389 research outputs found
Benefits of biomarker selection and clinico-pathological covariate inclusion in breast cancer prognostic models
Introduction: Multi-marker molecular assays have impacted management of early stage breast cancer, facilitating adjuvant chemotherapy decisions. We generated prognostic models that incorporate protein-based molecular markers and clinico-pathological variables to improve survival prediction.
Methods: We used a quantitative immunofluorescence method to study protein expression of 14 markers included in the Oncotype DX™ assay on a 638 breast cancer patient cohort with 15-year follow-up. We performed cross-validation analyses to assess performance of multivariate Cox models consisting of these markers and standard clinico-pathological covariates, using an average time-dependent Area Under the Receiver Operating Characteristic curves and compared it to nested Cox models obtained by robust backward selection procedures.
Results: A prognostic index derived from of a multivariate Cox regression model incorporating molecular and clinico-pathological covariates (nodal status, tumor size, nuclear grade, and age) is superior to models based on molecular studies alone or clinico-pathological covariates alone. Performance of this composite model can be further improved using feature selection techniques to prune variables. When stratifying patients by Nottingham Prognostic Index (NPI), the most prognostic markers in high and low NPI groups differed. Similarly, for the node-negative, hormone receptor-positive sub-population, we derived a compact model with three clinico-pathological variables and two protein markers that was superior to the full model.
Conclusions: Prognostic models that include both molecular and clinico-pathological covariates can be more accurate than models based on either set of features alone. Furthermore, feature selection can decrease the number of molecular variables needed to predict outcome, potentially resulting in less expensive assays.This work was supported by a grant from the Susan G Komen Foundation (to YK)
Interactive Actor Analysis for Rural Water Management in The Netherlands
Recent developments in the policy sciences emphasize the social environment
in which decisions are made. The ‘network metaphor’ is often used to describe
the key role of interactions between interdependent actors involved in decision
making. These interactions take place in a policy arena drawn up by actors with an
interest in and control over decisions on the issues addressed. Interdependencies,
caused by the need for actors to increase their means of realizing objectives, are
the driving force behind these interactions. Dependency relations are of special
interest to water management and river basin management because of the fundamental
asymmetrical interdependencies that exist in river basins between upstream
and downstream stakeholders. Coleman’s linear system of action models decision
making process involving dependencies between multiple stakeholders as exchange
of control over issues, while interactions are required to negotiate exchanges of
control. We developed an interactive method for actor analysis based on Coleman’s
linear system of action and applied it to the national rural water management policy
domain in The Netherlands. The method is firmly rooted in mathematical sociology
and defies the criticism that methods for actor and stakeholder analysis do not specify
a theoretical basis explaining the causal relations between the variables analyzed and
policy change. With the application to the rural water management policy arena we
intended to increase our insight into the practical applicability of this analyticmethod
in an interactive workshop, the acceptability of the approach for the participating
actors, its contribution to the process of decision making and our understanding of
the rural water management policy arena in The Netherlands. We found that the
Association of Water Authorities, the Ministry of Public Works and the Ministry of
Agriculture are the most powerful actor in the policy domain, while governance and
cost and benefits of rural water management are the most salient issues. Progress
in policy development for rural water management is probably most promising for the issues governance, costs and benefits, safety and rural living conditions through
improved interaction between the Association of Water Authorities, the Ministry of
Agriculture and the Rural Credit Bank. Besides these analytic results the interactive
approach implemented increased the participants understanding of their dependency
on other actors in the rural water management policy domain and supported them
in developing a sound perspective on their dependency position. We concluded
that the method developed is acceptable to real-world policy decision makers, can
successfully be applied in an interactive setting, potentially contributes to the process
of decision making by increasing the participants understanding of their dependency
position, has the potential to delivers valuable advice for future decision-making and
increases our understanding of policy development for rural water management in
general
Natural Plasmodium infection in neotropical primates in the island of São Luís, state of Maranhão, Brazil
Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study
The aim was to investigate the efficacy of neoadjuvant docetaxel–cisplatin and identify prognostic factors for outcome in locally advanced stage IIIA (pN2 by mediastinoscopy) non-small-cell lung cancer (NSCLC) patients. In all, 75 patients (from 90 enrolled) underwent tumour resection after three 3-week cycles of docetaxel 85 mg m−2 (day 1) plus cisplatin 40 or 50 mg m−2 (days 1 and 2). Therapy was well tolerated (overall grade 3 toxicity occurred in 48% patients; no grade 4 nonhaematological toxicity was reported), with no observed late toxicities. Median overall survival (OS) and event-free survival (EFS) times were 35 and 15 months, respectively, in the 75 patients who underwent surgery; corresponding figures for all 90 patients enrolled were 28 and 12 months. At 3 years after initiating trial therapy, 27 out of 75 patients (36%) were alive and tumour free. At 5-year follow-up, 60 and 65% of patients had local relapse and distant metastases, respectively. The most common sites of distant metastases were the lung (24%) and brain (17%). Factors associated with OS, EFS and risk of local relapse and distant metastases were complete tumour resection and chemotherapy activity (clinical response, pathologic response, mediastinal downstaging). Neoadjuvant docetaxel–cisplatin was effective and tolerable in stage IIIA pN2 NSCLC, with chemotherapy contributing significantly to outcomes
Impact of disease duration on functional status of patients with spinocerebellar ataxia type 2
Evaluating the Fidelity of De Novo Short Read Metagenomic Assembly Using Simulated Data
A frequent step in metagenomic data analysis comprises the assembly of the sequenced reads. Many assembly tools have been published in the last years targeting data coming from next-generation sequencing (NGS) technologies but these assemblers have not been designed for or tested in multi-genome scenarios that characterize metagenomic studies. Here we provide a critical assessment of current de novo short reads assembly tools in multi-genome scenarios using complex simulated metagenomic data. With this approach we tested the fidelity of different assemblers in metagenomic studies demonstrating that even under the simplest compositions the number of chimeric contigs involving different species is noticeable. We further showed that the assembly process reduces the accuracy of the functional classification of the metagenomic data and that these errors can be overcome raising the coverage of the studied metagenome. The results presented here highlight the particular difficulties that de novo genome assemblers face in multi-genome scenarios demonstrating that these difficulties, that often compromise the functional classification of the analyzed data, can be overcome with a high sequencing effort
Vocal fold immobility after thyroidectomy with intraoperative recurrent laryngeal nerve monitoring
Multicenter phase II trial of accelerated cisplatin and high-dose epirubicin followed by surgery or radiotherapy in patients with stage IIIa non-small-cell lung cancer with mediastinal lymph node involvement (N2-disease)
To assess the therapeutic activity of accelerated cisplatin and high-dose epirubicin with erythropoietin and G-CSF support as induction therapy for patients with stage IIIa-N2 non-small-cell lung cancer (NSCLC). Patients with stage IIIa-N2 NSCLC were enrolled in a phase II trial. They received cisplatin 60 mg m−2 and epirubicin 135 mg m−2 every 2 weeks for three courses combined with erythropoietin and G-CSF. Depending on results of clinical response to induction therapy and restaging, patients were treated with surgery or radiotherapy. In total, 61 patients entered from March 2001 to April 2004. During 169 courses of induction chemotherapy, National Cancer Institute of Canada (NCI-C) grade III/IV leucocytopenia was reported in 35 courses (20.7%), NCI-C grade III/IV thrombocytopenia in 26 courses (15.4%) and NCI-C grade III/IV anaemia in six courses (3.6%). Main cause of cisplatin dose reduction was nephrotoxicity (12 courses). Most patients received three courses. There were no chemotherapy-related deaths. Three patients were not evaluable for clinical response. Twenty-eight patients had a partial response (48.3%, 95% CI: 36–61.1%), 24 stable disease and six progressive disease. After induction therapy, 30 patients underwent surgery; complete resection was achieved in 19 procedures (31.1%). Radical radiotherapy was delivered to 25 patients (41%). Six patients were considered unfit for further treatment. Median survival for all patients was 18 months. Response rate of accelerated cisplatin and high-dose epirubicin as induction chemotherapy for stage IIIa-N2 NSCLC patients is not different from more commonly used cisplatin-based regimen
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