Population-Based Precision Cancer Screening: A Symposium on Evidence, Epidemiology, and Next Steps

Precision medicine, an emerging approach for disease treatment that takes into account individual variability in genes, environment, and lifestyle, is under consideration for preventive interventions, including cancer screening. On September 29, 2015, the National Cancer Institute sponsored a symposium entitled “Precision Cancer Screening in the General Population: Evidence, Epidemiology, and Next Steps”. The goal was two-fold: to share current information on the evidence, practices, and challenges surrounding precision screening for breast, cervical, colorectal, lung, and prostate cancers, and to allow for in-depth discussion among experts in relevant fields regarding how epidemiology and other population sciences can be used to generate evidence to inform precision screening strategies. Attendees concluded that the strength of evidence for efficacy and effectiveness of precision strategies varies by cancer site, that no one research strategy or methodology would be able or appropriate to address the many knowledge gaps in precision screening, and that issues surrounding implementation must be researched as well. Additional discussion needs to occur to identify the high priority research areas in precision cancer screening for pertinent organs and to gather the necessary evidence to determine whether further implementation of precision cancer screening strategies in the general population would be feasible and beneficial

Isolation and fine mapping of Rps6: An intermediate host resistance gene in barley to wheat stripe rust

A plant may be considered a nonhost of a pathogen if all known genotypes of a plant species are resistant to all known isolates of a pathogen species. However, if a small number of genotypes are susceptible to some known isolates of a pathogen species this plant maybe considered an intermediate host. Barley (Hordeum vulgare) is an intermediate host for Puccinia striiformis f. sp. tritici (Pst), the causal agent of wheat stripe rust. We wanted to understand the genetic architecture underlying resistance to Pst and to determine whether any overlap exists with resistance to the host pathogen, Puccinia striiformis f. sp. hordei (Psh). We mapped Pst resistance to chromosome 7H and show that host and intermediate host resistance is genetically uncoupled. Therefore, we designate this resistance locus Rps6. We used phenotypic and genotypic selection on F2:3 families to isolate Rps6 and fine mapped the locus to a 0.1 cM region. Anchoring of the Rps6 locus to the barley physical map placed the region on two adjacent fingerprinted contigs. Efforts are now underway to sequence the minimal tiling path and to delimit the physical region harbouring Rps6. This will facilitate additional marker development and permit identification of candidate genes in the region

Quantitative assessment of pain-related thermal dysfunction through clinical digital infrared thermal imaging

BACKGROUND: The skin temperature distribution of a healthy human body exhibits a contralateral symmetry. Some nociceptive and most neuropathic pain pathologies are associated with an alteration of the thermal distribution of the human body. Since the dissipation of heat through the skin occurs for the most part in the form of infrared radiation, infrared thermography is the method of choice to study the physiology of thermoregulation and the thermal dysfunction associated with pain. Assessing thermograms is a complex and subjective task that can be greatly facilitated by computerised techniques. METHODS: This paper presents techniques for automated computerised assessment of thermal images of pain, in order to facilitate the physician's decision making. First, the thermal images are pre-processed to reduce the noise introduced during the initial acquisition and to extract the irrelevant background. Then, potential regions of interest are identified using fixed dermatomal subdivisions of the body, isothermal analysis and segmentation techniques. Finally, we assess the degree of asymmetry between contralateral regions of interest using statistical computations and distance measures between comparable regions. RESULTS: The wavelet domain-based Poisson noise removal techniques compared favourably against Wiener and other wavelet-based denoising methods, when qualitative criteria were used. It was shown to improve slightly the subsequent analysis. The automated background removal technique based on thresholding and morphological operations was successful for both noisy and denoised images with a correct removal rate of 85% of the images in the database. The automation of the regions of interest (ROIs) delimitation process was achieved successfully for images with a good contralateral symmetry. Isothermal division complemented well the fixed ROIs division based on dermatomes, giving a more accurate map of potentially abnormal regions. The measure of distance between histograms of comparable ROIs allowed us to increase the sensitivity and specificity rate for the classification of 24 images of pain patients when compared to common statistical comparisons. CONCLUSIONS: We developed a complete set of automated techniques for the computerised assessment of thermal images to assess pain-related thermal dysfunction

Changes in Body Composition Over 8 Years in a Randomized Trial of a Lifestyle Intervention: The Look AHEAD Study

Objective To determine the effects of an intensive lifestyle intervention versus a comparison group on body composition in obese or overweight persons with type 2 diabetes at baseline and at 1, 4, and 8 years. Methods Body composition was measured by dual‐energy X‐ray absorptiometry in a subset of 1019 Look AHEAD study volunteers randomized to intervention or comparison groups. The intervention was designed to achieve and maintain ≥7% weight loss through increased physical activity and reduced caloric intake. The comparison group received social support and diabetes education. Results At 1 year, the intervention group lost fat (5.6 ± 0.2 kg) and lean mass (2.3 ± 0.1 kg) but regained fat (∼100%) and lost lean mass between years 1 and 8. Between baseline and year 8, weight loss was greater in intervention versus comparison groups (4.0 ± 0.4 vs. 2.3 ± 0.4 kg); comparison group weight loss was mostly lean mass (2.1 ± 0.17 kg). Fat mass in the intervention group was lower than that of the comparison group at all post‐baseline time points. Conclusions Reduced fat mass may place the intervention group at a lower risk of obesity‐linked sequelae, a hypothesis that can be tested by future studies of this cohort

Oral Bisphosphonates and Risk of Atrial Fibrillation and Flutter in Women: A Self-Controlled Case-Series Safety Analysis

Background: A recent trial unexpectedly reported that atrial fibrillation, when defined as serious, occurred more often in participants randomized to an annual infusion of the relatively new parenteral bisphosphonate, zoledronic acid, than among those given placebo, but had limited power. Two subsequent population-based case-control studies of patients receiving a more established oral bisphosphonate, alendronic acid, reported conflicting results, possibly due to uncontrolled confounding factors.Methodology/Principal Findings: We used the United Kingdom General Practice Research Database to assess the risk of atrial fibrillation and flutter in women exposed to the oral bisphosphonates, alendronic acid and risedronate sodium. The self-controlled case-series method was used to minimise the potential for confounding. The age-adjusted incidence rate ratio for atrial fibrillation or flutter in individuals during their exposure to these oral bisphosphonates (n = 2195) was 1.07 (95% CI 0.94 - 1.21). The age-adjusted incidence rate ratio for alendronic acid (n = 1489) and risedronate sodium (n = 649) exposed individuals were 1.09 (95% CI 0.93 - 1.26) and 0.99 (95% CI 0.78 - 1.26) respectively. In post-hoc analyses, an increased risk of incident atrial fibrillation or flutter was detected for patients during their first few months of alendronic acid therapy.Conclusions/Significance: We found no robust evidence of an overall long-term increased risk of atrial fibrillation or flutter associated with continued exposure to the oral bisphosphonates, alendronic acid and risedronate sodium. A possible signal for an increase in risk during the first few months of therapy with alendronic acid needs to be re-assessed in additional studies

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

First data from DM-Ice17

We report the first analysis of background data from DM-Ice17, a direct-detection dark matter experiment consisting of 17 kg of NaI(Tl) target material. It was codeployed with IceCube 2457 m deep in the South Pole glacial ice in December 2010 and is the first such detector operating in the Southern Hemisphere. The background rate in the 6.5–8.0 keVee region is measured to be 7.9 � 0.4 counts=day=keV=kg. This is consistent with the expected background from the detector assemblies with negligible contributions from the surrounding ice. The successful deployment and operation of DM-Ice17 establishes the South Pole ice as a viable location for future underground, low-background experiments in the Southern Hemisphere. The detector assembly and deployment are described here, as well as the analysis of the DM-Ice17 backgrounds based on data from the first two years of operation after commissioning, July 2011–June 2013

Synesthesia and Migraine: Case Report

<p>Abstract</p> <p>Background</p> <p>Synesthesia is, as visual migraine aura, a common and fascinating perceptual phenomenon. Here we present a unique case with synesthesias exclusively during visual migraine auras.</p> <p>Case presentation</p> <p>A 40-year-old woman with a cyclic mood disorder had suffered from migraine with visual aura for several years. On several occasions she had experienced "mixing of senses" during the aura phase. Staring at strong bright light she could experience intense taste of lemon with flow from the salivary glands.</p> <p>Conclusion</p> <p>Acquired synesthesia, exclusively coincident with migraine aura, gives support to the idea of an anomalous cortical processing underlying the phenomenon.</p