Implicit artificial grammar learning: effects of complexity and usefulness of the structure

The artificial grammar learning experiments reported in this thesis pertain to the question of whether implicit learning is ineluctable and unselective or selective and accidental. The results of Chapter 2 showed that implicit learning was negatively affected by complexity, suggesting that the process does not automatically acquire any structure present in the environment. Chapter 3 provided direct evidence that implicit learning is selective. When two aspects of the structure could facilitate the participants__ task in the induction phase, only the most useful aspect was selected and learned implicitly. Chapter 4 showed that explicit learning could be more successful than implicit learning when participants were specifically instructed to look for rules of letter-order. In Chapter 5, implicit learning was demonstrated when the structure was useful to the participants__ induction task, but not when it was useless. This finding was replicated in 10 to 11-year-old children in Chapter 6. Chapter 7 showed that the negative effect of complexity could not be counterbalanced by adding a semantic reference field. These findings indicate that implicit learning is a selective process that does not occur ineluctably. Rather than being accidental, however, implicit learning seems to occur whenever the structure is useful to one__s current task.UBL - phd migration 201

Cardiac regeneration by cell therapy

__Abstract__ During the last fifty years, we have seen enormous progress in the prevention and treatment of acute myocardial infarction (MI), one of the most prominent diseases in the Western world. As a result, the incidence and prevalence of acute MI has gradually declined, and mortality and morbidity have been reduced. However, due to the increased lifespan post MI, the incidence of congestive heart failure (CHF) is rapidly increasing. Heart failure directly results from the death or dysfunction of cardiomyocytes and an inability of the heart to effectively regenerate this damaged region. These pathophysiologic events lead to a process of cardiac remodeling that involves fibrosis, changes in wall stress, scar expansion and - if the injury is large enough - heart failure. Although pharmacological treatment has significantly improved s

Effects of adolescent socio-cognitive development on the cortisol response to social evaluation

Pathways through Adolescenc

Orgasm induced torsades de pointes in a patient with a novel mutation with long-QT syndrome type 2: A case report

Introduction Congenital long-QT (LQT) syndrome can lead to torsades de pointes (TdP), which can deteriorate into ventricular fibrillation resulting in sudden death. Thus far, more than 16 genes have been linked to the LQT syndrome. We report an orgasm-induced TdP in a patient with LQT syndrome type 2 with a novel mutation in the KCNH2 gene. Case presentation A 24-year-old Caucasian woman with a medical history of depression, no medication use and no family history of sudden death, presented with recurrent syncope during sexual activity. Immediately after achieving orgasm during sexual intercourse she lost consciousness. Baseline 12-lead electrocardiogram revealed a wide based T-wave with a prolonged QTc-interval of 507 ms. During hospital admission runs of TdP were recorded. The patient was treated with magnesium, an oral beta-blocker, and an implantable cardioverter-defibrillator. Genetic testing (Sanger sequencing) revealed a novel mutation (c.361del) in the KCNH2 gene (chromosome 7q36). Discussion To date, orgasm-induced TdP as a first symptom in a patient with LQT2 has not been published previously. In studies with continuous blood sampling in healthy volunteers, large peaks in plasma epinephrine levels during orgasm were observed with fast post-orgasmic decline. However, in a large cohort study (402 patients of which 129 with LQT2), no patients experienced cardiac events during sexual activity, suggesting that these are indeed very rare. Nevertheless, the high levels of sympathetic adrenal hormones during orgasm may explain the timing of the TdP in our patient. The patient has remained free of syncope at 6 months of follow-up

External validation of six COVID-19 prognostic models for predicting mortality risk in older populations in a hospital, primary care, and nursing home setting

Objectives: To systematically evaluate the performance of COVID-19 prognostic models and scores for mortality risk in older populations across three health-care settings: hospitals, primary care, and nursing homes.Study Design and Setting: This retrospective external validation study included 14,092 older individuals of >=70 years of age with a clinical or polymerase chain reaction-confirmed COVID-19 diagnosis from March 2020 to December 2020. The six validation cohorts include three hospital-based (CliniCo, COVID-OLD, COVID-PREDICT), two primary care-based (Julius General Practitioners Network/Academisch network huisartsgeneeskunde/Network of Academic general Practitioners, PHARMO), and one nursing home cohort (YSIS) in the Netherlands. Based on a living systematic review of COVID-19 prediction models using Prediction model Risk Of Bias ASsessment Tool for quality and risk of bias assessment and considering predictor availability in validation cohorts, we selected six prognostic models predicting mortality risk in adults with COVID-19 infection (GAL-COVID-19 mortality, 4C Mortality Score, National Early Warning Score 2-extended model, Xie model, Wang clinical model, and CURB65 score). All six prognostic models were validated in the hospital cohorts and the GAL-COVID-19 mortality model was validated in all three healthcare settings. The primary outcome was in-hospital mortality for hospitals and 28-day mortality for primary care and nursing home settings. Model performance was evaluated in each validation cohort separately in terms of discrimination, calibration, and decision curves. An intercept update was performed in models indicating miscalibration followed by predictive performance re-evaluation. Main Outcome Measure: In-hospital mortality for hospitals and 28-day mortality for primary care and nursing home setting. Results: All six prognostic models performed poorly and showed miscalibration in the older population cohorts. In the hospital settings, model performance ranged from calibration-in-the-large 1.45 to 7.46, calibration slopes 0.24e0.81, and C-statistic 0.55e0.71 with 4C Mortality Score performing as the most discriminative and well-calibrated model. Performance across health-care settings was similar for the GAL-COVID-19 model, with a calibration-in-the-large in the range of 2.35 to 0.15 indicating overestimation, calibration slopes of 0.24e0.81 indicating signs of overfitting, and C-statistic of 0.55e0.71. Conclusion: Our results show that most prognostic models for predicting mortality risk performed poorly in the older population with COVID-19, in each health-care setting: hospital, primary care, and nursing home settings. Insights into factors influencing predictive model performance in the older population are needed for pandemic preparedness and reliable prognostication of health-related outcomes in this demographicGeriatrics in primary carePublic Health and primary carePrevention, Population and Disease management (PrePoD

The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype

Because of genetic heterogeneity, the identification of breast cancer-susceptibility genes has proven to be exceedingly difficult. Here, we define a new subset of families with breast cancer characterized by the presence of colorectal cancer cases. The 1100delC variant of the cell cycle checkpoint kinase CHEK2 gene was present in 18% of 55 families with hereditary breast and colorectal cancer (HBCC) as compared with 4% of 380 families with non-HBCC (P<.001), thus providing genetic evidence for the HBCC phenotype. The CHEK2 1100delC mutation was, however, not the major predisposing factor for the HBCC phenotype but appeared to act in synergy with another, as-yet-unknown susceptibility gene(s). The unequivocal definition of the HBCC phenotype opens new avenues to search for thi