Effectiveness of psychoeducational interventions for family carers of people with psychosis: A systematic review and meta-analysis.

Psychoeducational interventions for family carers of people with psychosis are effective for improving compliance and preventing relapse. Whether carers benefit from these interventions has been little explored. This systematic review investigated the effectiveness of psychoeducation for improving carers' outcomes, and potential treatment moderators. We searched for randomised controlled trials (RCTs) published in English or Chinese in eight databases. Carers' outcomes included wellbeing, quality of life, global morbidities, burden, and expressed emotion. Thirty-two RCTs were included, examining 2858 carers. Intervention duration ranged from 4 to 52weeks, and contact times ranged from 6 to 42hours. At post intervention, findings were equivocal for carers' wellbeing (SMD 0.103, 95% CI -0.186 to 0.392). Conversely, psychoeducation was superior in reducing carers' global morbidities (SMD -0.230, 95% CI -0.386 to -0.075), perceived burden (SMD -0.434, 95% CI -0.567 to -0.31), negative caregiving experiences (SMD -0.210, 95% CI -0.396 to -0.025) and expressed emotion (SMD -0.161, 95% CI -0.367 to -0.045). The lack of available data precluded meta-analysis of outcomes beyond short-term follow-up. Meta-regression revealed no significant associations between intervention modality, duration, or contact time and outcomes. Further research should focus on improving carers' outcomes in the longer-term and identifying factors to optimise intervention design

Effectiveness of psychoeducational interventions for family carers of people

Psychoeducational interventions for family carers of people with psychosis are effective for improving compliance and preventing relapse. Whether carers benefit from these interventions has been little explored. This systematic review investigated the effectiveness of psychoeducation for improving carers' outcomes, and potential treatment moderators. We searched for randomised controlled trials (RCTs) published in English or Chinese in eight databases. Carers' outcomes included wellbeing, quality of life, global morbidities, burden, and expressed emotion. Thirty-two RCTs were included, examining 2858 carers. Intervention duration ranged from 4 to 52 weeks, and contact times ranged from 6 to 42 hours. At post intervention, findings were equivocal for carers' wellbeing (SMD 0.103, 95% CI − 0.186 to 0.392). Conversely, psychoeducation was superior in reducing carers' global morbidities (SMD − 0.230, 95% CI − 0.386 to − 0.075), perceived burden (SMD − 0.434, 95% CI − 0.567 to − 0.31), negative caregiving experiences (SMD − 0.210, 95% CI − 0.396 to − 0.025) and expressed emotion (SMD − 0.161, 95% CI − 0.367 to − 0.045). The lack of available data precluded meta-analysis of outcomes beyond short-term follow-up. Meta-regression revealed no significant associations between intervention modality, duration, or contact time and outcomes. Further research should focus on improving carers' outcomes in the longer-term and identifying factors to optimise intervention design

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Philosophy Bakes No Bread

Philosophy Bakes No Bread Far from baking bread, far from practical applicability, philosophy traditionally sought to explain the world, ideally so. Thus, when Marx argued that it was high time philosophy “change the world,” his was a revolutionary challenge. Today, philosophy is an analytic affair and analytic philosophers seek less to explain the world than to squirrel out arguments or, more descriptively, to resolve the minutiae of this or that name problem. Faced with diminishing student demand, analytic philosophers have taken to urging that everyone from primary school students to scientists be required to study (analytic) philosophy. Just so, applied philosophers demand to be engaged as consultants on practical projects. Granting that the demand that philosophers be appointed to public policy projects is understandable, inasmuch as everyone, as Hegel observed, desires recognition, this article argues that no argument has been made that the results would benefit any but the appointees while reinforcing current administrative quantitative evaluative schemes