PREDICT: a new UK prognostic model that predicts survival following surgery for invasive breast cancer.

INTRODUCTION: The aim of this study was to develop and validate a prognostication model to predict overall and breast cancer specific survival for women treated for early breast cancer in the UK. METHODS: Using the Eastern Cancer Registration and Information Centre (ECRIC) dataset, information was collated for 5,694 women who had surgery for invasive breast cancer in East Anglia from 1999 to 2003. Breast cancer mortality models for oestrogen receptor (ER) positive and ER negative tumours were derived from these data using Cox proportional hazards, adjusting for prognostic factors and mode of cancer detection (symptomatic versus screen-detected). An external dataset of 5,468 patients from the West Midlands Cancer Intelligence Unit (WMCIU) was used for validation. RESULTS: Differences in overall actual and predicted mortality were <1% at eight years for ECRIC (18.9% vs. 19.0%) and WMCIU (17.5% vs. 18.3%) with area under receiver-operator-characteristic curves (AUC) of 0.81 and 0.79 respectively. Differences in breast cancer specific actual and predicted mortality were <1% at eight years for ECRIC (12.9% vs. 13.5%) and <1.5% at eight years for WMCIU (12.2% vs. 13.6%) with AUC of 0.84 and 0.82 respectively. Model calibration was good for both ER positive and negative models although the ER positive model provided better discrimination (AUC 0.82) than ER negative (AUC 0.75). CONCLUSIONS: We have developed a prognostication model for early breast cancer based on UK cancer registry data that predicts breast cancer survival following surgery for invasive breast cancer and includes mode of detection for the first time. The model is well calibrated, provides a high degree of discrimination and has been validated in a second UK patient cohort.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Using informative behavior to increase engagement while learning from human reward

In this work, we address a relatively unexplored aspect of designing agents that learn from human reward. We investigate how an agent’s non-task behavior can affect a human trainer’s training and agent learning. We use the TAMER framework, which facilitates the training of agents by human-generated reward signals, i.e., judgements of the quality of the agent’s actions, as the foundation for our investigation. Then, starting from the premise that the interaction between the agent and the trainer should be bi-directional, we propose two new training interfaces to increase a human trainer’s active involvement in the training process and thereby improve the agent’s task performance. One provides information on the agent’s uncertainty which is a metric calculated as data coverage, the other on its performance. Our results from a 51-subject user study show that these interfaces can induce the trainers to train longer and give more feedback. The agent’s performance, however, increases only in response to the addition of performance-oriented information, not by sharing uncertainty levels. These results suggest that the organizational maxim about human behavior, “you get what you measure”—i.e., sharing metrics with people causes them to focus on optimizing those metrics while de-emphasizing other objectives—also applies to the training of agents. Using principle component analysis, we show how trainers in the two conditions train agents differently. In addition, by simulating the influence of the agent’s uncertainty–informative behavior on a human’s training behavior, we show that trainers could be distracted by the agent sharing its uncertainty levels about its actions, giving poor feedback for the sake of reducing the agent’s uncertainty without improving the agent’s performance

An Ethical Façade? Medical Students' Miscomprehensions of Substituted Judgment

Background: We studied how well first-year medical students understand and apply the concept of substituted judgment, following a course on clinical ethics. Method: Students submitted essays on one of three ethically controversial scenarios presented in class. One scenario involved a patient who had lost decisional capacity. Through an iterative process of textual analysis, the essays were studied and coded for patterns in the ways students misunderstood or misapplied the principle of substituted judgment. Results: Students correctly articulated course principles regarding patient autonomy, substituted judgment, and nonimposition of physician values. However, students showed misunderstanding by giving doctors the responsibility of balancing the interests of the patient against the interests of the family, by stating doctors and surrogates should be guided primarily by a best-interest standard, and by suggesting that patient autonomy becomes the guiding principle only when patients can no longer express their wishes. Conclusion: Students did not appear to internalize or correctly apply the substituted judgment standard, even though they could describe it accurately. This suggests the substituted judgment standard may run counter to students ’ moral intuitions

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

Impact of socioeconomic deprivation on rate and cause of death in severe mental illness

Background: Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated.&lt;p&gt;&lt;/p&gt; Aims: To assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations.&lt;p&gt;&lt;/p&gt; Methods: Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations.&lt;p&gt;&lt;/p&gt; Results: Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = &#60;0.001 and 5.1% p = 0.002 respectively). A lower proportion of deaths due to cancer in those with SMI living in the most deprived quintile were also observed, relative to the local Glasgow and wider Scottish populations (12.3% vs. 25.1% p = 0.013 and 26.3% p = &#60;0.001). The proportion of suicides was significantly higher in those with SMI living in the more affluent quintiles relative to Glasgow and Scotland (54.6% vs. 5.8%, p = &#60;0.001 and 5.5%, p = &#60;0.001). Discussion and conclusions: Excess mortality in those with SMI occurred across all socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed

Radiation dose reduction at a price: the effectiveness of a male gonadal shield during helical CT scans

BACKGROUND: It is estimated that 60 million computed tomography (CT) scans were performed during 2006, with approximately 11% of those performed on children age 0–15 years. Various types of gonadal shielding have been evaluated for reducing exposure to the gonads. The purpose of this study was to quantify the radiation dose reduction to the gonads and its effect on image quality when a wrap-around male pediatric gonad shield was used during CT scanning. This information is obtained to assist the attending radiologist in the decision to utilize such male gonadal shields in pediatric imaging practice. METHODS: The dose reduction to the gonads was measured for both direct radiation and for indirect scattered radiation from the abdomen. A 6 cm(3 )ion chamber (Model 10X5-6, Radcal Corporation, Monrovia, CA) was placed on a Humanoid real bone pelvic phantom at a position of the male gonads. When exposure measurements with shielding were made, a 1 mm lead wrap-around gonadal shield was placed around the ion chamber sensitive volume. RESULTS: The use of the shields reduced scatter dose to the gonads by a factor of about 2 with no appreciable loss of image quality. The shields reduced the direct beam dose by a factor of about 35 at the expense of extremely poor CT image quality due to severe streak artifacts. CONCLUSION: Images in the direct exposure case are not useful due to these severe artifacts and the difficulties in positioning these shields on patients in the scatter exposure case may not be warranted by the small absolute reduction in scatter dose unless it is expected that the patient will be subjected to numerous future CT scans

The textual characteristics of traditional and Open Access scientific journals are similar

<p>Abstract</p> <p>Background</p> <p>Recent years have seen an increased amount of natural language processing (NLP) work on full text biomedical journal publications. Much of this work is done with Open Access journal articles. Such work assumes that Open Access articles are representative of biomedical publications in general and that methods developed for analysis of Open Access full text publications will generalize to the biomedical literature as a whole. If this assumption is wrong, the cost to the community will be large, including not just wasted resources, but also flawed science. This paper examines that assumption.</p> <p>Results</p> <p>We collected two sets of documents, one consisting only of Open Access publications and the other consisting only of traditional journal publications. We examined them for differences in surface linguistic structures that have obvious consequences for the ease or difficulty of natural language processing and for differences in semantic content as reflected in lexical items. Regarding surface linguistic structures, we examined the incidence of conjunctions, negation, passives, and pronominal anaphora, and found that the two collections did not differ. We also examined the distribution of sentence lengths and found that both collections were characterized by the same mode. Regarding lexical items, we found that the Kullback-Leibler divergence between the two collections was low, and was lower than the divergence between either collection and a reference corpus. Where small differences did exist, log likelihood analysis showed that they were primarily in the area of formatting and in specific named entities.</p> <p>Conclusion</p> <p>We did not find structural or semantic differences between the Open Access and traditional journal collections.</p

A New Approach to Monitoring Dengue Activity

Discusses informal surveillance tools for monitoring dengue activity, such as ProMED, GPHIN HealthMap and BioCaster

The impact of socio-economic disadvantage on rates of hospital separations for diabetes-related foot disease in Victoria, Australia

<p>Abstract</p> <p>Background</p> <p>Information describing variation in health outcomes for individuals with diabetes related foot disease, across socioeconomic strata is lacking. The aim of this study was to investigate variation in rates of hospital separations for diabetes related foot disease and the relationship with levels of social advantage and disadvantage.</p> <p>Methods</p> <p>Using the Index of Relative Socioeconomic Disadvantage (IRSD) each local government area (LGA) across Victoria was ranked from most to least disadvantaged. Those LGAs ranked at the lowest end of the scale and therefore at greater disadvantage (Group D) were compared with those at the highest end of the scale (Group A), in terms of total and per capita hospital separations for peripheral neuropathy, peripheral vascular disease, foot ulceration, cellulitis and osteomyelitis and amputation. Hospital separations data were compiled from the Victorian Admitted Episodes Database.</p> <p>Results</p> <p>Total and per capita separations were 2,268 (75.3/1,000 with diabetes) and 2,734 (62.3/1,000 with diabetes) for Group D and Group A respectively. Most notable variation was for foot ulceration (Group D, 18.1/1,000 <it>versus </it>Group A, 12.7/1,000, rate ratio 1.4, 95% CI 1.3, 1.6) and below knee amputation (Group D 7.4/1,000 <it>versus </it>Group A 4.1/1,000, rate ratio 1.8, 95% CI 1.5, 2.2). Males recorded a greater overall number of hospital separations across both socioeconomic strata with 66.2% of all separations for Group D and 81.0% of all separations for Group A recorded by males. However, when comparing mean age, males from Group D tended to be younger compared with males from Group A (mean age; 53.0 years <it>versus </it>68.7 years).</p> <p>Conclusion</p> <p>Variation appears to exist for hospital separations for diabetes related foot disease across socioeconomic strata. Specific strategies should be incorporated into health policy and planning to combat disparities between health outcomes and social status.</p

Nut production in Bertholletia excelsa across a logged forest mosaic: implications for multiple forest use

Although many examples of multiple-use forest management may be found in tropical smallholder systems, few studies provide empirical support for the integration of selective timber harvesting with non-timber forest product (NTFP) extraction. Brazil nut (Bertholletia excelsa, Lecythidaceae) is one of the world’s most economically-important NTFP species extracted almost entirely from natural forests across the Amazon Basin. An obligate out-crosser, Brazil nut flowers are pollinated by large-bodied bees, a process resulting in a hard round fruit that takes up to 14 months to mature. As many smallholders turn to the financial security provided by timber, Brazil nut fruits are increasingly being harvested in logged forests. We tested the influence of tree and stand-level covariates (distance to nearest cut stump and local logging intensity) on total nut production at the individual tree level in five recently logged Brazil nut concessions covering about 4000 ha of forest in Madre de Dios, Peru. Our field team accompanied Brazil nut harvesters during the traditional harvest period (January-April 2012 and January-April 2013) in order to collect data on fruit production. Three hundred and ninety-nine (approximately 80%) of the 499 trees included in this study were at least 100 m from the nearest cut stump, suggesting that concessionaires avoid logging near adult Brazil nut trees. Yet even for those trees on the edge of logging gaps, distance to nearest cut stump and local logging intensity did not have a statistically significant influence on Brazil nut production at the applied logging intensities (typically 1–2 timber trees removed per ha). In one concession where at least 4 trees ha-1 were removed, however, the logging intensity covariate resulted in a marginally significant (0.09) P value, highlighting a potential risk for a drop in nut production at higher intensities. While we do not suggest that logging activities should be completely avoided in Brazil nut rich forests, when a buffer zone cannot be observed, low logging intensities should be implemented. The sustainability of this integrated management system will ultimately depend on a complex series of socioeconomic and ecological interactions. Yet we submit that our study provides an important initial step in understanding the compatibility of timber harvesting with a high value NTFP, potentially allowing for diversification of forest use strategies in Amazonian Perù