Recommendations for gonadotoxicity surveillance in male childhood, adolescent, and young adult cancer survivors : a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium

Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. The aim of the recommendations is to enhance evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, highlighting the need for further targeted research.Peer reviewe

Catching the Right Wave: Evaluating Wave Energy Resources and Potential Compatibility with Existing Marine and Coastal Uses

Many hope that ocean waves will be a source for clean, safe, reliable and affordable energy, yet wave energy conversion facilities may affect marine ecosystems through a variety of mechanisms, including competition with other human uses. We developed a decision-support tool to assist siting wave energy facilities, which allows the user to balance the need for profitability of the facilities with the need to minimize conflicts with other ocean uses. Our wave energy model quantifies harvestable wave energy and evaluates the net present value (NPV) of a wave energy facility based on a capital investment analysis. The model has a flexible framework and can be easily applied to wave energy projects at local, regional, and global scales. We applied the model and compatibility analysis on the west coast of Vancouver Island, British Columbia, Canada to provide information for ongoing marine spatial planning, including potential wave energy projects. In particular, we conducted a spatial overlap analysis with a variety of existing uses and ecological characteristics, and a quantitative compatibility analysis with commercial fisheries data. We found that wave power and harvestable wave energy gradually increase offshore as wave conditions intensify. However, areas with high economic potential for wave energy facilities were closer to cable landing points because of the cost of bringing energy ashore and thus in nearshore areas that support a number of different human uses. We show that the maximum combined economic benefit from wave energy and other uses is likely to be realized if wave energy facilities are sited in areas that maximize wave energy NPV and minimize conflict with existing ocean uses. Our tools will help decision-makers explore alternative locations for wave energy facilities by mapping expected wave energy NPV and helping to identify sites that provide maximal returns yet avoid spatial competition with existing ocean uses

The Use of Agent-Based Modeling and Data Farming for Planning System of Systems Tests in Joint Environments

Military Operations Research Society Symposium (76th) Held in New London, Connecticut on June 10-12, 200

Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

SIMPLE SUMMARY: Age-related macular degeneration (AMD) is an eye disease that results in permanent loss of vision due to degeneration in the central portion of the retina called the macula. Patients with severe visual loss have reduced quality of life and the risk of death is 2.4 times higher than the general population. Currently, there is no treatment to stop or cure dry AMD. Aging-associated chronic oxidative stress and inflammation are known to be involved in AMD pathology. To investigate the molecular mechanism behind the cause and to develop novel therapy, we have created and validated an animal model mimicking clinical features of dry AMD. Here, we show previously unknown thrombin-mediated complement component C5a activation in the degenerative retina without upregulation of C3. Our model might provide insight into AMD progression and help to develop novel therapies. ABSTRACT: Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD). Previously, we reported the presence of dry AMD-like signs, such as elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the retinal pigment epithelial (RPE) cells of nuclear factor erythroid 2-related factor 2, and a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (NFE2L2/PGC1α) double knockout (dKO) mouse model. Here, we investigated the dynamics of inflammatory markers in one-year-old NFE2L2/PGC1α dKO mice. Immunohistochemical analysis revealed an increase in levels of Toll-like receptors 3 and 9, while those of NOD-like receptor 3 were decreased in NFE2L2/PGC1α dKO retinal specimens as compared to wild type animals. Further analysis showed a trend towards an increase in complement component C5a independent of component C3, observed to be tightly regulated by complement factor H. Interestingly, we found that thrombin, a serine protease enzyme, was involved in enhancing the terminal pathway producing C5a, independent of C3. We also detected an increase in primary acute phase C-reactive protein and receptor for advanced glycation end products in NFE2L2/PGC1α dKO retina. Our main data show C5 and thrombin upregulation together with decreased C3 levels in this dry AMD-like model. In general, the retina strives to mount an orchestrated inflammatory response while attempting to maintain tissue homeostasis and resolve inflammation

Correction: Benchmarking of survival outcomes following haematopoietic stem cell transplantation: A review of existing processes and the introduction of an international system from the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)

An amendment to this paper has been published and can be accessed via a link at the top of the pape

Kinase pathway dependence in primary human leukemias determined by rapid inhibitor screening

Kinases are dysregulated in most cancers, but the frequency of specific kinase mutations is low, indicating a complex etiology in kinase dysregulation. Here, we report a strategy to rapidly identify functionally important kinase targets, irrespective of the etiology of kinase pathway dysregulation, ultimately enabling a correlation of patient genetic profiles to clinically effective kinase inhibitors. Our methodology assessed the sensitivity of primary leukemia patient samples to a panel of 66 small-molecule kinase inhibitors over 3 days. Screening of 151 leukemia patient samples revealed a wide diversity of drug sensitivities, with 70% of the clinical specim