Suitability of PSA-detected localised prostate cancers for focal therapy: Experience from the ProtecT study

This article is available through a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. Copyright @ 2011 Cancer Research UK.Background: Contemporary screening for prostate cancer frequently identifies small volume, low-grade lesions. Some clinicians have advocated focal prostatic ablation as an alternative to more aggressive interventions to manage these lesions. To identify which patients might benefit from focal ablative techniques, we analysed the surgical specimens of a large sample of population-detected men undergoing radical prostatectomy as part of a randomised clinical trial. Methods: Surgical specimens from 525 men who underwent prostatectomy within the ProtecT study were analysed to determine tumour volume, location and grade. These findings were compared with information available in the biopsy specimen to examine whether focal therapy could be provided appropriately. Results: Solitary cancers were found in prostatectomy specimens from 19% (100 out of 525) of men. In addition, 73 out of 425 (17%) men had multiple cancers with a solitary significant tumour focus. Thus, 173 out of 525 (33%) men had tumours potentially suitable for focal therapy. The majority of these were small, well-differentiated lesions that appeared to be pathologically insignificant (38–66%). Criteria used to select patients for focal prostatic ablation underestimated the cancer's significance in 26% (34 out of 130) of men and resulted in overtreatment in more than half. Only 18% (24 out of 130) of men presumed eligible for focal therapy, actually had significant solitary lesions. Conclusion: Focal therapy appears inappropriate for the majority of men presenting with prostate-specific antigen-detected localised prostate cancer. Unifocal prostate cancers suitable for focal ablation are difficult to identify pre-operatively using biopsy alone. Most lesions meeting criteria for focal ablation were either more aggressive than expected or posed little threat of progression.National Institute for Health Researc

A rapid screening tool for psychological distress in children 3--6years old: results of a validation study.

International audienceABSTRACT: BACKGROUND: The mental health needs of young children in humanitarian contexts often remain unaddressed. The lack of a validated, rapid and simple tool for screening combined with few mental health professionals able to accurately diagnose and provide appropriate care mean that young children remain without care. Here, we present the results of the principle cross-cultural validation of the "Psychological Screening for Young Children aged 3 to 6" (PSYCAa3-6). The PSYCa 3--6 is a simple scale for children 3 to 6 years old administered by non-specialists, to screen young children in crises and thereby refer them to care if needed. METHODS: This study was conducted in Maradi, Niger. The scale was translated into Hausa, using corroboration of independent translations. A cross-cultural validation was implemented using quantitative and qualitative methods. A random sample of 580 mothers or caregivers of children 3 to 6 years old were included. The tool was psychometrically examined and diagnostic properties were assessed comparing the PSYCa 3--6 against a clinical interview as the gold standard. RESULTS: The PSYCa 3--6 Hausa version demonstrated good concurrent validity, as scores correlated with the gold standard and the Clinical Global Impression Severity Scale (CGI-S) [rho = 0.41, p-value = 0.00]. A reduction procedure was used to reduce the scale from 40 to 22 items. The test-retest reliability of the PSYCa 3--6 was found to be high (ICC 0.81, CI95% [0.68; 0.89]). In our sample, although not the purpose of this study, approximately 54 of 580 children required subsequent follow-up with a psychologist. CONCLUSIONS: To our knowledge, this is the first validation of a screening scale for children 3 to 6 years old with a cross-cultural validation component, for use in humanitarian contexts. The Hausa version of the PSYCa 3--6 is a reliable and a valuable screening tool for psychological distress. Further studies to replicate our findings and additional validations of the PSYCa 3--6 in other populations may help improve the delivery of mental health care to children

Using jasmonates and salicylates to reduce losses within the fruit supply chain

The fresh produce industry is constantly growing, due to increasing consumer demand. The shelf-life of some fruit, however, is relatively short, limited by microbial contamination or visual, textural and nutritional quality loss. Thus, techniques for reducing undesired microbial contamination, spoilage and decay, as well as maintaining product’s visual, textural and nutritional quality are in high demand at all steps within the supply chain. The postharvest use of signalling molecules, i.e. jasmonates and salicylates seems to have unexplored potential. The focus of this review is on the effects of treatment with jasmonates and salicylates on the fresh produce quality, defined by decay incidence and severity, chilling injury, maintenance of texture, visual quality, taste and aroma, and nutritional content. Postharvest treatments with jasmonates and salicylates have the ability to reduce decay by increasing fruit resistance to diseases and reducing chilling injury in numerous products. These treatments also possess the ability to improve other quality characteristics, i.e. appearance, texture maintenance and nutritional content. Furthermore, they can easily be combined with other treatments, e.g. heat treatment, ultrasound treatment. A good understanding of all the benefits and limitations related to the postharvest use of jasmonates and salicylates is needed, and relevant information has been reviewed in this paper

TRIM5 is an innate immune sensor for the retrovirus capsid lattice

TRIM5 is a RING domain-E3 ubiquitin ligase that restricts infection by human immunodeficiency virus (HIV)-1 and other retroviruses immediately following virus invasion of the target cell cytoplasm. Antiviral potency correlates with TRIM5 avidity for the retrovirion capsid lattice and several reports indicate that TRIM5 has a role in signal transduction, but the precise mechanism of restriction is unknown. Here we demonstrate that TRIM5 promotes innate immune signalling and that this activity is amplified by retroviral infection and interaction with the capsid lattice. Acting with the heterodimeric, ubiquitin-conjugating enzyme UBC13-UEV1A (also known as UBE2N-UBE2V1), TRIM5 catalyses the synthesis of unattached K63-linked ubiquitin chains that activate the TAK1 (also known as MAP3K7) kinase complex and stimulate AP-1 and NFκB signalling. Interaction with the HIV-1 capsid lattice greatly enhances the UBC13-UEV1A-dependent E3 activity of TRIM5 and challenge with retroviruses induces the transcription of AP-1 and NF-κB-dependent factors with a magnitude that tracks with TRIM5 avidity for the invading capsid. Finally, TAK1 and UBC13-UEV1A contribute to capsid-specific restriction by TRIM5. Thus, the retroviral restriction factor TRIM5 has two additional activities that are linked to restriction: it constitutively promotes innate immune signalling and it acts as a pattern recognition receptor specific for the retrovirus capsid lattice