46 research outputs found

    Transdisciplinary Collaboration as a Basis for Enhancing the Science and Prevention of Substance Use and ?Abuse?

    Get PDF
    Transdisciplinary scientific collaborations (TDSCs) have the potential to strengthen substance use and misuse research and prevention. Despite its growing prominence as a mode for scientific research, research on TDSC remains in a nascent form and its value to the field of substance use and misuse merits further exploration. The overarching purpose of this article is to examine the potential contributions of transdisciplinary science to research and prevention using conceptualizations, methods, and evidence from a case study of two university-based research centers. The article provides (a) a discussion of the societal context and historical developments that have prompted increasing interest in TDSC; (b) a definition and conceptualization of TDSC; (c) a methodological approach for studying TDSC; (d) initial findings from the case study that reflect instances of transdisciplinary intellectual integration and it examines implications of these methods and findings for future research and policy development relevant to substance use and misuse

    A Randomized Multicentre Phase II Trial Comparing Adjuvant Therapy in Patients with Interferon Alpha-2b and 5-FU Alone or in Combination with Either External Radiation Treatment and Cisplatin (CapRI) or Radiation alone regarding Event-Free Survival – CapRI-2

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>The 5-year survival of patients with resected pancreatic adenocarcinoma is still unsatisfying. The ESPAC-1 and the CONKO 001 trial proofed that adjuvant chemotherapy improves 5-year survival significantly from approximately 14% to 21%. In parallel, investigators from the Virginia Mason Clinic reported a 5-year survival rate of 55% in a phase II trial evaluating a combination of adjuvant chemotherapy, immunotherapy and external beam radiation (CapRI-scheme). Two other groups confirmed in phase II trials these results to a certain extent. However, these groups reported severe gastrointestinal toxicity (up to 93% grade 3 or 4 toxicity). In a randomized controlled phase III trial, called CapRI, 110 patients were enrolled from 2004 to 2007 in Germany and Italy to check for reproducibility. Interestingly, much less gastrointestinal toxicity was observed. However, dose-reduction due to haematological side effects had to be performed in nearly all patients. First clinical results are expected for the end of 2009.</p> <p>Methods/Design</p> <p>CapRI-2 is an open, controlled, prospective, randomized, multicentre phase II trial with three parallel arms. A de-escalation of the CapRI-scheme will be tested in two different modifications. Patients in study arm A will be treated as outpatients with the complete CapRI-scheme consisting of cisplatin, Interferon alpha-2b and external beam radiation and three cycles of 5-fluorouracil continuous infusion. In study arm B the first de-escalation will be realised by omitting cisplatin. Next, patients in study arm C will additionally not receive external beam radiation. A total of 135 patients with pathologically confirmed R0 or R1 resected pancreatic adenocarcinoma are planned to be enrolled. Primary endpoint is the comparison of the treatment groups with respect to six-month event-free-survival. An event is defined as grade 3 or grade 4 toxicity, objective tumour recurrence, or death.</p> <p>Discussion</p> <p>The aim of this clinical trial is to evaluate de-escalation of the CapRI-scheme. It is hypothesised that removal of cisplatin and radiotherapy will have no significant effect or only a minor impact on the clinical response but result in substantially lower toxicity.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN79802092</p

    Mapping genetic variations to three- dimensional protein structures to enhance variant interpretation: a proposed framework

    Get PDF
    The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are predicted to modify a protein, their functional implications may be unclear. Many diseases are caused by genetic variants affecting important protein features, such as enzyme active sites or interaction interfaces. The scientific community has catalogued millions of genetic variants in genomic databases and thousands of protein structures in the Protein Data Bank. Mapping mutations onto three-dimensional (3D) structures enables atomic-level analyses of protein positions that may be important for the stability or formation of interactions; these may explain the effect of mutations and in some cases even open a path for targeted drug development. To accelerate progress in the integration of these data types, we held a two-day Gene Variation to 3D (GVto3D) workshop to report on the latest advances and to discuss unmet needs. The overarching goal of the workshop was to address the question: what can be done together as a community to advance the integration of genetic variants and 3D protein structures that could not be done by a single investigator or laboratory? Here we describe the workshop outcomes, review the state of the field, and propose the development of a framework with which to promote progress in this arena. The framework will include a set of standard formats, common ontologies, a common application programming interface to enable interoperation of the resources, and a Tool Registry to make it easy to find and apply the tools to specific analysis problems. Interoperability will enable integration of diverse data sources and tools and collaborative development of variant effect prediction methods

    Using Joomla

    No full text

    Comparison of toxicity profile and tolerability between two standard of care paclitaxel-based adjuvant chemotherapy regimens in breast cancer

    No full text
    In breast cancer, there are two widely used paclitaxel-based adjuvant chemotherapies, either dose dense paclitaxel (ddP) or weekly paclitaxel (wP). To our knowledge, the comparisons of toxicity and tolerability between the two regimens have never been reported in the literature. This is a retrospective single-institution charts review of breast cancer patients who were treated with paclitaxel-based chemotherapy either ddP or wP. In total, 76 and 45 patients with breast cancer received adjuvant standard ddP and wP, respectively. Patient characteristics in both groups were comparable. Our results showed no statistical significant difference in toxicity profile and tolerability between the two regimens. Particularly, chemotherapy-induced peripheral neuropathy (CIPN) was equally observed in both schedules. Furthermore, grade 3 and 4 CIPN was observed in 17 and 18 %, respectively (p = 0.93). In terms of tolerability, both regimens resulted in similar rates of hospitalization and treatment discontinuation. Our data analysis indicates no significant difference in toxicity profile between the two standard paclitaxel regimens in breast cancer. However, this is a small samplesized retrospective study and further prospective trial with a larger sample size is warranted
    corecore