The peritoneal tumour microenvironment of high-grade serous ovarian cancer

High-grade serous ovarian cancer (HGSC) disseminates early and extensively throughout the peritoneal space, causing multiple lesions that are a major clinical problem. The aim of this study was to investigate the cellular composition of peritoneal tumour deposits in patient biopsies and their evolution in mouse models using immunohistochemistry, intravital microscopy, confocal microscopy, and 3D modelling. Tumour deposits from the omentum of HGSC patients contained a prominent leukocyte infiltrate of CD3(+) T cells and CD68(+) macrophages, with occasional neutrophils. Alpha-smooth muscle actin(+) (α-SMA(+) ) pericytes and/or fibroblasts surrounded these well-vascularized tumour deposits. Using the murine bowel mesentery as an accessible mouse peritoneal tissue that could be easily imaged, and two different transplantable models, we found multiple microscopic tumour deposits after i.p. injection of malignant cells. Attachment to the peritoneal surface was rapid (6-48 h) with an extensive CD45(+) leukocyte infiltrate visible by 48 h. This infiltrate persisted until end point and in the syngeneic murine ID8 model, it primarily consisted of CD3(+) T lymphocytes and CD68(+) macrophages with α-SMA(+) cells also involved from the earliest stages. A majority of tumour deposits developed above existing mesenteric blood vessels, but in avascular spaces new blood vessels tracked towards the tumour deposits by 2-3 weeks in the IGROV-1 xenografts and 6 weeks in the ID8 syngeneic model; a vigorous convoluted blood supply was established by end point. Inhibition of tumour cell cytokine production by stable expression of shRNA to CXCR4 in IGROV-1 cells did not influence the attachment of cells to the mesentery but delayed neovascularization and reduced tumour deposit size. We conclude that the multiple peritoneal tumour deposits found in HGSC patients can be modelled in the mouse. The techniques described here may be useful for assessing treatments that target the disseminated stage of this disease

Highly enriched uranium (HEU) storage and disposition program plan

Recent changes in international relations and other changes in national priorities have profoundly affected the management of weapons-usable fissile materials within the United States (US). The nuclear weapon stockpile reductions agreed to by the US and Russia have reduced the national security requirements for these fissile materials. National policies outlined by the US President seek to prevent the accumulation of nuclear weapon stockpiles of plutonium (Pu) and HEU, and to ensure that these materials are subjected to the highest standards of safety, security and international accountability. The purpose of the Highly Enriched Uranium (HEU) Storage and Disposition Program Plan is to define and establish a planned approach for storage of all HEU and disposition of surplus HEU in support of the US Department of Energy (DOE) Fissile Material Disposition Program. Elements Of this Plan, which are specific to HEU storage and disposition, include program requirements, roles and responsibilities, program activities (action plans), milestone schedules, and deliverables

Scales for rating motor impairment in Parkinson's disease: studies of reliability and convergent validity.

Study 1 examined the reliability of the ratings assigned to the performance of five sign-and-symptom items drawn from tests of motor impairment in Parkinson's disease. Patients with Parkinson's disease of varying severity performed gait, rising from chair, and hand function items. Video recordings of these performances were rated by a large sample of experienced and inexperienced neurologists and by psychology undergraduates, using a four point scale. Inter-rater reliability was moderately high, being higher for gait than hand function items. Clinical experience proved to have no systematic effect on ratings or their reliability. The idiosyncrasy of particular performances was a major source of unreliable ratings. Study 2 examined the intercorrelation of several standard rating scales, comprised of sign-and-symptom items as well as activities of daily living. The correlation between scales was high, ranging from 0.70 to 0.83, despite considerable differences in item composition. Inter-item correlations showed that the internal cohesion of the tests was high, especially for the self-care scale. Regression analysis showed that the relationship between the scales could be efficiently captured by a small selection of test items, allowing the construction of a much briefer test

The Obsessive Beliefs Questionnaire (OBQ) : Examination in nonclinical samples and development of a short version

The study aimed to examine the factor structure of the Obsessive Beliefs Questionnaire (OBQ), the most widely used measure of dysfunctional beliefs in obsessive—compulsive disorder (OCD). Multiple exploratory methods (exploratory factor analysis, cluster analysis by variable, multidimensional scaling) were used to examine the questionnaire. Confirmatory factor analyses were also performed in two large nonclinical samples from Australia (N = 1,234) and Israel ( N = 617). Our analyses suggested a four-factor solution with 38 items, where threat and responsibility formed separate dimensions (the “OBQ-TRIP”). This version had superior fit statistics across the two divergent confirmatory samples, when compared with four alternative models suggested by previous authors. Of the OBQ dimensions, the threat scale correlated most strongly with OCD symptom measures, even when controlling for depression. A short, 20-item version of the scale is offered for further study. Implications and limitations are discussed