The diffuse γ-ray background is dominated by star-forming galaxies.

The Fermi Gamma-ray Space Telescope has revealed a diffuse γ-ray background at energies from 0.1 gigaelectronvolt to 1 teraelectronvolt, which can be separated into emission from our Galaxy and an isotropic, extragalactic component1. Previous efforts to understand the latter have been hampered by the lack of physical models capable of predicting the γ-ray emission produced by the many candidate sources, primarily active galactic nuclei2-5 and star-forming galaxies6-10, leaving their contributions poorly constrained. Here we present a calculation of the contribution of star-forming galaxies to the γ-ray background that does not rely on empirical scalings and is instead based on a physical model for the γ-ray emission produced when cosmic rays accelerated in supernova remnants interact with the interstellar medium11. After validating the model against local observations, we apply it to the observed cosmological star-forming galaxy population and recover an excellent match to both the total intensity and the spectral slope of the γ-ray background, demonstrating that star-forming galaxies alone can explain the full diffuse, isotropic γ-ray background.

Epigenomic Deconvolution of Breast Tumors Reveals Metabolic Coupling between Constituent Cell Types.

Cancer progression depends on both cell-intrinsic processes and interactions between different cell types. However, large-scale assessment of cell type composition and molecular profiles of individual cell types within tumors remains challenging. To address this, we developed epigenomic deconvolution (EDec), an in silico method that infers cell type composition of complex tissues as well as DNA methylation and gene transcription profiles of constituent cell types. By applying EDec to The Cancer Genome Atlas (TCGA) breast tumors, we detect changes in immune cell infiltration related to patient prognosis, and a striking change in stromal fibroblast-to-adipocyte ratio across breast cancer subtypes. Furthermore, we show that a less adipose stroma tends to display lower levels of mitochondrial activity and to be associated with cancerous cells with higher levels of oxidative metabolism. These findings highlight the role of stromal composition in the metabolic coupling between distinct cell types within tumors.

Assessing the learning needs of oncology nurses.

The Nurse Oncology Education Program (NOEP) is a nonprofit organization of the Texas Nurses Foundation that develops and provides education for nurses in all fields of practice on cancer prevention, detection, treatment, and survivorship. To meet the most current educational needs of nurses, NOEP conducts a biannual needs assessment survey to better understand its audience and inform its course development. The 2013 NOEP needs assessment survey used a convenience sample of licensed nurses throughout the United States. Nurses completed the online survey, and results revealed several priority areas for educational programs, including management of cancer symptoms and treatment side effects, complementary and alternative or integrative medicine, and screening recommendations. Time was noted as the largest barrier to educating patients and families about primary prevention practices. Results from this survey can be compared to those from previous surveys, particularly the 2009 and 2011 surveys, to determine changes in the demographics of NOEP's constituency, as well as consistencies in educational gaps. The results from the 2013 NOEP needs assessment survey offer valuable information about the learning needs of nurses across the country. The data can be used by the nurse educators and faculty who are responsible for providing cancer-specific education to nurses.

Stress fractures: diagnosis, treatment, and prevention.

Stress fractures are common injuries in athletes and military recruits. These injuries occur more commonly in lower extremities than in upper extremities. Stress fractures should be considered in patients who present with tenderness or edema after a recent increase in activity or repeated activity with limited rest. The differential diagnosis varies based on location, but commonly includes tendinopathy, compartment syndrome, and nerve or artery entrapment syndrome. Medial tibial stress syndrome (shin splints) can be distinguished from tibial stress fractures by diffuse tenderness along the length of the posteromedial tibial shaft and a lack of edema. When stress fracture is suspected, plain radiography should be obtained initially and, if negative, may be repeated after two to three weeks for greater accuracy. If an urgent diagnosis is needed, triple-phase bone scintigraphy or magnetic resonance imaging should be considered. Both modalities have a similar sensitivity, but magnetic resonance imaging has greater specificity. Treatment of stress fractures consists of activity modification, including the use of nonweight-bearing crutches if needed for pain relief. Analgesics are appropriate to relieve pain, and pneumatic bracing can be used to facilitate healing. After the pain is resolved and the examination shows improvement, patients may gradually increase their level of activity. Surgical consultation may be appropriate for patients with stress fractures in high-risk locations, nonunion, or recurrent stress fractures. Prevention of stress fractures has been studied in military personnel, but more research is needed in other populations.

Alterations in DNA repair gene expression under hypoxia: elucidating the mechanisms of hypoxia-induced genetic instability.

Hypoxia is a common feature of solid tumors and is associated with genetic instability and tumor progression. It has been shown previously that alterations in the expression of DNA repair genes in response to hypoxic stress may account for a proportion of such genetic instability. Here, we demonstrate that the expression of RAD51, a critical mediator of homologous recombination (HR), is repressed by hypoxia in numerous cell lines derived from a wide range of tissues. Repression of this gene by hypoxia occurs in a cell cycle- and hypoxia-inducible factor (HIF)-independent manner, and decreased RAD51 expression was observed to persist during the post-hypoxic period. In addition, decreases in Rad51 expression were correlated with functional impairments in HR repair in hypoxic and post-hypoxic cells. Based on these data, we propose a novel mechanism of hypoxia-induced genetic instability via suppression of the HR pathway in cancer cells within the tumor microenvironment.

Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells.

There is an emerging concept that acquired genetic instability in cancer cells can arise from the dysregulation of critical DNA repair pathways due to cell stresses such as inflammation and hypoxia. Here we report that hypoxia specifically down-regulates the expression of RAD51, a key mediator of homologous recombination in mammalian cells. Decreased levels of Rad51 were observed in multiple cancer cell types during hypoxic exposure and were not associated with the cell cycle profile or with expression of hypoxia-inducible factor. Analyses of RAD51 gene promoter activity, as well as mRNA and protein stability, indicate that the hypoxia-mediated regulation of this gene occurs via transcriptional repression. Decreased expression of Rad51 was also observed to persist in posthypoxic cells for as long as 48 h following reoxygenation. Correspondingly, we found reduced levels of homologous recombination in both hypoxic and posthypoxic cells, suggesting that the hypoxia-associated reduction in Rad51 expression has functional consequences for DNA repair. In addition, hypoxia-mediated down-regulation of Rad51 was confirmed in vivo via immunofluorescent image analysis of experimental tumors in mice. Based on these findings, we propose a novel mechanism of genetic instability in the tumor microenvironment mediated by hypoxia-induced suppression of the homologous recombination pathway in cancer cells. The aberrant regulation of Rad51 expression may also create heterogeneity in the DNA damage response among cells within tumors, with implications for the response to cancer therapies.