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In order to discern the causes of the health and developmental problems of children, and thence develop preventative strategies, longitudinal cohort studies offer major advantages. They can monitor the consequences of exposure to physical and psychological events and thence identify antecedents of various disorders. We describe the historical background to the development in the UK of this study design, and the uptake of longitudinal birth cohorts in low- and middle-income countries (LMICs), using the cohorts in Jamaica, South Africa and Brazil as exemplars. We describe the benefits of such studies and show how undertaking longitudinal cohort studies can have major health and financial benefits to the populations concerned. Additionally, the paper outlines the advantages of collaboration between studies and the pooling of data. [ABSTRACT FROM AUTHOR]

In preparation to the launch of a pharmaceutical product, an estimate of its shelf life via stability testing is required by regulatory agencies. The ICH-Q1E guidance has been the worldwide reference to reach this objective, but in recent years several authors have criticized many of its aspects. To that end we discuss a complete Bayesian transcript of the ICH-Q1E, treating all the apparent shortcomings, while also addressing the presence of multiple batches using a linear mixed model (LMM) for proper shelf life prediction by explicitly modelling the batch-to-batch variability. This comprises a redefinition of the linear models proposed in the ICH-Q1E by suitable LMM counterparts, and a Bayesian analogue for model selection, which is more intuitive and remedies detrimental features of the ICH approach. In that context, a proper mathematical foundation of shelf life is provided that we use to investigate and mathematically compare the two available approaches to shelf life determination via shelf life distribution and batch distribution. The discussed method is then tested and evaluated using real data in comparison with the ICH-Q1E approach demonstrating their approximate equivalency for 6 batches. As a major objective, we extended the LMM with auxiliary fixed effects, here the concentration, which interconnect data sets allowing a prediction of shelf lives for concentrations lacking a sufficient number of batches. This establishes a novel approach to accelerate the speed to submission while retaining the patients' safety. Both case studies underline the inherent superiority of LMMs within a Bayesian framework regarding predictability and interpretability, and we hope that the relevant authorities will accept this approach in the future. [ABSTRACT FROM AUTHOR]

Background: The PHERGain study (NCT03161353) is assessing early metabolic responses to neoadjuvant treatment with trastuzumab-pertuzumab and chemotherapy de-escalation using a [18Fluorine]fluorodeoxyglucose-positron emission tomography ([18F]FDG-PET) and a pathological complete response-adapted strategy in HER2-positive (HER2+) early breast cancer (EBC). Herein, we present RESPONSE, a PHERGain substudy, where clinicopathological and molecular predictors of [18F]FDG-PET disease detection were evaluated. Methods: A total of 500 patients with HER2 + EBC screened in the PHERGain trial with a tumor size > 1.5 cm by magnetic resonance imaging (MRI) were included in the RESPONSE substudy. PET[−] criteria entailed the absence of ≥ 1 breast lesion with maximum standardized uptake value (SUVmax) ≥ 1.5 × SUVmean liver + 2 standard deviation. Among 75 PET[−] patients screened, 21 with SUVmax levels < 2.5 were randomly selected and matched with 21 PET[+] patients with SUVmax levels ≥ 2.5 based on patient characteristics associated with [18F]FDG-PET status. The association between baseline SUVmax and [18F]FDG-PET status ([−] or [+]) with clinicopathological characteristics was assessed. In addition, evaluation of stromal tumor-infiltrating lymphocytes (sTILs) and gene expression analysis using PAM50 and Vantage 3D™ Cancer Metabolism Panel were specifically compared in a matched cohort of excluded and enrolled patients based on the [18F]FDG-PET eligibility criteria. Results: Median SUVmax at baseline was 7.2 (range, 1–39.3). Among all analyzed patients, a higher SUVmax was associated with a higher tumor stage, larger tumor size, lymph node involvement, hormone receptor-negative status, higher HER2 protein expression, increased Ki67 proliferation index, and higher histological grade (p < 0.05). [18F]FDG-PET [−] criteria patients had smaller tumor size (p = 0.014) along with the absence of lymph node involvement and lower histological grade than [18F]FDG-PET [+] patients (p < 0.01). Although no difference in the levels of sTILs was found among 42 matched [18F]FDG-PET [−]/[+] criteria patients (p = 0.73), [18F]FDG-PET [−] criteria patients showed a decreased risk of recurrence (ROR) and a lower proportion of PAM50 HER2-enriched subtype than [18F]FDG-PET[+] patients (p < 0.05). Differences in the expression of genes involved in cancer metabolism were observed between [18F]FDG-PET [−] and [18F]FDG-PET[+] criteria patients. Conclusions: These results highlight the clinical, biological, and metabolic heterogeneity of HER2+ breast cancer, which may facilitate the selection of HER2+ EBC patients likely to benefit from [18F]FDG-PET imaging as a tool to guide therapy. Trial registration: Clinicaltrials.gov; NCT03161353; registration date: May 15, 2017. [ABSTRACT FROM AUTHOR]

Adolescence represents a fundamental stage for interactions between excessive food intake and drug consumption. The association between obesity and drug use is unclear, but inhibitory control has been proposed as a common mechanism. The current study aimed to examine differences in inhibitory control measures in adolescents with overweight and/or substance use. Eighty-five adolescents 15–16 years of age were grouped according to a factorial design as cannabis users (n = 44) versus abstainers (n = 41), and alcohol users (n = 50) versus abstainers (n = 35). Participants were also classified depending on their BMI range as normal weight (n = 47) or overweight (n = 38). To measure inhibitory control, participants completed a Go-Nogo task while their brain activity was registered through electroencephalography, recording the event-related potentials during the task. No behavioral differences were found, but overweight teens exhibited lower P3 amplitudes (for both Go and Nogo conditions) compared with normal-BMI teens, indicating general difficulties in recruiting cognitive resources. Also, alcohol users showed higher Nogo-P3 amplitudes compared with alcohol abstainers, suggesting increased need of inhibitory control effort to achieve a good behavioral performance. Results indicate distinct altered inhibitory control functions in overweight adolescents and alcohol users. These findings suggest that different specific mechanisms of modulation of inhibitory control brain processes are involved in excessive food versus drug consumption, against the notion of food-drug competition. Understanding of associations between excessive food intake and substance use in adolescence will require identification of both common and specific risk factors. [ABSTRACT FROM AUTHOR]

Current environmental crises call for an integrated knowledge of landscapes and their ecosystems in a broader sense. This article presents a pedagogical framework for cross-disciplinary landscape research at postgraduate level. The framework is grounded in the use of geospatial epistemic discomfort as a creative force to develop and enhance inquiry skills able to cross and merge disciplinary boundaries. Developed within the Erasmus+ KA2 project “CROSSLAND”, the pedagogical framework is based on the scaffolding of epistemic discomfort through four key didactic elements: 1) cross-disciplinary group work and open-ended assignment, 2) in-field inquiry as pre-training on space-time, 3) replacement of traditional lectures by student-led seminars, 4) GIS labs centred on the exploration of cross-disciplinary portfolios of geospatial approaches and methods given as worked-out examples. Main results from the evaluation of the framework implementation in a Summer School show how learning cross-disciplinarity happened thanks to a scaffolding that allowed, first and foremost, the socialisation of different conceptualisations of space. While students felt at ease with geospatial epistemic discomfort, we can conclude that spatial cognitive processes are powerful in improving abilities beyond the spatial domain. [ABSTRACT FROM AUTHOR]