Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large‐scale studies. In response, we used cross‐sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to infer age‐related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta‐analysis and one‐way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3–90 years

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to examine age‐related trajectories inferred from cross‐sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter‐individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age‐related morphometric patterns

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

Prevalência de violência física relatada contra crianças em uma população de ambulatório pediátrico Prevalence of reported child abuse by parents in a pediatric out-patient population

Foi realizado um estudo transversal para se estimar a prevalência da violência física contra crianças de 0 a 13 anos, enquanto método disciplinar, em pacientes do Ambulatório de Pediatria do Hospital de Clínicas da Universidade Estadual de Campinas. A cidade conta com 1 milhão de habitantes com cobertura universal de serviços de saúde. Foi aplicado um questionário a 130 responsáveis que trouxeram as crianças à consulta ambulatorial, através de um esquema aleatório de seleção. A prevalência de crianças agredidas foi de 10,8%. O critério adotado considerou como agredidas as crianças cujos responsáveis relataram o uso de força física, batendo em menores de 1 ano, ou crianças com mais de 1 ano que apresentaram lesões após a agressão física. A aplicação do questionário evidenciou a necessidade de se realizar a avaliação do mesmo enquanto instrumento de medida quantitativa em uma população, visando futuros estudos de prevalência ou incidência. Evidenciou-se também a necessidade do emprego de métodos quantitativos para se aprofundar a pesquisa sobre a gênese sócio-psicológica da agressão física com finalidade supostamente disciplinatórias.A cross-sectional study was carried out to estimate prevalence of child abuse with battering among patients under age 14 for alleged disciplinary purposes. The reference population were children attending pediatric out-patient services at the University Hospital in Campinas, State of São Paulo, Brazil, a city of one million inhabitants with universal coverage in terms of accessing health care in the unit under study. Interviews were carried out with 130 parents or guardians in a randomly selected group according to order of attendance, and the prevalence of child abuse was estimated at 10.8%, considering as positive cases those where parents referred child battering under age one year or where there was evidence of bodily lesion over age one year. A validation study for the experimental questionnaire is proposed in order to allow for future estimation of population prevalence or incidence. The use of qualitative methods is also recommended as a means of gathering detailed data on socio-psychological determination for the supposedly disciplinary aggression with child abuse

Prevalence of reported child abuse by parents in a pediatric out-patient population

A cross-sectional study was carried out to estimate prevalence of child abuse with battering among patients under age 14 for alleged disciplinary purposes. The reference population were children attending pediatric out-patient services at the University Hospital in Campinas, State of São Paulo, Brazil, a city of one million inhabitants with universal coverage in terms of accessing health care in the unit under study. Interviews were carried out with 130 parents or guardians in a randomly selected group according to order of attendance, and the prevalence of child abuse was estimated at 10.8%, considering as positive cases those where parents referred child battering under age one year or where there was evidence of bodily lesion over age one year. A validation study for the experimental questionnaire is proposed in order to allow for future estimation of population prevalence or incidence. The use of qualitative methods is also recommended as a means of gathering detailed data on socio-psychological determination for the supposedly disciplinary aggression with child abuse.Foi realizado um estudo transversal para se estimar a prevalência da violência física contra crianças de 0 a 13 anos, enquanto método disciplinar, em pacientes do Ambulatório de Pediatria do Hospital de Clínicas da Universidade Estadual de Campinas. A cidade conta com 1 milhão de habitantes com cobertura universal de serviços de saúde. Foi aplicado um questionário a 130 responsáveis que trouxeram as crianças à consulta ambulatorial, através de um esquema aleatório de seleção. A prevalência de crianças agredidas foi de 10,8%. O critério adotado considerou como agredidas as crianças cujos responsáveis relataram o uso de força física, batendo em menores de 1 ano, ou crianças com mais de 1 ano que apresentaram lesões após a agressão física. A aplicação do questionário evidenciou a necessidade de se realizar a avaliação do mesmo enquanto instrumento de medida quantitativa em uma população, visando futuros estudos de prevalência ou incidência. Evidenciou-se também a necessidade do emprego de métodos quantitativos para se aprofundar a pesquisa sobre a gênese sócio-psicológica da agressão física com finalidade supostamente disciplinatórias.929

Prevalência de violência física relatada contra crianças em uma população de ambulatório pediátrico

Foi realizado um estudo transversal para se estimar a prevalência da violência física contra crianças de 0 a 13 anos, enquanto método disciplinar, em pacientes do Ambulatório de Pediatria do Hospital de Clínicas da Universidade Estadual de Campinas. A cidade conta com 1 milhão de habitantes com cobertura universal de serviços de saúde. Foi aplicado um questionário a 130 responsáveis que trouxeram as crianças à consulta ambulatorial, através de um esquema aleatório de seleção. A prevalência de crianças agredidas foi de 10,8%. O critério adotado considerou como agredidas as crianças cujos responsáveis relataram o uso de força física, batendo em menores de 1 ano, ou crianças com mais de 1 ano que apresentaram lesões após a agressão física. A aplicação do questionário evidenciou a necessidade de se realizar a avaliação do mesmo enquanto instrumento de medida quantitativa em uma população, visando futuros estudos de prevalência ou incidência. Evidenciou-se também a necessidade do emprego de métodos quantitativos para se aprofundar a pesquisa sobre a gênese sócio-psicológica da agressão física com finalidade supostamente disciplinatórias

Epidemiological characteristics, practice of ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international, multicentre, prospective study

Background Scant information exists about the epidemiological characteristics and outcome of patients in the intensive care unit (ICU) at risk of acute respiratory distress syndrome (ARDS) and how ventilation is managed in these individuals. We aimed to establish the epidemiological characteristics of patients at risk of ARDS, describe ventilation management in this population, and assess outcomes compared with people at no risk of ARDS. Methods PRoVENT (PRactice of VENTilation in critically ill patients without ARDS at onset of ventilation) is an international, multicentre, prospective study undertaken at 119 ICUs in 16 countries worldwide. All patients aged 18 years or older who were receiving mechanical ventilation in participating ICUs during a 1-week period between January, 2014, and January, 2015, were enrolled into the study. The Lung Injury Prediction Score (LIPS) was used to stratify risk of ARDS, with a score of 4 or higher defining those at risk of ARDS. The primary outcome was the proportion of patients at risk of ARDS. Secondary outcomes included ventilatory management (including tidal volume [VT] expressed as mL/kg predicted bodyweight [PBW], and positive end-expiratory pressure [PEEP] expressed as cm H2O), development of pulmonary complications, and clinical outcomes. The PRoVENT study is registered at ClinicalTrials.gov, NCT01868321. The study has been completed. Findings Of 3023 patients screened for the study, 935 individuals fulfilled the inclusion criteria. Of these critically ill patients, 282 were at risk of ARDS (30%, 95% CI 27–33), representing 0·14 cases per ICU bed over a 1-week period. VT was similar for patients at risk and not at risk of ARDS (median 7·6 mL/kg PBW [IQR 6·7–9·1] vs 7·9 mL/kg PBW [6·8–9·1]; p=0·346). PEEP was higher in patients at risk of ARDS compared with those not at risk (median 6·0 cm H2O [IQR 5·0–8·0] vs 5·0 cm H2O [5·0–7·0]; p&lt;0·0001). The prevalence of ARDS in patients at risk of ARDS was higher than in individuals not at risk of ARDS (19/260 [7%] vs 17/556 [3%]; p=0·004). Compared with individuals not at risk of ARDS, patients at risk of ARDS had higher in-hospital mortality (86/543 [16%] vs 74/232 [32%]; p&lt;0·0001), ICU mortality (62/533 [12%] vs 66/227 [29%]; p&lt;0·0001), and 90-day mortality (109/653 [17%] vs 88/282 [31%]; p&lt;0·0001). VT did not differ between patients who did and did not develop ARDS (p=0·471 for those at risk of ARDS; p=0·323 for those not at risk). Interpretation Around a third of patients receiving mechanical ventilation in the ICU were at risk of ARDS. Pulmonary complications occur frequently in patients at risk of ARDS and their clinical outcome is worse compared with those not at risk of ARDS. There is potential for improvement in the management of patients without ARDS. Further refinements are needed for prediction of ARDS