The importance for immunoregulation for long-term cancer control.

Immune checkpoint blockades have recently emerged as a breakthrough treatment for solid tumors showing high response rates and long durability. In melanoma, the combination of ipilimumab with nivolumab showed high efficacy. However, still half the patients do not respond to this treatment. In order to increase the therapeutic ratio in melanoma and other cancers, different approaches are under evaluation. Three relevant questions are at the moment driving the research community: how to maximize benefit while minimizing toxicity; how to better identify patients who are more likely to benefit from immunotherapy; how to convert nonresponders into responders. In this review we summarize the most recent findings and we outline the most likely future challenges

Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects

The anti-tumour effects of thalidomide have been associated with its anti-angiogenic properties. Second generation thalidomide analogues are distinct compounds with enhanced therapeutic potential. Although these compounds are beginning to enter trials for the treatment of cancer there is very little information regarding the anti-angiogenic activity of these clinically relevant compounds. Furthermore, it is not known how the various immunomodulatory activities of these compounds relate to anti-angiogenic activity. In this study we assessed the anti-angiogenic activity of compounds from both IMiD™ and SelCID™ classes of analogues using a novel in vitro multicellular human assay system and the established rat aorta assay. Our results show that both the IMiDs and SelCIDs tested are significantly more potent than thalidomide. The anti-angiogenic potency of the analogues was not related to inhibition of endothelial cell proliferation, nor their TNF-α/PDE type 4 inhibitory properties. However, anti-migratory effects in vitro and inhibition of tumour growth in vivo was observed with the analogue IMiD-1 (clinically known as REVIMID™). Our results show that anti-angiogenic activity spans both currently defined classes of thalidomide analogue and is not related to their previously described immunomodulatory properties. Identification of the differential effects of these compounds will enable targeting of such compounds into the appropriate clinical setting

Agro-materials : a bibliographic review

Facing the problems of plastic recycling and fossil resources exhaustion, the use of biomass to conceive new materials appears like a reasonable solution. Two axes of research are nowadays developed : on the one hand the synthesis of biodegradable plastics, whichever the methods may be, on the other hand the utilization of raw biopolymers, which is the object of this paper. From this perspective, the “plastic” properties of natural polymers, the caracteristics of the different classes of polymers, the use of charge in vegetable matrix and the possible means of improving the durability of these agro-materials are reviewed

Susceptibility to prosocial and antisocial influence in adolescence.

INTRODUCTION: Adolescents are particularly susceptible to social influence and previous studies have shown that this susceptibility decreases with age. The current study used a cross-sectional experimental paradigm to investigate the effect of age and puberty on susceptibility to both prosocial and antisocial influence. METHODS: Participants (N = 520) aged 11-18 from London and Cambridge (United Kingdom) rated how likely they would be to engage in a prosocial (e.g. "help a classmate with their work") or antisocial (e.g. "make fun of a classmate") act. They were then shown the average rating (in fact fictitious) that other adolescents had given to the same question, and were then asked to rate the same behaviour again. RESULTS: Both prosocial and antisocial influence decreased linearly with age, with younger adolescents being more socially influenced when other adolescents' ratings were more prosocial and less antisocial than their own initial rating. Both antisocial and prosocial influence significantly decreased across puberty for boys but not girls (independent of age). CONCLUSIONS: These findings suggest that social influence declines with increasing maturity across adolescence. However, the exact relationship between social influence and maturity is dependent on the nature of the social influence and gender. Understanding when adolescents are most susceptible to different types of social influence, and how this might influence their social behaviour, has important implications for understanding adolescent social development

Parent and child agreement for acute stress disorder, post-traumatic stress disorder and other psychopathology in a prospective study of children and adolescents exposed to single-event trauma

Examining parent-child agreement for Acute Stress Disorder (ASD) and Post-Traumatic Stress Disorder (PTSD) in children and adolescents is essential for informing the assessment of trauma-exposed children, yet no studies have examined this relationship using appropriate statistical techniques. Parent-child agreement for these disorders was examined by structured interview in a prospective study of assault and motor vehicle accident (MVA) child survivors, assessed at 2-4 weeks and 6 months post-trauma. Children were significantly more likely to meet criteria for ASD, as well as other ASD and PTSD symptom clusters, based on their own report than on their parent's report. Parent-child agreement for ASD was poor (Cohen's κ = -.04), but fair for PTSD (Cohen's κ = .21). Agreement ranged widely for other emotional disorders (Cohen's κ = -.07-.64), with generalised anxiety disorder found to have superior parent-child agreement (when assessed by phi coefficients) relative to ASD and PTSD. The findings support the need to directly interview children and adolescents, particularly for the early screening of posttraumatic stress, and suggest that other anxiety disorders may have a clearer presentation post-trauma

The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study protocol: a cross-sectional, lifespan, multidisciplinary examination of healthy cognitive ageing.

BACKGROUND: As greater numbers of us are living longer, it is increasingly important to understand how we can age healthily. Although old age is often stereotyped as a time of declining mental abilities and inflexibility, cognitive neuroscience reveals that older adults use neural and cognitive resources flexibly, recruiting novel neural regions and cognitive processes when necessary. Our aim in this project is to understand how age-related changes to neural structure and function interact to support cognitive abilities across the lifespan. METHODS/DESIGN: We are recruiting a population-based cohort of 3000 adults aged 18 and over into Stage 1 of the project, where they complete an interview including health and lifestyle questions, a core cognitive assessment, and a self-completed questionnaire of lifetime experiences and physical activity. Of those interviewed, 700 participants aged 18-87 (100 per age decile) continue to Stage 2 where they undergo cognitive testing and provide measures of brain structure and function. Cognition is assessed across multiple domains including attention and executive control, language, memory, emotion, action control and learning. A subset of 280 adults return for in-depth neurocognitive assessment in Stage 3, using functional neuroimaging experiments across our key cognitive domains.Formal statistical models will be used to examine the changes that occur with healthy ageing, and to evaluate age-related reorganisation in terms of cognitive and neural functions invoked to compensate for overall age-related brain structural decline. Taken together the three stages provide deep phenotyping that will allow us to measure neural activity and flexibility during performance across a number of core cognitive functions. This approach offers hypothesis-driven insights into the relationship between brain and behaviour in healthy ageing that are relevant to the general population. DISCUSSION: Our study is a unique resource of neuroimaging and cognitive measures relevant to change across the adult lifespan. Because we focus on normal age-related changes, our results may contribute to changing views about the ageing process, lead to targeted interventions, and reveal how normal ageing relates to frail ageing in clinicopathological conditions such as Alzheimer's disease.The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) research was supported by the Biotechnology and Biological Sciences Research Council (grant number BB/H008217/1).This is the final published version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s12883-014-0204-

Cognitive Diversity in a Healthy Aging Cohort: Cross-Domain Cognition in the Cam-CAN Project.

Objective: Studies of "healthy" cognitive aging often focus on a limited set of measures that decline with age. The current study argues that defining and supporting healthy cognition requires understanding diverse cognitive performance across the lifespan. Method: Data from the Cambridge Centre for Aging and Neuroscience (Cam-CAN) cohort was examined across a range of cognitive domains. Performance was related to lifestyle including education, social engagement, and enrichment activities. Results: Results indicate variable relationships between cognition and age (positive, negative, or no relationship). Principal components analysis indicated maintained cognitive diversity across the adult lifespan, and that cognition-lifestyle relationships differed by age and domain. Discussion: Our findings support a view of normal cognitive aging as a lifelong developmental process with diverse relationships between cognition, lifestyle, and age. This reinforces the need for large-scale studies of cognitive aging to include a wider range of both ages and cognitive tasks.The Cambridge Centre for Aging and Neuroscience (Cam-CAN) research was supported by the Biotechnology and Biological Sciences Research Council (grant number BB/H008217/1)

Reduced specificity of autobiographical memory and depression: The role of executive control

It has been widely established that depressed mood states and clinical depression, as well as a range of other psychiatric disorders, are associated with a relative difficulty in accessing specific autobiographical information in response to emotion-related cue words on an Autobiographical Memory Test (AMT; J. M. G. Williams & K. Broadbent, 1986). In 8 studies the authors examined the extent to which this relationship is a function of impaired executive control associated with these mood states and clinical disorders. Studies 1-4 demonstrated that performance on the AMT is associated with performance on measures of executive control, independent of depressed mood. Furthermore, Study 1 showed that executive control (as measured by verbal fluency) mediated the relationship between both depressed mood and a clinical diagnosis of eating disorder and AMT performance. Using a stratified sample in Study 5, the authors confirmed the positive association between depressed mood and impaired performance on the AMT. Studies 6-8 involved experimental manipulations of the parameters of the AMT designed to further indicate that reduced executive control is to a significant extent driving the relationship between depressed mood and AMT performance. The potential role of executive control in accounting for other aspects of the AMT literature is discussed. (PsycINFO Database Record (c) 2007 APA, all rights reserved)

Young people’s mental health changes, risk and resilience during the Covid-19 pandemic

This is the final version. Available on open access from the American Medical Association via the DOI in this recordData Sharing Statement: Data are available upon reasonable request. The de-identified baseline data and codebook from the MYRIAD trial are available from Prof. Kuyken ([email protected]) upon request (release of data is subject to an approved proposal and a signed data access agreement).Importance As young people’s mental health difficulties increase, understanding risk and resilience factors under challenging circumstances becomes critical. Objective To explore the outcomes of the COVID-19 pandemic on secondary school students’ mental health difficulties, as well as the associations with individual, family, friendship, and school characteristics. Design, Setting, and Participants For this cohort study, follow-up data from the My Resilience in Adolescence (MYRIAD) cluster randomized clinical trial were collected across 2 representative UK cohorts. Mainstream UK secondary schools with a strategy and structure to deliver social-emotional learning, with an appointed head teacher, and that were not rated “inadequate” in their latest official inspection were recruited. A total of 5663 schools were approached, 532 showed interest, and 84 consented. Cohort 1 included 12 schools and 864 students, and cohort 2 included 72 schools and 6386 students. COVID-19 was declared a pandemic after cohort 1 had completed all assessments (September 2018 to January 2020), but cohort 2 had not (September 2019 to June 2021). Exposures Cohort 2 was exposed to the COVID-19 pandemic, including 3 national lockdowns. Associations of individual, family, friendship, and school characteristics with students’ mental health were explored. Main Outcomes and Measures Changes in students’ risk for depression (Center for Epidemiological Studies-Depression scale); social, emotional, and behavioral difficulties (Strengths and Difficulties Questionnaire); and mental well-being (Warwick-Edinburgh Mental Well-Being Scale). Results Of the 7250 participants included, the mean (SD) age was 13.7 (0.6) years, 3947 (55.4%) identified as female, and 5378 (73.1%) self-reported their race as White. Twelve schools and 769 of the 864 students (89.0%) in cohort 1 and 54 schools and 2958 of the 6386 students (46.3%) in cohort 2 provided data and were analyzed. Mental health difficulties increased in both cohorts but to a greater extent among students exposed to the pandemic, including for risk of depression (adjusted mean difference [AMD], 1.91; 95% CI, 1.07-2.76); social, emotional, and behavioral difficulties (AMD, 0.76; 95% CI, 0.33-1.18); and mental well-being (AMD, −2.08; 95% CI, −2.80 to −1.36). Positive school climate, high home connectedness, and having a friend during lockdown were protective factors during the pandemic. Female gender and initial low risk for mental health difficulties were associated with greater mental health deteriorations. Partial school attendance during lockdown was associated with better adjustment than no attendance when returning to school. Conclusions and Relevance This cohort study of secondary school students demonstrated that to promote mental health and adjustment, policy interventions should foster home connectedness, peer friendship, and school climate; avoid full school closures; and consider individual differences.Wellcome TrustNational Institute for Health and Care Research (NIHR)Instituto de Salud Carlos IIIConsortium for Biomedical Research of Epidemiology and Public Healt