cssi/SciSciGPT-SciSciNet huggingface dataset:
An Investigation on the Accuracy of Numerical Simulations for Single Point Incremental Forming with Continuum Elements

Finite element methods (FEM) have been widely used in simulating the single point incremental forming (SPIF) process to investigate the effects of process parameters, such as incremental depth, tool size and tool path on the thickness/strain distributions, deformed shapes, and the formability. However, due to the complexity of the process and the continuous change of the contact area in SPIF, numerical simulations tend to be time‐consuming and hard to converge when an implicit integration method is used. To meet these challenges, most simulation work found in literature utilized the explicit integration method with shell elements to simulate the SPIF process. However, results have not been found satisfactory as evident by mismatches of the predicted shape, strain/thickness distribution and/or forming force between simulation and experimental results. In our past work, in order to obtain a more accurate result and consider the contact force in the thickness direction, solid continuum elements were introduced combined with the implicit method. Although the trends of the forming force in the Z direction were very similar between simulations and experimental results, there still existed a relatively large discrepancy in absolute values. In this paper, effects of yield criterion, element size and element type on the predicted forming force are investigated. Additionally, a new damage model has been incorporated into FEM simulation that, for the first time, predicts the force curve, the location of fracture and the maximum thinning with remarkable accuracy.
The Liberal Arts and the Arts of Liberty

Abstract Even today's self-appointed defenders of the liberal arts often lack clarity about what a liberal arts education is and what it means. Especially in a time when, as we all recognize, the liberal arts are being challenged from almost every conceivable corner, those of us who know the immeasurable and irreplaceable value of liberal education need to give a better account. To do this, we might begin by looking back to the question of what kind of education is needed to preserve and support human liberty. We must also be attuned to growing inequalities when it comes to liberal arts education.
A Molecular Model for Intercellular Synchronization in the Mammalian Circadian Clock

The mechanisms and consequences of synchrony among heterogeneous oscillators are poorly understood in biological systems. We present a multicellular, molecular model of the mammalian circadian clock that incorporates recent data implicating the neurotransmitter vasoactive intestinal polypeptide (VIP) as the key synchronizing agent. The model postulates that synchrony arises among circadian neurons because they release VIP rhythmically on a daily basis and in response to ambient light. Two basic cell types, intrinsically rhythmic pacemakers and damped oscillators, are assumed to arise from a distribution of Period gene transcription rates. Postsynaptic neurons show time-of-day dependent responses to VIP binding through a signaling cascade that activates Period mRNA transcription. The heterogeneous cell ensemble model self-synchronizes, entrains to ambient light-dark cycles, and desynchronizes in constant bright light or upon removal of VIP signaling. The degree of synchronicity observed depends on cell-specific features (e.g., mean and variability of parameters within the rhythm-generating loop), in addition to the more commonly studied effect of intercellular coupling strength. These simulations closely replicate experimental data and predict that heterogeneous oscillations (e.g., sustained, damped, and arrhythmic) arise from small differences in the molecular parameters between cells, that damped oscillators participate in entrainment and synchrony of the ensemble of cells, and that constant light desynchronizes oscillators by maximizing VIP release.
Accurate halftoning using the Gibbs sampler

By defining a performance metric in terms of a model of the human visual system, we can develop a criterion for the accuracy of a halftoning algorithm. Directly optimizing this criterion leads to an algorithm based on the Gibbs sampler. The resulting algorithm is more computationally expensive than error diffusion: however, it is local, highly parallel, and has a number of other desirable properties. For high quality halftoning, it is necessary to take into account the physical characteristics of the display device. The proposed algorithm can do this in a direct manner. For black and white monitors, this leads to an adjustment in the calculated brightness of the first pixel turned on in raster order; this brightness adjustment is significant, as the first pixel in such a run has been measured at only 70% of the brightness of succeeding pixels. In printed halftoned images, ink overlap leads to a decrease in the perceived darkness of adjacent dark pixels; again, the difference is significant, having been measured at 16% effective overlap. On color patterns, it is possible to directly measure the colors produced by the printer and use them in formulating the error measure for halftoning. Adjusting for these effects, which cannot be done with error diffusion algorithms, leads to perceivable increase in halftoned image quality.
Abstract 19: Reducing Time to Intra-Arterial Therapy in Acute Ischemic Stroke

Background: Time to recanalization is known to predict clinical outcome in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). Unlike for IV tPA, there is no established goal time to intra-arterial therapy (IAT), resulting in potential delays and worse outcomes. We assessed the effect of a quality improvement (QI) initiative on reducing door-to-angio suite arrival times modeled after similar efforts in the AHA Target Stroke program. Methods: We examined two cohorts: pre- and post-implementation of a protocol for early alert of the neurointerventional radiology (NIR) team based on patient presentation within the treatment window (anterior circulation 8 hours, posterior circulation 24 hours) and clinical suspicion for LVO (NIHSS >10). We compared time from patient arrival to completion of imaging and arrival into the angio suite by Wilcoxon and multivariable linear regression. Results: Seventy one patients (48 pre- vs. 23 post-QI) with mean age of 68 years (36 (51%) male; median NIHSS 16, IQR 14-20) were included. Of these, 37 (52%) presented during work hours (weekdays 6am to 6pm). Post-QI, the NIR team was alerted early in 83% of cases. Overall QI impact was a reduction in absolute median door-to-suite time of 48 minutes (124 vs. 76 min, p Conclusions: Early notification of the NIR team resulted in a major reduction in time from door-to-angio suite arrival of ~50 minutes. This time savings was achieved through parallel work flow of the multidisciplinary teams during AIS evaluation. As the certification of Comprehensive Stroke Centers commences, such QI initiatives aimed at improving rapid delivery of time-sensitive therapies will be critical.
Multiport network approach for modelling and analysis of microstrip patch antennas and arrays

This chapter describes the multiport network approach, segmentation desegmentation techniques, and their applications to design of microstrip antennas. Relevant aspects of various models for microstrip antennas are presented. The multiport network model, which is an extension of the well known cavity model for microstrip patches, is discussed. Evaluation of multiport impedance matrices from the Green's functions for various types of segments is described. Modelling of external fields (including fringing, radiation and surface wave) by edge-admittance networks is detailed.
Inhibition of glucose uptake by acidosis in vitro.

SummaryGlucose uptakes of rat diaphragms in vitro were compared at pH 7.4 and 6.8. The acid medium inhibited glucose uptake but the degree of inhibition could be decreased by adding insulin to both media. At insulin concentrations in excess of 0.08 i.u./ml, glucose uptake was the same at each pH. With 0.008 i.u./ml insulin a pH of 7.1 was almost as inhibitory as pH 6.8. There was no enhancement of glucose uptake at pH 7.8.
Integrated QoS Multicast Routing Algorithm Based on Tabu Search

An integrated QoS multicast routing algorithm in IP/DWDM optical Internet is proposed.Considering load balancing,given a multicast request and flexible QoS requirement,to find a QoS multicast routing tree is NP-hard.Thus,a tabu search based algorithm is introduced to construct a cost suboptimal QoS multicast routing tree,embedding the wavelength assignment procedure based on segment and wavelength graph ideas.Hence,the multicast routing and wavelength assignment is solved integratedly.Simulation results show that the proposed algorithm is both feasible and effective.
Dynamic Characteristic Analysis of Distributed Generation System Based on Modular Multilevel Converters

According to the working principle and topological structure of modular multilevel converter(MMC) and condering the operational feature of distributed generation(DG) system,an equivalent inversion-type of DG system based on MMC and the mathematical model of its AC current controller are built.The dynamic characteristic of inversion-type of DG system is analyzed by PSCAD and it is found that under DC voltage fluctuation over wide range the AC current of inversion-type of DG system based on MMC and its output power fluctuate over wide range as well.To solve this problem,an improved AC current controller is proposed and whose effectiveness are verified by simulation results.
Moral Development During Surgical Residency Training

A recent article by Self et al. focussed on the moral development of students during medical school. The study found that moral reasoning scores did not increase over the four years of medical education as expected, suggesting that the educational experience somehow inhibited, rather than facilitated, moral reasoning development. Since the medical profession— and surgeons in particular— appears to accept the importance of moral character and the pursuit of a high moral code of ethics for its members, closer attention may need to be paid to this area of cognitive development, and the research expanded to investigate the impact of residency training.
Racial Differences in the Effects of Neighborhood Disadvantage on Residential Mobility in Later Life

OBJECTIVES Past research on the residential mobility of older adults has focused on individual-level factors and life course events. Less attention has been paid to the role of the residential environment in explaining residential mobility in older adults. We sought to understand whether neighborhood disadvantage had predictive utility in explaining residential relocation patterns, and whether associations differed between Whites and non-Whites. METHOD Data are from the National Social Life, Health and Aging Project, a nationally representative sample of community-dwelling older adults. Neighborhoods were defined at the census tract level. Local movers (different census tract, same county) and distant movers (different county) were compared with stayers. RESULTS After adjusting for individual-level factors, neighborhood disadvantage increased the likelihood of a local move, regardless of race/ethnicity. For non-Whites, higher neighborhood disadvantage decreased the likelihood of a distant move. Among local movers, Blacks and Latinos were less likely to improve neighborhood quality than Whites. DISCUSSION Neighborhood disadvantage may promote local mobility by undermining person-environment fit. Racial differences in access to better neighborhoods persist in later life. Future research should explore how older adults optimize person-environment fit in the face of neighborhood disadvantage when the possibility of relocation to a better neighborhood may be restricted.
Glucuronidation of the active metabolites of tamoxifen by human liver microsome and individual UDP-glucuronosyltransferases (UGTs)

3108 Tamoxifen (TAM) is a nonsteroidal anti-estrogen that has been commonly used for the treatment and prevention of estrogen-dependent breast cancer. Trans-4-OH-TAM exhibits up to 100-fold the level of anti-estrogenic activity as compared to its parent compound, and, in the presence of estrodiol, cis-4-OH-TAM also exhibits significant anti-estrogenic activity. A major mode of metabolism of TAM and its metabolites is by glucuronidation via UGTs. In the present study, the glucuronidating activities of trans- and cis-4-OH-TAM by human liver microsomes (HLMs) and individual UGTs were examined. HLMs exhibited significant glucuronidating activities against both cis-and trans-4-OH-TAM. Up to 4-fold difference in the ratio of trans-4-OH-TAM-O-Gluc to trans-4-OH-TAM-N+-Gluc was observed in a screening of 10 HLMs prepared from normal livers from individual subjects. Although high levels of cis-4-OH-TAM-O-Gluc formation were also observed in HLMs, significantly less cis-4-OH-TAM-N+-Gluc formation activities were observed in the same samples. In a screening of all known UGTs (except UGT1A5), only UGT1A4 exhibited N-glucuronidating activity towards either trans- or cis-4-OH-TAM. The apparent Km values of trans-4-OH-TAM-N+-glucuronide formation were similar for both HLMs and UGT1A4 over-expressing cell microsomes (3.10 μM versus 2.86 μM for HLMs and UGT1A4, respectively). UGTs 1A1, 1A7, 1A8, 1A9, 1A10, 2B7, 2B15 and 2B17 all exhibited O-glucuronidating activities against both trans- and cis-4-OH-TAM, with UGTs 2B7 and 2B15 exhibiting the highest activities against trans- and cis-4-OH-TAM, respectively, as determined by kinetic analysis. UGTs 1A3, 1A6, 2B4, 2B10, 2B11 and 2B28 showed no detectable activity towards these two substrates. These results suggest that HLMs are highly active against 4-OH-TAM and that several UGTs including UGT1A4 play an important role in the metabolism of trans-and cis-4-OH-TAM in vivo.
A retrospective analysis of the use of ureteral stents in children undergoing ureteroneocystotomy

Ureteral reimplantation is used widely for the correction of ureterovesical reflux. To determine the effect of ureteral stents we reviewed the charts of 63 children undergoing ureteral reimplantation for reflux. Of this group 31 patients had the ureterovesical anastomosis stented while 32 did not. Morbidity and operative failure were comparable in both groups. Our results do not support the use of ureteral stents in patients undergoing ureteroneocystotomy for primary ureterovesical reflux.
Is There a Difference in Tachycardia Cycle Length during SVT in Children with AVRT and AVNRT

Background There are limited adult data suggesting the tachycardia cycle length (TCL) of atrioventricular reentry tachycardia (AVRT) is shorter than atrioventricular nodal reentry tachycardia (AVNRT), though little data exist in children. We sought to determine if there is a difference in TCL between AVRT and AVNRT in children. Methods A single-center retrospective review of children with supraventricular tachycardia (SVT) from 2000 to 2015 was performed. Inclusion criteria: Age ≤ 18 years, invasive electrophysiology study (EPS) confirming AVRT or AVNRT. Exclusion criteria: Atypical AVNRT, congenital heart disease, antiarrhythmic medication use at time of EPS. Data were compared between patients with AVRT and AVNRT via t-test, χ2 test, and linear regression. Results A total of 835 patients were included (12 ± 4 years, 52 ± 31 kg, TCL 321 ± 55 ms), 539 (65%) with AVRT (270 Wolff-Parkinson-White, 269 concealed pathways) and 296 (35%) with AVNRT. Patients with AVRT were younger (11.7 ± 4.1 years vs 13.0 ± 3.6 years, P < 0.001) and smaller (49 ± 22 kg vs 57 ± 43 kg, P < 0.001). In the baseline state, the TCL was shorter in AVRT than AVRNT (329 ± 51 ms vs 340 ± 60 ms, P = 0.04). In patients requiring isoproterenol to induce SVT, there was no difference in TCL (290 ± 49 ms vs 297 ± 49 ms, P = 0.26). When controlling for age, there was no difference in TCL between AVRT and AVNRT at baseline or on isoproterenol. The regression equation for TCL in the baseline state was TCL = 290 + 4 (age), indicating the TCL will increase by 4 ms above a baseline of 290 ms for each year of life. Conclusions When controlling for age, there is no difference in the TCL between AVRT and AVNRT in children. Age, not tachycardia mechanism, is the most significant factor in predicting TCL.
Origins in the Womb: Potential Role of the Physical Therapist in Modulating the Deleterious Effects of Obesity on Maternal and Offspring Health Through Movement Promotion and Prescription During Pregnancy

Maternal obesity and associated metabolic disease contribute to adverse outcomes in women and their offspring, and many of these outcomes have significant acute and chronic implications for both mother and neonate. Targeted movement (ie, physical activity or exercise training) during pregnancy has been shown to be safe and effective for improving many of these outcomes in women at a healthy weight and women who are obese. However, movement prescription and advice during pregnancy are often not addressed by health care providers; this situation creates a unique opportunity for physical therapists to use their expertise in movement with patients who are pregnant. The objective of this article is to briefly review the adverse maternal and neonatal outcomes associated with maternal obesity, the benefits of intentional maternal movement during pregnancy for women who are obese, the evidence-based guidelines for prescribing intentional movement during pregnancy for women who are obese, and the potential for physical therapists to become the driving force behind a necessary increase in movement levels in women who are pregnant. Physical therapists can play a significant role in encouraging movement in women who are healthy and women who have metabolic challenges during pregnancy and thus assist in combating the vicious cycle of obesity by improving maternal and offspring health.
Simulation of stimuli-triggered release of molecular species from halloysite nanotubes

A Monte Carlo model is used to study the effect of environmental variables (pH and temperature) on the transport and release of dexamethasone molecules from Halloysite Nanotubes (HNTs) in a dielectric fluid medium. The model used for this study was introduced elsewhere and it is based on basic physics interactions without experimental parameters for these interactions. An intermediate phase between the burst and saturation phase is found and explained. Molecules experience a 1-D diffusion process that is different from the diffusion in the burst phase or the surface diffusion experienced by molecules attached to the wall. It is predicted that this phase exists when the molecule-wall interaction is attractive but not always noticeable in the release profile. In this work, it is shown that an agreement with the experiment better than previously reported is obtained when simulated delivery curves are produced by the weighted average of the release profiles from a collection of HNTs with diameters and lengths distributed according to the experimental sample, highlighting the relevance of HNTs' morphology in the release. HNTs are suitable for environment-triggered release and thus the effect of temperature, molecule zeta potential, and pH is studied. It is observed that for temperatures that significantly differ from room temperature (by 100's of degrees), the release profile changes significantly, increasing the delivery speed at high temperature and reducing that speed at low temperature. Finally, it is observed that as the pH becomes more acidic, both the molecule and inner wall surface become more positive (or less negative) with both eventually becoming positive leading to a repulsive interaction; thus, molecules are pushed out by electrostatic repulsion. On the contrary, as the pH becomes more basic, positive molecules become more positive while the wall becomes less negative, but even at pH 12, the wall remains negative and the interaction is attractive. Changes in pH between different regions may act as a trigger for delivery or as a control in the delivery rate.
Rolling contact fatigue of case carburized steels

Abstract Case carburized steels are widely used in high performance ball and rolling element bearings. They are characterized by the hardened exterior and gradient in the material properties as a function of depth. In this investigation, an elastic-plastic finite element model based on micro-indentation tests was developed to investigate the rolling contact fatigue of case carburized steels. A series of micro-indentation tests were conducted to obtain the hardness gradient in the case carburized 8620 steel. The results demonstrated that the hardness varies linearly from the surface to the core of the material. The finite element modeling approach employs Mises based plasticity model with kinematic hardening to incorporate the effect of material plasticity. The hardness gradient in the material was modeled by changing the yield strength as a function of depth. Linear relationship between hardness and yield strength was assumed. The FE model was coupled with continuum damage mechanics approach to capture material degradation due to fatigue damage. It considers both; stress and accumulated plastic strain based damage evolution laws for fatigue failure initiation and propagation. The residual stress distribution due to carburization process was modeled by modifying the damage evolution law. Material dependent parameters used in the damage evolution laws were determined using the SN results for torsional fatigue of the bearing steel. The effects of topological randomness in the material microstructure are accounted in the model through the use of Voronoi tessellations. The model was used to compare the rolling contact fatigue (RCF) lives of through hardened and case carburized bearing steel with different case depths at contact pressures ranging from 2 to 3.5 GPa. The effect of residual stress distribution on RCF lives was also investigated. The results show that there is an optimum case depth for which maximum RCF lives can be attained. The spall shapes and the depth below the surface where damage initiates were found to be dependent on the case depth. The model was also used to study the effect of initial material imperfections. The fatigue lives and their dispersion quantified by Weibull slopes obtained from the model correlate well with the experiments.
Intention Inference for Human-Robot Collaboration in Assistive Robotics

In this chapter, we present an algorithm to infer the intent of a human operator’s arm movements based on the observations from a Microsoft Kinect sensor. Intentions are modeled as the goal locations of reaching motions in the three-dimensional space. Human intention inference is a critical step towards realizing safe human-robot collaboration. We model a human arm’s nonlinear motion dynamics using an unknown nonlinear function with intentions represented as parameters. The unknown model is learned by using a neural network. Based on the learned model, an approximate expectation-maximization algorithm is developed to infer human intentions. Furthermore, an identifier-based online model-learning algorithm is developed to adapt to the variations in the arm motion dynamics, the motion trajectory, the goal locations, and the initial conditions of different human subjects. We present the results of the proposed algorithm via experiments conducted on Kinect data obtained from different users performing a variety of reaching motions. We also evaluate the performance of the algorithm by using Cornell’s CAD-120 dataset.
Sickle cell vaso-occlusive crisis: it's a gut feeling.

Insights in the pathogenesis of vaso-occlusive crisis in patients with sickle cell disease have changed significantly in the last decade. Various laboratory and clinical evidence have provided support to the pivotal role of activated neutrophils in this process. A recent study in murine sickle cell disease indicated that the intestinal microbiota is responsible for regulating the number of aged neutrophils, a subset of neutrophils that are overly activated. Reduction of these neutrophils in vivo protected the mice from fatal TNFα-induced vaso-occlusive crisis. In this paper, we discuss the reasons why patients with sickle cell disease may have an abnormal intestinal microbiota and how this could contribute to the development of vaso-occlusive crisis. We also highlight the recent interest in studying the intestinal microbiota of patients with sickle cell disease and suggest that the next therapeutic approach for these patients may well be in the manipulation of the intestinal microbiota to restore the individual’s microbial landscape.
Antisynthetase syndrome (ASS) presenting as acute respiratory distress syndrome (ARDS) in a patient without myositis features.

A woman aged 61 years presented to the emergency room with a 1-week history of dyspnoea on exertion and dry cough. X-ray of the chest showed diffuse interstitial opacities and was started on antibiotics and furosemide, and despite these measures, patient9s respiratory status worsened, prompting endotracheal intubation. CT of the chest showed diffuse bilateral ground glass opacities and underwent bronchoscope with trans-bronchial biopsy that showed chronic bronchitis. Pt was empirically started on intravenous steroids due to concerns for interstitial lung disease (ILD). Autoimmune work up was sent and underwent video-assisted thoracoscopic surgery-guided biopsy of the lung that showed non-specific interstitial pattern with fibrosis. The patient was diagnosed as having antisynthetase syndrome with pulmonary involvement (ILD) as the cause of her acute respiratory failure. Azathioprine was started as steroid-sparing agent and was weaned off the ventilator to a tracheostomy collar and discharged to long-term rehabilitation centre.
MODFLOW/MT3DMS-Based Simulation of Variable-Density Groundwater Flow with Simultaneous Heat and Solute Transport

SEAWAT is a finite-difference computer code, based on MODFLOW and MT3DMS, designed to simulate coupled variable-density groundwater flow and solute transport. This paper describes a new version of SEAWAT, which adds the ability to simultaneously model energy and solute transport. This is necessary for simulating the transport of heat and salinity in coastal aquifers for example. This work extends the equation of state for fluid density to vary as a function of temperature and/or solute concentration. The program has also been modified to represent the effects of variable fluid viscosity as a function of temperature and/or concentration. The viscosity mechanism is verified against an analytical solution and a test of temperature-dependent viscosity is provided. Finally, the classic Henry-Hilleke problem is solved with the new code and the results are compared with other published solutions.
Beliefs About a Complementary and Alternative Therapy-Based Chronic Pain Management Program for a Medicaid Population.

Objective Rhode Island Medicaid offers high emergency department utilizers the opportunity to take part in the Chronic Pain Program, an integrated treatment approach that includes free complementary therapies (massage, chiropractic, and acupuncture). The aim of the current analysis was to understand beliefs about the Rhode Island Chronic Pain Program from the perspective of the patient receiving services, the provider delivering services, and the administrator implementing the program. Design A qualitative interview-based study. Subjects Patients (N = 24), providers (N = 13), and administrators (N = 11) who were already involved, or were eligible to be involved, in the Chronic Pain Program. Methods Semistructured interviews were conducted to elicit information about experiences with the program. Transcriptions of audio recordings were analyzed according to principles of deductive thematic analysis. Results Patient interviews revealed five themes: 1) relationship between stress and pain, 2) trusting patient-provider relationships, 3) increased quality of life, 4) temporary pain relief, and 5) anxiety and discomfort associated with acupuncture. Provider interviews revealed three themes: 1) a way to reach the disenfranchised, 2) not enough visits with patients, and 3) opportunity to build relationships with patients. Administrator interviews revealed two themes: 1) a means to offer a range of support services to complicated patients and 2) unanswered questions over whether the program adequately serves patients with the greatest needs. Conclusions Key stakeholders in this new initiative agree that the Rhode Island Chronic Pain Program shows promise and that the holistic approach may be a good match for this hard-to-reach population.
Influence of provider and health system factors on uptake and disparities in breast cancer gene expression profile testing.

250Background: Gene expression profiles (GEPs) have been rapidly and widely adopted to guide chemotherapy decisions in early hormone receptor-positive (HR+) breast cancer, but not all eligible patients receive testing. Patient-level predictors of testing have been reported. However, the role of provider and insurance factors in GEP use has not been well described. Racial disparities in access to testing are also under-studied. Methods: We used state cancer registry data linked to claims from multiple insurance payers to identify 11,958 patients eligible for GEP testing between 2005 and 2012. For each patient, we characterized specialty and breast cancer volume for the provider deemed most likely to make the testing decision. We identified claims for the most commonly used GEP (OncotypeDX) and used adjusted incidence rate models to examine predictors of testing, stratified by nodal status (N0 versus N1). Results: Overall, 26% of eligible patients were tested with rates increasing over time. In multivariabl...
Tandem-hopped OFDM communications in spectral gaps of FM noise radar

It was recently demonstrated that hopped spectral gaps can be incorporated into a physically realizable form of FM noise radar emission. Here it is shown using experimental loopback measurements how OFDM communications can be embedded into these spectral gaps and, by virtue of proper spectral shaping, realize a composite emission with low autocorrelation sidelobes. The impact of tandem hopping of the radar spectral gap and embedded communication signal is evaluated. An example of a spectrally shaped OFDM emission for use in a notional commensal radar setting is also presented.
Characterization of simvastatin acid uptake by organic anion transporting polypeptide 3A1 (OATP3A1) and influence of drug-drug interaction

Human organic anion transporting polypeptide 3A1 (OATP3A1) is predominately expressed in the heart. The ability of OATP3A1 to transport statins into cardiomyocytes is unknown, although other OATPs are known to mediate the uptake of statin drugs in liver. The pleiotropic effects and uptake of simvastatin acid were analyzed in primary human cardiomyocytes and HEK293 cells transfected with the OATP3A1 gene. Treatment with simvastatin acid reduced indoxyl sulfate-mediated reactive oxygen species and modulated OATP3A1 expression in cardiomyocytes and HEK293 cells transfected with the OATP3A1 gene. We observed a pH-dependent effect on OATP3A1 uptake, with more efficient simvastatin acid uptake at pH5.5 in HEK293 cells transfected with the OATP3A1 gene. The Michaelis-Menten constant (Km) for simvastatin acid uptake by OATP3A1 was 0.017±0.002μM and the Vmax was 0.995±0.027fmol/min/105 cells. Uptake of simvastatin acid was significantly increased by known (benzylpenicillin and estrone-3-sulfate) and potential (indoxyl sulfate and cyclosporine) substrates of OATP3A1. In conclusion, the presence of OATP3A1 in cardiomyocytes suggests that this transporter may modulate the exposure of cardiac tissue to simvastatin acid due to its enrichment in cardiomyocytes. Increases in uptake of simvastatin acid by OATP3A1 when combined with OATP substrates suggest the potential for drug-drug interactions that could influence clinical outcomes.
Factors That Contribute to Differences in Survival of Black vs White Patients With Colorectal Cancer

Abstract Background & Aims Previous studies reported that black vs white disparities in survival among elderly patients with colorectal cancer (CRC) were due to differences in tumor characteristics (tumor stage, grade, nodal status, and comorbidity) rather than differences in treatment. We sought to determine the sequential contribution of differences in insurance, comorbidity, tumor characteristics, and treatment receipt to the black-white survival disparity among patients with CRC in 18–64 years old. Methods We used data from the National Cancer Database, a hospital-based cancer registry database sponsored by the American College of Surgeons and the American Cancer Society, on non-Hispanic black (black) and non-Hispanic white (white) patients, 18–64 years old, diagnosed from 2004 through 2012 with single or first primary invasive stage I–IV CRC. Blacks were sequentially matched by demographics, insurance, comorbidity, tumor characteristics, and treatment with 5 white partially overlapping subgroups using propensity score and greedy matching algorithm. We used the Kaplan-Meier method to estimate 5-year survival, and Cox proportional hazards models to generate hazard ratios (HR). Results The absolute 5-year survival difference between black and white unmatched patients with CRC was 9.2% (57.3% for black patients vs 66.5% for white patients; P Conclusions In an analysis of data from the National Cancer Database, we found that insurance coverage differences accounted for approximately one-half of the disparity in survival rate between black vs white patients with CRC in 18–64 years old; tumor characteristics accounted for a quarter of the disparity. Affordable health insurance coverage for all populations could substantially reduce differences in survival times of black vs white patients with CRC.
Design and fabrication of a 3D–printed oral stent for head and neck radiotherapy from routine diagnostic imaging

Oral stents have been shown to reduce the deleterious effects of head and neck radiotherapy through the displacement of normal tissues away from the areas of high dose irradiation. While these stents are commonly used in the treatment of patients with head and neck cancer at many large academic cancer centers, their use is much more limited outside of these institutions due to the time and expertise required for their fabrication. In the study, we describe a novel method to design and manufacture oral stents from routine computed tomography (CT) imaging studies through the use of 3D printing technologies. Our proposed method may help to greatly expand access to these beneficial devices for patients undergoing radiation treatment at centers without access to dental and oral/maxillofacial specialists.
The development eraser: fantastical schemes, aspirational distractions and high modern mega-events in the Oecusse enclave, Timor-Leste

The array of challenges to durably improving rural peoples' lives in remote regions is so daunting that it can be tempting to erase what is there, and to seek a blank slate. This tension is being played out in the OecusseAmbeno enclave of Timor-Leste, a region long familiar with geographic and political isolation. Residents now encounter a new iteration of their unique status: rapid declaration of their region as a special economic zone (ZEESM), with a new regional governance structure and an appointed leadership. The advent of this new zone is meant to catapult Oecusse from its current state of chronic infrastructure and basic development challenges to a booming economic center and a fount of national income in short order. Early emphasis is placed on rapid, major coastal infrastructure construction deemed necessary for the November 2015 commemoration of the 500th anniversary of Portuguese arrival, with the hallmarks associated with high modernism and mega-event preparation worldwide: spatial re-ordering and regulation; a strong orientation to external inputs, resources, and services; and centralized control of rapid infrastructure change. This article investigates the ideological underpinnings of these plans, and explores the irony of how the proposals and their governance arrangement are a disjuncture with Oecusse as a historically important place. It concludes with observations on this project's place in the national development context, and the likely costs and impacts of development for the Oecusse population. Risks include further political and economic marginalization of the mountain-dwelling and rural population, local residents' loss of productive agricultural land and access to water, reduced protection through administrative exclusion from national political structures, and the opportunity costs of misdevelopment's aspirational distractions. Key words: Special Economic Zone; high modernism; mega-event; Timor-Leste; Oecusse Ambeno; economic development
Prognostic Implications of Mitral Annular Plane Systolic Excursion in Patients with Hypertension and a Clinical Indication for Cardiac Magnetic Resonance Imaging: A Multicenter Study

Abstract Objectives This study sought to evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived mitral annular plane systolic excursion (MAPSE) in a large multicenter population of patients with hypertension. Background In patients with hypertension, cardiac abnormalities are powerful predictors of adverse outcomes. Long-axis mitral annular movement plays a fundamental role in cardiac mechanics and is an early marker for a number of pathological processes. Given the adverse consequences of cardiac involvement in hypertension, the authors hypothesized that lateral MAPSE may provide incremental prognostic information in these patients. Methods Consecutive patients with hypertension and a clinical indication for CMR at 4 U.S. medical centers were included in this study (n = 1,735). Lateral MAPSE was measured in the 4-chamber cine view. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the association between lateral MAPSE and death. The incremental prognostic value of lateral MAPSE was assessed in nested models. Results Over a median follow-up period of 5.1 years, 235 patients died. By Kaplan-Meier analysis, risk of death was significantly higher in patients with a lateral MAPSE Conclusions CMR-derived lateral MAPSE is a powerful, independent predictor of mortality in patients with hypertension and a clinical indication for CMR, incremental to common clinical and CMR risk factors. These findings may suggest a role for CMR-derived lateral MAPSE in identifying hypertensive patients at highest risk of death.
Integral solutions to the Pythagorean Equation

In this chapter we present two different methods to find the solutions of the Pythagorean Equation, one algebraic and one geometric. We then apply the geometric method to find solutions of some other equations.
Discovery of N-(4-Methoxy-7-methylbenzo[d]thiazol-2-yl)isonicatinamide, ML293, as a Novel, Selective and Brain Penetrant Positive Allosteric Modulator of the Muscarinic 4 (M4) Receptor.

Title compound (I) represents a novel muscarinic 4 (M4) receptor tool with superior in vivo PK properties compared to previously published molecules.
MRI and ultrasound of the hands and wrists in rheumatoid arthritis. I. Imaging findings

The management of patients with rheumatoid arthritis (RA) has rapidly evolved with the development of newer disease-modifying drugs and the recognition that long-term damage can be mitigated by an earlier and more-informed use of these medications. Historically, radiographs were the mainstay of imaging in RA patients, but radiographic joint narrowing and erosions are late and insensitive findings in the disease. MRI (with intravenous contrast agent) and ultrasound (with power Doppler interrogation) of the hands and wrists are able to demonstrate erosions earlier and with greater sensitivity than radiographs. More importantly, these imaging studies also depict synovitis and active soft-tissue inflammation, which represents a precursor to structural damage. Additionally, MRI can show inflammation within the bones (osteitis), which is proving to be the most important prognosticator of an aggressive disease course. Part I of this review discusses the imaging techniques, pitfalls, definitions, and comparative studies of MRI and ultrasound for identifying and quantifying erosions, synovitis, and osteitis. Part II will demonstrate how these imaging findings influence the clinical management of RA patients throughout their disease course, from presentation through clinical remission.
Mid-flight trunk flexion and extension altered segment and lower extremity joint movements and subsequent landing mechanics.

Abstract Objectives To assess the effect of mid-flight trunk flexion and extension on the movements of body segments and lower extremity joints and subsequent landing mechanics during a jump-landing task. Design Participants performed three jump-landing conditions in a randomized order. Methods Forty-one participants completed jump-landing trials when performing three different mid-flight trunk motion: reaching forward, reaching up, and reaching backward. Whole-body kinematic and ground reaction force data were collected. Results The reaching backward condition resulted in a more posteriorly positioned upper body center of mass (COM) and more anteriorly positioned pelvis COM, legs COM, hip, and knee joint positions relative to the whole-body COM in flight and at initial contact of landing. The reaching backward condition showed the least hip flexion and ankle plantarflexion angles at initial contact as well as the least hip and knee flexion angles and the greatest ankle dorsiflexion angles at 100 ms after landing. The reaching backward condition also demonstrated the greatest peak posterior ground reaction forces, peak and average knee extension moments, peak and average hip flexion moments, and peak knee varus moments within the first 100 ms after landing. Opposite changes were observed for the reaching forward condition. Conclusions Mid-flight trunk extension resulted in body postures that predisposed individuals to land with increased knee extension and varus moments and decreased knee flexion angles, which are indirectly associated with increased ACL loading. These findings may help to understand altered trunk motion during certain ACL injury events and provide information for developing jump-landing training strategies.
Modeling of the Acoustic Field Produced by Diagnostic Ultrasound Arrays in Plane and Diverging Wave Modes

Recent advances in ultrafast contrast imaging have facilitated innovations, such as superresolution imaging and ultrafast contrast-enhanced Doppler imaging. Combining plane and diverging wave imaging (PWI/DWI) with tissue harmonic imaging (THI) may offer improvements in image quality in applications such as 3-D THI and harmonic color flow. However, no studies have reported simulations of the nonlinear acoustic fields produced by diagnostic arrays in either plane or diverging wave mode. The aim of this study is to model three typical diagnostic arrays that are used in clinical practice and research, Verasonics L11-4v linear array, C5-2v convex array, and P4-2v phased array with the Khokhlov–Zabolotskaya–Kuznetsov (KZK) equation. We have two specific objectives: first, to investigate whether there is increased bubble destruction due to the nature of the plane and diverging fields in contrast imaging; and second, to investigate the feasibility of combining PWI/DWI and THI by quantifying the second harmonic generated by these fields. We showed in linear simulations that using such arrays for ultrafast contrast imaging produced pressures that are greater in the near field and lower in the far field than those of focused beams and thus may induce more near-field bubble destruction. In nonlinear simulations, the second harmonic produced by ultrafast THI was found to be 2–16 dB lower than that of focused beams for all arrays considered when operated at the same MI. This moderate difference of the second harmonic between PWI/DWI and focused ultrasound suggests that it is feasible to combine PWI/DWI and THI.
Shrink Films Get a Grip

Robotics and active materials have forged the path for grasping and manipulating delicate objects of various geometries and sizes. To date, the majority of soft robotic grippers have used hydrogels or elastomers, which can repeatably grasp and manipulate small objects. Many of these grippers achieve their grip (due to shape change) only in the presence of either solvent exposure or external pneumatic pressure. Here, we demonstrate thermoplastic polystyrene sheets that actuate from flat sheets into grippers in response to light exposure and maintain their shape upon removal of the light. Black ink patterned on the sheet converts global light illumination to localized heating that causes the planar sheet to deform into the shape of a gripper. These grippers have significantly improved endurance and strength compared to their hydrogel or elastomeric counterparts as they can support >24 000 times their own mass. These grippers release objects upon additional uniform heating, and each gripper serves as a singl...
Role of phospholipase D in bleomycin-induced mitochondrial reactive oxygen species generation, mitochondrial DNA damage, and pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a pernicious lung disease characterized by alveolar epithelial apoptosis, dysregulated repair of epithelial injury, scar formation, and respiratory failure. I...
Critical Model Parameters: A Security Vulnerability in Electricity Market Operation

In power grids, a critical parameter is a type of network model parameter whose error is not detectable due to the existing measurement configuration. In this paper, the effect of incorrect critical parameters on the calculation of locational marginal prices (LMP) will be investigated. Such errors will present a security vulnerability in the operation of electricity markets. It will be shown that model parameter errors can severely bias LMPs by affecting the injection shift factors (ISFs) and congestion patterns. If the error is undetectable, as is the case for a critical parameter, economic interests of the market participants will be compromised. This implies that it may be possible for potential adversaries to manipulate electricity market operations if they have access the network data base and can manipulate critical model parameters. Simulations on an IEEE test system will be used to illustrate the identified security vulnerabilities related to critical network parameters.
Staff Perceptions of Chaplains in a Neurosciences Critical Care Unit

Hospital chaplains often visit critically ill patients, but neurosciences critical care unit (NCCU) staff beliefs surrounding chaplains have not been characterized. In this study, we used Qualtrics® to survey 70 NCCU healthcare workers about their attitudes toward chaplains in the NCCU. Chaplains were seen positively by staff but were less likely to be viewed as part of the care team by staff with more than five years of NCCU experience. The results of this study will allow chaplaincy programs to target staff education efforts in order to enhance the care provided to patients in critical care settings.
Neurosarcoidosis Directly Involving the Cervical Vagus Nerve

Objectives:To present a novel location in which neurosarcoidomatous inflammation is identified and its accompanying presentation.Methods:The authors present a case of bilateral vocal fold paresis a...