cssi/SciSciGPT-SciSciNet huggingface dataset:
Recovering stimulus locations using populations of eye-position modulated neurons in dorsal and ventral visual streams of non-human primates.

We recorded visual responses while monkeys fixated the same target at different gaze angles, both dorsally (lateral intraparietal cortex, LIP) and ventrally (anterior inferotemporal cortex, AIT). While eye-position modulations occurred in both areas, they were both more frequent and stronger in LIP neurons. We used an intrinsic population decoding technique, multidimensional scaling, to recover eye positions, equivalent to recovering fixated target locations. We report that eye-position based visual space in LIP was more accurate (i.e., metric). Nevertheless, the AIT spatial representation remained largely topologically correct, perhaps indicative of a categorical spatial representation (i.e., a qualitative description such as “left of” or “above” as opposed to a quantitative, metrically precise description). Additionally, we developed a simple neural model of eye position signals and illustrate that differences in single cell characteristics can influence the ability to recover target position in a population of cells. We demonstrate for the first time that the ventral stream contains sufficient information for constructing an eye-position based spatial representation. Furthermore we demonstrate, in dorsal and ventral streams as well as modeling, that target locations can be extracted directly from eye position signals in cortical visual responses without computing coordinate transforms of visual space.
And see ourselves as others see us: using general systems theory to differentiate managers from problems

This paper explains how General Systems Theory (GST)(1) can help managers. GST is more than a metaphor of complexity and interconnectedness. It is a specific scientific philosophy with extensions, such as cybernetics, that offer precise, and often counterintuitive, prescriptions for managing complex entities. The paper uses one company history to differentiate GST/cybernetic interpretation from traditional theory and to show why managers may find the GST interpretation useful.
Dynamics of the ITCZ Boundary Layer

AbstractThis paper presents high-resolution numerical solutions of a nonlinear zonally symmetric slab model of the intertropical convergence zone (ITCZ) boundary layer. The boundary layer zonal and meridional flows are forced by a specified pressure field, which can also be interpreted as a specified geostrophically balanced zonal wind field ug(y). One narrow on-equatorial peak in boundary layer pumping is produced when the forcing is easterly geostrophic flow along the equator and two narrow peaks in boundary layer pumping are produced on opposite sides of the equator (a double ITCZ) when the forcing is westerly geostrophic flow along the equator. In the case when easterlies are surrounding a westerly wind burst, once again a double ITCZ is produced, but the ITCZs have significantly more intense boundary layer pumping than the case of only westerly geostrophic flow. A comparison of the numerical solutions to those of classical Ekman theory suggests that the meridional advection term υ(∂υ/∂y) plays a vita...
Targeted therapies: GIST adjuvant therapy-some answers and more questions.

Imatinib is known to be effective in the first-line treatment of metastatic gastrointestinal stromal tumors. A randomized, placebo-controlled trial has now shown that imatinib is safe and improves recurrence-free survival when used as adjuvant therapy after surgical resection of a primary gastrointestinal stromal tumor.
Patterns of the Jurisdiction of the International Court

The jurisprudential attempts to classify the substantive jurisdiction of the Court are many.1 The criterion followed in each relates in most cases to the form, character, or timing of the consent of the parties to submit the dispute to the Court. In this study a classification based on the nature of the different patterns of substantive jurisdiction is suggested. Though objective in character, this suggested classification is clearly established on the differences that result from the involvement of different jurisdictional instruments in each pattern. Consequently, the easier method of distinguishing the suggested patterns would follow a “formai” criterion (examining the instruments) to reach the “objective” distinction.
TRANSIENT TESTING TECHNIQUES FOR JET NOISE RESEARCH

This paper presents the analysis and design of a shock tunnel to be used to study noise suppressor nozzles for supersonic and subsonic aircraft. The shock tube geometry is established using an ideal one-dimensional gas dynamic model with corrections to account for the growth of an unsteady boundary-layer. The nozzle and jet starting processes are described and estimates are made of the duration of the quasi-steady, fully-developed jet. Requirements for noise measurements are discussed, including frequency scaling, high frequency measurement limits, uncertainties in power spectral analysis, and required sampling times. The results suggest that a shock tunnel can be used as an effective and inexpensive means to conduct jet noise research. The short duration of the tests is the principal constraint associated with the use of such a facility and care must be taken in the design of the facility to ensure sufficiently long test times to allow useful acoustic measurements to be obtained. NOMENCLATURE
Mapping Novel Subcutaneous Angiogenesis Quantitative Trait Loci in [B6×MRL]F2 Mice.

Objective: MRL/MpJ mice are known for enhanced healing, but mechanistic details or how specific aspects of wounding (e.g., angiogenesis) contribute to healing are unknown. While previous studies investigated the systemic effects of immunity in MRL/MpJ healing, few have focused on tissue-intrinsic effects. Approach: Ex vivo skin biopsies from MRL/MpJ and C57BL/6J mice were cultured in ex vivo conditions that favor endothelial cell growth to compare their angiogenic potential. We localized enhanced angiogenesis quantitative trait loci (QTL) in an F2 intercross. We then performed an expression analysis in cultured skin biopsies from MRL/MpJ and C57BL/6J mice to determine the pathways that are associated with the capacity for differential growth. Results: MRL/MpJ biopsies have a two- to threefold greater growth potential than C57BL/6J mice, supporting the hypothesis that angiogenesis may contribute to enhanced healing in MRL/MpJ skin. We mapped two QTLs that are unique from previously mapped MRL/MpJ wound healing QTLs and detected interactions between wound healing QTLs and loci in this cross. Additionally, we found that pathways previously implicated in MRL/MpJ healing are also enriched in skin biopsies. Innovation: We have developed a novel approach to determine how specific aspects of tissue development contribute to wound healing that will ultimately lead to the discovery of unidentified genes that contribute to enhanced healing. Conclusion: We have shown that, consistent with previous studies following wound closure in MRL/MpJ mice, vessel growth during healing is also influenced by genetic background. Our ongoing work will identify the genetic factors that should be useful biomarkers or as therapeutic targets for enhanced wound healing.
Estimates of Eddy Heat Flux Crossing the Antarctic Circumpolar Current from Observations in Drake Passage

AbstractThe 4-yr measurements by current- and pressure-recording inverted echo sounders in Drake Passage produced statistically stable eddy heat flux estimates. Horizontal currents in the Antarctic Circumpolar Current (ACC) turn with depth when a depth-independent geostrophic current crosses the upper baroclinic zone. The dynamically important divergent component of eddy heat flux is calculated. Whereas full eddy heat fluxes differ greatly in magnitude and direction at neighboring locations within the local dynamics array (LDA), the divergent eddy heat fluxes are poleward almost everywhere. Case studies illustrate baroclinic instability events that cause meanders to grow rapidly. In the southern passage, where eddy variability is weak, heat fluxes are weak and not statistically significant. Vertical profiles of heat flux are surface intensified with ~50% above 1000 m and uniformly distributed with depth below. Summing poleward transient eddy heat transport across the LDA of −0.010 ± 0.005 PW with the stat...
Research on Light Metal Matrix Composites Reinforced by In-situ Synthesized Al_3Ti

Research on in-situ synthesized Al3Ti/Al and Al3Ti/Mg composites is reviewed.Reaction systems of in-situ Al3Ti,processing technology methods and characteristics of microstructures of composites are specifically introduced.Recent main problems and trends of further study on in-situ synthesized Al3Ti/Al and Al3Ti/Mg composites are pointed out.
Solitary leiomyoma of the prostate presenting as an encrusted intravesical mass.

AbstractA leiomyoma of the prostate presented as an encrusted intravesical mass on excretory urography. A prostatic leiomyoma usually is benign and is relatively rare with only 41 cases reported previously. Surgical and pathological findings and differential diagnosis are presented.
Reliability and Novelty: Information Gain in Multi-Level Selection Systems

Information about the environment is captured in human biological systems on a variety of interacting levels – in distributions of genes, linguistic particulars, concepts, methods, theories, preferences, and overt behaviors. I investigate some of the basic principles which govern such a hierarchy by constructing a comparatively simple three-level selection model of bee foraging preferences and behaviors. The information-theoretic notion of ''mutual information'' is employed as a measure of efficiency in tracking a changing environment, and its appropriateness in epistemological applications is discussed at some length. In particular, information accumulated in mid-level preference distributions exhibits suggestive properties for the purposes of naturalistic epistemology. It also appears that the novelty of scientific objects and representations and the rapidity of scientific change relative to genetic change need present no obstacle to the use of such models in explanations of scientific progress and the reliability of scientific judgement.
The Politics of Pure Science: Yukawa and Tomonaga

In 1954, the U.S. Information Service (USIS) produced the film “The Yukawa Story,” which was based on the life of the Nobel Prize-winning physicist Hideki Yukawa who had recently worked in the United States and returned to Japan to great acclaim. Narrated by one of his two sons, Takaaki, the film documented the life and work of Yukawa. Takaaki relates to the audience how he faced an Initial dilemma in reconciling his father’s world with his mother’s traditional one. He finally realizes that inductive reasoning and emotional appreciation of cultural heritages are synthesized in his parents’ lives.1
Finger Pain out of Proportion to Exam: A Case of Occult Hydrofluoric Acid Toxicity

Background: Hydrofluoric acid (HFA) toxicity can have significant morbidity and even mortality associated with seemingly small exposures. As a result of a delayed time to symptom onset, low concentration exposures may present as a diagnostic dilemma. Objective: To demonstrate an atypical case presentation of HFA exposure, the inherent diagnostic difficulty, and subtle clues to confirming the diagnosis. Case Report: We present the case of a 21 year old male day laborer who presented to the emergency department 12 hours after exposure to a cleaning agent used to “polish” metal with significant finger pain, minimal physical exam findings, and refractory to analgesics. He demonstrated hypocalcemiaand hypomagnesemia. The patient reported symptom resolution after treatment with topical calcium gluconate. Conclusion: This case demonstrates the importance of considering HFA toxicity in any patient who presents with pain, minimal physical exam findings, after exposure to an unknown chemical cleaning agent.Screening for the common electrolyte depletion associated with HFA toxicity may help to confirm the diagnosis as well as guide therapy.
Impaired fasting glucose is associated with increased severity of subclinical coronary artery disease compared to patients with diabetes and normal fasting glucose: evaluation by coronary computed tomographic angiography

Objective This study was designed to evaluate the severity of subclinical atherosclerosis in patients with asymptomatic impaired fasting glucose (IFG) compared to those with diabetes mellitus (DM) and normal fasting glucose (NFG), as measured by coronary computed tomographic angiography (CCTA). Design Subjects were divided into three groups: NFG ( Setting University hospital, single centre. Participants 216 asymptomatic participants prospectively underwent CCTA for the evaluation of coronary artery disease (CAD). Primary and secondary outcome measures Atherosclerotic plaque burden in IFG compared to NFG patients. Results 2664 segments were analysed in 120 NFG, 44 IFG and 52 DM participants. The mean calcium scores were 178±395, 259±510 and 414±836 for NFG, IFG and DM, respectively (p=0·037). The mean plaque burdens in the NFG, IFG and DM groups were 0.31±0.45, 0.50±0.69 and 0.68±0.69, respectively (p=0·0007). A greater proportion of patients with DM (19/52, 36.5%) and IFG (13/44, 29.5%) had obstructive CAD compared to those with NFG (16/120, 13.3%) (p=0.0015). The number of segments with severe disease was significantly higher in the DM (60/637, 9.4%) and IFG (42/539, 7.8%) groups compared to that in the NFG group (34/1488, 2.3%) (p=0.0001). Conclusions (1) IFG and DM have significantly higher, but comparable, calcium scores, plaque burden and obstructive CAD compared to NFG in asymptomatic individuals. (2) Pending corroboration by other reports, more intensive efforts may be devoted to the evaluation and treatment of patients with IFG.
The Long View of World Theatre History

The mere chronicling of events is the barest sort of history, for it makes little effort to understand why those events happened when and as they did. This chapter explores world theatre history’s temporal dimension by using Fernand Braudel’s concept of the longue duree. Given that this concept might seem to render human actions irrelevant, the chapter also takes up the issue of agency, arguing that although people operate within the historical contexts of the longue duree, they are the makers of theatre history. As aspects of the longue duree, the chapter discusses three kinds of structures that provide long-lived contexts in which theatre artists work: theatre forms themselves; theatrical structures within regional theatre complexes; and structures of the societal context such as language, religion, and ethnicity/race. It then discusses three long-term historical trends that have directly and indirectly impacted theatre history: technological expansion; increasing societal interactions; and accelerating urbanization.
Symptomatic Gallstones in the Young: Changing Trends of the Gallstone Disease-Related Hospitalization in the State of New York: 1996 - 2010

Background: The aim of the study was to evaluate if the gallstone-related hospitalizations in the young (< 20 years of age) have increased over time in both the Bronx County and New York State as a whole. Methods: We retrospectively reviewed 15 years (1996 - 2010) of Statewide Planning and Research Cooperative System (SPARCS) data of New York State Department of Health. Patients with ICD-9 code diagnosis of 574 (cholelithiasis) among the first three discharge diagnoses were reviewed. Results: Total number of all cause admissions to hospitals had increased from 2.44 million to 2.77 million (1996 - 2010). However, gallstone-related hospitalizations had decreased from 1.7% to 1.2%. It was noted that there was a 30% increment in the proportion of those below 20 years of age with gallstone disease requiring hospitalization over the same period. This young patient population contributed only 2.04% to all gallstone-related hospitalizations in 1996, whereas it had increased to 2.96% in 2010. This trend was more pronounced in women, Hispanics and in those who were residing in the Bronx County as compared to all other New York counties combined. Conclusion: The gallstone-related hospitalizations in the young (< 20 years of age) have increased over time in both the Bronx County and New York State as a whole. This could be due to increasing prevalence of risk factors such as obesity, physical inactivity, diabetes and early pregnancy. J Clin Med Res. 2017;9(2):117-123 doi: https://doi.org/10.14740/jocmr2847w
Exercise with weight loss improves adipose tissue and skeletal muscle markers of fatty acid metabolism in postmenopausal women.

Objective The effects of 6-month weight loss (WL) versus aerobic exercise training (AEX)+WL on fat and skeletal muscle markers of fatty acid metabolism were determined in normal (NGT) and impaired (IGT) glucose tolerant African-American and Caucasian postmenopausal women with overweight/obesity. Methods Fat (gluteal and abdominal) lipoprotein lipase (LPL), skeletal muscle LPL, acyl-CoA synthase (ACS), s-hydroxacyl-CoA dehydrogenase, carnitine palmitoyltransferase (CPT-1), and citrate synthase (CS) activities were measured at baseline (n = 104) and before and after WL (n = 34) and AEX+WL (n = 37). Results After controlling for age and race, muscle LPL and CPT-1 were lower in IGT, and the ratios of fat/muscle LPL activity were higher in IGT compared to NGT. Muscle LPL was related to insulin sensitivity (M value) and inversely related to G120, fasting insulin, and homeostatic model assessment of insulin resistance. AEX+WL decreased abdominal fat LPL and increased muscle LPL, ACS, and CS. The ratios of fat/muscle LPL decreased after AEX+WL. The change in VO2max was related to the changes in LPL, ACS, and CS and inversely related to the changes in fat/muscle LPL activity ratios. Conclusions Six-month AEX+WL, and not WL alone, is capable of enhancing skeletal muscle fatty acid metabolism in postmenopausal African-American and Caucasian women with NGT, IGT, and overweight/obesity.
Energy and carbon metabolisms in a deep terrestrial subsurface fluid microbial community

The terrestrial deep subsurface is a huge repository of microbial biomass, but in relation to its size and physical heterogeneity, few sites have been investigated in detail. Here, we applied a culture-independent metagenomic approach to characterize the microbial community composition in deep (1500 meters below surface) terrestrial fluids. Samples were collected from a former gold mine in Lead, South Dakota, USA, now Sanford Underground Research Facility (SURF). We reconstructed 74 genomes from metagenomes (MAGs), enabling the identification of common metabolic pathways. Sulfate and nitrate/nitrite reduction were the most common putative energy metabolisms. Complete pathways for autotrophic carbon fixation were found in more than half of the MAGs, with the reductive acetyl-CoA pathway by far the most common. Nearly 40% (29 of 74) of the recovered MAGs belong to bacterial phyla without any cultivated members—microbial dark matter. Three of our MAGs constitute two novel phyla previously only identified in 16 S rRNA gene surveys. The uniqueness of this data set—its physical depth in the terrestrial subsurface, the relative abundance and completeness of microbial dark matter genomes and the overall diversity of this physically deep, dark, community—make it an invaluable addition to our knowledge of deep subsurface microbial ecology.
Issues related to renal artery angioplasty and stenting

Renal artery stenosis may play a significant role in the pathogenesis of secondary hypertension, renal dysfunction, and flash pulmonary edema. Currently correction of renal arterial inflow stenosis is reserved for resistant hypertension patients who have failed maximal medical therapy, have worsening renal function and/or unexplained proximal congestive failure. With the recent advances in minimally invasive percutaneous stent placement techniques, open surgical revascularization has been largely replaced by renal artery stenting. The potential benefit of revascularization seemed intuitive; however, the initial enthusiasm and rise in the number of percutaneous interventions have been tempered by many subsequent negative randomized clinical trials that failed to prove the proposed benefits of the percutaneous intervention. The negative randomized trial results have fallen under scrutiny due to trial design concerns and inconsistent outcomes of these studies compared to pivotal trials undertaken under US Food and Drug Administration scrutiny. Treatment of atherosclerotic renal artery occlusive disease has become one of the most debatable topics in the field of vascular disease. The results from recent randomized clinical trials of renal artery stenting have basically limited the utilization of the procedure in many centers, but not every clinical scenario was covered in those trials. There are potential areas for improvement focusing mainly on procedural details and patient selection with respect to catheter based treatment of atherosclerotic renal artery stenosis. We believe, limiting patient selection, enrollment criteria and outcomes measured functioned to reduce the benefit of renal artery stenosis stenting by not enrolling patients likely to benefit. Future studies incorporating potential procedural improvements and that include patients more likely to benefit from renal stenting than were included in ASTRAL and CORAL are needed to more carefully examine specific patient subgroups so that "the baby is not thrown out with the bath water." We also discuss several other concerns related to renal artery stenting which include diagnostic, procedure, indication, and reimbursement issues.
A Formative Qualitative Evaluation to Inform Implementation of a Research Participation Enhancement and Advocacy Training Program for Diverse Seniors: The DREAMS Program.

This article reports on a formative qualitative evaluation conducted to identify potential barriers and facilitators prior to implementation of a two-part educational intervention designed to incre...
House of Mirrors:A Contextual Model of Reflected Appraisal in Organizations

Reflected appraisal refers to what individuals believe others think of them and has been studied under different guises in the organizational literature that includes (but is not limited to) percei...
Blue Light Endoscopy

The ability to accurately predict pathologic stage and grade of Upper Tract Urothelial Cell Carcinoma (UTUC) is crucial for prognostication and selection of appropriate therapeutic intervention. The advent of high definition flexible ureteroscopy has increased the use of minimally invasive endoscopic evaluation and treatment of UTUC. Nonetheless, accurate endoscopic staging of upper tract tumors remains challenged by difficult visualization and the limited size of the pathologic specimen obtained. Adjunct technology that could help accurately stage endoscopic biopsies would be of benefit to patients with UTUC. Blue light endoscopy (HAL-BLC) is such a technology, and has been recently adopted adjunct to standard white light endoscopy in bladder cancer management. Data on HAL-BLC show increasing rates of tumor detection and an increase in recurrence free survival. There are small, but promising early studies using photodynamic therapy in the upper tract which are reviewed herein.
Improving regression test efficiency with an awareness of refactoring changes

Abstract Context. Developers often improve software quality through refactorings—the practice of behavior-preserving changes to existing code. Recent studies showed that, despite their awareness of tool support for automated refactorings, developers prefer manual refactorings. This practice can be often error-prone and increase testing cost. Objective. To address the problem, we present the Refactorings Investigation and Testing technique, called R it . R it improves the testing efficiency for validating refactoring changes and providing confidence that changed parts behave as intended. As testing is expensive for developers of high-assurance software, R it reduces a considerable amount of its costs by only identifying dependent statements on a failure in each test and by detecting specific refactoring edits responsible for testing failures. Method. Our approach identifies refactorings by analyzing original and edited versions of a program. It then uses the semantic impact of a set of identified refactoring changes to detect tests whose behavior may have been affected and modified by refactoring edits. Given each failed asserts after running regression test suites, R it helps developers focus their attention on logically related program statements by applying program slicing for minimizing each test. For debugging purposes, R it determines specific failure-inducing refactoring edits, separating from other changes that only affect other asserts or tests. Results. We evaluated R it on three open source projects, and found that R it detected tests affected by refactorings with 80.9% accuracy on average. Furthermore, it identified and formed partitions relating program statements only dependent on failed asserts with 97.2% accuracy on average. Conclusion. R it , which combines a refactoring reconstruction technique with change impact analysis to localize failure-inducing program edits, helps developers localize fault causes by focusing on refactoring changes as opposed to all the code fragments in the new version.
Arctocebus calabrensis (Angwantibo)

The karyotypes were made from lymphocyte cultures and kindly donated by Dr. L.E.M. de Boer (Rotterdam). Identification of the sex chromosomes is tentative. An idiogram and measurements are provided by de Boer (1973).
Konzeption und Strategie in der chirurgischen Gastroenterologie

Erfolgreiche Chirurgie verlangt Studium, genaue Planung, klares Denken und technische Genauigkeit. Die „brillante“ Ausfuhrung einer Operation zum falschen Zeitpunkt kann nur zum Desaster fuhren. Um aber in jeder chirurgischen Situation gute Ergebnisse zu erzielen, mus der Chirurg ein Konzept entwickeln, das grundliches Literaturstudium, die Kenntnis der Physiologie und die logischen Grundlagen der beabsiehtigten Operation zum Inhalt hat.
Powerful Modelling Tools for High School Algebra Students

The high school algebra curriculum can be significantly enhanced by incorporating modelling problems, tools, and techniques. In particular, difference equations, matrices, and spreadsheets serve the dual purpose of enhancing students content knowledge and socializing students into the world of mathematical modelling. Especially when used together, these simple tools have great power for predicting behavior “in the long run” and for investigating changes in initial conditions that can affect what happens in the future—a major concern in almost every field of application that uses mathematics today. But merely incorporating new material is not enough; the psychology and previous experience of the learners must be considered.
Ascending Sensory Pathways

The classic view of two largely independent somatosensory channels, the dorsal column-medial lemniscus system for tactile sensitivity and position sense, and the spinothalamic system for pain and temperature sensitivity, has been modified in recent years through the discovery of additional spinal pathways for transmission of sensory impulses to the brain. This is highly significant, because the sensory symptoms that appear in patients with lesions in the CNS have sometimes been difficult to explain by the traditional dual-processing theory. They can now be better appreciated on the basis of a more dynamic view of the somatosensory pathways.
Distributed Hierarchal Clustering Algorithm Utilizing a Distance Matrix

Dividing similar objects into a smaller number of clusters is of importance in many applications. These include search engines, monitoring of academic performance, biology and wireless networks. We first discuss a number of clustering methods. We present a parallel algorithm for the efficient clustering of proteins into groups. The input consists of an n by n distance matrix. This matrix would be built differently for different applications. A two simple points in space can have the Euclidean distance in the matrix. As another example, the Root-Mean-Square-Deviations (RMSD) values can be computed for any two 3-D structures and used and the distance between them. The second step is to utilize parallel processors to calculate a hierarchal cluster of these n items based on this matrix. We have implemented our algorithm and have found it to be scalable.
Experimental Studies on Seismic Response of Skew Bridges with Seat-Type Abutments. I: Shake Table Experiments

AbstractGirder unseating in skewed bridges with seat-type abutments has been frequently observed in past earthquakes. This has been attributed to excessive in-plane rotation of the superstructure, ...
Capturing the Friedmans

Directed by Andrew Jarecki HBO Video 2003, 107 minutes, Not Rated, $21.99 Andrew Jarecki's Capturing the Friedmans is an ambiguous unsettling film that documents the crude investigation and predict...
Reasons and influential recommendations associated with HPV vaccination among Chinese college students in the USA.

Objectives: To evaluate (a) reasons for not receiving recommended doses of the human papillomavirus (HPV) vaccine, (b) the most influential recommending source in getting the HPV vaccine, and (c) a...
Characterization of on-target adverse events caused by TRK inhibitor therapy

Background The tropomyosin receptor kinase (TRK) pathway controls appetite, balance, and pain sensitivity. While these functions are reflected in the on-target adverse events (AEs) observed with TRK inhibition, these AEs remain under-recognized, and pain upon drug withdrawal has not previously been reported. As TRK inhibitors are approved by multiple regulatory agencies for TRK or ROS1 fusion-positive cancers, characterizing these AEs and corresponding management strategies is crucial. Patients and methods Patients with advanced or unresectable solid tumors treated with a TRK inhibitor were retrospectively identified in a search of clinical databases. Among these patients, the frequency, severity, duration, and management outcomes of AEs including weight gain, dizziness or ataxia, and withdrawal pain were characterized. Results Ninety-six patients with 15 unique cancer histologies treated with a TRK inhibitor were identified. Weight gain was observed in 53% [95% confidence interval (CI), 43%–62%] of patients and increased with time on TRK inhibition. Pharmacologic intervention, most commonly with glucagon-like peptide 1 analogs or metformin, appeared to result in stabilization or loss of weight. Dizziness, with or without ataxia, was observed in 41% (95% CI, 31%–51%) of patients with a median time to onset of 2 weeks (range, 3 days to 16 months). TRK inhibitor dose reduction was the most effective intervention for dizziness. Pain upon temporary or permanent TRK inhibitor discontinuation was observed in 35% (95% CI, 24%–46%) of patients; this was more common with longer TRK inhibitor use. TRK inhibitor reinitiation was the most effective intervention for withdrawal pain. Conclusions TRK inhibition-related AEs including weight gain, dizziness, and withdrawal pain occur in a substantial proportion of patients receiving TRK inhibitors. This safety profile is unique relative to other anticancer therapies and warrants careful monitoring. These on-target toxicities are manageable with pharmacologic intervention and dose modification.
1169-P: Democratizing Type 1 Diabetes Specialty Care in the Primary Care Setting: Project ECHO T1D

Project ECHOTM (Extension for Community Healthcare Outcomes) is a hub-spoke telehealth outreach model that democratizes specialty knowledge to reduce disparities and improve health outcomes. Limited access to endocrinologists forces many primary care providers (PCPs) to manage patients with type 1 diabetes (T1D) without specialty support. As such, Stanford and the University of Florida partnered to develop and pilot “ECHO T1D”, a teleECHOTM clinic focused on T1D in California (CA) and Florida (FL), respectively. Our goal was to demonstrate the feasibility of ECHO T1D and improve PCPs’ abilities to manage patients with T1D. Primary care spokes were recruited targeting Federally Qualified Health Centers (FQHCs) where vulnerable T1D patient populations more likely rely on PCPs for care. In CA, 11 spokes enrolled with 37 clinics serving ∼900 patients with T1D who do not receive routine specialty T1D care. In FL, 12 spokes enrolled with 67 clinics serving ∼1,000 patients with T1D. Multidisciplinary hub team specialists were recruited and a 6-month curriculum was developed. Weekly 1-hour teleECHO sessions consisting of didactic presentations and case reviews were offered for 27 sessions. Weekly engagement of the 70 participating PCPs (69% in CA) ranged from 0 to 27 (mean 14) sessions and 65 completed both baseline and exit surveys. Baseline data demonstrated low confidence in providing T1D care, especially related to diabetes technology. Pre/post surveys demonstrated statistically significant improvements in provider confidence in T1D management and knowledge (p=0.02). PCPs who attended ≥ 50% sessions had the largest improvements. Over 90% of PCPs reported changes in medical practice (e.g., insulin and pump adjustments) and 95% would recommend the program to colleagues. The ECHO model can be applied to T1D to improve PCPs’ ability to manage patients with T1D. Future directions include evaluating influence on patient level outcomes and applying the model to insulin-requiring T2D patients. Disclosure N. Cuttriss: None. C. Anez-Zabala: None. L.G. Baer: None. S.L. Filipp: None. M. Basina: None. M.J. Gurka: None. L. Figg: None. M.J. Haller: Advisory Panel; Self; SAB Biotherapeutics, Inc. K.K. Hood: Research Support; Self; Dexcom, Inc. Speaker’s Bureau; Self; LifeScan, Inc., MedIQ. X. Roque: None. R. Lal: Consultant; Self; Abbott, Biolinq. S.C. Westen: None. D.M. Maahs: Advisory Panel; Self; Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk A/S. Consultant; Self; Abbott, Sanofi. Research Support; Self; Bigfoot Biomedical, Dexcom, Inc., Roche Diabetes Care, Tandem Diabetes Care. M. Town: Other Relationship; Self; Insulet Corporation. C. Wang: None. J.J. Wong: None. K. Yabut: None. A.F. Walker: None. Funding The Leona M. and Harry B. Helmsley Charitable Trust
Observability Driven Path Generation for Delay Test Coverage Improvement in Scan Limited Circuits

Delay test is used to verify the timing performance of integrated circuits. The test requires launching rising or falling transitions into the circuit and capturing the results after the specified delay. All the sequential elements in the design are required to be implemented with scan flip-flops such that the captured data can be observed for correct behavior. If the result is captured at a non-scan flip-flop, or a memory, it cannot be read out, resulting in fault coverage loss. This research describes an observability-based algorithm to transfer results captured in non-scan flip-flops to scan flip-flops using low speed functional clock cycles, termed coda cycles, so the results can be read out. We demonstrate the algorithm using path delay test on ISCAS89 benchmark circuits, where a fraction of the scan flip-flops have been made non-scan, and demonstrate the improvement in coverage when adding coda cycles to the clocking method.
Data models, representation and adequacy-for-purpose

We critically engage two traditional views of scientific data and outline a novel philosophical view that we call the pragmatic-representational (PR) view of data. On the PR view, data are representations that are the product of a process of inquiry, and they should be evaluated in terms of their adequacy or fitness for particular purposes. Some important implications of the PR view for data assessment, related to misrepresentation, context-sensitivity, and complementary use, are highlighted. The PR view provides insight into the common but little-discussed practices of iteratively reusing and repurposing data, which result in many datasets’ having a phylogeny—an origin and complex evolutionary history—that is relevant to their evaluation and future use. We relate these insights to the open-data and data-rescue movements, and highlight several future avenues of research that build on the PR view of data.
MRI-assessed locus coeruleus integrity is heritable and associated with multiple cognitive domains, mild cognitive impairment, and daytime dysfunction

Author(s): Elman, Jeremy A; Puckett, Olivia K; Beck, Asad; Fennema-Notestine, Christine; Cross, Latonya K; Dale, Anders M; Eglit, Graham ML; Eyler, Lisa T; Gillespie, Nathan A; Granholm, Eric L; Gustavson, Daniel E; Hagler, Donald J; Hatton, Sean N; Hauger, Richard; Jak, Amy J; Logue, Mark W; McEvoy, Linda K; McKenzie, Ruth E; Neale, Michael C; Panizzon, Matthew S; Reynolds, Chandra A; Sanderson-Cimino, Mark; Toomey, Rosemary; Tu, Xin M; Whitsel, Nathan; Williams, McKenna E; Xian, Hong; Lyons, Michael J; Franz, Carol E; Kremen, William S | Abstract: IntroductionThe locus coeruleus (LC) undergoes extensive neurodegeneration in early Alzheimer's disease (AD). The LC is implicated in regulating the sleep-wake cycle, modulating cognitive function, and AD progression.MethodsParticipants were 481 men (ages 62 to 71.7) from the Vietnam Era Twin Study of Aging. LC structural integrity was indexed by neuromelanin-sensitive magnetic resonance imaging (MRI) contrast-to-noise ratio (LCCNR ). We examined LCCNR , cognition, amnestic mild cognitive impairment (aMCI), and daytime dysfunction.ResultsHeritability of LCCNR was .48. Participants with aMCI showed greater daytime dysfunction. Lower LCCNR was associated with poorer episodic memory, general verbal fluency, semantic fluency, and processing speed, as well as increased odds of aMCI and greater daytime dysfunction.DiscussionReduced LC integrity is associated with widespread differences across cognitive domains, daytime sleep-related dysfunction, and risk for aMCI. These findings in late-middle-aged adults highlight the potential of MRI-based measures of LC integrity in early identification of AD risk.
Biologic disease modifying antirheumatic drugs and Janus kinase inhibitors in paediatric rheumatology - what we know and what we do not know from randomized controlled trials.

Biologic disease modifying antirheumatic drugs (bDMARDs) and Janus Kinase (JAK) inhibitors are prescribed in adult and paediatric rheumatology. Due to age-dependent changes, disease course, and pharmacokinetic processes paediatric patients with inflammatory rheumatic diseases (PiRD) differ from adult rheumatology patients. A systematic literature search for randomized clinical trials (RCTs) in PiRD treated with bDMARDs/JAK inhibitors was conducted on Medline, clinicaltrials.gov , clinicaltrialsregister.eu and conference abstracts as of July 2020. RCTs were included if (i) patients were aged ≤20 years, (ii) patients had a predefined rheumatic diagnosis and (iii) RCT reported predefined outcomes. Selected studies were excluded in case of (i) observational or single arm study or (ii) sample size ≤5 patients. Study characteristics were extracted. Out of 608 screened references, 65 references were selected, reporting 35 unique RCTs. All 35 RCTs reported efficacy while 34/3 provided safety outcomes and 16/35 provided pharmacokinetic data. The most common investigated treatments were TNF inhibitors (60%), IL-1 inhibitors (17%) and IL-6 inhibitors (9%). No RCTs with published results were identified for baricitinib, brodalumab, certolizumab pegol, guselkumab, risankizumab, rituximab, sarilumab, secukinumab, tildrakizumab, or upadacitinib. In patients with juvenile idiopathic arthritis (JIA) 25/35 RCTs were conducted. The remaining 10 RCTs were performed in non-JIA patients including plaque psoriasis, Kawasaki Disease, systemic lupus erythematosus and non-infectious uveitis. In JIA-RCTs, the control arm was mainly placebo and the concomitant treatments were either methotrexate, non-steroidal anti-inflammatory drugs (NSAID) or corticosteroids. Non-JIA patients mostly received NSAID. There are ongoing trials investigating abatacept, adalimumab, baricitinib, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, risankizumab, secukinumab, tofacitinib and tildrakizumab. Despite the FDA Modernization Act and support of major paediatric rheumatology networks, such as the Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organization (PRINTO), which resulted in drug approval for PiRD indications, there are limited RCTs in PiRD patients. As therapy response is influenced by age-dependent changes, pharmacokinetic processes and disease course it is important to consider developmental changes in bDMARDs/JAK inhibitor use in PiRD patients. As such it is critical to collaborate and conduct international RCTs to appropriately investigate and characterize efficacy, safety and pharmacokinetics of bDMARDs/JAK inhibitors in paediatric rheumatology.
Carbon Nanotubes: Nanotoxicity Testing and Bioapplications

With the growing use of nanomaterials in bioapplications, the nanotoxicity of new nanomaterials has become a safety concern when used in various applications. In this chapter, technical developments on carbon nanotubes are described including a historical account, experimental models and potential bioapplications. Carbon nanotube (CNT) materials display superior properties in electric current carrying capacity, thermal conductivity, and thermal stability. Due to the unique CNT structure with high-aspect ratio, CNT may show unusual toxicity and complicate its safe use in a target tissue. To test nanotoxicity of CNT, we describe a set of protocols of prior knowledgebased physical and chemical characteristics to develop 3-dimensional in vitro models of the intact skin, and a 3D in vitro model of the human airway using a co-culture of normal human bronchial epithelial cells and normal human fi broblasts. The human airway 3D model served as a tool of health risk assessment of CNTs on the human respiratory systems. To test functionality at different CNT concentrations in a 3D model, physical characteristics of multiwalled CNTs and production of nitric oxide (NO) served as cell viability and infl ammatory marker; mitochondrial activity (MTT assay) served as the cytotoxic response of the epithelial cell layers; transepithelial electrical resistance (TER) measured nanotoxicity in the changes in airway physiological function. Cytoxicity and infl ammatory responses of CNTs were dependent on different size, mass, shape, and functionality of CNTs as viable in vivo tests were conducted to evaluate the 98 Nanomaterials in Drug Delivery toxicity of engineered CNTs. We monitored the transport across skin, and the physiological perturbation of transepithelial electrical resistance (TER) during the exposure of different concentrations of CNTs. The mechanisms of CNTs’ toxicity are closely related to their structure, functional group, and surface charge on the molecule. We established the nanoscale toxicity of fullerenes of CNTs.
Dual-camera system for multi-level activity recognition

This paper describes a dual-camera system intended to accomplish the task of vision-based activity recognition at multiple resolutions. The system is comprised of a wide-angle, fixed field of view camera coupled with a computer-controlled pan/tilt/zoom-lens camera to make detailed measurements of people for activity recognition applications. We demonstrate the use of the system in both indoor and outdoor environments.
Solving One Dimensional Scalar Conservation Laws by Particle Management

We present a meshfree numerical solver for scalar conservation laws in one space dimension. Points representing the solution are moved according to their characteristic velocities. Particle interaction is resolved by purely local particle management. Since no global remeshing is required, shocks stay sharp and prpagate at the correct speed, while rarefaction waves are created where appropriate. The method is TVD, entropy decreasing, exactly conservative, and has no numerical dissipation. Difficulties involving transonic points do not occur, however inflection points of the flux function pose a slight challenge, which can be overcome by a special treatment. Away from shocks the method is second order accurate, while shocks are resolved with first order accuracy. A postprocessing step can recover the second order accuracy. The method is compared to CLAWPACK in test cases and is found to yield an increase in accuracy for comparable resolutions.
Contrasting genetic architectures in different mouse reference populations used for studying complex traits

Quantitative trait loci (QTLs) are being used to study genetic networks, protein functions, and systems properties that underlie phenotypic variation and disease risk in humans, model organisms, agricultural species, and natural populations. The challenges are many, beginning with the seemingly simple tasks of mapping QTLs and identifying their underlying genetic determinants. Various specialized resources have been developed to study complex traits in many model organisms. In the mouse, remarkably different pictures of genetic architectures are emerging. Chromosome Substitution Strains (CSSs) reveal many QTLs, large phenotypic effects, pervasive epistasis, and readily identified genetic variants. In contrast, other resources as well as genome-wide association studies (GWAS) in humans and other species reveal genetic architectures dominated with a relatively modest number of QTLs that have small individual and combined phenotypic effects. These contrasting architectures are the result of intrinsic differences in the study designs underlying different resources. The CSSs examine context-dependent phenotypic effects independently among individual genotypes, whereas with GWAS and other mouse resources, the average effect of each QTL is assessed among many individuals with heterogeneous genetic backgrounds. We argue that variation of genetic architectures among individuals is as important as population averages. Each of these important resources has particular merits and specific applications for these individual and population perspectives. Collectively, these resources together with high-throughput genotyping, sequencing and genetic engineering technologies, and information repositories highlight the power of the mouse for genetic, functional, and systems studies of complex traits and disease models.
Criterion-Related Validity: Assessing the Value of Subscores.

Criterion-related profile analysis (CPA) can be used to assess whether subscores of a test or test battery account for more criterion variance than does a single total score. Application of CPA to subscore evaluation is described, compared to alternative procedures, and illustrated using SAT data. Considerations other than validity and reliability are discussed, including broad societal goals (e.g., affirmative action), fairness, and ties in expected criterion predictions. In simulation data, CPA results were sensitive to subscore correlations, sample size, and the proportion of criterion-related variance accounted for by the subscores. CPA can be a useful component in a thorough subscore evaluation encompassing subscore reliability, validity, distinctiveness, fairness, and broader societal goals.