Explore the vast range of titles available.

Background The social determinants of health that influence steps in the entire Hepatitis C Virus (HCV) treatment cascade must be identified to achieve HCV elimination goals. This project aimed to evaluate the association of these factors with HCV treatment completion and return for sustained virologic response (SVR) testing. Methods We used retrospective cohort data from our primary care-based HCV treatment program that provides comprehensive harm reduction care to those who use or formerly used drugs. Among persons who began direct-acting antiviral HCV treatment between December 2014 and March 2018, we identified two outcomes: HCV treatment completion and return for SVR assessment 12 weeks after treatment end. Several predictors were ascertained including sociodemographic information, substance use, psychiatric symptoms and history, housing instability, and HCV treatment regimen. We then evaluated associations between predictors and outcomes using univariate and multivariable statistical methods. Results From a cohort of 329 patients treated in an urban primary care center, multivariable analysis identified housing instability as a single significant predictor for HCV treatment completion (odds ratio [OR]: 0.3; 95% confidence interval [CI]: 0.1–0.9). Among patients completing treatment, 226 (75%) returned for SVR assessment; the sole predictor of this outcome was Medicaid as primary insurance (compared to other insurances; OR 0.3; 0.1–0.7). Conclusions Innovative strategies to help unstably housed persons complete HCV treatment are urgently needed in order to reach HCV elimination targets. Educational and motivational strategies should be developed to promote individuals with Medicaid in particular to return for SVR viral load testing, a critical post-treatment component of the HCV treatment cascade. Trial registration Not applicable.

The COVID-19 pandemic led to a large disruption in the clinical education of medical students, particularly in-person clinical activities. To address the resulting challenges faced by students interested in emergency medicine (EM), we proposed and held a peer-led, online learning course for rising fourth-year medical students. A total of 61 medical students participated in an eight-lecture EM course. Students were evaluated through pre- and post-course assessments designed to ascertain perceived comfort with learning objectives and overall course feedback. Pre- and post-lecture assignments were also used to increase student learning. Mean confidence improved in every learning objective after the course. Favored participation methods were three-person call-outs, polling, and using the \"chat\" function. Resident participation was valued for \"real-life\" examples and clinical pearls. This interactive model for online EM education can be an effective format for dissemination when in-person education may not be available.

Amyotrophic Lateral Sclerosis (ALS) causes motor neuron degeneration, with 97% of cases exhibiting TDP-43 proteinopathy. Elucidating pathomechanisms has been hampered by disease heterogeneity and difficulties accessing motor neurons. Human induced pluripotent stem cell-derived motor neurons (iPSMNs) offer a solution; however, studies have typically been limited to underpowered cohorts. Here, we present a comprehensive compendium of 429 iPSMNs from 15 datasets, and 271 post-mortem spinal cord samples. Using reproducible bioinformatic workflows, we identify robust upregulation of p53 signalling in ALS in both iPSMNs and post-mortem spinal cord. p53 activation is greatest with C9orf72 repeat expansions but is weakest with SOD1 and FUS mutations. TDP-43 depletion potentiates p53 activation in both post-mortem neuronal nuclei and cell culture, thereby functionally linking p53 activation with TDP-43 depletion. ALS iPSMNs and post-mortem tissue display enrichment of splicing alterations, somatic mutations, and gene fusions, possibly contributing to the DNA damage response. The causes of ALS remain unclear with many proposed pathomechanisms. Here, the authors integrate iPSC-derived motor neuron and post-mortem datasets and identify a heightened DNA damage response accompanied by accumulation of somatic mutations in ALS.

In this article, we generalize known formulas for crossing probabilities. Prior crossing results date back to J. Cardy's prediction of a formula for the probability that a percolation cluster in two dimensions connects the left and right sides of a rectangle at the percolation critical point in the continuum limit. Here, we predict a new formula for crossing probabilities of a continuum limit loop-gas model on a planar lattice inside a \\(2N\\)-sided polygon. In this model, boundary loops exit and then re-enter the polygon through its vertices, with exactly one loop passing once through each vertex, and these loops join the vertices pairwise in some specified connectivity through the polygon's exterior. The boundary loops also connect the vertices through the interior, which we regard as a crossing event. For particular values of the loop fugacity, this formula specializes to FK cluster (resp. spin cluster) crossing probabilities of a critical \\(Q\\)-state random cluster (resp. Potts) model on a lattice inside the polygon in the continuum limit. This includes critical percolation as the \\(Q=1\\) random cluster model. These latter crossing probabilities are conditioned on a particular side-alternating free/fixed (resp. fluctuating/fixed) boundary condition on the polygon's perimeter, related to how the boundary loops join the polygon's vertices pairwise through the polygon's exterior in the associated loop-gas model. For \\(Q\\in\\{2,3,4\\}\\), we compare our predictions of these random cluster (resp. Potts) model crossing probabilities in a rectangle (\\(N=2\\)) and in a hexagon (\\(N=3\\)) with high-precision computer simulation measurements. We find that the measurements agree with our predictions very well for \\(Q\\in\\{2,3\\}\\) and reasonably well if \\(Q=4\\).

In a recent article, one of the authors used \\(c=0\\) logarithmic conformal field theory to predict crossing-probability formulas for percolation clusters inside a hexagon with free boundary conditions. In this article, we verify these predictions with high-precision computer simulations. Our simulations generate percolation-cluster perimeters with hull walks on a triangular lattice inside a hexagon. Each sample comprises two hull walks, and the order in which these walks strike the bottom and upper left/right sides of the hexagon determines the crossing configuration of the percolation sample. We compare our numerical results with the predicted crossing probabilities, finding excellent agreement.

We recently described aberrant cytoplasmic SFPQ intron-retaining transcripts (IRTs) and concurrent SFPQ protein mislocalization as a new hallmark of amyotrophic lateral sclerosis (ALS). However the generalizability and potential roles of cytoplasmic IRTs in health and disease remain unclear. Here, using time-resolved deep-sequencing of nuclear and cytoplasmic fractions of hiPSCs undergoing motor neurogenesis, we reveal that ALS-causing VCP gene mutations lead to compartment-specific aberrant accumulation of IRTs. Specifically, we identify >100 IRTs with increased cytoplasmic (but not nuclear) abundance in ALS samples. Furthermore, these aberrant cytoplasmic IRTs possess sequence-specific attributes and differential predicted binding affinity to RNA binding proteins (RBPs). Remarkably, TDP-43, SFPQ and FUS – RBPs known for nuclear-to-cytoplasmic mislocalization in ALS – avidly and specifically bind to this aberrant cytoplasmic pool of IRTs, as opposed to any individual IRT. Our data are therefore consistent with a novel role for cytoplasmic IRTs in regulating compartment-specific protein abundance. This study provides new molecular insight into potential pathomechanisms underlying ALS and highlights aberrant cytoplasmic IRTs as potential therapeutic targets.

Making use of a recent complete calculation of a chiral six-point correlation function C(z) in a rectangle we calculate various quantities of interest for percolation (SLE parameter \\kappa = 6) and many other two-dimensional critical points. In particular, we specify the density at z of critical clusters conditioned to touch either or both vertical sides of the rectangle, with these sides 'wired,' i.e. constrained to be in a single cluster, and the horizontal sides free. These quantities probe the structure of various cluster configurations, including those that contribute to the crossing probability. We first examine the effects of boundary conditions on C for the critical O(n) loop models in both high and low density phases and for both Fortuin-Kasteleyn (FK) and spin clusters in the critical Q-state Potts models. A Coulomb gas analysis then allows us to calculate the cluster densities with various conditionings in terms of the known conformal blocks. Explicit formulas generalizing Cardy's horizontal crossing probability to these models (using previously known results) are also presented. These solutions are employed to generalize previous results demonstrating factorization of higher-order correlation functions to the critical systems mentioned. An explicit formula for the density of critical percolation clusters that cross a rectangle horizontally with free boundary conditions is also given. Simplifications of the hypergeometric functions in our solutions for various models are presented. High precision simulations verify these predictions for percolation and for the Q=2 and 3-state Potts models, including both FK and spin clusters. Our formula for the density of crossing clusters in percolation in open systems is also verified.

Recently, Delfino and Viti have examined the factorization of the three-point density correlation function P_3 at the percolation point in terms of the two-point density correlation functions P_2. According to conformal invariance, this factorization is exact on the infinite plane, such that the ratio R(z_1, z_2, z_3) = P_3(z_1, z_2, z_3) [P_2(z_1, z_2) P_2(z_1, z_3) P_2(z_2, z_3)]^{1/2} is not only universal but also a constant, independent of the z_i, and in fact an operator product expansion (OPE) coefficient. Delfino and Viti analytically calculate its value (1.022013...) for percolation, in agreement with the numerical value 1.022 found previously in a study of R on the conformally equivalent cylinder. In this paper we confirm the factorization on the plane numerically using periodic lattices (tori) of very large size, which locally approximate a plane. We also investigate the general behavior of R on the torus, and find a minimum value of R approx. 1.0132 when the three points are maximally separated. In addition, we present a simplified expression for R on the plane as a function of the SLE parameter kappa.

By use of conformal field theory, we discover several exact factorizations of higher-order density correlation functions in critical two-dimensional percolation. Our formulas are valid in the upper half-plane, or any conformally equivalent region. We find excellent agreement of our results with high-precision computer simulations. There are indications that our formulas hold more generally.