Deletion of chromosome 11q predicts response to anthracycline-based chemotherapy in early breast cancer

Despite the recent consensus on the eligibility of adjuvant systemic therapy in patients with lymph node–negative breast cancer (NNBC) based on clinicopathologic criteria, specific biological markers are needed to predict sensitivity to the different available therapeutic options.W e examined the feasibility of developing a genomic predictor of chemotherapy response and recurrence risk in 185 patients with NNBC using assembled arrays containing 2,460 bacterial artificial chromosome clones for scanning the genome for DNA copy number changes.Aft er surgery, 90 patients received anthracyclinebased chemotherapy, whereas 95 did not.T amoxifen was administered to patients with hormone receptor–positive tumors. The association of genomic and clinicopathologic data and outcome was computed using Cox proportional hazard models and multiple testing adjustment procedures.Analysis of NNBC genomes revealed a common genomic signature.Specific DNA copy number aberrations were associated with hormonal receptor status, but not with other clinicopathologic variables. In patients treated with chemotherapy, none of the genomic changes were significantly correlated with recurrence.In patients not receiving chemotherapy, deletion of eight bacterial artificial chromosome clones clustered to chromosome 11q was independently associated with relapse (disease-free survival at 10 years F SE, 40% F 14% versus 86% F 6%; P < 0.0001). The 54 patients with deletion of 11q (29%) did not present more aggressive clinicopathologic features than those without 11q loss.The adverse influence of 11q deletion on clinical outcome was confirmed in an independent validation series of 88 patients with NNBC.Our data suggests that patients with NNBC with the 11q deletion might benefit from anthracycline-based chemotherapy despite other clinical, pathologic, or genetic features.However , these initial findings should be evaluated in randomized clinical trials

Mapping SF-36 onto the EQ-5D index: how reliable is the relationship?

<p>Abstract</p> <p>Background</p> <p>Mapping from health status measures onto generic preference-based measures is becoming a common solution when health state utility values are not directly available for economic evaluation. However the accuracy and reliability of the models employed is largely untested, and there is little evidence of their suitability in patient datasets. This paper examines whether mapping approaches are reliable and accurate in terms of their predictions for a large and varied UK patient dataset.</p> <p>Methods</p> <p>SF-36 dimension scores are mapped onto the EQ-5D index using a number of different model specifications. The predicted EQ-5D scores for subsets of the sample are compared across inpatient and outpatient settings and medical conditions. This paper compares the results to those obtained from existing mapping functions.</p> <p>Results</p> <p>The model including SF-36 dimensions, squared and interaction terms estimated using random effects GLS has the most accurate predictions of all models estimated here and existing mapping functions as indicated by MAE (0.127) and MSE (0.030). Mean absolute error in predictions by EQ-5D utility range increases with severity for our models (0.085 to 0.34) and for existing mapping functions (0.123 to 0.272).</p> <p>Conclusion</p> <p>Our results suggest that models mapping the SF-36 onto the EQ-5D have similar predictions across inpatient and outpatient setting and medical conditions. However, the models overpredict for more severe EQ-5D states; this problem is also present in the existing mapping functions.</p

Neural Net Classification Combined With Movement Analysis to Evaluate Setaria viridis as a Model System for Time of Day of Anther Appearance

In many plant species, the time of day at which flowers open to permit pollination is tightly regulated. Proper time of flower opening, or Time of Day of Anther Appearance (TAA), may coordinate flowering opening with pollinator activity or may shift temperature sensitive developmental processes to cooler times of the day. The genetic mechanisms that regulate the timing of this process in cereal crops are unknown. To address this knowledge gap, it is necessary to establish a monocot model system that exhibits variation in TAA. Here, we examine the suitability of Setaria viridis, the model for C4 photosynthesis, for such a role. We developed an imaging system to monitor the temporal regulation of growth, flower opening time, and other physiological characteristics in Setaria. This system enabled us to compare Setaria varieties Ames 32254, Ames 32276, and PI 669942 variation in growth and daily flower opening time. We observed that TAA occurs primarily at night in these three Setaria accessions. However, significant variation between the accessions was observed for both the ratio of flowers that open in the day vs. night and the specific time of day where the rate is maximal. Characterizing this physiological variation is a requisite step toward uncovering the molecular mechanisms regulating TAA. Leveraging the regulation of TAA could provide researchers with a genetic tool to improve crop productivity in new environments

Patient and prescriber perspectives on long-acting injectable (LAI) antipsychotics and analysis of in-office discussion regarding LAI treatment for schizophrenia

BACKGROUND: The research goal is to better understand prescriber, patient, and caregiver perspectives about long-acting injectable (LAI) antipsychotic therapy and how these perspectives affect LAI use. Addressing these perspectives in the clinic may lead to greater success in achieving therapeutic goals for the patient with schizophrenia. METHODS: Ethnographic information was collected from a non-random sample of 69 prescriber-patient conversations (60 with community mental health center [CMHC] psychiatrists; 9 with nurse-practitioners) recorded during treatment visits from August 2011 to February 2012, transcribed and analyzed. Discussions were categorized according to 11 predetermined CMHC topics. In-person observations were also conducted at 4 CMHCs, including home visits by researchers (n = 15 patients) prior to the CMHC visit and observations of patients receiving injections and interacting with staff. Telephone in-depth interviews with psychiatrists, patients, and caregivers to gather additional information on LAI discussion, prescription, or use were conducted. RESULTS: Antipsychotic treatment decisions were made without patient or caregiver input in 40 of 60 (67%) of psychiatrist-patient conversations. Involvement of patients or caregivers in treatment decisions was greater when discussing LAI (15 of 60 [25%]) vs oral antipsychotic treatment (5 of 60 [8%]). LAIs were not discussed by psychiatrists in 11 of 22 (50%) patients taking oral antipsychotics. When offered, more LAI-naïve patients expressed neutral (9 of 19 [47%]) rather than favorable (3 of 19 [16%]) or unfavorable (7 of 19 [37%]) responses. Prescribers were most concerned about potentially damaging the therapeutic relationship and side-effects when discussing LAIs while patient resistance was often related to negative feelings about injections. Psychiatrists had some success in overcoming patient objections to LAIs by addressing and decomposing initial resistance. More than half (11 of 19 [58%]) of LAI-naïve patients agreed to start LAI treatment following office visits. Patient-described benefits of LAIs vs orals included perceived rapid symptom improvement and greater overall efficacy. CONCLUSIONS: In this study, many psychiatrists did not offer LAIs and most patients and caregivers were not involved in antipsychotic treatment decision making. Opportunities to increase active patient engagement, address resistances, guide patient drug-formulation selection, and provide better LAI-relevant information for more individualized approaches to treating the patient with schizophrenia were present

Bolivia and the paradoxes of democratic consolidation

In Bolivia from the 1990s on, two presidents were ousted by popular protests, and protests were rampant. The protests expressed a growing discontent not only with successive administrations and their policies but with politics itself. The polity failed to built trust in democracy, ignored or repressed protests, and thus contributed to a process of democratic "deconsolidation." The main factors were corruption and the reluctance of the traditional political parties to discuss the neoliberal economic model. As a result, the current administration of Evo Morales faces two challenges: to change economic policies and to repair the support for democracy

A description of a knowledge broker role implemented as part of a randomized controlled trial evaluating three knowledge translation strategies

<p>Abstract</p> <p>Background</p> <p>A knowledge broker (KB) is a popular knowledge translation and exchange (KTE) strategy emerging in Canada to promote interaction between researchers and end users, as well as to develop capacity for evidence-informed decision making. A KB provides a link between research producers and end users by developing a mutual understanding of goals and cultures, collaborates with end users to identify issues and problems for which solutions are required, and facilitates the identification, access, assessment, interpretation, and translation of research evidence into local policy and practice. Knowledge-brokering can be carried out by individuals, groups and/or organizations, as well as entire countries. In each case, the KB is linked with a group of end users and focuses on promoting the integration of the best available evidence into policy and practice-related decisions.</p> <p>Methods</p> <p>A KB intervention comprised one of three KTE interventions evaluated in a randomized controlled trial.</p> <p>Results</p> <p>KB activities were classified into the following categories: initial and ongoing needs assessments; scanning the horizon; knowledge management; KTE; network development, maintenance, and facilitation; facilitation of individual capacity development in evidence informed decision making; and g) facilitation of and support for organizational change.</p> <p>Conclusion</p> <p>As the KB role developed during this study, central themes that emerged as particularly important included relationship development, ongoing support, customized approaches, and opportunities for individual and organizational capacity development. The novelty of the KB role in public health provides a unique opportunity to assess the need for and reaction to the role and its associated activities. Future research should include studies to evaluate the effectiveness of KBs in different settings and among different health care professionals, and to explore the optimal preparation and training of KBs, as well as the identification of the personality characteristics most closely associated with KB effectiveness. Studies should also seek to better understand which combination of KB activities are associated with optimal evidence-informed decision making outcomes, and whether the combination changes in different settings and among different health care decision makers.</p

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The Use Of Mapping To Estimate Health State Utility Values

Mapping functions are estimated using regression analyses and are frequently used to predict health state utility values (HSUVs) in decision analytic models. Mapping functions are used when evidence on the required preference-based measure (PBM) is not available, or where modelled values are required for a decision analytic model, for example to control for important sociodemographic variables (such as age or gender). This article provides an overview of the latest recommendations including pre-mapping considerations, the mapping process including data requirements for undertaking the estimation of mapping functions, regression models for estimating mapping functions, assessing performance and reporting standards for mapping studies. Examples in rheumatoid arthritis are used for illustration. When reporting the results of mapping standards the following should be reported: a description of the dataset used (including distributions of variables used) and any analysis used to inform the selection of the model type and model specification. The regression method and specification should be justified, and as summary statistics may mask systematic bias in errors, plots comparing observed and predicted HSUVs. The final model (coefficients, error term(s), variance and covariance) should be reported together with a worked example. It is important to ensure that good practice is followed as any mapping functions will only be as appropriate and accurate as the method used to obtain them; for example, mapping should not be used if there is no overlap between the explanatory and target variables

HIV epidemiologic trends among occupational groups in Rakai, Uganda: A population-based longitudinal study, 1999–2016

Certain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including female bar and restaurant work and male transportation work. However, data on changes in population prevalence of HIV infection and HIV incidence within occupations following mass scale-up of African HIV treatment and prevention programs is very limited. We evaluated prospective data collected between 1999 and 2016 from the Rakai Community Cohort Study, a longitudinal population-based study of 15- to 49-year-old persons in Uganda. Adjusted prevalence risk ratios for overall, treated, and untreated, prevalent HIV infection, and incidence rate ratios for HIV incidence with 95% confidence intervals were estimated using Poisson regression to assess changes in HIV outcomes by occupation. Analyses were stratified by gender. There were 33,866 participants, including 19,113 (56%) women. Overall, HIV seroprevalence declined in most occupational subgroups among men, but increased or remained mostly stable among women. In contrast, prevalence of untreated HIV substantially declined between 1999 and 2016 in most occupations, irrespective of gender, including by 70% among men (12.3 to 4.2%; adjPRR = 0.30; 95%CI:0.23–0.41) and by 78% among women (14.7 to 4.0%; adjPRR = 0.22; 95%CI:0.18–0.27) working in agriculture, the most common self-reported primary occupation. Exceptions included men working in transportation. HIV incidence similarly declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers, women working in local crafts, or men working in transportation. In summary, untreated HIV infection and HIV incidence have declined within most occupational groups in Uganda. However, women working in bars/restaurants and local crafts and men working in transportation continue to have a relatively high burden of untreated HIV and HIV incidence, and as such, should be considered priority populations for HIV programming