Computed tomographic appearance of urachal adenocarcinomas: review of 25 cases

Twenty-five cases of surgically proven urachal carcinomas were retrospectively reviewed. The radiological archives at the Armed Forces Institute of Pathology were searched for cases of surgically proven urachal carcinomas that had a computed tomographic (CT) scan as a part of their radiologic evaluation. CT images from all cases were evaluated to determine tumor morphology, presence and localization of calcification, extent of bladder invasion and metastases. Tumor size at presentation averaged 6cm. Twenty-one of 25 (84%) were mixed cystic solid lesions and 4/25 (16%) were completely solid. Calcifications were present in 18/25 (72%), with 11 peripherally located, 3 central only and 4 both. Bladder wall invasion was present in 23/25 (92%), but was seen as an intraluminal mass in only 13/25 (52%). The bulk of the mass was extravesicular in 22/25 (88%). Metastases were present in 12/25 (48%). Our series supports observations from other smaller series that a midline, calcified, supravesicular mass is highly suspicious, if not pathognomonic, for urachal carcinom

A NEW RUSSIAN WASTE MANAGEMENT INSTALLATION

ABSTRACT The Polyarninsky Shipyard (sometimes called Navy Yard No. 10 or the Shkval Shipyard) has been designated as the recipient for Solid Radioactive Waste (SRW) management facilities under the Arctic Military Environmental Cooperation (AMEC) Program. The existing SRW storage site at this shipyard is filled to capacity, which is forcing the shipyard to reduce its submarine dismantlement activities. The Polyarninsky Shipyard Waste Management Installation is planned as a combination of several AMEC projects. It will have several elements, including a set of hydraulic metal cutting tools, containers for transport and storage, the Mobile Pretreatment Facility (MPF) for Solid Radioactive Waste, the PICASSO system for radiation monitoring, and a Waste Storage Facility. Hydraulically operated cutting tools can cut many metal items via shearing so that dusts or particulates are not generated. The AMEC Program procured a cutting tool system, consisting of a motor and hydraulic pumping unit, a 38-mm conduit-cutting tool, a 100-mm pipe-cutting tool, and a spreading tool all mounted on a wheeled cart. The vendor modified the tool system for extremely cold conditions and Russian electrical standards, then delivered the tool system to the Polyarninsky shipyard

Adolescent suicidal ideation: a comparison of incarcerated and school-based samples

and risk-taking behavior. RESULTS: Suicidal ideations during the past year were reported by 21.5% of detained males, compared to 6.7% in the general population. In females, 58.1% of detained individuals reported suicidal thoughts during the past year, compared to 14.4% of the general population. In girls and boys from the general population, both internalizing and externalizing problems were higher in suicidal ideators than in non-suicidal youth, while in the detention group mainly internalizing problems were higher in suicidal ideators. When comparing detention suicidal ideators with those from the general population, male suicidal ideators scored higher on delinquency, while detained female suicidal ideators also scored higher on posttraumatic stress, but lower on prosocial beliefs. LIMITATIONS: Information used in this study was solely based on self-report measures only and limited to Flemish adolescents. CONCLUSION: Since suicidal ideation is a frequent problem in detained youth, adequate recognition and treatment seems clinically relevant. While both internalizing and externalizing psychopathology may be an indicator of suicidal ideation in the general population, internalizing problems may be the main clinical predictor in detained yout

Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression

Early-onset major depressive disorder (MDD) is a serious and prevalent psychiatric illness in adolescents and young adults. Current treatments are not optimally effective. Biological markers of early-onset MDD could increase diagnostic specificity, but no such biomarker exists. Our innovative approach to biomarker discovery for early-onset MDD combined results from genome-wide transcriptomic profiles in the blood of two animal models of depression, representing the genetic and the environmental, stress-related, etiology of MDD. We carried out unbiased analyses of this combined set of 26 candidate blood transcriptomic markers in a sample of 15–19-year-old subjects with MDD (N=14) and subjects with no disorder (ND, N=14). A panel of 11 blood markers differentiated participants with early-onset MDD from the ND group. Additionally, a separate but partially overlapping panel of 18 transcripts distinguished subjects with MDD with or without comorbid anxiety. Four transcripts, discovered from the chronic stress animal model, correlated with maltreatment scores in youths. These pilot data suggest that our approach can lead to clinically valid diagnostic panels of blood transcripts for early-onset MDD, which could reduce diagnostic heterogeneity in this population and has the potential to advance individualized treatment strategies

Ferroptosis in health and disease.

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark of ferroptosis is uncontrolled and overwhelming peroxidation of polyunsaturated fatty acids contained in membrane phospholipids, which eventually leads to rupture of the plasma membrane. Ferroptosis is unique in that it is essentially a spontaneous, uncatalyzed chemical process based on perturbed iron and redox homeostasis contributing to the cell death process, but that it is nonetheless modulated by many metabolic nodes that impinge on the cells susceptibility to ferroptosis. Among the various nodes affecting ferroptosis sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets for the treatment of numerous currently incurable diseases. Herein, the current members of a Germany-wide research consortium focusing on ferroptosis research, as well as key external experts in ferroptosis who have made seminal contributions to this rapidly growing and exciting field of research, have gathered to provide a comprehensive, state-of-the-art review on ferroptosis. Specific topics include: basic mechanisms, in vivo relevance, specialized methodologies, chemical and pharmacological tools, and the potential contribution of ferroptosis to disease etiopathology and progression. We hope that this article will not only provide established scientists and newcomers to the field with an overview of the multiple facets of ferroptosis, but also encourage additional efforts to characterize further molecular pathways modulating ferroptosis, with the ultimate goal to develop novel pharmacotherapies to tackle the various diseases associated with - or caused by - ferroptosis

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Computed tomographic appearance of urachal adenocarcinomas: review of 25 cases

Twenty-five cases of surgically proven urachal carcinomas were retrospectively reviewed. The radiological archives at the Armed Forces Institute of Pathology were searched for cases of surgically proven urachal carcinomas that had a computed tomographic (CT) scan as a part of their radiologic evaluation. CT images from all cases were evaluated to determine tumor morphology, presence and localization of calcification, extent of bladder invasion and metastases. Tumor size at presentation averaged 6 cm. Twenty-one of 25 (84%) were mixed cystic solid lesions and 4/25 (16%) were completely solid. Calcifications were present in 18/25 (72%), with 11 peripherally located, 3 central only and 4 both. Bladder wall invasion was present in 23/25 (92%), but was seen as an intraluminal mass in only 13/25 (52%). The bulk of the mass was extravesicular in 22/25 (88%). Metastases were present in 12/25 (48%). Our series supports observations from other smaller series that a midline, calcified, supravesicular mass is highly suspicious, if not pathognomonic, for urachal carcinoma

SHARP: An Architecture for Secure Resource Peering

This paper presents Sharp, a framework for secure distributed resource management in an Internet-scale computing infrastructure. The cornerstone of Sharp is a construct to represent cryptographically protected resource claims--- promises or rights to control resources for designated time intervals---together with secure mechanisms to subdivide and delegate claims across a network of resource managers. These mechanisms enable flexible resource peering: sites may trade their resources with peering partners or contribute them to a federation according to local policies. A separation of claims into tickets and leases allows coordinated resource management across the system while preserving site autonomy and local control over resources. Sharp also introduces mechanisms for controlled, accountable oversubscription of resource claims as a fundamental tool for dependable, efficient resource management. We present experimental results from a Sharp prototype for PlanetLab, and illustrate its use with a decentralized barter economy for global PlanetLab resources. The results demonstrate the power and practicality of the architecture, and the e#ectiveness of oversubscription for protecting resource availability in the presence of failures

SHARP: An Architecture for Secure Resource Peering

This paper presents Sharp, a framework for secure distributed resource management in an Internet-scale computing infrastructure. The cornerstone of Sharp is a construct to represent cryptographically protected resource claims--- promises or rights to control resources for designated time intervals---together with secure mechanisms to subdivide and delegate claims across a network of resource managers. These mechanisms enable flexible resource peering: sites may trade their resources with peering partners or contribute them to a federation according to local policies. A separation of claims into tickets and leases allows coordinated resource management across the system while preserving site autonomy and local control over resources. Sharp also introduces mechanisms for controlled, accountable oversubscription of resource claims as a fundamental tool for dependable, efficient resource management. We present experimental results from a Sharp prototype for PlanetLab, and illustrate its use with a decentralized barter economy for global PlanetLab resources. The results demonstrate the power and practicality of the architecture, and the e#ectiveness of oversubscription for protecting resource availability in the presence of failures

A New Russian Waste Management Installation

The Polyarninsky Shipyard (sometimes called Navy Yard No. 10 or the Shkval Shipyard) has been designated as the recipient for Solid Radioactive Waste (SRW) management facilities under the Arctic Military Environmental Cooperation (AMEC) Program. The existing SRW storage site at this shipyard is filled to capacity, which is forcing the shipyard to reduce its submarine dismantlement activities. The Polyarninsky Shipyard Waste Management Installation is planned as a combination of several AMEC projects. It will have several elements, including a set of hydraulic metal cutting tools, containers for transport and storage, the Mobile Pretreatment Facility (MPF) for Solid Radioactive Waste, the PICASSO system for radiation monitoring, and a Waste Storage Facility. Hydraulically operated cutting tools can cut many metal items via shearing so that dusts or particulates are not generated. The AMEC Program procured a cutting tool system, consisting of a motor and hydraulic pumping unit, a 38-mm conduit-cutting tool, a 100- mm pipe-cutting tool, and a spreading tool all mounted on a wheeled cart. The vendor modified the tool system for extremely cold conditions and Russian electrical standards, then delivered the tool system to the Polyarninsky shipyard. A new container for transportation and storage of SRW and been designed and fabricated. The first 400 of these containers have been delivered to the Northern Fleet of the Russian Navy for use at the Polyarninsky Shipyard Waste Management Installation. These containers are cylindrical in shape and can hold seven standard 200-liter drums. They are the first containers ever certified in Russia for the offsite transport of military SRW. These containers can be transported by truck, rail, barge, or ship. The MPF will be the focal point of the Polyarninsky Shipyard Waste Management Installation and a key element in meeting the nuclear submarine dismantlement and waste processing needs of the Russian Federation. It will receive raw waste in various conditions, treat it, package it in standard 200-liter drums, and load these drums into the new transportation and storage containers. The MPF has been designed, fabricated, and assembled at the fabrication site, the Zvezdochka Shipyard. It passed a demonstration test in September 2002. The entire MPF has been disassembled into its transportable modules, which are currently stored at the Zvezdochka Shipyard. In the spring of 2003, the MPF modules will be transported to the Polyarninsky Shipyard, where they will be reassembled and the facility will be cold tested. The site preparation work is already under way for the installation at the Polyarninsky Shipyard. An automatic radiation monitoring system, PICASSO-AMEC, has been developed and will be installed at Polyarninsky Shipyard as one of the elements of the installation. The radiation monitoring system is based on the software package PICASSO-3, developed by the Institute for Energy Technology in Norway. Treated waste f rom the MPF will require safe and secure storage. The Waste Storage Facility will be connected to the MPF, and it will be large enough to store all 400 of the new containers. Incoming waste boxes in overpacks will enter one part of the storage facility on trucks. Then they will be inspected and transferred into the MPF through the receiving area. Drums of processed waste in containers will be removed from the MPF and stacked in another part of the storage facility via a bridge crane. This facility will be designed and construction will begin during the winter of 2002/2003