Clear cell chondrosarcoma in Von Hippel-Lindau disease

A diagnosis of clear cell chondrosarcoma of the ulna was made in a patient with Von Hippel-Lindau disease (VHL). After surgery, genetic analysis of the tumor tissue showed loss of heterozygosity at the VHL gene locus. Immunohistochemical analysis confirmed loss of expression of the VHL protein in the tumor cells. In addition, abundant Cyclin D1 expression in the tumor was observed. Chondrosarcoma has been described before in a VHL patient and VHL protein expression has been correlated to tumor grade in a series of sporadic chondrosarcomas. In this report, we show that clear cell chondrosarcoma may be a rare but canonical VHL manifestation through a cell-autonomous mechanism involving somatic loss-of-heterozygosity of the VHL tumor suppressor gene. We discuss the relevance of this observation with regard to the pathogenesis of clear cell chondrosarcoma in the context of VHL

Clues For Genetic Anticipation In Multiple Endocrine Neoplasia Type 1

CONTEXT: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disease caused by the loss of function of the MEN1 gene, a tumor-suppressor gene that encodes the protein menin. It is characterized by the occurrence of primary hyperparathyroidism (pHPT), duodenopancreatic neuroendocrine tumors (dpNET), pituitary tumors (PIT), adrenal adenomas, and bronchopulmonary (bp-NET), thymic, and gastric neuroendocrine tumors. More insight into factors influencing the age-related penetrance of MEN1 manifestations could provide clues for more personalized screening programs. OBJECTIVE: To investigate whether genetic anticipation plays a role in the largest known MEN1 families in the Netherlands. METHODS: All Dutch MEN1 families with ≥ 10 affected members in ≥ 2 successive generations were identified. Age at detection of the different MEN1-related manifestations were compared among generations using regression analyses adjusted for competing risks. To correct for the beneficial effect of being under surveillance, manifestations occurring during surveillance were also separately compared. RESULTS: A total of 152 MEN1 patients from 10 families were included. A significantly decreased age at detection of pHPT, dpNET, PIT, and bp-NET was found in successive generations (P < 0.0001). Adjusted analyses led to the same results. CONCLUSIONS: These results suggest the presence of genetic anticipation. However, due to a risk of residual bias, the results must be interpreted with caution. After independent validation in other cohorts and further translational research investigating the molecular mechanisms explaining this phenomenon in MEN1, the results might add to future, more personalized, screening protocols and earlier screening for future generations of MEN1 patients

The Study of Education Effect on Knowledge of, and Attitudes Toward Electroconvulsive Therapy Among Iranian Nurses and Patients’ Relatives in a Psychiatric Hospital, 2009-2010

AbstractElectroconvulsive therapy (ECT) is a cost effective method in the treatment of some psychiatric disorders. Although, service users such as health providers and nurses, also patients and their relatives may refuse ECT when indicated, due to the myths and little or lack of knowledge about the procedure. The knowledge of and attitudes toward ECT among nurses, may reflect on patients and influence treatment choice. For doing this procedure relatives informed consent is necessary, so their knowledge of and attitude toward ECT is important for getting informed consent and following treatment sessions. Objective: This research was conducted as a quasi-experimental study to measure knowledge of and attitudes toward ECT in 2 groups: relatives and nursing. Also, to study the effect of education on knowledge of and attitudes toward ECT in 2 groups. Methods: In this research the pre and post test self – administered questionnaires were completed by 46 relatives and 46 nurses before and after education about ECT. Results: Nurses in this research received a mean score of X=34.97 knowledge before education and X=39.78 after education (t=2.02, p<0.05), and a mean score of X=33.41 attitude before education and, X=42.82 after education (t=-14.25, p<0.001). Relatives received a mean score of X=23.41 knowledge before education and X=30.15 after education (t=-12.44, p<0.001), and a mean score of X=33.39 attitude before education and, X=41.13 after education (t=-9.10, p<0.001). The differences between the 2 means among two groups were found to be statistically significant. Conclusion: Education given to nurses and relatives about ECT increased their knowledge of, and improved their attitudes toward ECT. For this reason it is recommended that continuing education about ECT process should be planned and given at regular intervals

DeltaScan for the Assessment of Acute Encephalopathy and Delirium in ICU and non-ICU Patients, a Prospective Cross-Sectional Multicenter Validation Study

Objectives: To measure the diagnostic accuracy of DeltaScan: a portable real-time brain state monitor for identifying delirium, a manifestation of acute encephalopathy (AE) detectable by polymorphic delta activity (PDA) in single-channel electroencephalograms (EEGs). Design: Prospective cross-sectional study. Setting: Six Intensive Care Units (ICU's) and 17 non-ICU departments, including a psychiatric department across 10 Dutch hospitals. Participants: 494 patients, median age 75 (IQR:64-87), 53% male, 46% in ICUs, 29% delirious. Measurements: DeltaScan recorded 4-minute EEGs, using an algorithm to select the first 96 seconds of artifact-free data for PDA detection. This algorithm was trained and calibrated on two independent datasets. Methods: Initial validation of the algorithm for AE involved comparing its output with an expert EEG panel's visual inspection. The primary objective was to assess DeltaScan's accuracy in identifying delirium against a delirium expert panel's consensus. Results: DeltaScan had a 99% success rate, rejecting 6 of the 494 EEG's due to artifacts. Performance showed and an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.86 (95% CI: 0.83-0.90) for AE (sensitivity: 0.75, 95%CI=0.68-0.81, specificity: 0.87 95%CI=0.83-0.91. The AUC was 0.71 for delirium (95%CI=0.66-0.75, sensitivity: 0.61 95%CI=0.52-0.69, specificity: 72, 95%CI=0.67-0.77). Our validation aim was an NPV for delirium above 0.80 which proved to be 0.82 (95%CI: 0.77-0.86). Among 84 non-delirious psychiatric patients, DeltaScan differentiated delirium from other disorders with a 94% (95%CI: 87-98%) specificity. Conclusions: DeltaScan can diagnose AE at bedside and shows a clear relationship with clinical delirium. Further research is required to explore its role in predicting delirium-related outcomes.</p

Diagnostic Utility of Menin Immunohistochemistry in Patients With Multiple Endocrine Neoplasia Type 1 Syndrome

A clinical diagnosis of multiple endocrine neoplasia type 1 (MEN1) syndrome is usually confirmed with genetic testing in the germline. It is expected that menin protein expression is lost in MEN1-related tumors. Therefore, we investigated the potential of menin immunohistochemistry in parathyroid adenomas as an additional tool in the recognition and genetic diagnosis of MEN1 syndrome. Local pathology archives were searched for parathyroid tumors from patients with MEN1 syndrome and without MEN1, including sporadic, patients with multiple endocrine neoplasia type 2A and hyperparathyroidism-jaw parathyroid tumors. Menin immunohistochemistry was performed and its use to identify MEN1-related tumors was assessed. Twenty-nine parathyroid tumors from 16 patients with MEN1 and 61 patients with parathyroid tumors from 32 non-MEN1 were evaluated. Immunohistochemical nuclear menin loss in one or more tumors was found in 100% of patients with MEN1 and 9% of patients with non-MEN1. In patients with multiple tumors, menin loss in at least one tumor was seen in 100% of 8 patients with MEN1 and 21% of patients with 14 non-MEN1. Using a cutoff of at least 2 tumors showing menin loss per patient, the positive and negative predictive values for the diagnosis MEN1 were both 100%. The practical and additional value of menin immunohistochemistry in clinical genetic MEN1 diagnosis is further illustrated by menin immunohistochemistry in 2 cases with a germline variant of unknown significance in the MEN1 gene. Menin immunohistochemistry is useful in the recognition of MEN1 syndrome as well as in the clinical genetic analysis of patients with inconclusive MEN1 germline testing

Experimental and numerical investigation into the drag performance of dimpled surfaces in a turbulent boundary layer

Although several previous studies have reported a potential drag-reducing effect of dimpled surfaces in turbulent boundary layers, there is a lack of replicability across experiments performed by different research groups. To contribute to the dialogue, we scrutinize one of the most studied dimple geometries reported in the literature, which has a dimple diameter of 20 mm and a depth of 0.5 mm. There is no general consensus in literature on the drag-reduction performance of this particular dimple geometry, with some studies suggesting a drag reduction, while others report a drag increase. The present combined experimental and numerical study comprises two sets of wind tunnel experiments and a well-resolved large-eddy simulation. The wind tunnel experiments and the large-eddy simulation both depict a total drag increase of around 1%–2% compared to the flat reference case. This finding agrees with a recent study by Spalart et al. (2019). Furthermore, the present wind tunnel experiments have shed light on a plausible reason behind the discrepancy between the study by Spalart et al. (2019) and earlier results from van Nesselrooij et al. (2016). Lastly, the large-eddy simulation results reveal that the pressure drag is the main contributor to the increase in the total drag of the dimpled surface. We believe that these results will contribute to a new consensus on the drag performance of this dimple geometry.</p

Flow visualization over drag reducing dimpled surfaces in turbulent boundary layers using Particle Image Velocimetry

Although various experimental studies have confirmed a potential drag reduction of dimpled surfaces in turbulent boundary layers, the working mechanism behind the effect remains largely unresolved. The goal of this experimental study is to reveal the flow structures that could explain this drag reduction. To this end, flow visualizations over drag reducing dimpled surfaces are performed, using planar and stereoscopic Particle Image Velocimetry (PIV). The PIV measurements show that there is no significant vortex generation in the present dimples, but that instead a converger-diffuser type of flow occurs. It can be therefore concluded that it is not the generation of vortices which causes the drag reduction, in contrast to what has been proposed in literature. Based on the present measurements, a new drag reducing mechanism is proposed: the interaction between dimples causes alternating spanwise excitations of the near-wall flow which interacts with the turbulent coherent structures and leads to a reduction of the turbulent drag.AerodynamicsFlight Performance and Propulsio

Development of an experimental apparatus for flat plate drag measurements and considerations for such measurements

Accurately measuring small changes in aerodynamic drag over a flat surface stands at the core of the development of technologies capable of reducing turbulent friction drag. A wind tunnel drag measurement system was developed which improves significantly on the state of the art. Experimental tests demonstrated that an uncertainty of less than 0.5% of C D at a 95% confidence level was typically achieved, already at drag values below 1 N. This was replicated in two different wind tunnels. A match with literature on riblet performance within 1% of C D was obtained. A crucial aspect of the design is the implementation of a correction for the pressure forces on the streamwise-facing surfaces of the test plate assembly. The flexible architecture of the system in the present realisation makes it suitable for most wind tunnels having a test section width of 400 mm or larger, which allows for accelerated development of turbulent drag reduction concepts from moderate-size low-cost facilities towards flow conditions relevant to the intended industrial application.AerodynamicsAerodynamics, Wind Energy & Propulsio

An experimental investigation into the flow mechanics of dimpled surfaces in turbulent boundary layers

Although various experimental studies have confirmed the potential drag reducing effect of dimpled surfaces in a turbulent boundary layer, the working mechanism remains largely unresolved. An experimental investigation has been performed with the objective to strengthen the understanding of this aerodynamic surface and its interaction with the turbulent boundary layer. Direct force measurements were combined with Particle Image Velocimetry (PIV) and Particle Image Surface Flow Visualization (PISFV). The direct force measurements reveal that the drag reduction is highly sensitive to flow conditions: a finding with significant implications for further research as well as for potential applications. Furthermore, the PIV and PISFV measurements reveal a spanwise oscillation of the flow near the surface due to the interaction of individual dimple flow topologies, which are of the converger-diffuser type. The measurement of this oscillation provides evidence for a novel drag reduction theory: the interaction between dimples causes alternating spanwise excitations of the near-wall flow which interacts with the turbulent coherent structures which leads to a reduction of the turbulent drag.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.AerodynamicsFlight Performance and Propulsio