Opportunities and Challenges: Hepatitis C Testing and Treatment Access Experiences Among People in Methadone and Buprenorphine Treatment During COVID-19, Arizona, 2021

Introduction: The purpose of this study was to characterize hepatitis C virus screening and treatment access experiences among people in treatment for opioid use disorder in Arizona during COVID-19. Methods: Arizonans receiving treatment for opioid use disorder from methadone clinics and buprenorphine providers during COVID-19 were interviewed about hepatitis C virus testing, curative treatment, and knowledge about screening recommendations. Interviews were conducted with 121 people from August 4, 2021 to October 10, 2021. Qualitative data were coded using the categories of hepatitis C virus testing, knowledge of screening recommendations, diagnosis, and experiences seeking curative treatment. Data were also quantitated for bivariate testing with outcome variables of last hepatitis C virus test, diagnosis, and curative treatment process. Findings were arrayed along an adapted hepatitis C virus cascade framework to inform program and policy improvements. Results: Just over half of the sample reported ever having tested for hepatitis C virus (51.2%, n=62) and of this group, 58.1% were tested in the past 12 months. Among those who were ever tested, 54.8% reported a hepatitis C virus diagnosis and 16.1% reported either being in treatment or having been declared cured of the hepatitis C virus. Among those who were diagnosed with hepatitis C, 14.7% indicated that they unsuccessfully tried to access curative treatment and would not attempt to again. Reasons cited for not accessing or receiving curative treatment included beliefs about treatment safety, barriers created by access requirements, natural resolution of the infection, and issues with healthcare coverage and authorization. Conclusions: Structural barriers continue to prevent curative hepatitis C virus treatment access. Given that methadone and buprenorphine treatment providers serve patients who are largely undiagnosed or treated for hepatitis C virus, opportunities exist for them to screen their patients regularly and provide support for and/or navigation to hepatitis C virus curative treatment

Bistability in Apoptosis by Receptor Clustering

Apoptosis is a highly regulated cell death mechanism involved in many physiological processes. A key component of extrinsically activated apoptosis is the death receptor Fas, which, on binding to its cognate ligand FasL, oligomerize to form the death-inducing signaling complex. Motivated by recent experimental data, we propose a mathematical model of death ligand-receptor dynamics where FasL acts as a clustering agent for Fas, which form locally stable signaling platforms through proximity-induced receptor interactions. Significantly, the model exhibits hysteresis, providing an upstream mechanism for bistability and robustness. At low receptor concentrations, the bistability is contingent on the trimerism of FasL. Moreover, irreversible bistability, representing a committed cell death decision, emerges at high concentrations, which may be achieved through receptor pre-association or localization onto membrane lipid rafts. Thus, our model provides a novel theory for these observed biological phenomena within the unified context of bistability. Importantly, as Fas interactions initiate the extrinsic apoptotic pathway, our model also suggests a mechanism by which cells may function as bistable life/death switches independently of any such dynamics in their downstream components. Our results highlight the role of death receptors in deciding cell fate and add to the signal processing capabilities attributed to receptor clustering.Comment: Accepted by PLoS Comput Bio

Amici Curiae Brief of New York law school professors in People v. Harris: Constitutionality of the New York Death Penalty Statute Under the State Constitution\u27s Cruel and Unusual Punishments and Antidiscrimination Clauses

Amici are teachers in New York law schools who have studied the operation of the death penalty for the purpose of teaching the subject, writing about it in scholarly journals, or representing persons accused or convicted of capital crimes. Most of us have worked in the field both as academics and as pro bono counsel for condemned inmates. Collectively, we have had first-hand experience in hundreds of death cases, in dozens of jurisdictions, extending over more than a third of a century. Our experience has convinced us that capital punishment cannot be administered with the fairness, reliability, and freedom from discrimination that a penalty so grave and irreversible requires. This is no accident or transitory condition; it is the consequence of certain innate attributes of the penalty of death. The purpose of our brief is to analyze those attributes and explain why they are fundamentally at war with the Cruel and Unusual Punishments Clause and the Antidiscrimination Clause of New York’s Bill of Rights. We hope to persuade the Court that it should not temporize with the death penalty in the face of this basic incompatibility but should hold the 1995 death penalty statute altogether unconstitutional

Jim Crow 2.0?: Why States Consider and Adopt Restrictive Voter Access Policies

In recent years there has been a dramatic increase in state legislation likely to reduce access for some voters, including photo identification and proof of citizenship requirements, registration restrictions, absentee ballot voting restrictions, and reductions in early voting. Political operatives often ascribe malicious motives when their opponents either endorse or oppose such legislation. In an effort to bring empirical clarity and epistemological standards to what has been a deeply charged, partisan and frequently anecdotal debate, this paper uses multiple specialized regression approaches to examine factors associated with both the proposal and adoption of restrictive voter access legislation from 2006-11. Our results indicate that proposal and passage are highly partisan, strategic, and racialized affairs. These findings are consistent with a scenario in which the targeted demobilization of minority voters and African Americans is a central driver of recent legislative developments. We discuss the implications of these results for current partisan and legal debates regarding voter restrictions and our understanding of the conditions incentivizing modern suppression efforts. Further, we situate these policies within developments in social welfare and criminal justice policy that collectively reduce electoral access among the socially marginalized

Industrial Structure and Political Outcomes: The Case of the 2016 US Presidential Election

This paper analyzes the US presidential election of 2016, examining the patterns of industrial structure and party competition in both the major party primaries and the general election. It attempts to identify the new, historically specific factors that led to the upheavals, especially the steady growth of a “dual economy” that locks more and more Americans out of the middle class. It draws extensively on a newly assembled, more comprehensive database to identify the specific political forces that coalesced around each candidate, including the various stages of the Trump campaign

Normative and self-perceived orthodontic treatment need of a Peruvian university population

BACKGROUND: Previous studies on orthodontic treatment need in young adults have shown that up to 50% had malocclusions that needed orthodontic treatment. The aims of this study were to assess the normative and self-perceived need for orthodontic treatment using the Index of Orthodontic Treatment Need (IOTN) and to determine if the treatment need levels were influenced by sex, age and socio-economic status (SES) in a sample of Peruvian young adults. METHODS: 281 first-year students (157 male and 124 female students) with a mean age of 18.1 +/- 1.6 years were randomly selected and evaluated through the Dental Health Component (DHC) and Aesthetic Component (AC) of the IOTN. Structured interview and clinical examination were used to assess the students. Descriptive statistics and Chi-square tests were used for data analysis with statistical significance set at P < 0.05. RESULTS: An intra-examiner reliability of 0.89 was obtained (weighted Kappa). The percentage of students according to SES was 51.2%, 40.6% and 8.2% corresponding to low, medium and high SES respectively. The percentage of students with DHC grades 4–5 was 29.9% whereas the percentage of students with AC grades 8–10 was 1.8%. There were no significant differences in the distribution of normative and self-perceived orthodontic treatment need based on sex, age and SES comparisons. CONCLUSION: Normative orthodontic treatment need was not matched by a similar level of self-perceived treatment need in these young adults. Sex, age and SES were non-significant factors associated with levels of treatment need

Global Analysis of Dynamical Decision-Making Models through Local Computation around the Hidden Saddle

Bistable dynamical switches are frequently encountered in mathematical modeling of biological systems because binary decisions are at the core of many cellular processes. Bistable switches present two stable steady-states, each of them corresponding to a distinct decision. In response to a transient signal, the system can flip back and forth between these two stable steady-states, switching between both decisions. Understanding which parameters and states affect this switch between stable states may shed light on the mechanisms underlying the decision-making process. Yet, answering such a question involves analyzing the global dynamical (i.e., transient) behavior of a nonlinear, possibly high dimensional model. In this paper, we show how a local analysis at a particular equilibrium point of bistable systems is highly relevant to understand the global properties of the switching system. The local analysis is performed at the saddle point, an often disregarded equilibrium point of bistable models but which is shown to be a key ruler of the decision-making process. Results are illustrated on three previously published models of biological switches: two models of apoptosis, the programmed cell death and one model of long-term potentiation, a phenomenon underlying synaptic plasticity

Calcium Signals Driven by Single Channel Noise

Usually, the occurrence of random cell behavior is appointed to small copy numbers of molecules involved in the stochastic process. Recently, we demonstrated for a variety of cell types that intracellular Ca2+ oscillations are sequences of random spikes despite the involvement of many molecules in spike generation. This randomness arises from the stochastic state transitions of individual Ca2+ release channels and does not average out due to the existence of steep concentration gradients. The system is hierarchical due to the structural levels channel - channel cluster - cell and a corresponding strength of coupling. Concentration gradients introduce microdomains which couple channels of a cluster strongly. But they couple clusters only weakly; too weak to establish deterministic behavior on cell level. Here, we present a multi-scale modelling concept for stochastic hierarchical systems. It simulates active molecules individually as Markov chains and their coupling by deterministic diffusion. Thus, we are able to follow the consequences of random single molecule state changes up to the signal on cell level. To demonstrate the potential of the method, we simulate a variety of experiments. Comparisons of simulated and experimental data of spontaneous oscillations in astrocytes emphasize the role of spatial concentration gradients in Ca2+ signalling. Analysis of extensive simulations indicates that frequency encoding described by the relation between average and standard deviation of interspike intervals is surprisingly robust. This robustness is a property of the random spiking mechanism and not a result of control

Progress in Diamond Detector Development

Detectors based on Chemical Vapor Deposition (CVD) diamond have been used successfully in Luminosity and Beam Condition Monitors (BCM) in the highest radiation areas of the LHC. Future experiments at CERN will accumulate an order of magnitude larger fluence. As a result, an enormous effort is underway to identify detector materials that can operate under fluences of 1 · 1016 n cm−2 and 1 · 1017 n cm−2. Diamond is one candidate due to its large displacement energy that enhances its radiation tolerance. Over the last 30 years the RD42 collaboration has constructed diamond detectors in CVD diamond with a planar geometry and with a 3D geometry to extend the material's radiation tolerance. The 3D cells in these detectors have a size of 50 µm×50 µm with columns of 2.6 µm in diameter and 100 µm×150 µm with columns of 4.6 µm in diameter. Here we present the latest beam test results from planar and 3D diamond pixel detectors