examine the presence of these and related methods in image science and introduce some relevant level set techniques that are potentially useful for this class of applications. We will show that image science demands multidisciplinary knowledge and flexible but still robust methods, and that is why the level set method has become a thriving technique in this field.
Timing Driven Placement for Quasi Delay-Insensitive Circuits

Asynchronous circuits offer promise in handling current and future technology scaling challenges. Unfortunately, their impact has been limited by the lack of design automation. We present A-NTUPLACE, a timing-driven placer uniquely suited to handling quasi delay-insensitive circuits. Our tool uses a generalization of repetitive event rule systems to identify critical signal transitions. The cell placement engine, based on a leading academic placer, NTUPlace3, incorporates net weights to minimize critical wire lengths as well as a novel balancing scheme to ensure isochronic fork constraints are met. We show that our placer is effective at both prioritizing selected nets and balancing forks, demonstrating improvements in 3 of our 4 benchmarks.
Nucleic acid chaperone activity of HIV-1 nucleocapsid protein: critical role in reverse transcription and molecular mechanism.

Publisher Summary This chapter focuses on recent biochemical and biophysical studies that examine the nucleic acid chaperone function of HIV‐1 nucleocapsid protein (NC) and its critical role in facilitating specific and efficient reverse transcription. This chapter also describes the effect of NC on individual steps in viral DNA synthesis. This chapter also summarizes what is known about NC structure, NC nucleic acid binding properties, and the contribution of the zinc fingers to chaperone activity. In addition, this chapter also discusses new evidence that provides a model to explain the mechanism of NC's nucleic acid chaperone activity at the molecular level. Characterization of the mechanism of NC's chaperone activity in molecular terms has been invaluable for understanding NC's effect on specific steps in reverse transcription. NC binds nucleic acids noncooperatively and does not rely on protein– protein interactions to drive aggregation and annealing. Instead, NC‐induced nucleic acid aggregation appears to be facilitated by simple polyelectrolyte attraction, similar to that observed for many multivalent cations.
Ultra heavy nuclei in the cosmic radiation

This paper describes the measurements of the Ultra-Heavy cosmic ray abundances obtained by the Heavy Nuclei Experiment aboard the NASA High Energy Astronomy Observatory-3. A subset of the HEAO data which has been recently determined to give improved resolution in the charge region from Z = 40 to 60 is described and preliminary abundances from these data are given. In general we find that the cosmic ray abundances are in broad agreement with solar system abundances with a step-FIP fractionation model applied although in detail there are some differences. In particular Ge and Pb appear to be underabundant in the cosmic radiation. However if the recent solar photospheric abundance estimates of Grevesse and Meyer for Ge and Pb are used, solar system abundances are brought into agreement with our data. Although the platinum/lead ratio and the actinides are consistent with some r-process enhancement, we see that the cosmic ray source is not dominated by the r-process up through the 50’s as evidenced by the Sr/Rb ratio and by the abundance of Sn and Ba. In addition the actinides are not greatly enhanced, ruling out freshly synthesized r-process production as the primary source of the heavy cosmic rays.
Outcome of Patients With Low-Risk and Intermediate-1-Risk Myelodysplastic Syndrome After Hypomethylating Agent Failure A Report on Behalf of the MDS Clinical Research Consortium

Background The hypomethylating agents (HMAs) azacitidine and decitabine are most commonly used to treat patients with higher-risk myelodysplastic syndromes (MDS). To the authors' knowledge, the prognosis of patients with low-risk and intermediate-1– risk MDS by the International Prognostic Scoring System (IPSS) after HMA failure has not been explored comprehensively.
Relative contribution of synaptic and non-synaptic influences to response decrements in a post-synaptic neurone.

1. Repeated trans-synaptic stimulation of the giant neurone in the abdominal ganglion from Aplysia californica produced decrements of nervous activity. 2. Although the EPSP amplitude decreased during the stimulation, the firing probability of the post-synaptic neurone continued to decrease after the amplitude had reached a constant low value. 3. When the cell was hyperpolarized and stimulated until the EPSP had decreased to a constant low value, the firing probability immediately after removal of the hyper polarization was the same as with no previous stimulation. 4. These results and previous work suggest that a process occurring in the post-synaptic neurone, independent of synaptic modification, may contribute significantly to habituation-like phenomena.