Biologics May Prevent Cardiovascular Events in Rheumatoid Arthritis by Inhibiting Coronary Plaque Formation and Stabilizing High-Risk Lesions.

ObjectiveTo evaluate whether biologic disease-modifying antirheumatic drugs (DMARDs) decrease cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) and whether biologic DMARDs might have a beneficial effect on coronary plaque formation or progression.MethodsIn this single-center observational cohort study, 150 patients underwent computed tomographic angiography for evaluation of coronary atherosclerosis (total, noncalcified, mixed/calcified, and low-attenuation plaque); 101 had repeat assessments within a mean ± SD of 6.9 ± 0.3 years to evaluate plaque progression. All CVD events were prospectively recorded, including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication, and hospitalization for heart failure. The Framingham-D'Agostino score was used to assess cardiovascular risk. The segment stenosis score was used to measure plaque burden. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.ResultsAfter adjustment for the segment stenosis score, the Framingham-D'Agostino score, and time-varying Disease Activity Score in 28 joints using the C-reactive protein level using marginal structural models, current biologic DMARD use was associated with lower long-term CVD risk (OR 0.15 [95% CI 0.04-0.60]). Noncalcified and low-attenuation plaque presence moderated the effect of biologic DMARDs on CVD risk; specifically, biologic DMARD use was associated with lower CVD risk in patients with noncalcified or low-attenuation plaque at baseline (OR 0.21 [95% CI 0.04-0.99] and OR 0.08 [95% CI 0.01-0.70], respectively), but not in those without noncalcified or low-attenuation plaque. Per-segment plaque progression analyses showed that biologic DMARD exposure was associated with transition of noncalcified to mixed/calcified plaque (OR 4.00 [95% CI 1.05-15.32]). Biologic DMARD exposure predicted a lower likelihood of new plaque forming in segments without plaque among patients without mixed/calcified plaque in other coronary segments (OR 0.40 [95% CI 0.17-0.93]), but not among those with calcification. Biologic DMARD treatment also predicted low-attenuation plaque loss (P = 0.042).ConclusionOur findings indicate that in RA, biologic DMARD use is associated with reduced CVD risk, protective calcification of noncalcified lesions, and lower likelihood of new plaque formation in patients with early atherosclerosis

Microbial Challenges to Extending Usage of Rio Grande River Water

Despite its critical role in agriculture and potable water supply for the region, few studies have evaluated the microbial quality of the Rio Grande River, especially for the parasites Cryptosporidium and Giardia. Cryptosporidium and Giardia cause diarrheal illness and have been responsible for numerous waterborne and foodborne disease outbreaks. Cryptosporidiosis, the disease caused by Cryptosporidium, may be fatal in people with weakened immune systems and there is currently no effective treatment for the disease. During the irrigation season, water is released from upstream reservoirs and the river water is used by El Paso as a potable supply. During the non-irrigation season (October through February), river flows are comprised of agricultural return flows and wastewater treatment plant effluents. Due to recent drought conditions in the region, winter return flows in the El Paso area are largely wastewater effluents. Our monitoring results revealed that winter return flows contain 5 and 100 times higher average levels of Cryptosporidium and Giardia, respectively, than irrigation season river water. Recently, research has been proposed to evaluate the use of winter return flows for potable supply and irrigation. Conventional filtration and disinfection followed by nanofiltration or reverse osmosis have been proposed for treatment of the water to remove total dissolved solids and microorganisms. Besides Cryptosporidium and Giardia, viruses may also be present in wastewater effluents. Therefore, in addition to chemical quality issues, these microbial water quality challenges must be overcome before this underutilized water resource can be put to beneficial use

The Role of Macrophage Migration Inhibitory Factor (MIF) in Apoptotic Extracellular Vesicle Mediated Signaling in Breast Cancer

https://openworks.mdanderson.org/sumexp21/1208/thumbnail.jp

What’s Your CQ? A Framework to Assess and Develop Individual Student Cultural Intelligence

This article’s goal is to provide suggestions for teaching students about culture and cultural intelligence. This article pursues this goal by first exploring and defining culture and presenting the nuances and challenges of teaching students about culture in an environment supportive of multiple cultures (e.g., national, regional, local, corporate, etc.). Finally, the article concludes with a discussion of a cultural intelligence development process consisting of a cultural intelligence pre assessment and feedback, cultural intelligence transformation activities, and a cultural intelligence post assessment and feedback

A Multilayer Interval Type-2 Fuzzy Extreme Learning Machine for the Recognition of Walking Activities and Gait Events using Wearable Sensors

In this paper, a novel Multilayer Interval Type-2 Fuzzy Extreme Learning Machine (ML-IT2-FELM) for the recognition of walking activities and Gait events is presented. The ML-IT2-FELM uses a hierarchical learning scheme that consists of multiple layers of IT2 Fuzzy Autoencoders (FAEs), followed by a final classification layer based on an IT2-FELM architecture. The core building block in the ML-IT2-FELM is an IT2-FELM, which is a generalised model of the Interval Type-2 Radial Basis Function Neural Network (IT2-RBFNN) and that is functionally equivalent to a class of simplified IT2 Fuzzy Logic Systems (FLSs). Each FAE in the ML-IT2-FELM employs an output layer with a direct-defuzzification process based on the Nie-Tan algorithm, while the IT2-FELM classifier includes a Karnik-Mendel type-reduction method (KM). Real data was collected using three inertial measurements units attached to the thigh, shank and foot of twelve healthy participants. The validation of the ML-IT2-FELM method is performed with two different experiments. The first experiment involves the recognition of three different walking activities: Level-Ground Walking (LGW), Ramp Ascent (RA) and Ramp Descent (RD). The second experiment consists of the recognition of stance and swing phases during the gait cycle. In addition, to compare the efficiency of the ML-IT2-FELM with other ML fuzzy methodologies, a kernel-based ML-IT2-FELM that is inspired by kernel learning and called KML-IT2-FELM is also implemented. The results from the recognition of walking activities and gait events achieved an average accuracy of 99.98% and 99.84% with a decision time of 290.4ms and 105ms, respectively, by the ML-IT2-FELM, while the KML-IT2-FELM achieved an average accuracy of 99.98% and 99.93% with a decision time of 191.9ms and 94ms. The experiments demonstrate that the ML-IT2-FELM is not only an effective Fuzzy Logic-based approach in the presence of sensor noise, but also a fast extreme learning machine for the recognition of different walking activities

BAMM (BRAF autophagy and MEK inhibition in melanoma): A phase I/II trial of dabrafenib, trametinib, and hydroxychloroquine in advanced BRAFV600-mutant melanoma

PURPOSE: Autophagy is a resistance mechanism to BRAF/MEK inhibition in BRAFV600-mutant melanoma. Here we used hydroxychloroquine (HCQ) to inhibit autophagy in combination with dabrafenib 150 mg twice daily and trametinib 2 mg every day (D+T). PATIENTS AND METHODS: We conducted a phase I/II clinical trial in four centers of HCQ + D+T in patients with advanced BRAFV600-mutant melanoma. The primary objectives were the recommended phase II dose (RP2D) and the one-year progression-free survival (PFS) rate of \u3e53%. RESULTS: Thirty-four patients were evaluable for one-year PFS rate. Patient demographics were as follows: elevated lactate dehydrogenase: 47%; stage IV M1c/M1d: 52%; prior immunotherapy: 50%. In phase I, there was no dose-limiting toxicity. HCQ 600 mg orally twice daily with D+T was the RP2D. The one-year PFS rate was 48.2% [95% confidence interval (CI), 31.0%-65.5%], median PFS was 11.2 months (95% CI, 5.4-16.9 months), and response rate (RR) was 85% (95% CI, 64%-95%). The complete RR was 41% and median overall survival (OS) was 26.5 months. In a patient with elevated LDH (n = 16), the RR was 88% and median PFS and OS were 7.3 and 22 months, respectively. CONCLUSIONS: HCQ + D+T was well tolerated and produced a high RR but did not meet criteria for success for the one-year PFS rate. There was a high proportion of patients with pretreated and elevated LDH, an increasingly common demographic in patients receiving targeted therapy. In this difficult-to-treat population, the RR and PFS were encouraging. A randomized trial of D+T + HCQ or placebo in patients with BRAFV600-mutant melanoma with elevated LDH and previous immunotherapy is being conducted

Displacement sensing using bi-modal resonance in over-coupled inductors

This paper presents the theory and key experimental findings for an investigation into the generation of bimodal resonance (frequency splitting) phenomena in mutually over-coupled inductive sensors, and its exploitation to evaluate relative separation and angular displacement between coils. This innovative measurement technique explores the bimodal resonant phenomena observed between two coil designs - solenoid and planar coil geometries. The proposed sensors are evaluated against first-order analytical functions and finite element models, before experimentally validating the predicted phenomenon for the different sensor configurations. The simulated and experimental results show excellent agreement and first-order best-fit functions are employed to predict displacement variables experimentally. Co-planar separation and angular displacement are shown to be experimentally predictable to within $\pm1mm$ and $\pm1^o$ using this approach. This study validates the first-order physics-based models employed, and demonstrates the first proof-of-principle for using resonant phenomena in inductive array sensors for evaluating relative displacement between array elements

Interdisciplinary Integrated Primary and Behavioral Healthcare (I2PBH) Initiative

Purpose: The Interdisciplinary Integrated Primary and Behavioral Healthcare (I2PBH) Initiative will train University of Texas Rio Grande Valley (UTRGV) mental health graduates to deliver high quality, evidence-based Integrated Behavioral Health (IBH) services in the Rio Grande Valley (RGV) – a high-need, high-demand, medically underserved Hispanic region along the US-Mexico border. Specifically, the I2PBH initiative will train 24 UTRGV mental health graduates annually to deliver high-quality IBH clinical services through the evidence based Primary Care Behavioral Health (PCBH) model. With a training emphasis on basic/advanced theory and clinical skills in the PCBH model, students will serve as Behavioral Health Consultants (BHC) to meet practicum/internship requirements while working alongside healthcare professionals in a primary care setting. The I2PBH initiative increases the presence of culturally concordant, primary care competent BHCs on the front lines of four rural clinics to function as primary care providers (PCP) extenders for all behaviorally informed needs of patients, increasing access and delivering whole-person care. Description: The I2PBH initiative will train 6 graduate students each year from 4 mental health disciplines in basic and advanced theory and clinical skills through the evidence based PCBH model. As BHCs, these Behavioral Health Workforce Education and Training (BHWET) stipend recipients in Social Work (SW), Clinical Mental Health Counseling (CMHC), Rehabilitation Counseling (RC), and Psychology (PSY) will work alongside healthcare providers and other health profession trainees in three (3) Area Health Education Center (AHEC) Primary Care Clinics (PCC) and one (1) mobile clinic, located in four rural counties of South Texas. Academic training for PCBH-focused courses and PCBH oriented advanced clinical supervision will be delivered through in-person classes, role-playing, digitally enhanced training using Mixed-Reality Simulation (MRS), and asynchronous distance learning via virtual platforms (e.g., Blackboard, Zoom). All BHWET stipend recipients will complete the trauma-informed, culturally adaptive PCBH-focused courses –Foundations of IBH; Clinical Skills for the BHC; and Latinx Health Issues in IBH. Based on a discipline-agnostic approach, this teaches PCBH specific competencies while also providing concurrent, primary-care focused clinical experiences, resulting in a behavior health workforce that is primary-care ready and trauma-informed. Partners: The I2PBH initiative coordinates these experiential training opportunities with three (3) Area Health Education Center (AHEC) Primary Care Clinics (PCC) and one (1) mobile clinic to promote community-based partnerships in four rural counties in South Texas. Looking Ahead: By the year 2025, the I2PBH initiative will have: 96 students complete three PCBH courses and an associated internship and practicum experience in a UTRGV rural AHEC or Mobile Clinic PCC. Implemented PCBH-focused education and clinical supervision for BHWET stipend recipients and faculty facilitators from different disciplines. Collaborated with community partners to increase access for behavioral health services and connect trainees with potential employment opportunities. Integrated technology to facilitate learning/teaching and enhance community reach and impact