Cognitive Behavioural Therapy for schizophrenia - outcomes for functioning, distress and quality of life : A meta-analysis

Background: The effect of cognitive behavioural therapy for psychosis (CBTp) on the core symptoms of schizophrenia has proven contentious, with current meta-analyses finding at most only small effects. However, it has been suggested that the effects of CBTp in areas other than psychotic symptoms are at least as important and potentially benefit from the intervention. Method: We meta-analysed RCTs investigating the effectiveness of CBTp for functioning, distress and quality of life in individuals diagnosed with schizophrenia and related disorders. Data from 36 randomised controlled trials (RCTs) met our inclusion criteria- 27 assessing functioning (1579 participants); 8 for distress (465 participants); and 10 for quality of life (592 participants). Results: The pooled effect size for functioning was small but significant for the end-of-trial (0.25: 95% CI: 0.14 to 0.33); however, this became non-significant at follow-up (0.10 [95%CI -0.07 to 0.26]). Although a small benefit of CBT was evident for reducing distress (0.37: 95%CI 0.05 to 0.69), this became nonsignificant when adjusted for possible publication bias (0.18: 95%CI -0.12 to 0.48). Finally, CBTp showed no benefit for improving quality of life (0.04: 95% CI: -0.12 to 0.19). Conclusions: CBTp has a small therapeutic effect on functioning at end-of-trial, although this benefit is not evident at follow-up. Although CBTp produced a small benefit on distress, this was subject to possible publication bias and became nonsignificant when adjusted. We found no evidence that CBTp increases quality of life post-intervention.Peer reviewedFinal Published versio

Amyloid precursor-like protein 2 (APLP2) affects the actin cytoskeleton and increases pancreatic cancer growth and metastasis.

Amyloid precursor-like protein 2 (APLP2) is aberrantly expressed in pancreatic cancer. Here we showed that APLP2 is increased in pancreatic cancer metastases, particularly in metastatic lesions found in the diaphragm and intestine. Examination of matched human primary tumor-liver metastasis pairs showed that 38.1% of the patients had positive APLP2 expression in both the primary tumor and the corresponding liver metastasis. Stable knock-down of APLP2 expression (with inducible shRNA) in pancreatic cancer cells reduced the ability of these cells to migrate and invade. Loss of APLP2 decreased cortical actin and increased intracellular actin filaments in pancreatic cancer cells. Down-regulation of APLP2 decreased the weight and metastasis of orthotopically transplanted pancreatic tumors in nude mice

Reimagining large river management using the Resist–Accept–Direct (RAD) framework in the Upper Mississippi River

Background: Large-river decision-makers are charged with maintaining diverse ecosystem services through unprecedented social-ecological transformations as climate change and other global stressors intensify. The interconnected, dendritic habitats of rivers, which often demarcate jurisdictional boundaries, generate complex management challenges. Here, we explore how the Resist–Accept–Direct (RAD) framework may enhance large-river management by promoting coordinated and deliberate responses to social-ecological trajectories of change. The RAD framework identifies the full decision space of potential management approaches, wherein managers may resist change to maintain historical conditions, accept change toward different conditions, or direct change to a specified future with novel conditions. In the Upper Mississippi River System, managers are facing social-ecological transformations from more frequent and extreme high-water events. We illustrate how RAD-informed basin-, reach-, and site-scale decisions could: (1) provide cross-spatial scale framing; (2) open the entire decision space of potential management approaches; and (3) enhance coordinated inter-jurisdictional management in response to the trajectory of the Upper Mississippi River hydrograph. Results: The RAD framework helps identify plausible long-term trajectories in different reaches (or subbasins) of the river and how the associated social-ecological transformations could be managed by altering site-scale conditions. Strategic reach-scale objectives may reprioritize how, where, and when site conditions could be altered to contribute to the basin goal, given the basin’s plausible trajectories of change (e.g., by coordinating action across sites to alter habitat connectivity, diversity, and redundancy in the river mosaic). Conclusions: When faced with long-term systemic transformations (e.g., \u3e 50 years), the RAD framework helps explicitly consider whether or when the basin vision or goals may no longer be achievable, and direct options may open yet unconsidered potential for the basin. Embedding the RAD framework in hierarchical decision-making clarifies that the selection of actions in space and time should be derived from basin-wide goals and reach-scale objectives to ensure that site-scale actions contribute effectively to the larger river habitat mosaic. Embedding the RAD framework in large-river decisions can provide the necessary conduit to link flexibility and innovation at the site scale with stability at larger scales for adaptive governance of changing social-ecological systems

Overdose Prevention Centres, Safe Consumption Sites, and Drug Consumption Rooms: A Rapid Evidence Review

This rapid review on overdose prevention centres (OPCs) aims to collate and summarise existing evidence. It describes the impact of OPCs on individuals who use drugs, communities, and public health. This is to support decision making and understanding of service provision for health departments, potential providers, researchers, and elected officials (1). This document also covers some practical matters of running a service including day-to-day matters, costs, and any cost savings from their operation. We conclude with information on evaluation; services should be robustly evaluated

Overdose prevention centres, safe consumption sites, and drug consumption rooms: A rapid evidence review

This rapid review on overdose prevention centres (OPCs) aims to collate and summarise existing evidence. It describes the impact of OPCs on individuals who use drugs, communities, and public health

Correction to: Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study

Following publication of the original article [1], it was reported that the legend for Fig. 1 was incomplete. The complete figure legend is:https://deepblue.lib.umich.edu/bitstream/2027.42/148648/1/12885_2019_Article_5568.pd

Rare Variants in Ischemic Stroke: An Exome Pilot Study

The genetic architecture of ischemic stroke is complex and is likely to include rare or low frequency variants with high penetrance and large effect sizes. Such variants are likely to provide important insights into disease pathogenesis compared to common variants with small effect sizes. Because a significant portion of human functional variation may derive from the protein-coding portion of genes we undertook a pilot study to identify variation across the human exome (i.e., the coding exons across the entire human genome) in 10 ischemic stroke cases. Our efforts focused on evaluating the feasibility and identifying the difficulties in this type of research as it applies to ischemic stroke. The cases included 8 African-Americans and 2 Caucasians selected on the basis of similar stroke subtypes and by implementing a case selection algorithm that emphasized the genetic contribution of stroke risk. Following construction of paired-end sequencing libraries, all predicted human exons in each sample were captured and sequenced. Sequencing generated an average of 25.5 million read pairs (75 bp×2) and 3.8 Gbp per sample. After passing quality filters, screening the exomes against dbSNP demonstrated an average of 2839 novel SNPs among African-Americans and 1105 among Caucasians. In an aggregate analysis, 48 genes were identified to have at least one rare variant across all stroke cases. One gene, CSN3, identified by screening our prior GWAS results in conjunction with our exome results, was found to contain an interesting coding polymorphism as well as containing excess rare variation as compared with the other genes evaluated. In conclusion, while rare coding variants may predispose to the risk of ischemic stroke, this fact has yet to be definitively proven. Our study demonstrates the complexities of such research and highlights that while exome data can be obtained, the optimal analytical methods have yet to be determined

Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma

Cellular plasticity contributes to intra-tumoral heterogeneity and phenotype switching, which enable adaptation to metastatic microenvironments and resistance to therapies. Mechanisms underlying tumor cell plasticity remain poorly understood. SOX10, a neural crest lineage transcription factor, is heterogeneously expressed in melanomas. Loss of SOX10 reduces proliferation, leads to invasive properties, including the expression of mesenchymal genes and extracellular matrix, and promotes tolerance to BRAF and/or MEK inhibitors. We identify the class of cellular inhibitor of apoptosis protein-1/2 (cIAP1/2) inhibitors as inducing cell death selectively in SOX10-deficient cells. Targeted therapy selects for SOX10 knockout cells underscoring their drug tolerant properties. Combining cIAP1/2 inhibitor with BRAF/MEK inhibitors delays the onset of acquired resistance in melanomas in vivo. These data suggest that SOX10 mediates phenotypic switching in cutaneous melanoma to produce a targeted inhibitor tolerant state that is likely a prelude to the acquisition of resistance. Furthermore, we provide a therapeutic strategy to selectively eliminate SOX10-deficient cells

Women and ARVâ based prevention: opportunities and challenges

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138349/1/jia29419.pd