Practice patterns and outcomes of equivocal bone scans for patients with castration-resistant prostate cancer: Results from SEARCH.

ObjectiveTo review follow-up imaging after equivocal bone scans in men with castration resistant prostate cancer (CRPC) and examine the characteristics of equivocal bone scans that are associated with positive follow-up imaging.MethodsWe identified 639 men from five Veterans Affairs Hospitals with a technetium-99m bone scan after CRPC diagnosis, of whom 99 (15%) had equivocal scans. Men with equivocal scans were segregated into "high-risk" and "low-risk" subcategories based upon wording in the bone scan report. All follow-up imaging (bone scans, computed tomography [CT], magnetic resonance imaging [MRI], and X-rays) in the 3 months after the equivocal scan were reviewed. Variables were compared between patients with a positive vs. negative follow-up imaging after an equivocal bone scan.ResultsOf 99 men with an equivocal bone scan, 43 (43%) received at least one follow-up imaging test, including 32/82 (39%) with low-risk scans and 11/17 (65%) with high-risk scans (p = 0.052). Of follow-up tests, 67% were negative, 14% were equivocal, and 19% were positive. Among those who underwent follow-up imaging, 3/32 (9%) low-risk men had metastases vs. 5/11 (45%) high-risk men (p = 0.015).ConclusionWhile 19% of all men who received follow-up imaging had positive follow-up imaging, only 9% of those with a low-risk equivocal bone scan had metastases versus 45% of those with high-risk. These preliminary findings, if confirmed in larger studies, suggest follow-up imaging tests for low-risk equivocal scans can be delayed while high-risk equivocal scans should receive follow-up imaging

7700-Year Persistence of an Isolated, Free-Living Coral Assemblage in the Galapagos Islands: A Model for Coral Refugia?

In an eastern-Pacific coral assemblage at Devil’s Crown, Galápagos Islands, Ecuador, two coral species, Psammocora stellata and Cycloseris (Diaseris) distorta, form dense populations of unattached colonies on sand and rubble substrata. In the Galápagos, living C. (D.) distorta is found only at this single site, whereas populations of P. stellata are found throughout the Archipelago. Six cores dating to ~ 7700 yBP showed P. stellata to be dominant throughout the history of this isolated community, but C. (D.) distorta increased in abundance from ~ 2200 yBP and reached peak abundance between 1471 yBP and the present. The relative frequency of the two coral species may be linked to millennial-scale climatic variability, and this site may represent a refuge for C. (D.) distorta from unfavorable climatic fluctuations on millennial timescales. Our results demonstrate that some corals can persist in isolated populations for millennia

Number of Unfavorable Intermediate‐Risk Factors Predicts Pathologic Upstaging and Prostate Cancer‐Specific Mortality Following Radical Prostatectomy: Results From the SEARCH Database

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135480/1/pros23255.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135480/2/pros23255_am.pd

Modified risk stratification grouping using standard clinical and biopsy information for patients undergoing radical prostatectomy: Results from SEARCH

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139104/1/pros23436_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139104/2/pros23436.pd

Ecological Invasion, Roughened Fronts, and a Competitor's Extreme Advance: Integrating Stochastic Spatial-Growth Models

Both community ecology and conservation biology seek further understanding of factors governing the advance of an invasive species. We model biological invasion as an individual-based, stochastic process on a two-dimensional landscape. An ecologically superior invader and a resident species compete for space preemptively. Our general model includes the basic contact process and a variant of the Eden model as special cases. We employ the concept of a "roughened" front to quantify effects of discreteness and stochasticity on invasion; we emphasize the probability distribution of the front-runner's relative position. That is, we analyze the location of the most advanced invader as the extreme deviation about the front's mean position. We find that a class of models with different assumptions about neighborhood interactions exhibit universal characteristics. That is, key features of the invasion dynamics span a class of models, independently of locally detailed demographic rules. Our results integrate theories of invasive spatial growth and generate novel hypotheses linking habitat or landscape size (length of the invading front) to invasion velocity, and to the relative position of the most advanced invader.Comment: The original publication is available at www.springerlink.com/content/8528v8563r7u2742

Mapping genetic vulnerabilities reveals BTK as a novel therapeutic target in oesophageal cancer

Objective Oesophageal cancer is the seventh most common cause of cancer-related death worldwide. Disease relapse is frequent and treatment options are limited. Design To identify new biomarker-defined therapeutic approaches for patients with oesophageal cancer, we integrated the genomic profiles of 17 oesophageal tumour-derived cell lines with drug sensitivity data from small molecule inhibitor profiling, identifying drug sensitivity effects associated with cancer driver gene alterations. We also interrogated recently described RNA interference screen data for these tumour cell lines to identify candidate genetic dependencies or vulnerabilities that could be exploited as therapeutic targets. Results By integrating the genomic features of oesophageal tumour cell lines with siRNA and drug screening data, we identified a series of candidate targets in oesophageal cancer, including a sensitivity to inhibition of the kinase BTK in MYC amplified oesophageal tumour cell lines. We found that this genetic dependency could be elicited with the clinical BTK/ERBB2 kinase inhibitor, ibrutinib. In both MYC and ERBB2 amplified tumour cells, ibrutinib downregulated ERK-mediated signal transduction, cMYC Ser-62 phosphorylation and levels of MYC protein, and elicited G(1) cell cycle arrest and apoptosis, suggesting that this drug could be used to treat biomarker-selected groups of patients with oesophageal cancer. Conclusions BTK represents a novel candidate therapeutic target in oesophageal cancer that can be targeted with ibrutinib. On the basis of this work, a proof-of-concept phase II clinical trial evaluating the efficacy of ibrutinib in patients with MYC and/or ERBB2 amplified advanced oesophageal cancer is currently underway (NCT02884453). Trial registration number NCT02884453; Pre-result

Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women

Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values < 5 × 10–8 as genome-wide significant, and p-values < 1 × 10–5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants. None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values < 1 × 105. The strongest evidence was found for rs4674019 (p-value = 2.27 × 10–7), which showed genome-wide significant interaction (p-value = 3.8 × 10–8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen–progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association

Environmentally sustainable food consumption : a review and research agenda from a goal-directed perspective

The challenge of convincing people to change their eating habits toward more environmentally sustainable food consumption (ESFC) patterns is becoming increasingly pressing. Food preferences, choices and eating habits are notoriously hard to change as they are a central aspect of people's lifestyles and their socio-cultural environment. Many people already hold positive attitudes toward sustainable food, but the notable gap between favorable attitudes and actual purchase and consumption of more sustainable food products remains to be bridged. The current work aims to (1) present a comprehensive theoretical framework for future research on ESFC, and (2) highlight behavioral solutions for environmental challenges in the food domain from an interdisciplinary perspective. First, starting from the premise that food consumption is deliberately or unintentionally directed at attaining goals, a goal-directed framework for understanding and influencing ESFC is built. To engage in goal-directed behavior, people typically go through a series of sequential steps. The proposed theoretical framework makes explicit the sequential steps or hurdles that need to be taken for consumers to engage in ESFC. Consumers need to positively value the environment, discern a discrepancy between the desired versus the actual state of the environment, opt for action to reduce the experienced discrepancy, intend to engage in behavior that is expected to bring them closer to the desired end state, and act in accordance with their intention. Second, a critical review of the literature on mechanisms that underlie and explain ESFC (or the lack thereof) in high-income countries is presented and integrated into the goal-directed framework. This contribution thus combines a top-down conceptualization with a bottom-up literature review; it identifies and discusses factors that might hold people back from ESFC and interventions that might promote ESFC; and it reveals knowledge gaps as well as insights on how to encourage both short- and long-term ESFC by confronting extant literature with the theoretical framework. Altogether, the analysis yields a set of 33 future research questions in the interdisciplinary food domain that deserve to be addressed with the aim of fostering ESFC in the short and long term