Implicit and Implicit-Explicit Strong Stability Preserving Runge-Kutta Methods with High Linear Order

When evolving in time the solution of a hyperbolic partial differential equation, it is often desirable to use high order strong stability preserving (SSP) time discretizations. These time discretizations preserve the monotonicity properties satisfied by the spatial discretization when coupled with the first order forward Euler, under a certain time-step restriction. While the allowable time-step depends on both the spatial and temporal discretizations, the contribution of the temporal discretization can be isolated by taking the ratio of the allowable time-step of the high order method to the forward Euler time-step. This ratio is called the strong stability coefficient. The search for high order strong stability time-stepping methods with high order and large allowable time-step had been an active area of research. It is known that implicit SSP Runge-Kutta methods exist only up to sixth order. However, if we restrict ourselves to solving only linear autonomous problems, the order conditions simplify and we can find implicit SSP Runge-Kutta methods of any linear order. In the current work we aim to find very high linear order implicit SSP Runge-Kutta methods that are optimal in terms of allowable time-step. Next, we formulate an optimization problem for implicit-explicit (IMEX) SSP Runge-Kutta methods and find implicit methods with large linear stability regions that pair with known explicit SSP Runge-Kutta methods of orders plin=3,4,6 as well as optimized IMEX SSP Runge-Kutta pairs that have high linear order and nonlinear orders p=2,3,4. These methods are then tested on sample problems to verify order of convergence and to demonstrate the sharpness of the SSP coefficient and the typical behavior of these methods on test problems

Répercussions d’une enfance vécue en institution : le cas des Enfants de Duplessis

Les conséquences négatives d’un placement en institution sur les enfants ont été documentées, mais aucune étude n’a porté sur les orphelins et les enfants placés une fois devenus adultes. Au Québec, les Enfants de Duplessis offrent un témoignage poignant des répercussions à long terme d’une enfance vécue en institution. Les histoires recueillies auprès de 40 hommes et 41 femmes ayant grandi en institution à l’époque de Duplessis font état d’un nombre élevé d’abus et d’expériences adverses, incluant les agressions physiques, psychologiques et sexuelles. Le milieu était peu stimulant et offrait peu d’opportunités de développer des relations d’attachement positives et significatives. Lorsqu’ils sont appariés et comparés à des adultes provenant de l’enquête Santé-Québec, les Enfants de Duplessis devenus adultes rapportent plus de problèmes de santé liés au stress et une détresse psychologique plus importante. Nos résultats indiquent également que les personnes ayant disposé de peu de ressources et d’aptitudes personnelles dans l’enfance sont les plus affectées par les expériences adverses.Whereas the immediate consequences of institutionalized placements on children have been documented, no study has investigated adults who were raised in orphanages or institutions. In Quebec, les enfants de Duplessis offer a unique testimony of the long term consequences of an institutionalized childhood. Stories collected from 40 men and 41 women who grew up in institution in Duplessis’era indicate a high number of abuse and aversive experiences, including physical, psychological and sexual aggressions. In addition, the environment was poor in stimulation and opportunities to develop positive attachment relationships with adults. When matched and compared to adults from the Santé-Québec survey, les enfants de Duplessis report a higher number of health problems associated with stress and more psychological distress. Moreover, our results indicate that those who had fewer strengths and aptitudes in childhood are the most affected by unfavourable experiences.Se han documentado las consecuencias negativas del ingreso de los niños a una institución, pero ningún estudio trata acerca de los adultos que fueron internados cuando eran niños o quedaron huérfanos. En Quebec los niños de Duplessis son un testimonio desgarrador de las repercusiones a largo plazo de una infancia vivida en una institución. Las historias recopiladas de 40 hombres y 41 mujeres que crecieron en una institución en la época de Duplessis constatan el número elevado de abusos y experiencias adversas, incluyendo agresiones físicas, psicológicas y sexuales. El medio era poco estimulante y ofrecía pocas oportunidades de desarrollar relaciones de apego positivas y significativas. Al emparejarlos y compararlos a los adultos provenientes de la encuesta de Salud Quebec, los niños de Duplessis, quienes ya son adultos, reportan más problemas de salud relacionados al estrés y un desasosiego psicológico más importante. Nuestros resultados indican también que las personas que disponen de pocos recursos y aptitudes personales en su infancia son las más afectadas por las experiencias adversas.As conseqüências negativas de uma internação em instituição sobre as crianças foram documentadas, mas nenhum estudo foi realizado sobre os órfãos e as crianças internadas quando já se tornaram adultas. No Quebec, as “crianças de Duplessis” testemunham de maneira profunda das repercussões a longo prazo de uma infância vivida em instituição. As histórias recolhidas junto a 40 homens e 41 mulheres que cresceram em instituição na época do governo de Duplessis relatam um alto número de abusos e de experiências adversas, incluindo agressões físicas, psicológicas e sexuais. O meio era pouco estimulante e oferecia poucas oportunidades de desenvolver relações de apego positivas e significativas. Quando eles foram colocados lado a lado e comparados aos adultos vindos da pesquisa de Santé-Québec, as “crianças de Duplessis” que se tornaram adultas sofrem mais de problemas de saúde ligados ao estresse e a uma depressão psicológica mais importante. Nossos resultados indicam igualmente que as pessoas que dispuseram de poucos recursos e aptidões pessoais na infância são mais afetadas pelas experiências adversas

Les expériences vécues par les enfants de Duplessis institutionnalisés : les conséquences après plus de 50 ans

Dans cet article, les auteurs présentent les résultats qualitatifs recueillis à partir de questionnaires et d’entrevues semi-structurées destinés à documenter les expériences tant actuelles que passées des enfants de Duplessis institutionnalisés (EDI). Des exemples typiques et deux cas représentatifs sont présentés. Les résultats indiquent que les abus et la négligence subis par les EDI pendant l’enfance ont compromis leur ajustement psychosocial à long terme. Ils révèlent aussi que les EDI qui ont rapporté au moins quatre forces pendant leur enfance étaient plus susceptibles d’être protégés à l’âge adulte contre les effets négatifs de leur placement.In this article, the authors present qualitative results, derived from questionnaires and semi-structured interviews, to describe past and present experiences of the Duplessis children. Examples representative of their experience and a detailed description of two cases are provided. Results indicate that childhood abuse and negligence are related to poorer long-term psychological adjustment. The findings also demonstrate that reporting at least four strengths in childhood can have long-term protective effects.En este artículo, los autores presentan los resultados cualitativos recopilados a partir de cuestionarios y entrevistas semiestructuradas destinadas a documentar las experiencias, tanto recientes como pasadas, de los niños de Duplessis que fueron institucionalizados (EDI). Se presentan ejemplos típicos y dos casos representativos. Los resultados indican que los abusos y la negligencia sufridos por los EDI durante la infancia han comprometido su ajuste psicosocial a largo plazo. También revelan que los EDI que han reportado al menos cuatro fuerzas durante su infancia eran más susceptibles de estar protegidos en la edad adulta contra los efectos negativos de su colocación.Neste artigo, os autores apresentam os resultados qualitativos coletados a partir de questionários e entrevistas semi-estruturadas destinados a documentar as experiências tanto atuais quanto passadas das crianças de Duplessis institucionalizadas (CDI). São apresentados exemplos típicos e dois casos representativos. Os resultados indicam que os abusos e a negligência sofridos pelas CDI durante a infância comprometeram seu ajuste psicossocial a longo prazo. Eles revelam também que as CDI que relataram, pelo menos, quatro aspectos positivos durante sua infância eram mais susceptíveis de ser protegidas durante a idade adulta contra os efeitos negativos de sua internação

HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells

HIV-1 replicates in CD4+ T cells, leading to AIDS. Determining how HIV-1 shapes its niche to create a permissive environment is central to informing efforts to limit pathogenesis, disturb reservoirs, and achieve a cure. A key roadblock in understanding HIV-T cell interactions is the requirement to activate T cells in vitro to make them permissive to infection. This dramatically alters T cell biology and virus-host interactions. Here we show that HIV-1 cell-to-cell spread permits efficient, productive infection of resting memory T cells without prior activation. Strikingly, we find that HIV-1 infection primes resting T cells to gain characteristics of tissue-resident memory T cells (TRM), including upregulating key surface markers and the transcription factor Blimp-1 and inducing a transcriptional program overlapping the core TRM transcriptional signature. This reprogramming is driven by Vpr and requires Vpr packaging into virions and manipulation of STAT5. Thus, HIV-1 reprograms resting T cells, with implications for viral replication and persistence

Community Service: Editor pride and user preference on local newspaper websites

Armed with readily accessible online traffic logs that provide detailed information about the items users are selecting to view, editors are voicing concern about the potential effect on their own content decisions. Through a survey of local British newspaper editors, this article examines the overlap between user preferences, as suggested by assessments of website traffic, and content that editors identify as their best. Results are considered in the context of two related subsets of agenda-setting theory, as well as the sociological process of “making news.” The study finds overlap between broad categories of stories preferred by editors and users, but a considerable disconnect over the nature of the items within those categories

Noise-Driven Phenotypic Heterogeneity with Finite Correlation Time in Clonal Populations

There has been increasing awareness in the wider biological community of the role of clonal phenotypic heterogeneity in playing key roles in phenomena such as cellular bet-hedging and decision making, as in the case of the phage-λ lysis/lysogeny and B. Subtilis competence/vegetative pathways. Here, we report on the effect of stochasticity in growth rate, cellular memory/intermittency, and its relation to phenotypic heterogeneity. We first present a linear stochastic differential model with finite auto-correlation time, where a randomly fluctuating growth rate with a negative average is shown to result in exponential growth for sufficiently large fluctuations in growth rate. We then present a non-linear stochastic self-regulation model where the loss of coherent self-regulation and an increase in noise can induce a shift from bounded to unbounded growth. An important consequence of these models is that while the average change in phenotype may not differ for various parameter sets, the variance of the resulting distributions may considerably change. This demonstrates the necessity of understanding the influence of variance and heterogeneity within seemingly identical clonal populations, while providing a mechanism for varying functional consequences of such heterogeneity. Our results highlight the importance of a paradigm shift from a deterministic to a probabilistic view of clonality in understanding selection as an optimization problem on noise-driven processes, resulting in a wide range of biological implications, from robustness to environmental stress to the development of drug resistance

Diagnostic challenges of early Lyme disease: Lessons from a community case series

<p>Abstract</p> <p>Background</p> <p>Lyme disease, the most common vector-borne infection in North America, is increasingly reported. When the characteristic rash, erythema migrans, is not recognized and treated, delayed manifestations of disseminated infection may occur. The accuracy of diagnosis and treatment of early Lyme disease in the community is unknown.</p> <p>Methods</p> <p>A retrospective, consecutive case series of 165 patients presenting for possible early Lyme disease between August 1, 2002 and August 1, 2007 to a community-based Lyme referral practice in Maryland. All patients had acute symptoms of less than or equal to 12 weeks duration. Patients were categorized according to the Centers for Disease Control and Prevention criteria and data were collected on presenting history, physical findings, laboratory serology, prior diagnoses and prior treatments.</p> <p>Results</p> <p>The majority (61%) of patients in this case series were diagnosed with early Lyme disease. Of those diagnosed with early Lyme disease, 13% did not present with erythema migrans; of those not presenting with a rash, 54% had been previously misdiagnosed. Among those with a rash, the diagnosis of erythema migrans was initially missed in 23% of patients whose rash was subsequently confirmed. Of all patients previously misdiagnosed, 41% had received initial antibiotics likely to be ineffective against Lyme disease.</p> <p>Conclusion</p> <p>For community physicians practicing in high-risk geographic areas, the diagnosis of Lyme disease remains a challenge. Failure to recognize erythema migrans or alternatively, viral-like presentations without a rash, can lead to missed or delayed diagnosis of Lyme disease, ineffective antibiotic treatment, and the potential for late manifestations.</p

Eight Weeks of Treatment With Glecaprevir/Pibrentasvir Is Safe and Efficacious in an Integrated Analysis of Treatment-Naïve Patients With Hepatitis C Virus Infection

BACKGROUND & AIMS: The direct-acting antiviral combination glecaprevir/pibrentasvir has been approved by the Food and Drug Administration for 8 weeks of treatment in treatment-naïve patients with hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. We performed an integrated analysis of data from trials to evaluate the overall efficacy and safety of 8 weeks of glecaprevir/pibrentasvir in treatment-naïve patients without cirrhosis or with compensated cirrhosis. METHODS: We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir. RESULTS: Of 1248 patients, 343 (27%) had cirrhosis. Most patients were white (80%) and had HCV genotype 1 infection (47%) or genotype 3 infection (22%); the median age was 54 years. Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations. When we excluded patients with genotype 3 infections with compensated cirrhosis (consistent with the European label), rates of sustained virologic response at post-treatment week 12 were 97.6% in the ITT and 99.4% in the modified ITT populations. Eight virologic failures (7 in patients without cirrhosis and 1 in a patient with cirrhosis) occurred in the ITT population. Virologic failure was not associated with markers of advanced liver disease or populations of interest (current alcohol use, opioid substitution therapy, history of injection-drug use, and severe renal impairment). Treatment-emergent adverse events (AEs) occurred in 58% of patients. The most frequent AEs (>10%) were headache (12%) and fatigue (12%). Serious AEs and AEs that led to glecaprevir/pibrentasvir discontinuation were reported in 2% and less than 1% of patients, respectively. CONCLUSIONS: In a pooled analysis of data from 8 trials, we found that 8 weeks of treatment with glecaprevir/pibrentasvir is efficacious and well tolerated in treatment-naïve patients with HCV genotype 1 to 6 infections, with or without cirrhosis.status: publishe