Comorbidity: A Neglected Aspect of the Burden of RA

INTRODUCTION: RA is defined as a systemic inflammatory disease that manifests itself in multiple joints in the body (CDC). This inflammation affects the lining of the joints primarily, but can also affect other organs. The chronic inflammation leads to erosion on the cartilage and can cause joint deformity. The cause of RA is unknown, however many factors such as genetics, environment, and lifestyle are being evaluated. Symptoms can include joint pain, rash, fatigue, stiffness in joints, fever, and swollen joints. There is no cure, but there are a variety of medicines used to reduce inflammation. There are a number of comorbidities associated with the disease complex. The incidence of comorbidities is increasing, however, the data from current studies are not being used towards patient information. The availability of information of patients both online and through the doctor is severely lacking. AIM: The purpose of this capstone is to identify the types of comorbidities associated with arthritis, focusing specifically on rheumatoid arthritis (RA). I identify and review the non scientific literature that patients are likely to seek after a diagnosis to determine the span of information available to the general public as well as provide statistics and articles for comorbidities in RA. This information will inform a set of recommendations for future research and improvement of patient care. METHODS: This capstone focuses on statistics of comorbidities present in rheumatoid arthritis (RA) and online resources available to patients. Data were collected via Pubmed articles using the Georgia State University Library database list. Articles were analyzed for relevance and data was complied into a table for easy reference. The patient resource websites were found using a Google search and evaluated for usefulness and the level of information provided. RESULTS: My research indicated that the prevalence of comorbidities is high among patients diagnosed with arthritis. Patients are most frequently diagnosed with cardiac events, cancer, and respiratory diseases such as COPD. Nearly every researcher assessed that there was not enough research done and that results were conflicting. Patient online resources are lacking and the availability of information is subpar. DISCUSSION: There are articles that provided statistics on arthritis patients with comorbidities in almost every article within the discussion section, but it was stated that there was not enough data to make definitive statements and conclusions. The problem is that studies and data are being produced, but there is no movement forward to produce a treatment plan and thus the information available for patients should be reevaluated

Playable Personas: Using Games and Play to Expand the Repertoire of Learner Personas

This article explores how playing and co-creating games in higher education contexts contributes to expanding learner personas and facilitating a multimodal learning experience. Working from the interdisciplinary perspectives of media/games studies, pedagogy, and linguistic anthropology, we conceptualize in-class learning as the making and playing of games, reporting on game experiments and playful practices targeted at learning key theoretical concepts in our disciplines. Game-based modifications to established educational practices involved: replacing lectures with Educational Live Action Role Play (Bowman 2014) sessions, using acting/performance games (Flanagan 2009) to critically reflect on ideas of community and collective identity, and introducing Twine (Werning 2017; Wilson & Saklofske 2019) to defamiliarize the expected structures and media modalities of academia. Based on evidence from participant reflections and classroom ethnographies, we argue that games can serve as a resource for extending the expressive spectrum of learner personas, for enabling embodied, participatory learning of theory, and for empowering students and educators to reflect on our internalized rules of the game of education

The Effect of Instrument Assisted Soft Tissue Mobilization on Improving Joint Range of Motion in Active Individuals: A Critically Appraised Topic

CLINICAL SCENARIO In all activities that require physical movement, whether in athletics or in other daily tasks, it is important for joints to have adequate range of motion and flexibility. Soft tissue restrictions are very common pathologies in healthcare. Although a decrease in myofascial range of motion can arise from a variety of reasons such as biomechanical deformities, autoimmune diseases, or age, it is often caused by overtraining or musculoskeletal injuries in active populations. Instrument assisted soft tissue mobilization techniques are gaining popularity to assist in treating various soft tissue injuries and musculoskeletal pathologies. The belief is that by applying a stimulus to the soft tissue around a joint, it will increase the number of fibroblasts, through localized inflammation, and result in a realignment of collagen fibers2. While some studies have shown positive outcomes of instrument assisted soft tissue mobilization (IASTM), there has been limited evidence to determine the efficacy of this modality in improving joint range of motion (ROM)

D2^2NeRF: Self-Supervised Decoupling of Dynamic and Static Objects from a Monocular Video

Given a monocular video, segmenting and decoupling dynamic objects while recovering the static environment is a widely studied problem in machine intelligence. Existing solutions usually approach this problem in the image domain, limiting their performance and understanding of the environment. We introduce Decoupled Dynamic Neural Radiance Field (D$^2$NeRF), a self-supervised approach that takes a monocular video and learns a 3D scene representation which decouples moving objects, including their shadows, from the static background. Our method represents the moving objects and the static background by two separate neural radiance fields with only one allowing for temporal changes. A naive implementation of this approach leads to the dynamic component taking over the static one as the representation of the former is inherently more general and prone to overfitting. To this end, we propose a novel loss to promote correct separation of phenomena. We further propose a shadow field network to detect and decouple dynamically moving shadows. We introduce a new dataset containing various dynamic objects and shadows and demonstrate that our method can achieve better performance than state-of-the-art approaches in decoupling dynamic and static 3D objects, occlusion and shadow removal, and image segmentation for moving objects

Definition of Naturally Processed Peptides Reveals Convergent Presentation of Autoantigenic Topoisomerase I Epitopes in Scleroderma.

ObjectiveAutoimmune responses to DNA topoisomerase I (topo I) are found in a subset of scleroderma patients who are at high risk for interstitial lung disease (ILD) and mortality. Anti-topo I antibodies (ATAs) are associated with specific HLA-DRB1 alleles, and the frequency of HLA-DR-restricted topo I-specific CD4+ T cells is associated with the presence, severity, and progression of ILD. Although this strongly implicates the presentation of topo I peptides by HLA-DR in scleroderma pathogenesis, the processing and presentation of topo I has not been studied.MethodsWe developed a natural antigen processing assay (NAPA) to identify putative CD4+ T cell epitopes of topo I presented by monocyte-derived dendritic cells (mo-DCs) from 6 ATA-positive patients with scleroderma. Mo-DCs were pulsed with topo I protein, HLA-DR-peptide complexes were isolated, and eluted peptides were analyzed by mass spectrometry. We then examined the ability of these naturally presented peptides to induce CD4+ T cell activation in 11 ATA-positive and 11 ATA-negative scleroderma patients.ResultsWe found that a common set of 10 topo I epitopes was presented by Mo-DCs from scleroderma patients with diverse HLA-DR variants. Sequence analysis revealed shared peptide-binding motifs within the HLA-DRβ chains of ATA-positive patients and a subset of topo I epitopes with distinct sets of anchor residues capable of binding to multiple different HLA-DR variants. The NAPA-derived epitopes elicited robust CD4+ T cell responses in 73% of ATA-positive patients (8 of 11), and the number of epitopes recognized correlated with ILD severity (P = 0.025).ConclusionThese findings mechanistically implicate the presentation of a convergent set of topo I epitopes in the development of scleroderma

17,β-estradiol inhibits hepatitis C virus mainly by interference with the release phase of its life cycle

Rationale & Aim: Estrogen and estrogen-mediated signalling protect from hepatitis C virus through incompletely understood mechanisms. We aimed to ascertain which phase(s) of HCV life cycle is/are affected by estrogens. Methods: Huh7 cells infected with the JFH1 virus (genotype 2a) were exposed to dehydroepiandrosterone, testosterone, progesterone and 17β-estradiol (tested with/without its receptor antagonist fulvestrant). Dose-response curves were established to calculate IC50 values. To dissect how 17β-estradiol interferes with phases of HCV life cycle, its effects were measured on the HCV pseudo-particle system (viral entry), the sub-genomic replicon N17/JFH1 and the replicon cell line Huh7-J17 (viral replication). Finally, in a dual-step infection model, infectious supernatants, collected from infected cells exposed to hormones, were used to infect naïve cells. Results: Progesterone and testosterone showed no inhibitory effect on HCV; dehydroepiandrosterone was only mildly inhibitory. In contrast, 17β-estradiol inhibited infection by 64-67% (IC50 values 140 to 160 nM). Fulvestrant reverted the inhibition by 17β-estradiol in a dose-dependent manner. 17β-estradiol exerted only a slight inhibition (<20%) on HCV pseudo-particles, and had no effect on cells either transiently or stably (Huh7-J17 cells) expressing the N17/JFH1 replicon. In the dual-step infection model, a significant IC50 decline occurred between primary (134 nM) and secondary (100 nM) infections (p=0.02), with extracellular HCV RNA and infectivity being reduced to a higher degree in comparison to its intracellular counterpart. Conclusions: 17β-estradiol inhibits HCV acting through its intracellular receptors, mainly interfering with late phases (assembly/release) of the HCV life cycle

The tilting rate of the Milky Way's disc

We present tilting rates for galaxies comparable to the Milky Way (MW) in a Λ cold dark matter cosmological hydrodynamical simulation, and compare these with the predicted tilting rate detection limit of the Gaia satellite 0.28° Gyr−1. We first identify galaxies with mass comparable to the MW (9 × 1011 ≤ M200 ≤ 1.2 × 1012 M⊙) and consider the tilting rates between z = 0.3 and 0. This sample yields a tilting rate of 7.6° ± 4.5° Gyr−1. We constrain our sample further to exclude any galaxies that have high stellar accretion during the same time. We still find significant tilting, with an average rate of 6.3° Gyr−1. Both subsamples tilt with rates significantly above Gaia's predicted detection limit. We show that our sample of galaxies covers a wide range of environments, including some similar to the MW's. We find galaxies in denser regions tilt with higher rates then galaxies in less dense regions. We also find correlations between the angular misalignment of the hot gas corona and the tilting rate. Gaia is likely to be able to directly measure tilting in the MW. Such a detection will provide an important constraint on the environment of the MW, including the rate of gas cooling on to the disc, the shape and orientation of its dark matter halo, and the mass of the Large Magellanic Cloud. Conversely, failure to detect tilting may suggest the MW is in a very quiet configuration

Comparing cover crop research in farmer-led and researcher-led experiments in the Western Corn Belt

Cover crops can mitigate soil degradation and nutrient loss and can be used to achieve continuous living cover in cropping systems, although their adoption in the Western Corn Belt of the United States remains low. It is increasingly recognized that cover crop integration into corn (Zea mays L.)-based crop rotations is complex, requiring site and operation specific management. In this review, we compared on-farm, farmer-led field scale trials to researcher-led trials carried out in small plots on University of Nebraska-Lincoln experiment stations. Although there is a range of cover crop research conducted in the state, there is no synthesis of the scope and key results of such eorts. Common cover crop challenges and goals in the state are similar to those reported nationwide; challenges include adequate planting timing, associated costs, and weather, while a top goal of cover crop use is to improve soil health. Farmer-led trials most frequently compared a cover crop to a no-cover crop control, likely reflecting a desire to test a basic design determining site-specific performance. Both researcher-led and farmer-led trials included designs testing cash crop planting timing, while some portion of farmer-led trials tested cover crop seeding rates, which are directly related to reported cover crop challenges. Farmer-led trials were carried out on a greater variety of soils, including sandy soils, whereas sandy soils were absent from researcher-led trials. More than half of farmer- led experiments were conducted on fields with slopes of 6–17% while most researcher-led experiments were conducted on fields with slopes of \u3c1%. Mean cover crop biomass production was 600 kg/ha in farmer-led and 2,000 kg/ha in researcher-led trials. Crop yields were not significantly aected by cover crops in either farmer-led or researcher-led trials. Such comparisons demonstrate that in some instances, cover crop research is addressing challenges, and in some instances, it could be expanded. This synthesis expands our knowledge base in a way that can promote co-learning between dierent scales of experiments, and ultimately, reduce risks associated with cover crop management and further promote continuous living cover of agricultural landscapes

Cosmological Feedback from High-Redshift Dwarf Galaxies

We model how repeated supernova explosions in high-redshift dwarf starburst galaxies drive superbubbles and winds out of the galaxies. We compute the efficiencies of metal and mass ejection and energy transport from the galactic potentials, including the effect of cosmological infall of external gas. The starburst bubbles quickly blow out of small, high-redshift, galactic disks, but must compete with the ram pressure of the infalling gas to escape into intergalactic space. We show that the assumed efficiency of the star formation rate dominates the bubble evolution and the metal, mass, and energy feedback efficiencies. With star formation efficiency f*=0.01, the ram pressure of infall can confine the bubbles around high-redshift dwarf galaxies with circular velocities v_c>52 km/s. We can expect high metal and mass ejection efficiencies, and moderate energy transport efficiencies in halos with v_c~30-50 km/s and f*~0.01 as well as in halos with v_c~100 km/s and f*>>0.01. Such haloes collapse successively from 1-2 sigma peaks in LambdaCDM Gaussian density perturbations as time progresses. These dwarf galaxies can probably enrich low and high-density regions of intergalactic space with metals to 10^-3-10^-2 Zsun as they collapse at z~8 and z<5 respectively. They also may be able to provide adequate turbulent energy to prevent the collapse of other nearby halos, as well as to significantly broaden Lyman-alpha absorption lines to v_rms~20-40 km/s. We compute the timescales for the next starbursts if gas freely falls back after a starburst, and find that, for star formation efficiencies as low as f*<0.01, the next starburst should occur in less than half the Hubble time at the collapse redshift. This suggests that episodic star formation may be ubiquitous in dwarf galaxies.Comment: Accepted for ApJ v613, 60 pages, 15 figure

High levels of childhood obesity observed among 3- to 7-year-old New Zealand Pacific children is a public health concern.

This cross-sectional, community-based survey was designed to assess attained growth and body composition of 3- to 7-y-old Pacific children (n = 21 boys and 20 girls) living in Dunedin, New Zealand, and to examine nondietary factors associated with the percentage of body fat. Fat mass, lean tissue mass and the percentage of body fat were measured using dual energy X-ray absorptiometry. One trained anthropometrist also measured height, weight, skinfolds (triceps, subscapular) and circumferences (mid-upper arm, chest, waist, calf). Compared with the National Center for Health Statistics and National Health and Examination Surveys I and II reference data, these Pacific children were tall and heavy for their age with high arm-muscle-area-for-height. Median (quartiles) Z-scores for height and BMI-for-age and arm-muscle-area-for-height were 1.33 (0.60, 2.15), 1.20 (0.74, 4.43) and 1.09 (0.63, 1.85), respectively. Their median (quartile) percentage of body fat was 21.8% (15.0, 35.5) of which 38.5% was located in the trunk. The estimated percentage of children classified as obese ranged from 34 to 49% depending on the criterion used. Over 60% of the children had levels of trunk fat above 1 SD of reported age- and sex-specific Z-scores for New Zealand children. The nondietary factors examined (hours of television viewing and hours playing organized sports, as reported by parents) were not associated with variations in the percentage of body fat, after adjusting for age, sex and birth weight. These extremely high levels of obesity and truncal fat among very young New Zealand children will have major public health implications as these children age