Interruption of visually perceived forward motion in depth evokes a cortical activation shift from spatial to intentional motor regions

Forward locomotion generates a radially expanding flow of visual motion which supports goal-directed walking. In stationary mode, wide-field visual presentation of optic flow stimuli evokes the illusion of forward self-motion. These effects illustrate an intimate relation between visual and motor processing. In the present fMRI study, we applied optic flow to identify distinct interfaces between circuitries implicated in vision and movement. The dorsal premotor cortex (PMd) was expected to contribute to wide-field forward motion flow (FFw), reflecting a pathway for externally triggered motor control. Medial prefrontal activation was expected to follow interrupted optic flow urging internally generated action. Data of 15 healthy subjects were analyzed with Statistical Parametric Mapping and confirmed this hypothesis. Right PMd activation was seen in FFw, together with activations of posterior parietal cortex, ventral V5, and the right fusiform gyms. Conjunction analysis of the transition from wide to narrow forward flow and reversed wide-field flow revealed selective dorsal medial prefrontal activation. These findings point at equivalent visuomotor transformations in locomotion and goal-directed hand movement, in which parietal-premotor circuitry is crucially implicated. Possible implications of an activation shift from spatial to intentional motor regions for understanding freezing of gait in Parkinson's disease are discussed: impaired medial prefrontal function in Parkinson's disease may reflect an insufficient internal motor drive when visual support from optic flow is reduced at the entrance of a narrow corridor. (C) 2010 Elsevier B.V. All rights reserved

Stop sanitizing project management education: Embracing Desirable Difficulties to enhance practice-relevant online learning

By resisting the temptation to “sanitize” project management education, we show how embracing unpredictability and authenticity can enhance learning. In response to COVID-19 restrictions, we moved an interactive role-play online and explored the resultant learning through analysis of student performance and students’ individual reflections. Findings suggest that the online role-play boosted learning by exposing students to a challenging environment, which included tasks that stretched their capabilities and thus enhanced the level of “Desirable Difficulties”. Drawing on the concepts of Desirable Difficulties and “role-play-as-rehearsal”, we discuss the benefits of formative “testing” and propose a new concept: “role-play-as-testing”. Additionally, benefits to learning were attributed to the online setting, which reflects the increasing virtualization of practice. We hope to inspire other educators to embrace Desirable Difficulties and resist the temptation to sanitize project management education to create opportunities for future project leaders to test their learning in authentic settings

Susceptibility weighted imaging in intracranial hemorrhage:not all bleeds are black

To correctly recognize intracranial hemorrhage (ICH) and differentiate it from other lesions, knowledge of the imaging characteristics of an ICH on Susceptibility Weighted Imaging (SWI) is essential. It is a common misconception that blood is always black on SWI, and it is important to realize that hemorrhage has a variable appearance in different stages on SWI. Furthermore, the presence of a low signal on SWI does not equal the presence of blood products. In this review the appearance of ICH on SWI during all its stages and common other causes of a low signal on SWI are further discussed and illustrated.</p

Evaluation of an imaging-based in vitro screening platform for estrogenic activity with OECD reference chemicals

Estrogen receptor alpha (ERα) is often a primary target of endocrine disrupting chemicals (EDCs) and therefore several biochemical and cell-based assays for the detection of chemicals with estrogenic properties have been developed in the past. However, the current approaches are not suitable for the monitoring of pathway activation dynamics, and they are mostly based on expression constructs that lack physiological promoter regulation. We recently developed MCF7 fluorescent reporter cell lines of 3 different green fluorescent protein (GFP)-tagged ERα target genes: GREB1, PGR and TFF1. These reporters are under control of the full physiological promoter region and allow the monitoring of dynamic pro-proliferative pathway activation on a single cell level using a live-cell imaging set-up. In this study, we systematically characterized the response of these reporters to a full reference compound set of known estrogenic and non-estrogenic chemicals as defined by the Organization for Economic Co-Operation and Development (OECD). We linked activation of the pro-proliferative ERα pathway to a potential adverse outcome by additionally monitoring cell cycle progression and proliferation. The correct classification of the OECD reference compounds showed that our reporter platform has the same sensitivity and specificity as other validated artificial ERα pathway reporters, such as the ERα CALUX and VM7 Luc ER TA assay. By monitoring several key events (i.e. ER target activation, cell cycle progression and proliferation), and subsequently determining Point-of-Departure (POD) values, our reporter panel can be used in high-throughput testing for a physiologically more relevant, quantitative temporal endocrine modulation analysis to improve human carcinogen risk assessment.Toxicolog

Incidental findings during the diagnostic work-up in the head and neck cancer pathway:Effects on treatment delay and survival

Objectives: As a result of the increasing number of diagnostic scans, incidental findings (IFs) are more frequently encountered during oncological work-up in patients with head and neck squamous cell carcinomas (HNSCC). IFs are unintentional discoveries found on diagnostic imaging. Relevant IFs implicate clinical consequences, resulting in delay in oncologic treatment initiation, which is associated with unfavorable outcomes. This study is the first to investigate the incidence and nature of IFs over the years and establish the effect of relevant IFs on delay. Material and methods: This retrospective study compared two time periods (2010 & ndash;2011 and 2016 & ndash;2017), described associations between relevant IFs and delay in carepathway interval (days between first visit and treatment initiation) and assessed the effect of relevant IFs on overall two-year survival. Results: In total, 592 patients were included. At least one IF was found in 61.5% of the patients, most frequently on chest-CT. In 128 patients (21.6%) a relevant IF was identified, resulting for the majority in radiologist recommendations (e.g. additional scanning). Presence of a relevant IF was an independent significant factor associated with delay in treatment initiation. The risk of dying was higher for patients with a relevant IF, although not significant in the multivariable model (HR: 1.46, p = 0.079). Conclusion: In diagnostic work-up for HNSCC patients, relevant IFs are frequently encountered. As the frequency of additional imaging rises over the years, the number of IFs increased simultaneously. These relevant IFs yield clinical implications and this study described that relevant IFs result in significant delay in treatment initiation

Upper bounds for number of removed edges in the Erased Configuration Model

Models for generating simple graphs are important in the study of real-world complex networks. A well established example of such a model is the erased configuration model, where each node receives a number of half-edges that are connected to half-edges of other nodes at random, and then self-loops are removed and multiple edges are concatenated to make the graph simple. Although asymptotic results for many properties of this model, such as the limiting degree distribution, are known, the exact speed of convergence in terms of the graph sizes remains an open question. We provide a first answer by analyzing the size dependence of the average number of removed edges in the erased configuration model. By combining known upper bounds with a Tauberian Theorem we obtain upper bounds for the number of removed edges, in terms of the size of the graph. Remarkably, when the degree distribution follows a power-law, we observe three scaling regimes, depending on the power law exponent. Our results provide a strong theoretical basis for evaluating finite-size effects in networks

CT-measured skeletal muscle mass used to assess frailty in patients with head and neck cancer

BACKGROUND: Skeletal muscle depletion or sarcopenia is related to multiple adverse clinical outcome. However, frailty questionnaires are currently applied in the daily practice to identify patients who are potentially (un)suitable for treatment but are time consuming and straining for patients and the clinician. Screening for sarcopenia in patients with head and neck cancer (HNC) could be a promising fast biomarker for frailty. Our objective was to quantify sarcopenia with pre-treatment low skeletal muscle mass from routinely obtained neck computed tomography scans at level of third cervical vertebra in patients diagnosed with HNC and evaluate its association with frailty. METHODS: A total of 112 HNC patients with Stages III and IV disease were included from a prospective databiobank. The amount of skeletal muscle mass was retrospectively defined using the skeletal muscle index (SMI). Correlation analysis between SMI and continuous frailty data and the observer agreement were analysed with Pearson's r correlation coefficients. Sarcopenia was present when SMI felt below previously published non-gender specific thresholds (<43.2 cm2 /m2 ). Frailty was evaluated by Geriatrics 8 (G8), Groningen Frailty Indicator, Timed Up and Go test, and Malnutrition Universal Screening Tool. A univariate and multivariate logistic regression analysis was performed for all patients and men separately to obtain odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: The cohort included 82 men (73%) and 30 women (27%), with a total mean age of 63 (±9) years. The observer agreement for cross-sectional measurements was excellent for both intra-observer variability (r = 0.99, P < 0.001) and inter-observer variability (r = 0.98, P < 0.001). SMI correlated best with G8 frailty score (r = 0.38, P < 0.001) and did not differ per gender. Sarcopenia was present in 54 (48%) patients, whereof 25 (46%) men and 29 (54%) women. Prevalence of frailty was between 5% and 54% depending on the used screening tool. The multivariate regression analysis for all patients and men separately isolated the G8 questionnaire as the only independent variable associated with sarcopenia (OR 0.76, 95% CI 0.66-0.89, P < 0.001 and OR 0.76, 95% CI 0.66-0.88, P < 0.001, respectively). CONCLUSIONS: This is the first study that demonstrates that sarcopenia is independently associated with frailty based on the G8 questionnaire in HNC patients. These results suggest that in the future, screening for sarcopenia on routinely obtained neck computed tomography scans may replace time consuming frailty questionnaires and help to select the (un)suitable patients for therapy, which is highly clinically relevant

Scenariostudie materiaal-voorraad, vraag en secundair aanbod in gebouwen: Onderdeel van het werkprogramma Monitoring & Sturing Circulaire Economie

Industrial Ecolog

Radiologically Defined Sarcopenia as a Biomarker for Frailty and Malnutrition in Head and Neck Skin Cancer Patients

The aim of this study was to evaluate whether radiologically defined sarcopenia, or a low skeletal muscle index (SMI), could be used as a practical biomarker for frailty and postoperative complications (POC) in patients with head and neck skin cancer (HNSC). This was a retrospective study on prospectively collected data. The L3 SMI (cm2/m2) was calculated with use of baseline CT or MRI neck scans and low SMIs were defined using sex-specific cut-off values. A geriatric assessment with a broad range of validated tools was performed at baseline. POC was graded with the Clavien–Dindo Classification (with a grade of &gt; II as the cut-off). Univariate and multivariable regression analyses were performed with low SMIs and POC as the endpoints. The patients’ (n = 57) mean age was 77.0 ± 9 years, 68.4% were male, and 50.9% had stage III–IV cancer. Frailty was determined according to Geriatric 8 (G8) score (OR 7.68, 95% CI 1.19–49.66, p = 0.032) and the risk of malnutrition was determined according to the Malnutrition Universal Screening Tool (OR 9.55, 95% CI 1.19–76.94, p = 0.034), and these were independently related to low SMIs. Frailty based on G8 score (OR 5.42, 95% CI 1.25–23.49, p = 0.024) was the only variable related to POC. However, POC was more prevalent in patients with low SMIs (∆ 19%, OR 1.8, 95% CI 0.5–6.0, p = 0.356).To conclude, a low SMI is a practical biomarker for frailty and malnutrition in HNSC. Future research should be focused on interventions based on low SMI scores and assess the effect of the intervention on SMI, frailty, malnutrition, and POC.</p

Anacetrapib reduces progression of atherosclerosis, mainly by reducing non-HDL-cholesterol, improves lesion stability and adds to the beneficial effects of atorvastatin

The present study is the first intervention study in a well-established, translational mouse model for hyperlipidaemia and atherosclerosis showing that anacetrapib dose-dependently reduces atherosclerosis development and adds to the anti-atherogenic effects of atorvastatin. This effect is mainly ascribed to the reduction in non-HDL-C despite a remarkable increase in HDL-C and without affecting HDL functionality. In addition, anacetrapib improves lesion stabilit