Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Gastric Metastasis from a Primary Renal Leiomyosarcoma

Primary leiomyosarcoma of the kidney is rare. Here we report a case of metastasis of this tumor to the stomach. A 73-year-old man visited our hospital suffering from general weakness and intermittent tarry stools. He had undergone right nephrectomy for renal leiomyosarcoma 2 years previously. There had been no local recurrence or distant metastasis in the 2-year follow-up period. Endoscopy revealed two submucosal tumors in the stomach. These tumors were diagnosed histologically as leiomyosarcoma and distal gastrectomy was performed. Subsequent histochemical staining confirmed the diagnosis of gastric metastasis from renal leiomyosarcoma. The patient died due to metastases to the liver and bone 9 months after the operation. To the best of our knowledge, this is the first report of gastric metastasis from primary renal leiomyosarcoma

Systematic investigation of gastrointestinal diseases in China (SILC): validation of survey methodology

Background: Symptom-based surveys suggest that the prevalence of gastrointestinal diseases is lower in China than in Western countries. The aim of this study was to validate a methodology for the epidemiological investigation of gastrointestinal symptoms and endoscopic findings in China. Methods: A randomized, stratified, multi-stage sampling methodology was used to select 18 000 adults aged 18-80 years from Shanghai, Beijing, Xi'an, Wuhan and Guangzhou. Participants from Shanghai were invited to provide blood samples and undergo upper gastrointestinal endoscopy. All participants completed Chinese versions of the Reflux Disease Questionnaire (RDQ) and the modified Rome II questionnaire; 20% were also invited to complete the 36-item Short Form Health Survey (SF-36) and Epworth Sleepiness Scale (ESS). The psychometric properties of the questionnaires were evaluated statistically. Results: The study was completed by 16 091 individuals (response rate: 89.4%), with 3219 (89.4% of those invited) completing the SF-36 and ESS. All 3153 participants in Shanghai provided blood samples and 1030 (32.7%) underwent endoscopy. Cronbach's alpha coefficients were 0.89, 0.89, 0.80 and 0.91, respectively, for the RDQ, modified Rome II questionnaire, ESS and SF-36, supporting internal consistency. Factor analysis supported construct validity of all questionnaire dimensions except SF-36 psychosocial dimensions. Conclusion: This population-based study has great potential to characterize the relationship between gastrointestinal symptoms and endoscopic findings in China.Xiaoyan Yan, Rui Wang, Yanfang Zhao, Xiuqiang Ma, Jiqian Fang, Hong Yan, Xiaoping Kang, Ping Yin, Yuantao Hao, Qiang Li, John Dent, Joseph Sung, Duowu Zou, Saga Johansson, Katarina Halling, Wenbin Liu and Jia H

Acute kidney injury biomarkers: renal angina and the need for a renal troponin I

Acute kidney injury (AKI) in hospitalized patients is independently associated with increased morbidity and mortality in pediatric and adult populations. Continued reliance on serum creatinine and urine output to diagnose AKI has resulted in our inability to provide successful therapeutic and supportive interventions to prevent and mitigate AKI and its effects. Research efforts over the last decade have focused on the discovery and validation of novel urinary biomarkers to detect AKI prior to a change in kidney function and to aid in the differential diagnosis of AKI. The aim of this article is to review the AKI biomarker literature with a focus on the context in which they should serve to add to the clinical context facing physicians caring for patients with, or at-risk for, AKI. The optimal and appropriate utilization of AKI biomarkers will only be realized by understanding their characteristics and placing reasonable expectations on their performance in the clinical arena

A life course approach to injury prevention: a "lens and telescope" conceptual model

<p>Abstract</p> <p>Background</p> <p>Although life course epidemiology is increasingly employed to conceptualize the determinants of health, the implications of this approach for strategies to reduce the burden of injuries have received little recognition to date.</p> <p>Methods</p> <p>The authors reviewed core injury concepts and the principles of the life course approach. Based on this understanding, a conceptual model was developed, to provide a holistic view of the mechanisms that underlie the accumulation of injury risk and their consequences over the life course.</p> <p>Results</p> <p>A "lens and telescope" model is proposed that particularly draws on (a) the extended temporal dimension inherent in the life course approach, with links between exposures and outcomes that span many years, or even generations, and (b) an ecological perspective, according to which the contexts in which individuals live are critical, as are changes in those contexts over time.</p> <p>Conclusions</p> <p>By explicitly examining longer-term, intergenerational and ecological perspectives, life course concepts can inform and strengthen traditional approaches to injury prevention and control that have a strong focus on proximal factors. The model proposed also serves as a tool to identify intervention strategies that have co-benefits for other areas of health.</p

Do differences in understory light contribute to species distributions along a tropical rainfall gradient?

In tropical forests, regional differences in annual rainfall correlate with differences in plant species composition. Although water availability is clearly one factor determining species distribution, other environmental variables that covary with rainfall may contribute to distributions. One such variable is light availability in the understory, which decreases towards wetter forests due to differences in canopy density and phenology. We established common garden experiments in three sites along a rainfall gradient across the Isthmus of Panama in order to measure the differences in understory light availability, and to evaluate their influence on the performance of 24 shade-tolerant species with contrasting distributions. Within sites, the effect of understory light availability on species performance depended strongly on water availability. When water was not limiting, either naturally in the wetter site or through water supplementation in drier sites, seedling performance improved at higher light. In contrast, when water was limiting at the drier sites, seedling performance was reduced at higher light, presumably due to an increase in water stress that affected mostly wet-distribution species. Although wetter forest understories were on average darker, wet-distribution species were not more shade-tolerant than dry-distribution species. Instead, wet-distribution species had higher absolute growth rates and, when water was not limiting, were better able to take advantage of small increases in light than dry-distribution species. Our results suggest that in wet forests the ability to grow fast during temporary increases in light may be a key trait for successful recruitment. The slower growth rates of the dry-distribution species, possibly due to trade-offs associated with greater drought tolerance, may exclude these species from wetter forests

Growth Strategies of Tropical Tree Species: Disentangling Light and Size Effects

An understanding of the drivers of tree growth at the species level is required to predict likely changes of carbon stocks and biodiversity when environmental conditions change. Especially in species-rich tropical forests, it is largely unknown how species differ in their response of growth to resource availability and individual size. We use a hierarchical Bayesian approach to quantify the impact of light availability and tree diameter on growth of 274 woody species in a 50-ha long-term forest census plot in Barro Colorado Island, Panama. Light reaching each individual tree was estimated from yearly vertical censuses of canopy density. The hierarchical Bayesian approach allowed accounting for different sources of error, such as negative growth observations, and including rare species correctly weighted by their abundance. All species grew faster at higher light. Exponents of a power function relating growth to light were mostly between 0 and 1. This indicates that nearly all species exhibit a decelerating increase of growth with light. In contrast, estimated growth rates at standardized conditions (5 cm dbh, 5% light) varied over a 9-fold range and reflect strong growth-strategy differentiation between the species. As a consequence, growth rankings of the species at low (2%) and high light (20%) were highly correlated. Rare species tended to grow faster and showed a greater sensitivity to light than abundant species. Overall, tree size was less important for growth than light and about half the species were predicted to grow faster in diameter when bigger or smaller, respectively. Together light availability and tree diameter only explained on average 12% of the variation in growth rates. Thus, other factors such as soil characteristics, herbivory, or pathogens may contribute considerably to shaping tree growth in the tropics