Differences in strategic abilities but not associative processes explain memory development

Children’s learning capabilities change while growing up. One framework that describes the cognitive and neural development of children’s growing learning abilities is the two-component model. It distinguishes processes that integrate separate features into a coherent memory representation (associative component) and executive abilities, such as elaboration, evaluation and monitoring, that support memory processing (strategic component). In an fMRI study using an object-location association paradigm, we investigated how the two components influence memory performance across development. We tested children (10-12 yrs., n=31), late adolescents (18 yrs., n=29) and adults (25+ yrs., n=30) of either sex. For studying the associative component, we also probed how the utilisation of prior knowledge (schemas) facilitates memory across age groups. Children had overall lower retrieval performance, while adolescents and adults did not differ from each other. All groups benefitted from schemas, but this effect did not differ between groups. Performance differences between groups were associated with deactivation of the dorsal medial prefrontal cortex (dmPFC), which in turn was linked to executive functioning. These patterns were stronger in adolescents and adults and seemed absent in children. This pattern of results suggests the children’s executive system, the strategic component, is not as mature and thus cannot facilitate memory performance in the same way as in adolescents/adults. In contrast, we did not find age-related differences in the associative component; with activity in the angular gyrus predicting memory performance systematically across groups. Overall our results suggest that differences of executive rather than associative abilities explain memory differences between children, adolescents and adults

Potential for Integrating Entry Guidance into the Multi-Disciplinary Entry Vehicle Optimization Environment

The state-of-the-art in vehicle design decouples flight feasible trajectory generation from the optimization process of an entry spacecraft shape. The disadvantage to this decoupled process is seen when a particular aeroshell does not meet in-flight requirements when integrated into Guidance, Navigation, and Control simulations. It is postulated that the integration of a guidance algorithm into the design process will provide a real-time, rapid trajectory generation technique to enhance the robustness of vehicle design solutions. The potential benefit of this integration is a reduction in design cycles (possible cost savings) and increased accuracy in the aerothermal environment (possible mass savings). This work examines two aspects: 1) the performance of a reference tracking guidance algorithm for five different geometries with the same reference trajectory and 2) the potential of mass savings from improved aerothermal predictions. An Apollo Derived Guidance (ADG) algorithm is used in this study. The baseline geometry and five test case geometries were flown using the same baseline trajectory. The guided trajectory results are compared to separate trajectories determined in a vehicle optimization study conducted for NASA's Mars Entry, Descent, and Landing System Analysis. This study revealed several aspects regarding the potential gains and required developments for integrating a guidance algorithm into the vehicle optimization environment. First, the generation of flight feasible trajectories is only as good as the robustness of the guidance algorithm. The set of dispersed geometries modelled aerodynamic dispersions that ranged from +/-1% to +/-17% and a single extreme case was modelled where the aerodynamics were approximately 80% less than the baseline geometry. The ADG, as expected, was able to guide the vehicle into the aeroshell separation box at the target location for dispersions up to 17%, but failed for the 80% dispersion cases. Finally, the results revealed that including flight feasible trajectories for a set of dispersed geometries has the potential to save mass up to 430 kg

Progressive neurological deficits in multiple myeloma: meningeal myelomatosis without MRI abnormalities

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Comparison of oxygen-15 PET and transcranial Doppler CO2-reactivity measurements in identifying haemodynamic compromise in patients with symptomatic occlusion of the internal carotid artery

BACKGROUND: Transcranial Doppler (TCD) CO(2)-reactivity and oxygen-15 positron emission tomography (PET) have both been used to measure the cerebral haemodynamic state in patients who may have a compromised blood flow. Our purpose was to investigate whether PET and TCD identify the same patients with an impaired flow state of the brain in patients with internal carotid artery (ICA) occlusion. METHODS: Patients with recent transient ischaemic attack or minor ischaemic stroke associated with ICA occlusion underwent TCD with measurement of CO(2)-reactivity and oxygen-15 PET within a median time interval of 6 days. RESULTS: We included 24 patients (mean age 64 ± 10 years). Seventeen (71%) patients had impaired CO(2)-reactivity (≤20%), of whom six had absent reactivity (0%) or steal (<0%) in the hemisphere ipsilateral to the ICA occlusion. PET of the perfusion state of the hemisphere ipsilateral to the ICA occlusion demonstrated stage 1 haemodynamic compromise (decreased cerebral blood flow (CBF) or increased cerebral blood volume (CBV) without increased oxygen extraction fraction (OEF)) in 13 patients and stage 2 (increased OEF) in 2 patients. In 12 patients (50%), there was agreement between TCD and PET, indicating haemodynamic compromise in 10 and a normal flow state of the brain in 2 patients. There was no significant correlation between CO(2)-reactivity and CBF ipsilateral/contralateral hemispheric ratio (r = 0.168, p value = 0.432), OEF ratio (r = −0.242, p value = 0.255), or CBV/CBF ratio (r = −0.368, p value = 0.077). CONCLUSIONS: In patients with symptomatic ICA occlusion, identification of an impaired flow state of the brain by PET and TCD CO(2)-reactivity shows concordance in only half of the patients

Standard psychological consultations and follow up for women at increased risk of hereditary breast cancer considering prophylactic mastectomy

__Background:__ Women at increased (genetic) risk of breast cancer have to weigh the personal pros and cons of prophylactic mastectomy (PM) as an option to reduce their cancer risk. So far, no routine referral to a psychologist has been investigated for women considering PM. Aim of this study was to asses: 1) the acceptance of the offer of a standard psychological consultation as part of pre-surgical decision-making in high-risk women, 2) reasons for PM and reasons for postponing it, 3) the need for additional psychological interventions, and factors associated, and 4) the frequency of psychiatric/psychological treatment history. __Methods:__ During a 30 months period, women at high risk considering PM were offered a psychological consultation. The content of these, and follow-up, consultations were analyzed. __Results:__ Most women (70 out of 73) accepted the psychological consultation, and 81% proceeded with PM. Main reasons for undergoing PM were to reduce anxiety about cancer, and to reduce the cancer risk. Uncertainty about surgery and the need for further information were the reasons given most frequently for postponing PM. Additional psychological support was given to 31% before and 14% after PM. The uptake of additional support was significantly higher in women with a BRCA1/2 mutation. A history of psychiatric/psychological treatment was present in 36%, mainly consisting of depression and grief after death of a mother. __Conclusion:__ The uptake-rate of the standard psychological consultation indicates a high level of acceptability of this service for women deciding about PM. Since anxiety is one of the main reasons for considering PM, and depression and grief were present in a third, a standard consultation with a psychologist for high-risk women considering PM may be indicated. This may help them arrive at an informed decision, to detect and manage psychological distress, and to plan psychological support services

The urokinase system of plasminogen activation and prognosis in 2780 breast cancer patients

The antigen levels of components of the urokinase-type plasminogen activator (uPA) system of plasminogen activation are correlated with prognosis in several types of cancers, including breast cancer. In the present study involving 2780 patients with primary invasive breast cancer, we have evaluated the prognostic importance of the four major components of the uPA system [uPA, the receptor uPAR (CD87), and the inhibitors PAI-1 and PAI-2]. The antigen levels were determined by ELISA in cytosols prepared from primary breast tumors. The levels of the four factors significantly correlated with each other; the Spearman rank correlation coefficients (r(s)) ranged from 0.32 (between PAI-2 and PAI-1 or uPAR) to 0.59 (between uPA and PAI-1). The median duration of follow-up of patients still alive was 88 months. In the multivariate analyses for relapse-free survival (RFS) and overall survival (OS), we defined a basic model including age, menopausal status, tumor size and grade, lymph node status, adjuvant therapy, and steroid hormone receptor status. uPA, uPAR, PAI-1, and PAI-2 were considered as categorical variables, each with two cut points that were established by isotonic regression analysis. Compared with tumors with low levels, those with intermediate and high levels showed a relative hazard rate (RHR) and 95% confidence interval (95% CI) of 1.22 (1.02-1.45) and 1.69 (1.39-2.05) for uPA, and 1.32 (1.14-1.54) and 2.17 (1.74-2.70) for PAI-1, respectively, in multivariate analysis for RFS in all patients. Compared with tumors with high PAI-2 levels, those with intermediate and low levels showed a poor RFS with a RHR (95% CI) of 1.30 (1.14-1.48) and 1.76 (1.38-2.24), respectively. Similar results were obtained in the multivariate analysis for OS in all patients. Furthermore, uPA and PAI-1 were independent predictive factors of a poor RFS and OS in node-negative and node-positive patients. PAI-2 also added to the multivariate models for RFS in node-negative and node-positive patients, and in the analysis for OS in node-negative patients. uPAR did not further contribute to any of the multivariate models. A prognostic score was calculated based on the estimates from the final multivariate model for RFS. Using this score, the difference between the highest and lowest 10% risk groups was 66% in the analysis for RFS at 10 years and 61% in the analysis for OS. Moreover, separate prognostic scores were calculated for node-negative and node-positive patients. In the 10% highest risk groups, the proportion of disease-free patients was only 27 +/- 6% and 9 +/- 3% at 10 years for node-negative and node-positive patients, respectively. These proportions were 86 +/- 4% and 61 +/- 6% for the corresponding 10% lowest risk groups of relapse. We conclude that several components of the uPA system are potential predictors of RFS and OS in patients with primary invasive breast cancer. Knowledge of these factors could be helpful to assess the individual risk of patients, to select various types of adjuvant treatment and to identify patients who may benefit from targeted therapies that are currently being developed