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Both groups of veterans relied on their case management teams as a means of support and social engagement.Conclusions To reduce social isolation and loneliness, more attention is needed by program staff to provide varied social engagement opportunities, from one-on-one to group activities.Clinical Implications These findings can help providers recognize issues inhibiting formerly homeless veterans from being successful in supportive housing. Clinicians should consider how veterans' behavioral health impacts their ability to engage in social activities. Substance use disorder remains a challenge for many veterans interviewed. Its effects impact their perceptions of fellow residents, perceptions of housing, and recovery.The benefits of different levels of engagement with test, trace and isolate procedures are investigated for a pandemic in which there is little population immunity, in terms of productivity and public health. Simple mathematical modelling is used in the context of a single, relatively closed workplace such as a factory or back-office where, in normal operation, each worker has lengthy interactions with a fixed set of colleagues. A discrete-time SEIR model on a fixed interaction graph is simulated with parameters that are motivated by the recent COVID-19 pandemic in the UK during a post-peak phase, including a small risk of viral infection from outside the working environment. Two kinds of worker are assumed, transparents who regularly test, share their results with colleagues and isolate as soon as a contact tests positive for the disease, and opaques who do none of these. Moreover, the simulations are constructed as a 'playable model' in which the transparency level, disease parameters and mean interaction degree can be varied by the user. The model is also analysed in the continuum limit. All simulations point to the double benefit of transparency in both maximizing productivity and minimizing overall infection rates. Based on these findings, public policy implications are discussed for how to incentivise this mutually beneficial behaviour in different kinds of workplace, and simple recommendations are made.Hepatic fibrosis stage is the most important determinant of outcomes in patients with nonalcoholic fatty liver disease (NAFLD). There is an urgent need for noninvasive tests that can accurately stage fibrosis and determine efficacy of interventions. Here, we describe a novel cell-free (cf)-mRNA sequencing approach that can accurately and reproducibly profile low levels of circulating mRNAs and evaluate the feasibility of developing a cf-mRNA-based NAFLD fibrosis classifier. Using separate discovery and validation cohorts with biopsy-confirmed NAFLD (n = 176 and 59, respectively) and healthy subjects (n = 23), we performed serum cf-mRNA RNA-Seq profiling. Differential expression analysis identified 2,498 dysregulated genes between patients with NAFLD and healthy subjects and 134 fibrosis-associated genes in patients with NAFLD. Comparison between cf-mRNA and liver tissue transcripts revealed significant overlap of fibrosis-associated genes and pathways indicating that the circulating cf-mRNA transcriptome reflects molecular changes in the livers of patients with NAFLD. In particular, metabolic and immune pathways reflective of known underlying steatosis and inflammation were highly dysregulated in the cf-mRNA profile of patients with advanced fibrosis. Finally, we used an elastic net ordinal logistic model to develop a classifier that predicts clinically significant fibrosis (F2-F4). In an independent cohort, the cf-mRNA classifier was able to identify 50% of patients with at least 90% probability of clinically significant fibrosis. We demonstrate a novel and robust cf-mRNA-based RNA-Seq platform for noninvasive identification of diverse hepatic molecular disruptions and for fibrosis staging with promising potential for clinical trials and clinical practice.NEW & NOTEWORTHY This work is the first study, to our knowledge, to utilize circulating cell-free mRNA sequencing to develop an NAFLD diagnostic classifier.Head and neck cancer (HNC) is among the most common malignancy that has a profound impact on human health and life quality. The treatment for HNC, especially for the advanced cancer is stage-dependent and in need of combined therapies. Various forms of adjuvant treatments such as chemotherapy, phototherapy, hyperthermia, gene therapy have been included in the HNC therapy. However, there are still restrictions with traditional administration such as limited in situ therapeutic effect, systemic toxicity, drug resistance, etc. In recent years, stimuli-responsive drug delivery systems (DDSs) have attracted the great attention in HNC therapy. These intelligent DDSs could respond to unique tumor microenvironment, external triggers or dual/multi stimulus with more specific drug delivery and release, leading to enhanced treatment efficiency and less reduced side effects. In this article, recent studies on stimuli-responsive DDSs for HNC therapy were summarized, which could respond to endogenous and exogenous triggers including pH, matrix metalloproteinases (MMPs), reactive oxygen species (ROS), redox condition, light, magnetic field and multi stimuli. Their therapeutic remarks, current limits and future prospect for these intelligent DDSs were discussed. Furthermore, multifunctional stimuli-responsive DDSs have also been reviewed. With the modification of drug carriers or co-loading with therapeutic agents. Those intelligent DDSs showed more biofunctions such as combined therapeutic effects or integration of diagnosis and treatment for HNC. It is believed that stimuli-responsive drug delivery systems showed great potential for future clinic translation and application for the treatment of HNC.In this paper, we develop a general Bayesian hierarchical model for bridging across patient subgroups in phase I oncology trials, for which preliminary information about the dose-toxicity relationship can be drawn from animal studies. Parameters that re-scale the doses to adjust for intrinsic differences in toxicity, either between animals and humans or between human subgroups, are introduced to each dose-toxicity model. Appropriate priors are specified for these scaling parameters, which capture the magnitude of uncertainty surrounding the animal-to-human translation and bridging assumption. CX-5461 in vivo After mapping data onto a common, 'average' human dosing scale, human dose-toxicity parameters are assumed to be exchangeable either with the standardised, animal study-specific parameters, or between themselves across human subgroups. Random-effects distributions are distinguished by different covariance matrices that reflect the between-study heterogeneity in animals and humans. Possibility of non-exchangeability is allowed to avoid inferences for extreme subgroups being overly influenced by their complementary data.

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