cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 375: Combination of MEK and PI3K inhibition in BRAF wild-type and mutant melanoma

Introduction: Targeted therapy against BRAF-mutated melanoma with BRAF and MEK inhibitors has shown clinical efficacy. However, resistance to therapy occurred and lead to therapy failure. We evaluated the effect of combining downstream inhibition of RAS/RAF pathways with MEK (AZD6244) and PI3K (XL765) inhibition on BRAF wild-type and mutant melanoma with variable expression of NRAS as possible therapeutic option. Methods: Fifteen melanoma cell lines were screened for BRAF mutation status and NRAS expression. BRAF wildtype (Mel628, Mel1098) and BRAF-mutated (Mel1861, Mel1890) cell lines were selected. Drug concentration study with AZD6244 (A, 2.5-40 uM) and XL765 (X, 2.5-40 uM) were performed on Mel628 cells. Subsequently, cells were treated with A (5 uM), X (5 uM), or combination. Cell proliferation assay was performed using Cell Titer Blue assay. Western blotting was performed to for expression of PARP, caspase-9, LC3A/B, Beclin1, pMEK/MEK, pERK/ERK, p-P70S6/P70S6, and p4EBP1/4EBP1. GAPDH was used as internal control. Apoptosis was analyzed using FITC Annexin V Apoptosis Detection Kit (BD Biosciences). Cell migration assay was performed by artificial wounding of melanoma cell monolayer and observing migration of cells into the wound up to 72 hours. Data were presented as means ± SD for the three separate experiments. For comparison between groups, the student9s t test was used and p Results: There was dose-dependent inhibition of melanoma cell proliferation with both A and X. Combination A and X had synergistic effect on the anti-melanoma proliferative effect of BRAF mutated cells regardless of expression level of NRAS. Significantly increased apoptosis by Annnexin V assay was detected in BRAF mutated cells (Mel 1860 and Mel1890). Significantly increased expression (p Conclusion: We have observed a synergistic effect on suppressing BRAF-mutated melanoma proliferation with combined inhibition of MEK and PI3K. The effect is not dependent on NRAS expression levels of melanoma. Citation Format: Yanping Zhang, Guangyong Peng, Eddy C. Hsueh. Combination of MEK and PI3K inhibition in BRAF wild-type and mutant melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 375.
Interatrial Septum and its Role in Systemic Embolism

Summary It is apparent that the anatomy and physiology of the IAS are key to understanding its role in systemic embolization. Any communication may give rise to right to left flow across the septum under the right circumstances. The absolute degree of the association of IAS communications with systemic thromboembolic events cannot be precisely defined. The therapeutic approach must be tailored to the clinical situation.
Laboratory rearing of the brown marmorated stink bug (Hemiptera: Pentatomidae) and the impact of single and combination of food substrates on development and survival

The brown marmorated stink bug (BMSB), Halyomorpha halys (Stal) (Hemiptera: Pentatomidae) is non-native species that has rapidly expanded its range in the United States of America and Canada. This study was aimed at increasing our knowledge of the biology of BMSB and developing a rearing method. A laboratory culture maintained on 15 different foods (pear, peach, Granny Smith apple, red delicious apple, squash, tomato, carrot, green bean, grape, corn, leaves of princess tree, leaves of butterfly-bush, dry seeds of sunflower, cowpea, and peanut) had on average 26.0±2.1 eggs per egg mass, and an incubation period averaging 6.94±1.2 days. Developmental duration from second instar to adult averaged 28.2±0.9 days similar to second instars reared to adult on single diet of green beans, corn, sunflower, cowpea, and peanut seeds. Survival from egg to adult was 85.4% and a growth index (GI) of 2.2±0.2 for the laboratory culture comparable to ⩾2.0 GI and 80–90% reported nymphal development on a diet of dry sunflower, cowpea, and peanut seeds. We reared six generations of BMSB before the study was terminated. Our results indicate the foods that are better for BMSB growth, development, and survival.
Schwierigkeiten für die Rezeption von Kohlbergs Theorie

Drei verschiedene—aber nicht unabhangige—Hindernisse stellen sich dem zweifelsfreien Verstandnis von Kohlbergs Theorie in den Weg: 1. die Veranderungen der Theorie und der Methoden im Verlauf ihrer mehr als 25-jahrigen Entwicklungsgeschichte, 2. die unzureichende Dokumentation der jeweils aktuellen theoretischen und empirischen Erkenntnisse durch entsprechende Veroffentlichungen und 3. die haufig unvollstandige und teilweise widerspruchliche Darstellung der Forschungsergebnisse in den vorgelegten Publikationen. In diesem Kapitel sollen die Aussagen von Kohlberg und Mitarbeitern nicht inhaltlich diskutiert und bewertet werden, sondern nur in bezug auf die formalen Bedingungen fur die Moglichkeit der Rezeption seiner Theorie. Die inhaltliche Auseinandersetzung wird den spateren Kapiteln vorbehalten bleiben.
Thermo-mechanical creep characteristics of electrically conductive epoxy adhesives at room temperature

A series of thermo-mechanical creep tests have been performed on samples of several electrically conductive epoxy adhesives with some data from eutectic tin-lead solder used as a baseline. Results suggest that twenty-four hours of load exposure appears to be a sufficient amount of time in determining the stability of the material with regard to thermo-mechanical creep strain and strain rates. The presence of a transition point (at room temperature) in the creep/temperature and creep rate/temperature curves could be of significance to designers and some associated discussion is included to highlight the need for accounting for room temperature effects in interconnection (joint) design.
TX: algorithmic energy saving for distributed dense matrix factorizations

The pressing demands of improving energy efficiency for high performance scientific computing have motivated a large body of solutions using Dynamic Voltage and Frequency Scaling (DVFS) that strategically switch processors to low-power states, if the peak processor performance is unnecessary. Although OS level solutions have demonstrated the effectiveness of saving energy in a black-box fashion, for applications with variable execution patterns, the optimal energy efficiency can be blundered away due to defective prediction mechanism and untapped load imbalance. In this paper, we propose TX, a library level race-to-halt DVFS scheduling approach that analyzes Task Dependency Set of each task in distributed Cholesky/LU/QR factorizations to achieve substantial energy savings OS level solutions cannot fulfill. Partially giving up the generality of OS level solutions per requiring library level source modification, TX leverages algorithmic characteristics of the applications to gain greater energy savings. Experimental results on two clusters indicate that TX can save up to 17.8% more energy than state-of-the-art OS level solutions with negligible 3.5% on average performance loss.
Financial Impact of Direct-Acting Oral Anticoagulants in Medicaid: Budgetary Assessment Based on Number Needed to Treat

Faced with rising healthcare costs, state Medicaid programs need short-term, easily calculated budgetary estimates for new drugs, accounting for medical cost offsets due to clinical advantages. To estimate the budgetary impact of direct-acting oral anticoagulants (DOACs) compared with warfarin, an older, lower-cost vitamin K antagonist, on 12-month Medicaid expenditures for nonvalvular atrial fibrillation (NVAF) using number needed to treat (NNT). Medicaid utilization files, 2009 through second quarter 2015, were used to estimate OAC cost accounting for generic/brand statutory minimum (13/23%) and assumed maximum (13/50%) manufacturer rebates. NNTs were calculated from clinical trial reports to estimate avoided medical events for a hypothetical population of 500,000 enrollees (approximate NVAF prevalence × Medicaid enrollment) under two DOAC market share scenarios: 2015 actual and 50% increase. Medical service costs were based on published sources. Costs were inflation-adjusted (2015 US$). From 2009–2015, OAC reimbursement per claim increased by 173 and 279% under maximum and minimum rebate scenarios, respectively, while DOAC market share increased from 0 to 21%. Compared with a warfarin-only counterfactual, counts of ischemic strokes, intracranial hemorrhages, and systemic embolisms declined by 36, 280, and 111, respectively; counts of gastrointestinal hemorrhages increased by 794. Avoided events and reduced monitoring, respectively, offset 3–5% and 15–24% of increased drug cost. Net of offsets, DOAC-related cost increases were US$258–US$464 per patient per year (PPPY) in 2015 and US$309–US$579 PPPY after market share increase. Avoided medical events offset a small portion of DOAC-related drug cost increase. NNT-based calculations provide a transparent source of budgetary-impact information for new medications.
NK Cells Induce Alloreactive Donor T Cell Apoptosis and Decrease Proliferation in GVHD Induction.

Natural Killer (NK) cells have the ability to suppress graft-versus-host disease (GVHD) while inducing a graft-versus-tumor response (GVT) during allogeneic bone marrow transplantation (BMT). Previous studies in allogeneic BMT models have shown NK cell trafficking to and proliferation in lymphoid organs and GVHD target organs, which are also sites of donor T cell trafficking. This study aims to investigate the impact of NK cells on alloreactive, GVHD-inducing donor T cells. Interleukin-2 activated allogeneic NK cells isolated from C57Bl6 (H–2 b ) or FVB (H–2 q ) animals were transplanted along with T cell-depleted bone marrow into lethally irradiated BALB/c (H–2 d ) mice, followed 2 days later by luciferase-expressing CD4+ and CD8+ conventional T cells from the same donor strain (NK+Tcon group). Control mice received lethal irradiation and T cell-depleted bone marrow on day 0, and luciferase-expressing T cells on day 2 after transplant (Tcon group). Bioluminescence imaging of NK+Tcon mice revealed a significantly lower T cell bioluminescent signal (p=0.03 for FVB into BALB/c on day 6) than from Tcon mice. CFSE proliferation analysis of alloreactive T cells on day 3 after transplant showed no significant change in the percent of donor T cells that have divided in the spleen, and only a slight decrease in the percent of T cells that have divided in the lymph nodes when NK cells are present. However, at this timepoint 82% of the proliferating cells have divided past the third generation, in contrast to 64% in the NK+Tcon mice. Donor T cells in both groups become equally activated in vivo , expressing similar levels of the early-activation marker CD69. T cells re-isolated from NK+Tcon animals at day 5 stained 2 to 10-fold higher for the TUNEL apoptosis marker than those from Tcon mice in the mesenteric and peripheral lymph nodes, respectively (p
Designing telepresence robots for K-12 education

Telepresence robots have the potential to improve access to K-12 education for students who are unable to attend school for a variety of reasons. Since previous telepresence research has largely focused on the needs of adult users in workplace settings, it is unknown what challenges must be addressed for these robots to be effective tools in classrooms. In this paper, we seek to better understand how a telepresence robot should function in the classroom when operated by a remote student. Toward this goal, we conducted field sessions in which four designers operated a telepresence robot in a real K-12 classroom. Using the results, we identify key research challenges and present design insights meant to inform the HRI community in particular and robot designers in general.
A GENRE-BASED TEXTUAL ANALYSIS OF EXPERT ONLINE REVIEWS OF ELECTRIC GUITAR FUZZ PEDALS

This study uses genre analysis to analyze contemporary online text. Through an analysis of the linguistic features of text from a highly specialized discourse community, perceived expert online reviews of electric guitar fuzz pedals, findings from this study provide insight into the relevance of online reviews. Although there is a layman quality to the actual production of the textual online reviews, genre analysis reveals hybridized genres, authorial power within occluded genre chains, subconscious marketing techniques, and manipulation of perceived expert online reviews. Findings from this study indicate that online reviews have complex occluded genre chains, which are not readily obvious when the reviews are read only for entertainment purposes. This research has real world applications as relationships between textual generic qualities of online reviews and consumer spending habits are now easily acquired from online data-mining techniques to assist in targeting online consumers’ habits and to increase sales. Online reviews are now what consumers use to assist in shopping. Control of reviews translates to control of consumers’ shopping habits.
Steroid-Dependent Recurrent Optic Neuritis in Pediatric Multiple Sclerosis

Optic neuritis (ON) is a common clinically isolated syndrome. While multiple sclerosis or neuromyelitis optica are two possible outcomes following an initial ON event, relapsing forms of optic neuritis without other clinical or neuroimaging findings of disease outside of the optic nerves can pose a diagnostic challenge. Chronic relapsing inflammatory optic neuropathy (CRION) is a rare syndrome known for its severity, strong steroid dependence, and largely unremarkable brain imaging. This case presents a child with recurring episodes of optic neuritis and reviews the differential diagnostic considerations, treatment, and outcome of these patients.
Below-Room-Temperature C–H Bond Breaking on an Inexpensive Metal Oxide: Methanol to Formaldehyde on CeO2(111)

Upgrading of primary alcohols by C–H bond breaking currently requires temperatures of >200 °C. In this work, new understanding from simulation of a temperature-programmed reaction study with methanol over a CeO2(111) surface shows C–H bond breaking and the subsequent desorption of formaldehyde, even below room temperature. This is of particular interest because CeO2 is a naturally abundant and inexpensive metal oxide. We combine density functional theory and kinetic Monte Carlo methods to show that the low-temperature C–H bond breaking occurs via disproportionation of adjacent methoxy species. We further show from calculations that the same transition state with comparable activation energy exists for other primary alcohols; with ethanol, 1-propanol, and 1-butanol explicitly calculated. These findings indicate a promising class of transition states to search for in seeking low-temperature C–H bond breaking over inexpensive oxides.
A radiographic investigation of cervical spine kinematics when reading a tablet in a reclined trunk position.

Abstract The purpose of this study was to use radiographic measurements to compare cervical spine kinematics in various tablet computer reading postures. Radiographs were taken of twenty-two participants reading a tablet computer in five different postures. The lower cervical spine was more flexed in the semi-reclined (-8.2 ± 3.8°) and the reclined (-14.9 ± 4.0°) tablet positions compared to an upright (-4.43 ± 4.8°) tablet posture. Of the tablet reading positions, the reclined position had the lowest gravitational moment arm (5.2 ± 2.3 cm) and a skull angle closest to neutral (-9.4 ± 11.4°), while exhibiting the largest extension in the C1-C2 joint (34.4 ± 9.1°). Altering trunk position when reading a tablet could reduce the load required to support the head, but could put the head in a more forward head posture, stretch the cervical extensor muscles, and potentially result in pain.
Loss of Response to Anti-Tumor Necrosis Factor Alpha Therapy in Crohn's Disease Is Not Associated with Emergence of Novel Inflammatory Pathways.

While monoclonal antibodies against tumor necrosis factor-α (TNFα) are effective in treating Crohn’s disease (CD), approximately one-third of patients lose response. The mechanisms underlying this loss of response remain elusive. We sought to determine if novel biological pathways, including TNFα-independent inflammatory pathways, emerge in those with loss of response to anti-TNFα. Using RNA microarray technology in 28 patients with CD, we examined the colonic gene expression differences between those with active inflammation in the setting of loss of response to TNFα-antagonist therapy (“loss of responders”) compared to anti-TNFα naive patients with active inflammation and those on anti-TNF therapy in disease remission. Pathway enrichment analyses were performed. We found that colonic expression of chemokines known to drive inflammation (CXCL20, CXCL9, and CXCL10) was elevated in those with loss of response compared to those in remission. Expression of genes critical to modulating oxidative stress burden (DUOX2, DUOXA2, and NOS2) was also elevated. Additionally, MMP3, MMP1, and MMP12 were elevated in those with continued inflammation. Gene enrichment analysis revealed that loss of responders exhibited dysregulation in the cysteine and methionine metabolism pathway, suggesting alteration in oxidative stress burden. There were no differences in genes or pathways between loss of responders and those who were TNFα-naive. However, loss of response occurred despite the ability of anti-TNFα therapy to normalize APO gene expression. Our analyses suggest that loss of response to anti-TNFα is not driven by the emergence of pathways that bypass the action or induce resistance to anti-TNFα therapy.
Histologic Features and Prognosis of Spinal Intradural Extramedullary Ewing Sarcoma: Case Report, Literature Review, and Analysis of Prognosis.

Background Ewing sarcoma is a malignant neoplasm that primarily involves extremity long bones, the pelvis, and soft tissues of children. The intradural extramedullary space is an uncommon location for Ewing sarcoma, and there is therefore a paucity of information regarding the features and natural history of this particular presentation. There is controversy regarding preoperative diagnosis, surgical management, and postoperative care, and there are no accepted standards. Methods Herein we present a 61-year-old man with an L1-3 intradural extramedullary Ewing sarcoma who underwent gross total resection of the tumor via laminectomy. Pathologic analysis revealed a diagnosis of Ewing sarcoma based on the characteristic immunohistochemistry and the presence of EWSR1-FLI1 fusion transcript by reverse-transcription polymerase chain reaction. Results There have been 28 cases of intradural extramedullary Ewing sarcoma reported in the literature. Out of 29 cases including the current case, 18 cases (62.1%) were men. The median and mean ages were 32 and 34.0 years, respectively, with a peak age group of 10–20 years. Twenty-two of 29 (72.4%) cases involved the lumbar spine, followed by the cervical spine (n = 7, 24.1%). Long-term prognosis was poor, with 1-, 2-, 3-, and 5-year progression-free survival rate of 75.0%, 56.3%, 37.5%, and 18.8%, respectively. The 1-, 2-, 3-, and 5-year overall survival rate was 89.5%, 80.5%, 80.5%, and 43.0%, respectively. Conclusions Herein, we present imaging and pathologic findings of the case with review of the literature.
Chitosan based hydrogels and their applications for drug delivery in wound dressings: A review

Advanced development of chitosan hydrogels has led to new drug delivery systems that can release their active ingredients in response to environmental stimuli. This review considers more recent investigation of chitosan hydrogel preparations and the application of these preparations for drug delivery in wound dressings. Applications and structural characteristics of different types of active ingredients, such as growth factors, nanoparticles, nanostructures, and drug loaded chitosan hydrogels are summarized.
Role of Oxidative Injury in the Pathogenesis of Methylmercury Neurotoxicity

We have previously demonstrated (J. Neuropath. Exp. Neurol. 48:1–10, 1989) that the pathogenesis of methylmercury (MeHg) induced cytotoxicity in suspensions of cerebellar granule neurons was not strictly coupled to the reduction of ATP or combined inhibition of ATP or macromolecule synthesis, but suggested a component of free-radical injury. The present studies reveal that MeHg initiates a dose- and time-dependent lipoperoxidation measured as malonaldehyde generation or induction of a 2′,7′-dichlorofluorescein (DCFA) signal representing oxygen radical species generation. A simultaneous decline in GSH occurred. Partial protection was given by EGTA (a Ca2+ chelator) or desferoxamine (Fe2+ chelation with inhibition of the Fenton reaction and OH radical production). However, no cytoprotection was found with alpha-tocopherol succinate although significant inhibition of lipoperoxidation was observed. Analogous experiments in cerebellar granule cell culture revealed a dose-dependent (0.5–μM) increase in the specific activity of GSH accompanied by increased lipoperoxidation and neuronal cell injury. Such paradoxical induction of GSH occurred in glial cells, whose endogenous content was higher than that of neuron culture. Inhibition of gamma-glutamyl cysteine synthetase by buthionine sulfoximine (BSO) lowered cellular GSH and strongly potentiated MeHg-induced lipoperoxidation and cell death in neuron culture but had minimal effect in glial culture.
Oscillatory Doubly Diffusive Convection: Theory and Experiment

Doubly diffusive convection in its various forms offers an excellent opportunity to study the dynamics near a Hopf bifurcation in a continuous system. Over the last year theoretical and numerical studies have been complemented by a number of new experiments on binary fluid mixtures revealing a richness of behavior that has in turn stimulated further theoretical effort. It is the purpose of this brief report to compare existing theory with the experiments, and indicate directions for further research.
Rig Dayrates and Utilization

The contract drilling market is characterized by three interrelated measures: utilization, dayrates, and fleet size. Utilization describes the proportion of rigs working to the available fleet at a specific time and place, while dayrates represent the average daily rental charged by rigs of a given class operating in a specific water depth category and region over a specific period. Contractors build rigs to generate cash flow and capture market share. Rig movements between regions are usually not rapid enough to create strong interregional correlations in dayrates and utilization. Rig demand is associated with oil prices which vary dramatically over time, and dayrates are highly variable. When rig supply exceeds demand, low prices result. We characterize global and regional supply, utilization and dayrate trends over the 2000–2010 period. The U.S. Gulf of Mexico was the least expensive jackup market during the decade, followed by the Persian Gulf, while the North Sea was the most expensive jackup market. The chapter concludes with a brief discussion of the contracts used in the industry and the primary customers in each regional market.
Next-generation diamond cell and applications to single-crystal neutron diffraction.

A diamond cell optimized for single-crystal neutron diffraction is described. It is adapted for work at several of the single-crystal diffractometers of the Spallation Neutron Source and the High Flux Isotope Reactor at the Oak Ridge National Laboratory (ORNL). A simple spring design improves portability across the facilities and affords load maintenance from offline pressurization and during temperature cycling. Compared to earlier prototypes, pressure stability of polycrystalline diamond (Versimax®) has been increased through double-conical designs and ease of use has been improved through changes to seat and piston setups. These anvils allow ∼30%-40% taller samples than possible with comparable single-crystal anvils. Hydrostaticity and the important absence of shear pressure gradients have been established with the use of glycerin as a pressure medium. Large single-crystal synthetic diamonds have also been used for the first time with such a clamp-diamond anvil cell for pressures close to 20 GPa. The cell is made from a copper beryllium alloy and sized to fit into ORNL’s magnets for future ultra-low temperature and high-field studies. We show examples from the Spallation Neutron Source’s SNAP and CORELLI beamlines and the High Flux Isotope Reactor’s HB-3A and IMAGINE beamlines.
Counterrevolutionary friends: Caribbean basin dictators and guatemalan exiles against the guatemalan revolution, 1945–50

It was in January 1950 that Guatemalan Col. Carlos Castillo Armas, a rather unfamiliar figure at the time, headed for El Salvador, giving no sign that he would eventually become one of the most notorious antagonists in the destruction of the 1944-54 Guatemalan Revolution. Late in 1950, he and some 70 compatriots attacked Guatemala City's Base Militar, hoping to overthrow Juan Jose Arevalo's government and prevent Jacobo Arbenz from assuming the presidency. Though the assault failed and its participants were imprisoned, the dissident bribed his way out of jail and took into exile a newfound reputation as an influential conspirator.
Clinic Satisfaction Tool Improves Communication and Provides Real-Time Feedback

BACKGROUND Patient-reported assessments of the clinic experience are increasingly important for improving the delivery of care. The Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) survey is the current standard for evaluating patients' clinic experience, but its format gives 2-mo delayed feedback on a small proportion of patients in clinic. Furthermore, it fails to give specific actionable results on individual encounters. OBJECTIVE To develop and assess the impact of a single-page Clinic Satisfaction Tool (CST) to demonstrate real-time feedback, individualized responses, interpretable and actionable feedback, improved patient satisfaction and communication scores, increased physician buy-in, and overall feasibility. METHODS We assessed CST use for 12 mo and compared patient-reported outcomes to the year prior. We assessed all clinic encounters for patient satisfaction, all physicians for CG-CAHPS global rating, and physician communication scores, and evaluated the physician experience 1 yr after implementation. RESULTS During implementation, 14 690 patients were seen by 12 physicians, with a 96% overall CST utilization rate. Physicians considered the CST superior to CG-CAHPS in providing immediate feedback. CG-CAHPS global scores trended toward improvement and were predicted by CST satisfaction scores (P < .05). CG-CAHPS physician communication scores were also predicted by CST satisfaction scores (P < .01). High CST satisfaction scores were predicted by high utilization (P < .05). Negative feedback dropped significantly over the course of the study (P < .05). CONCLUSION The CST is a low-cost, high-yield improvement to the current method of capturing the clinic experience, improves communication and satisfaction between physicians and patients, and provides real-time feedback to physicians.
Robust path-following control of a container ship based on Serret–Frenet frame transformation

A novel disturbance observer-based backstepping controller (DOBBC) is developed and applied to the path-following system of a container ship. Our control objective is to enable the ships to follow a desired path despite the presence of environmental disturbances caused by current, wind, and wave actions. It is particularly challenging to achieve such an objective due to the underactuation and nonlinearity of container ships. To simplify controller design, a tracking error model is developed based on Serret–Frenet frame transformation. The proposed path-following control system is constructed on the model. In DOBBC, the disturbance observer estimates both constant and time-variant environmental disturbances. The backstepping controller compensates the nonlinearity and underactuation of the container ship. A feedback-dominance technique is utilized to design the controller parameters. The stability and robustness of the control system are successfully justified through Lyapunov approach. Simulation results demonstrate that the DOBBC effectively drives the ship to follow a desired trajectory in spite of the existence of time-varying environmental disturbances.
Association of a School-Based, Asthma-Focused Telehealth Program With Emergency Department Visits Among Children Enrolled in South Carolina Medicaid.

Importance Telehealth may improve access to care for populations in rural communities. However, little is known about the effectiveness of telehealth programs designed for children. Objective To examine the associations of a school-based telehealth program in Williamsburg county (South Carolina) with all-cause emergency department (ED) visits made by children enrolled in Medicaid. Design, Setting, and Participants This Medicaid claims data analysis was conducted in Williamsburg county and 4 surrounding counties in South Carolina and included children aged 3 to 17 years who were enrolled in Medicaid and living in any of the 5 counties from January 2012 to December 2017. Williamsburg served as the intervention and the 4 surrounding counties without a telehealth program as the control; 2012 to 2014 was designated as the preintervention period, whereas 2015 to 2017 served as the postintervention period. The study was designed with a difference-in-differences specification, in which the unit-of-analysis was a child-month, and a subsample included children with asthma. The data analysis was performed from July 2018 to February 2019. Exposures The school-based telehealth program implemented in Williamsburg county in 2015. Main Outcomes and Measures The binary outcome was the status of at least 1 all-cause ED visit by a child in a given month. Results The full sample included 2 443 405 child-months from 23 198 children in Williamsburg county and 213 164 children in the control counties. The mean (SD) proportions of monthly ED visits in Williamsburg were 3.65% (0.10%) during the preintervention and 3.87% (0.11%) during the postintervention. The corresponding proportions of the 4 control counties were 3.37% preintervention (0.04%), and 3.56% postintervention (0.04%), respectively. The trends in the proportion were paralleled. In the asthma subsample, the proportions in Williamsburg were 3.16% (0.31%) during the preintervention and 3.38% (0.34%) during the postintervention, respectively. The proportions for the control counties were 3.02% preintervention (0.10%) and 3.90% postintervention (0.11%), respectively. There was an interaction of the proportions between the pre/postintervention period and the intervention/control counties in this subsample. The regression analysis of the full sample showed no association of the telehealth program with ED visits. The additional analysis of the asthma subsample showed that this program was associated with a reduction of 0.66 (95% CI, −1.16 to −0.17;P Conclusions and Relevance Although we found no association of this program with the ED visits of the overall studied population, this study suggests that telehealth with a focus on chronic pediatric diseases, such as asthma, may deliver substantial health benefits to rural and medically underserved communities.
An Ensemble Kalman Filtering Approach for Discrete-Time Inverse Optimal Control Problems

Solving the inverse optimal control problem for discrete-time nonlinear systems requires the construction of a stabilizing feedback control law based on a control Lyapunov function (CLF). However, there are few systematic approaches available for defining appropriate CLFs. We propose a method that utilizes nonlinear Bayesian filtering to parameterize a quadratic CLF. In particular, we use the ensemble Kalman filter (EnKF) to estimate parameters used in defining the CLF within the control loop of the inverse optimal control problem formulation. Using the EnKF in this setting provides a natural link between uncertainty quantification and optimal design and control, as well as a novel and intuitive way to find the one control out of an ensemble that stabilizes the system the fastest. Results of the EnKF CLF procedure are demonstrated on both a linear and nonlinear test problem.
Identification of long thoracic nerve on high-resolution 3T MRI

Abstract Objective Long thoracic neuropathy results in serratus anterior muscle denervation and presents with scapular winging. Previously published studies have been unable to identify the long thoracic nerve on MRI; instead, secondary imaging features of serratus anterior muscle denervation are used to infer nerve injury. Our study's purpose was to evaluate the ability of high-resolution MRI to depict the long thoracic nerve. Materials and methods In this HIPAA-compliant, IRB-approved retrospective study, two musculoskeletal radiologists reviewed the brachial plexus MRI exans of 24 subjects performed for clinical suspicion of long thoracic neuropathy. The radiologists evaluated whether the long thoracic nerve could be identified and for the presence of serratus anterior denervation; when the nerve was seen, assessment for nerve enlargement, signal hyperintensity, and morphologic change was performed. Inter-observer reliability was estimated with Cohen's kappa (κ). Clinical presentation and electromyogram (EMG) were then reviewed. Results The long thoracic nerve was identified in 18 cases (75%), with high inter-observer reliability for nerve visualization. Kappa values of 1.0, 0.9, 1.0, and 0.9 were obtained for identification of the LTN on coronal sequences of the brachial plexus, identification of the LTN on proximal and mid segments of the nerve on oblique sagittal sequences, and identification of the distal segment of the LTN on axial sequences through the chest, respectively. The nerve was identified in 91% of patients with positive EMG findings for a long thoracic neuropathy. In patients with EMG features of long thoracic neuropathy, 70% had corresponding abnormal MRI features. When denervation edema was present, the nerve was identified 86% of the time. Conclusion High-resolution MRI can be used to visualize segments of the long thoracic nerve.
Chapter 3 – Water Relations and Nutrient Uptake

Grapevines consist mostly of water that serves as a solvent for organic and inorganic solutes. Plant cells grow by osmotically attracting water and loosening their rigid cell walls. During osmosis, water moves into a solute-containing compartment, such as a cell, across a semipermeable membrane, increasing the turgor pressure of the cell. The solute and pressure forces together make up the water potential. Growth is extremely sensitive to decreases in water potential due to water deficit. Water evaporates from plant surfaces during transpiration, mostly through stomatal pores, cooling the plant tissues and causing a tension that drives root water uptake and movement up the vine in the xylem to the leaves. The stomata function as valves that regulate water loss to avoid excessive dehydration and cavitation of the xylem, whose low hydraulic resistance provides for effective water transport. Along with water, the roots also take up mineral nutrients from the soil solution in a controlled fashion for accumulation and distribution via the transpiration stream throughout the vine. Nutrient uptake, mostly by ion exchange, and movement to the xylem can occur actively, through ATP-powered transport proteins, or passively, down an electrochemical potential gradient. Shallow roots preferentially take up immobile nutrients, and deep roots preferentially take up mobile nutrients.
Validating Use of Electronic Health Data to Identify Patients with Urinary Tract Infections in Outpatient Settings

Objective: To validate the use of electronic algorithms based on International Classification of Diseases (ICD)-10 codes to identify outpatient visits for urinary tract infections (UTI), one of the most common reasons for antibiotic prescriptions. Methods: ICD-10 symptom codes (e.g., dysuria) alone or in addition to UTI diagnosis codes plus prescription of a UTI-relevant antibiotic were used to identify outpatient UTI visits. Chart review (gold standard) was performed by two reviewers to confirm diagnosis of UTI. The positive predictive value (PPV) that the visit was for UTI (based on chart review) was calculated for three different ICD-10 code algorithms using (1) symptoms only, (2) diagnosis only, or (3) both. Results: Of the 1087 visits analyzed, symptom codes only had the lowest PPV for UTI (PPV = 55.4%; 95%CI: 49.3–61.5%). Diagnosis codes alone resulted in a PPV of 85% (PPV = 84.9%; 95%CI: 81.1–88.2%). The highest PPV was obtained by using both symptom and diagnosis codes together to identify visits with UTI (PPV = 96.3%; 95%CI: 94.5–97.9%). Conclusions: ICD-10 diagnosis codes with or without symptom codes reliably identify UTI visits; symptom codes alone are not reliable. ICD-10 based algorithms are a valid method to study UTIs in primary care settings.
Isolated choroidal melanocytosis: clinical update on 37 cases.

Isolated choroidal melanocytosis is a congenital melanocytic hyperpigmentation involving the choroid that is not associated with iridic or scleral features of ocular melanocytosis. The purpose of this work was to describe the clinical features and course of a relatively large series of patients with this disorder. A retrospective clinical study of 37 patients with isolated choroidal melanocytosis encountered in a single practice 1986–2018 was done. All lesions were 5 mm or larger in the largest basal diameter, homogeneously melanotic, and completely flat by conventional ocular ultrasonography. The 37 patients ranged in age from 2 weeks to 87 years (mean 31.5 years, median 18 years) at initial diagnosis of the melanotic choroidal lesion. Arc length largest basal diameter of the melanotic choroidal lesion ranged from 5.5 to 37 mm (mean 14.6 mm, median 13 mm). The lesion extended beneath the fovea in 18 eyes and to the optic disc margin in 6 eyes. Ten of the lesions straddled the ocular equator, but the center point of all of the lesions was posterior to the equator. The retina was fully attached and appeared normal over the melanotic choroidal lesion in each of these eyes. None of the melanotic choroidal lesions exhibited clumps of orange pigment or drusen on its surface. The lesion was unilateral and unifocal in 36 of the 37 patients. One patient had bilateral choroidal melanocytosis that was isolated in one eye but associated with partial iris melanocytosis in the fellow eye. Three adult patients had a choroidal melanoma localized to the patch of choroidal melanocytosis at baseline. One other adult patient had a choroidal melanoma in the fellow eye at baseline. One pediatric patient had viable unilateral non-familial retinoblastoma in the fellow eye and two adult patients had a classic choroidal nevus in the fellow eye. None of the flat patches of choroidal melanocytosis that were monitored periodically after initial diagnosis expanded appreciably during follow-up ranging from 4.9 months to 15.2 years (mean 5.0 years, median 2.3 years). Isolated choroidal melanocytosis is a distinct clinical entity that must be distinguished from broad-based choroidal nevus, choroidal melanocytoma, small choroidal malignant melanoma, acquired bilateral patchy-streaky choroidal melanocytic fundopathy associated with disorders such as cutaneous vitiligo and Waardenburg syndrome, acquired bilateral zonal choroidal melanocytic fundopathy, and diffuse uveal melanocytic proliferation associated with systemic cancer. This disorder appears to predispose affected eyes to development of choroidal melanoma arising from the hypermelanotic patch.
Search Trends and Quality of Online Resources Regarding Thyroidectomy.

ObjectiveThyroidectomy is one of the most common procedures performed in head and neck surgery. The quality of online resources for thyroidectomy is unknown. We aim to evaluate search trends and on...
Divergent controls on carbon concentration and persistence between forests and grasslands of the conterminous US

Variation in soil organic C (%OC) concentration has been associated with the concentration of reactive Fe- and Al-oxyhydroxide phases and exchangeable Ca, with the relative importance of these two stabilizing components shifting as soil pH moves from acid to alkaline. However, it is currently unknown if this pattern is similar or different with regard to measures of soil C persistence. We sampled soils from 3 horizons (uppermost A, uppermost B, C or lowest B horizons) across a pH gradient of 11 grass-dominated and 13 deciduous/mixed forest-dominated NEON sites to examine similarities and differences in the drivers of C concentration and persistence. Variation in C concentrations in all soils could be linked to abundances of Fe, Al and Ca, but were not significantly linked to variation in soil C persistence. Though pH was related to variation in Δ14OC, higher persistence was associated with more alkaline pH values. In forested soils, depth explained 75% of the variation in Δ14OC (p < 0.0001), with no significant additional correlations with extractable metal phases. In grasslands, soil organic C persistence was not associated with exchangeable Ca concentrations, but instead was explained by depth and inorganic C concentrations (R2 = 0.76, p < 0.0001), implying stabilization of organic C through association with carbonate precipitation. In grasslands, measures of substrate quality suggested greater persistence is also associated with a more advanced degree of decomposition. Results suggest that explanatory variables associated with C concentrations differ from those associated with persistence, and that reactive Fe- and Al-oxyhydroxide phases may not be present in high enough concentrations in most soils to offer any significant protective capacity. These results have significant implications for our understanding of how to model the soil C cycle and may suggest previously unrecognized stabilization mechanisms associated with carbonates and forms of extractable Si.
Evaluating Plant Potassium Status

Several methods exist for evaluating plant nutritional status. Looking for visual deficiency symptoms is perhaps the simplest approach, but once symptoms appear, crop performance has already been compromised. Several other techniques have been developed. All of them require correlation studies to provide plant performance interpretations. Reflectance is a remote sensing technique that detects changes in light energy reflected by plant tissue. It has proven successful in detecting nutrient deficiencies but does not yet have the ability to discriminate among more than one deficiency. Chemical assays of leaf tissue, known as tissue tests, require destructive sampling but are the standard against which other assessments are compared. Sufficiency ranges provide concentrations of each nutrient that are considered adequate for crop growth and development. They consider nutrients in isolation. Other approaches have been developed to consider how the concentration of one nutrient in tissue impacts the concentrations of other nutrients. These approaches strive to develop guidelines for maintaining nutrient balance within the plant. All approaches require large data sets for interpretation.
Bidirectional Associations between Child Conduct Problems and Parenting Practices in Early Childhood

In line with early theoretical frameworks suggesting reciprocal associations between child behavior problems and parenting behaviors, the present study examined bidirectional associations between child conduct problems and lax, overreactive, and positive parenting. Participants included 293 mothers recruited through Amazon’s Mechanical Turk (MTurk) who completed measures about their children, who were between the ages of three and six years of age, across a six-month period (82% White; 75.4% married). A cross-lagged panel model was conducted that examined associations between conduct problems and parenting (i.e., lax, overreactive, positive) across three waves that were each spaced approximately two months apart. This model also controlled for several demographic variables (i.e., income-to-needs ratio, race/ethnicity, marital status, child biological sex) and child hyperactivity. Findings demonstrated a parent-driven coercive pattern between lax parenting and child conduct problems, such that higher lax parenting at wave one was associated with higher child conduct problems at wave three, which was subsequently linked to higher lax parenting at wave five. Child-driven effects were identified for overreactive and positive parenting; higher child conduct problems were associated with higher overreactive and lower positive parenting behaviors. However. overreactive and positive parenting were not associated with child conduct problems at any wave. Findings support theories suggesting transactional associations between parenting and child behaviors. Further, results suggest lax parenting behaviors may demonstrate a unique effect on the development of early child conduct problems above and beyond overreactive and positive parenting behaviors.
Computational Aspects of the Nearest Neighbor Statistics

The distributions of the nearest neighbor statistics and its parameters are calculated in the case when points are generated from the multivariate uniform and multivariate standard normal distribution. A recursive function for the expected value of the k-th nearest neighbor is derived for the asymptotic distributions. Monte Carlo method is used to assess the presented approach.
Abstract 12903: Bendavia (MTP-131), a Mitochondria Targeting Peptide, Normalizes Dysregulation of Mitochondria Fission and Fusion Proteins in Myocardium of Dogs With Chronic Heart Failure

Introduction: Studies of mitochondria (MITO) ultrastructure in heart failure (HF) reveal considerable structural abnormalities along with marked hyperplasia and reduced organelle size. MITO are highly dynamic organelles whose morphology, distribution and activity is regulated by fission and fusion proteins that are also dysregulated in HF. We previously showed that chronic therapy with Bendavia (BEN, MTP-131), a novel mitochondria-targeting peptide, improves LV function in dogs with HF and normalizes MITO respiration and rate of ATP synthesis. Hypothesis: This study tested the hypothesis that chronic therapy with BEN in dogs with HF can reverse the dysregulation of MITO fission proteins (Fission-1, Fis1 and Dynamin-Related Protein-1, Drp1) and fusion proteins (Mitofusin-2, Mfn2 and Dominant Optic Atrophy-1, OPA1) in LV myocardium. Methods: 14 HF dogs were randomized to 3 months therapy with subcutaneous injections of BEN (0.5 mg/kg once daily, HF+BEN, n=7) or saline (HF-Control, n=7). LV tissue was obtained from all dogs at end of therapy and from 6 normal (NL) dogs for comparison. Protein level of Fis1 and Drp1 and of Mfn2 and OPA1 was measured with specific antibodies using Western blotting. In addition Porin, a MITO protein that is unaltered in HF, was also measured as internal control and all bands were quantified in densitometric units (du). Results: Results are shown in the table. Porin level was unchanged among the 3 study groups. Compared to NL, levels of Mfn2 and OPA1 were significantly reduced, and levels of Fis1 and Drp1 were significantly increased in HF-Controls. BEN restored protein levels of OPA1, Mfn2, Fis1, and Drp1 to near normal. Conclusions: Long-term therapy with BEN reversed the dysregulation of MITO fission and fusion proteins in LV myocardium of dogs with HF. These findings support the observations of improved MITO respiration and rate of ATP synthesis and the improved LV function seen in dogs with HF after chronic treatment with BEN.