Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

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Plus disease in retinopathy of prematurity: pilot study of computer-based and expert diagnosis.

PURPOSE: To measure accuracy of plus disease diagnosis by recognized experts in retinopathy of prematurity (ROP), and to conduct a pilot study examining performance of a computer-based image analysis system, Retinal Image multiScale Analysis (RISA). METHODS: Twenty-two ROP experts independently interpreted a set of 34 wide-angle retinal images for presence of plus disease. A reference standard diagnosis based on expert consensus was defined for each image. Images were analyzed by the computer-based system using individual and linear combinations of system parameters for arterioles and venules: integrated curvature (IC), diameter, and tortuosity index (TI). Sensitivity, specificity, and receiver operating characteristic areas under the curve (AUC) for plus disease diagnosis compared with the reference standard were determined for each expert, as well as for the computer-based system. RESULTS: Expert sensitivity ranged from 0.308 to 1.000, specificity ranged from 0.571 to 1.000, and AUC ranged from 0.784 to 1.000. Among individual computer system parameters, venular IC had highest AUC (0.853). Among all computer system parameters, the linear combination of arteriolar IC, arteriolar TI, venular IC, venular diameter, and venular TI had highest AUC (0.967), which was greater than that of 18 (81.8%) of 22 experts. CONCLUSIONS: Accuracy of ROP experts for plus disease diagnosis is imperfect. A computer-based image analysis system has potential to diagnose plus disease with high accuracy. Further research involving RISA system parameter cut-off values from this study are required to fully validate performance of this computer-based system compared with that of human experts.     

Preparatory activity in motor cortex reflects learning of local visuomotor skills

In humans, learning to produce correct visually guided movements to adapt to new sensorimotor conditions requires the formation of an internal model that represents the new transformation between visual input and the required motor command. When the new environment requires adaptation to directional errors, learning generalizes poorly to untrained locations and directions, indicating that such learning is local. Here we replicated these behavioral findings in rhesus monkeys using a visuomotor rotation task and simultaneously recorded neuronal activity. Specific changes in activity were observed only in a subpopulation of cells in the motor cortex with directional properties corresponding to the locally learned rotation. These changes adhered to the dynamics of behavior during learning and persisted between learning and relearning of the same rotation. These findings suggest a neural mechanism for the locality of newly acquired sensorimotor tasks and provide electrophysiological evidence for their retention in working memory.     

The great mimicker: Phenotypic overlap between constitutional mismatch repair deficiency and Tuberous Sclerosis complex

Constitutional mismatch repair deficiency is a rare cancer predisposition syndrome caused by biallelic mutations in one of the four mismatch repair genes. Patients are predisposed to various tumors including hematological malignancies, brain tumors and colorectal carcinomas. Phenotypic overlap with Neurofibromatosis-1 is well known, with most patients presenting with café-au-lait macules. Other common features include axillary and/or inguinal freckling and intracranial MRI foci of high T2W/FLAIR signal intensity similar to the typical FASI seen in Neurofibromatosis-1. In this cohort of eight patients with constitutional mismatch repair deficiency we describe overlapping phenotypical features with Tuberous Sclerosis complex. In addition to “ash-leaf like” hypomelanotic macules (five patients), we detected intracranial tuber-like lesions (three patients), renal cysts (three patients) and renal angiomyolipomas (two patients). All our patients also had Neurofibromatosis-1 like features, mainly café-au-lait macules. This study suggests that features of Tuberous sclerosis especially when overlapping with those of Neurofibromatosis 1 or malignancies atypical for these syndromes should raise the possibility of constitutional mismatch repair deficiency. Correct diagnosis is essential for appropriate genetic counseling and pre-emptive cancer surveillance.     

Prenatal diagnosis with repetitive in situ hybridization probes

We have used chromosome-specific repetitive sequences to detect the most common human aneuploidies prenatally. Together chromosome 21, 13, 18, X, and Y aneuploidy comprises 95% of the chromosome abnormalities that result in a high risk of abnormal phenotypes at birth. The X, Y, and 18 repetitive probes work reliably in multiple tissue types including directly examined and cultured amniocytes, chorionic villus cells, lymphocytes, and cultured fibroblasts. The probe that detects both chromosomes 13 and 21 routinely gives results in each cell type tested except directly studied amniocytes which can be interpreted in seven-ninths of the cases with protocol 1 and all tested samples with protocol 2. Our protocols diagnosed trisomy 21 in a 23-week fetus with low maternal serum AFP and a trisomy 18 in a direct chorionic villus sample 2 working days after the samples were obtained. Trisomy 21 also has been ruled out in a CVS karyotype first thought to be 47,XY,+21. These studies reflect the potential value of in situ hybridization to provide a more rapid, less expensive means to screen most at-risk fetal populations with less effort in first world cytogenetic laboratories, and to provide economical cytogenetic services in less developed countries. © 1992 Wiley-Liss, Inc.     

Left Main Myocardial Infarction in a Healthy Young Male—A Case Report

Acute left main coronary artery occlusion is a catastrophic and mostly fatal event. Patients may present with sudden death or cardiogenic shock. Intra-aortic balloon pump support and emergency revascularization is indicated to preserve the left ventricular function. We describe a case of left main thrombus in a health 24-year-old young male with no risk factors for coronary atherosclerosis.     

Development of a fragile X syndrome (FXS) knowledge scale: towards a modified multidimensional measure of informed choice for FXS population carrier screening

Background

Genetic carrier screening is increasingly possible for many conditions, but it is important to ensure decisions are informed. The multidimensional measure of informed choice (MMIC) is a quantitative instrument developed to evaluate informed choice in prenatal screening for Down syndrome, measuring knowledge, attitudes and uptake. To apply the MMIC in other screening settings, the knowledge scale must be modified.

Objective

To develop and validate a modified MMIC knowledge scale for use with women undergoing carrier screening for fragile X syndrome (FXS).

Setting and participants

Responses to MMIC items were collected through questionnaires as part of a FXS carrier screening pilot study in a preconception setting in Melbourne, Australia.

Design

Ten knowledge scale items were developed using a modified Delphi technique. Cronbach''s alpha and factor analysis were used to validate the new FXS knowledge scale. We summarized the knowledge, attitudes and informed choice status based on the modified MMIC.

Results

Two hundred and eighty‐five women were recruited, 241 eligible questionnaires were complete for analysis. The FXS knowledge scale items measured one salient construct and were internally consistent (alpha = 0.70). 71% (172/241) of participants were classified as having good knowledge, 70% (169/241) had positive attitudes and 27% (65/241) made an informed choice to accept or decline screening.

Discussion and conclusions

We present the development of a knowledge scale as part of a MMIC to evaluate informed choice in population carrier screening for FXS. This can be used as a template by other researchers to develop knowledge scales for other conditions for use in the MMIC.