Differential regulation of innate and adaptive immune responses in viral encephalitis.

Viral encephalitis is a global health concern. The ability of a virus to modulate the immune response can have a pivotal effect on the course of disease and the fate of the infected host. In this study, we sought to understand the immunological basis for the fatal encephalitis following infection with the murine coronavirus, mouse hepatitis virus (MHV)-JHM, in contrast with the more attenuated MHV-A59. Distinct glial cell cytokine and chemokine response patterns were observed within 3 days after infection, became progressively more polarized during the course of infection and with the infiltration of leukocytes. In the brain, MHV-JHM infection induced strong accumulation of IFNbeta mRNA relative to IFNgamma mRNA. This trend was reversed in MHV-A59 infection and was accompanied by increased CD8 T cell infiltration into brain compared to MHV-JHM infection. Increased apoptosis appeared to contribute to the diminished presence of CD8 T cells in MHV-JHM-infected brain with the consequence of a lower potential for IFNgamma production and antiviral activity. MHV-JHM infection also induced sustained mRNA accumulation of the innate immune response products interleukin (IL)-6 and IL-1. Furthermore, high levels of macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta, and MIP-2 mRNA were observed at the onset of MHV-JHM infection and correlated with a marked elevation in the number of macrophages in the brain on day 7 compared to MHV-A59 infection. These observations indicate that differences in the severity of viral encephalitis may reflect the differential ability of viruses to stimulate innate immune responses within the CNS and subsequently the character of infiltrating leukocyte populations

A qualitative formative evaluation of a patient facing intervention to improve care transitions for older people moving from hospital to home

Background The Partners at Care Transitions (PACTs) intervention was developed to support older people's involvement in hospital to improve outcomes at home. A booklet, question card, record sheet, induction leaflet, and patient‐friendly discharge letter support patients to be more involved in their health and wellbeing, medications, activities of daily living and post‐discharge care. We aimed to assess intervention acceptability, identify implementation tools, and further develop the intervention. Methods This was a qualitative formative evaluation involving three wards from one hospital. We recruited 25 patients aged 75 years and older. Ward staff supported intervention delivery. Data were collected in wards and patients' homes, through semi‐structured interviews, observation, and documentary analysis. Data were analysed inductively and iteratively with findings sorted according to the research aims. Results Patients and staff felt there was a need for, and understood the purpose of, the PACT intervention. Most patients read the booklet but other components were variably used. Implementation challenges included time, awareness, and balancing intervention benefits against risks. Changes to the intervention and implementation included clarifying the booklet's messages, simplifying the discharge letter to reduce staff burden, and using prompts and handouts to promote awareness. Conclusion Patients and staff felt there was a need for, and understood the purpose of, the PACT intervention. Most patients read the booklet but other components were variably used. Implementation challenges included time, awareness, and balancing intervention benefits against risks. Changes to the intervention and implementation included clarifying the booklet's messages, simplifying the discharge letter to reduce staff burden, and using prompts and handouts to promote awareness

Section 6.1 The finds: The pottery

The site of Warren Field in Scotland revealed two unusual and enigmatic features; an alignment of pits and a large, rectangular feature interpreted as a timber building. Excavations confirmed that the timber structure was an early Neolithic building and that the pits had been in use from the Mesolithic. This report details the excavations and reveals that the hall was associated with the storage and or consumption of cereals, including bread wheat, and pollen evidence suggests that the hall may have been part of a larger area of activity involving cereal cultivation and processing. The pits are fully documented and environmental evidence sheds light on the surrounding landscape

The Caddisfly Collective: Methods of assessing Trichoptera diversity on a continental scale with community scientists

Amidst a global biodiversity crisis, collecting data at large spatial scales can illuminate patterns. Community science can be an avenue to reduce costs, broaden the scope of sampling, and, most importantly, connect with members of the public who are interested in and impacted by long-term ecological change. In 2021, we formulated a community science project – The Caddisfly Collective. Our goal was to study the regional influences on the responses of stream caddisfly (Trichoptera) communities to urbanization in the United States and Canada. Community scientists helped us achieve this goal by collecting caddisflies across a wider geographic scale than we could have reached on our own. To build The Caddisfly Collective, we recruited participants through social media and other online forums. We mailed collecting kits with a USB-powered ultraviolet LED light, a collecting container, bottles of preservative, data sheets, and collection labels to each participant; participants mailed back specimens and completed data sheets. There was a 79.7% rate of follow-through from sign-up to collection. During the project, 63 participants set up light-traps near urban and non-urban streams in seven different North American geographic regions, collecting adult caddisflies at 141 sites across the United States and Canada. Most sites were in the Midwest region, while the fewest sites were in the Far North region. Urban areas, classified by land cover data, comprised ~29% of total sites. We hope the details of our project can help other interested scientists implement similar projects in the future, especially focused on ecologically important caddisfly communities

Zipf law in the popularity distribution of chess openings

We perform a quantitative analysis of extensive chess databases and show that the frequencies of opening moves are distributed according to a power-law with an exponent that increases linearly with the game depth, whereas the pooled distribution of all opening weights follows Zipf's law with universal exponent. We propose a simple stochastic process that is able to capture the observed playing statistics and show that the Zipf law arises from the self-similar nature of the game tree of chess. Thus, in the case of hierarchical fragmentation the scaling is truly universal and independent of a particular generating mechanism. Our findings are of relevance in general processes with composite decisions.Comment: 5 pages, 4 figure

Mouse hepatitis virus neurovirulence: evidence of a linkage between S glycoprotein expression and immunopathology.

Differences in disease outcome between the highly neurovirulent MHV-JHM and mildly neurovirulent MHV-A59 have been attributed to variations within the spike (S) glycoprotein. Previously, we found that MHV-JHM neurovirulence was marked by diminished expression of interferon-gamma (IFN-gamma) mRNA and a reduced presence of CD8 T cells in the CNS concomitant with heightened macrophage inflammatory protein (MIP)-1 transcript levels and greater macrophage infiltration relative to MHV-A59 infection. Here, the ability of the S and non-spike genes to regulate these immune responses was evaluated using chimeric viruses. Chimeric viruses WTR13 and S4R22 were made on MHV-A59 variant backgrounds and, respectively, contained the S gene of MHV-A59 and MHV-JHM. Unexpectedly, genes other than S appeared to modulate events critical to viral replication and survival. Unlike unresolving MHV-JHM infections, the clearance of WTR13 and S4R22 infections coincided with strong IFN-gamma transcription and an increase in the number of CD8 T cells infiltrating into the CNS. However, despite the absence of detectable viral titers, approximately 40% of S4R22-infected mice succumbed within 3 weeks, indicating that the enhanced mortality following S4R22 infection was not associated with high viral titers. Instead, similar to the MHV-JHM infection, reduced survival following S4R22 infection was observed in the presence of elevated MIP-1alpha and MIP-1beta mRNA accumulation and enhanced macrophage numbers within infected brains. These observations suggest that the S protein of MHV-JHM influences neurovirulence through the induction of MIP-1alpha- and MIP-1beta-driven macrophage immunopathology

The unified protocol for transdiagnostic treatment of emotional disorders compared with diagnosis-specific protocols for anxiety disorders a randomized clinical trial

IMPORTANCE: Transdiagnostic interventions have been developed to address barriers to the dissemination of evidence-based psychological treatments, but only a few preliminary studies have compared these approaches with existing evidence-based psychological treatments. OBJECTIVE: To determine whether the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) is at least as efficacious as single-disorder protocols (SDPs) in the treatment of anxiety disorders. DESIGN, SETTING, AND PARTICIPANTS: From June 23, 2011, to March 5, 2015, a total of 223 patients at an outpatient treatment center with a principal diagnosis of panic disorder with or without agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, or social anxiety disorder were randomly assigned by principal diagnosis to the UP, an SDP, or a waitlist control condition. Patients received up to 16 sessions of the UP or an SDP for 16 to 21 weeks. Outcomes were assessed at baseline, after treatment, and at 6-month follow-up. Analysis in this equivalence trial was based on intention to treat. INTERVENTIONS: The UP or SDPs. MAIN OUTCOMES AND MEASURES: Blinded evaluations of principal diagnosis clinical severity rating were used to evaluate an a priori hypothesis of equivalence between the UP and SDPs. RESULTS: Among the 223 patients (124 women and 99 men; mean [SD] age, 31.1 [11.0] years), 88 were randomized to receive the UP, 91 to receive an SDP, and 44 to the waitlist control condition. Patients were more likely to complete treatment with the UP than with SDPs (odds ratio, 3.11; 95% CI, 1.44-6.74). Both the UP (Cohen d, −0.93; 95% CI, −1.29 to −0.57) and SDPs (Cohen d, −1.08; 95% CI, −1.43 to −0.73) were superior to the waitlist control condition at acute outcome. Reductions in clinical severity rating from baseline to the end of treatment (β, 0.25; 95% CI, −0.26 to 0.75) and from baseline to the 6-month follow-up (β, 0.16; 95% CI, −0.39 to 0.70) indicated statistical equivalence between the UP and SDPs. CONCLUSIONS AND RELEVANCE: The UP produces symptom reduction equivalent to criterion standard evidence-based psychological treatments for anxiety disorders with less attrition. Thus, it may be possible to use 1 protocol instead of multiple SDPs to more efficiently treat the most commonly occurring anxiety and depressive disorders.This study was funded by grant R01 MH090053 from the National Institute of Mental Health. (R01 MH090053 - National Institute of Mental Health)First author draf

A qualitative formative evaluation of a patient facing intervention to improve care transitions for older people moving from hospital to home

Background The Partners at Care Transitions (PACTs) intervention was developed to support older people's involvement in hospital to improve outcomes at home. A booklet, question card, record sheet, induction leaflet, and patient-friendly discharge letter support patients to be more involved in their health and wellbeing, medications, activities of daily living and post-discharge care. We aimed to assess intervention acceptability, identify implementation tools, and further develop the intervention. Methods This was a qualitative formative evaluation involving three wards from one hospital. We recruited 25 patients aged 75 years and older. Ward staff supported intervention delivery. Data were collected in wards and patients' homes, through semi-structured interviews, observation, and documentary analysis. Data were analysed inductively and iteratively with findings sorted according to the research aims. Results Patients and staff felt there was a need for, and understood the purpose of, the PACT intervention. Most patients read the booklet but other components were variably used. Implementation challenges included time, awareness, and balancing intervention benefits against risks. Changes to the intervention and implementation included clarifying the booklet's messages, simplifying the discharge letter to reduce staff burden, and using prompts and handouts to promote awareness. Conclusion The PACT intervention offers a promising new way to improve care transitions for older people by supporting patient involvement in their care. After further development of the intervention and implementation package, it will undergo further testing. Patient or Public Contribution This study regularly consulted a panel representing the local patient community, who supported the development of this intervention and its implementation

Doing involvement: A qualitative study exploring the 'work' of involvement enacted by older people and their carers during transition from hospital to home

CONTEXT: Being involved in one's care is prioritised within UK healthcare policy to improve care quality and safety. However, research suggests that many older people struggle with this. DESIGN: We present focused ethnographic research exploring older peoples' involvement in healthcare from hospital to home. RESULTS: We propose that being involved in care is a dynamic form of labour, which we call 'involvement work' (IW). In hospital, many patients 'entrust' IW to others; indeed, when desired, maintaining control, or being actively involved, was challenging. Patient and professionals' expectations, alongside hospital processes, promoted delegation; staff frequently did IW on patients' behalf. Many people wanted to resume IW postdischarge, but struggled because they were out of practice. DISCUSSION: Preference and capacity for involvement was dynamic, fluctuating over time, according to context and resource accessibility. The challenges of resuming IW were frequently underestimated by patients and care providers, increasing dependence on others post-discharge and negatively affecting peoples' sense and experience of (in)dependence. CONCLUSIONS: A balance needs to be struck between respecting peoples' desire/capacity for non-involvement in hospital while recognising that 'delegating' IW can be detrimental. Increasing involvement will require patient and staff roles to be reframed, though this must be done acknowledging the limits of patient desire, capability,and resources. Hospital work should be (re)organised to maximise involvement where possible and desired. PATIENT/PUBLIC CONTRIBUTION: Our Patient and Public Involvement and Engagement Panel contributed to research design, especially developing interview guides and patient-facing documentation. Patients were key participants within the study; it is their experiences represented

A new mathematical model for environmental monitoring and assessment

Versão dos Autores para este artigo.In this paper we are concerned with a quantitative method of Landscape Ecology. More in details we consider an environmental system distributed in landscape units (ecological sectors) and we propose a new mathematical model in order to implement a method for the evaluation of the ecological state of the system under investigation. After having performed a stability analysis of the model, we apply the proposed procedure first by considering separately each landscape unit and then extending our investigation to the system as a whole, by taking into account the connections between all the landscape units themselves. Our investigation includes some numerical computations that were performed for a Northern district of the Turin Province, using an approximation procedure that should avoid stiffness problems.National Group GNFM of INdAM, Italyinfo:eu-repo/semantics/publishedVersio