205 research outputs found
Mobile Press-Register sleeve MP0095361
No full textUnited Way awards luncheon headshots of Sarah Danson, Bob Williams / (Fort Whiting
Striving for Contextual Ambidexterity: A Case Study Researching How an Organisation Can Manage the Tensions Brought About by the Strive to Simultaneously Exploit and Explore
No full textTitle: Striving for Contextual Ambidexterity: A Case Study Researching How an Organisation Can Manage the Tensions Brought About by the Strive to Simultaneously Exploit and Explore Date of the seminar: 18.05.2016 Course: ENTN39 Master´s Corporate Entrepreneurship and Innovation Internship and degree project (Master´s thesis 15 ECTS) Author: Alexander Danson and Carl Axel Kierulf Supervisor: Joakim Winborg Keywords: Organisational Ambidexterity; Contextual Ambidexterity; Tensions; Exploration; Exploitation Research question-/s: 1. What are the most significant tensions brought about by a company’s pursuit of contextual ambidexterity? 2. How are the tensions brought about by a company’s pursuit of contextual ambidexterity related to one another? Methodology: The approach taken was a single case study at a fast growing bank in Sweden. The research design was qualitative, primarily inductive and interpretative and the main data collection method was semi-structured interviews. Theoretical perspectives: This research paper focuses on the concept of contextual ambidexterity. By researching the most significant tensions, which come about as a result of pursuing exploration and exploitation activities within a single business unit, the authors hope to develop the theoretical understanding of the concept. Conclusions: The authors conclude that the tensions between the long and short term vision, predictability and uncertainty and efficiency and flexibility are the most significant for the contextually ambidextrous organisation. Furthermore, the authors found evidence of relationships between these tensions, among others, which are illustrated in a model. The research confirms the complexity of implementing contextual ambidexterity, whilst identifying areas where organisations should focus their efforts
The equilibrium model for the effect of temperature on enzymes: Insights and implications
No full textA new, experimentally-validated “Equilibrium Model” describes the effect of temperature on enzymes, and provides a new mechanism for the reversible loss of enzyme activity with temperature. It incorporates two new, fundamental parameters that allow a complete description of the effect of temperature on enzyme activity: ΔHeq and Teq. ΔHeq emerges as an intrinsic and quantitative measure of enzyme eurythermal adaptation, while Teq, the equilibrium temperature, has fundamental and technological significance for our understanding of the effect of temperature on enzymatic reactions. For biotechnological purposes, these parameters need to be considered when enzymes are applied or engineered for activity at high temperatures
Falling Off of the "Narwe Perche": A Reader's Quest for "Sentence" and "Solaas" in the Nun's Priest's Tale
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Economic burden of resected (stage IB-IIIA) non-small cell lung cancer in France, Germany and the United Kingdom: A retrospective observational study (LuCaBIS)
No full textOlaparib maintenance versus placebo monotherapy in patients with advanced non-small cell lung cancer (PIN): A multicentre, randomised, controlled, phase 2 trial
No full textBackground
Impaired double strand DNA repair by homologous repair deficiency (HRD) leads to sensitivity to poly ADP ribose polymerase (PARP) inhibition. Poly-ADP ribose polymerase (PARP) inhibitors target HRD to induce synthetic lethality and are used routinely in the treatment of BRCA1 mutated ovarian cancer in the platinum-sensitive maintenance setting. A subset of non-small cell lung cancers (NSCLCs) harbour impaired DNA double strand break repair. We therefore hypothesised that patients with metastatic non-small cell lung cancer exhibiting partial responses to platinum doublet-based chemotherapy, might enrich for impaired HRD, rendering these tumours more sensitive to inhibition of PARP inhibition by olaparib.
Methods
The Olaparib Maintenance versus Placebo Monotherapy in Patients with Advanced Non-Small Cell Lung Cancer trial (PIN) was a multicentre double-blind placebo controlled randomised phase II screening trial. This study was conducted at 23 investigative hospital sites in the UK. Patients had advanced (stage IIIB/IV) squamous (Sq) or non-squamous (NSq) NSCLC, and had to be chemo-naive, European Cooperative Oncology Group (ECOG) performance status 0-1. Prior immunotherapy with a PD1 or PDL1 inhibitor was allowed. Patients could be registered for PIN prior to (stage 1), or after (stage 2) initiation of induction chemotherapy. If any tumour shrinkage was observed (any shrinkage of RECIST target lesions), following a minimum of 3 cycles of platinum doublet chemotherapy, patients were randomised 1:1 using a centralised online system, to either olaparib (300 mg twice daily by mouth in 21-day cycles) or placebo, which was continued until disease progression, or unacceptable toxicity. Intention to treat (ITT) analyses of the primary endpoint included all randomised participants. Per protocol (PP) safety analysis included all participants who received at least one dose of study drug. Primary endpoint was progression-free survival (PFS), with a one-sided p-value of 0.2 to demonstrate statistical significance. Hazard ratios (HR) for PFS were both unadjusted and adjusted for the randomisation balancing factors (smoking status and histology). The trial was registered with ClinicalTrials.gov (NCT01788332) and EudraCT (2012-003383-51).
Findings
A total of 940 patients were assessed for stage 1 eligibility of whom 263 were registered between Feb 24, 2014 and Nov 7, 2017. 194 patients were excluded prior to stage 2 (no tumour shrinkage or unevaluable) and 70 were randomised; 32 (46%) to Olaparib and 38 (54%) to placebo. 4% (3/70) of patients randomised had a CR and 96% (67/70) had a PR (or other evidence of tumour response/mixed stable) during induction therapy. A total of 36 patients were registered in stage 2 only, i.e., post induction therapy. Intention to treat (ITT) unadjusted analysis showed a PFS hazard ratio (HR) of 0.83 (one-sided 80% CI upper limit 1.03, one-sided unadjusted log rank test p-value=0.23). ITT Cox-adjusted model showed a HR 0.73 (one-sided 80% CI upper limit 0.91, one sided p-value 0.11). Adverse events were reported in 31/32 subjects (97%) in the olaparib arm and 38/38 (100%) in the placebo group. The most commonly reported adverse events in the olaparib group were fatigue (20/31; 65%), nausea (17/31; 55%), anaemia (15/31; 48%) and dyspnea (13/31; 42%). In the placebo group the most common adverse events were fatigue (25/38; 66%), coughing (22/38; 58%), dyspnea (15/38; 39%) and nausea (11/38; 29%). There were no treatment-related deaths.
Interpretation
PFS was longer in the olaparib arm, but this did not reach statistical significance. When the PFS HR was adjusted for smoking status and histology, a significant difference at the one-sided 0.2 level was observed, suggesting that tumour control may be achieved for chemosensitive NSCLC treated with PARP monotherapy. We speculate that this signal may be driven by a molecular subgroup harbouring HRD
Defining the Infrastructure for a National Item Bank Service
No full textItem banks (sometimes known as question banks) have been around for many years but are not yet widely used in the UK. There are clear benefits such as economies of scale when items are built across a subject area or sector. When this is coordinated centrally items are more likely to be peer reviewed, validated properly and to adhere to technical, interoperability and accessibility standards. Quality can be enhanced by delivering the items to larger numbers of candidates, leading to improvements following analysis of item usage data. However there is currently no satisfactory way for these to be stored and made available to potential users; the available commercial learning object repositories are unable to deal with assessment content adequately. In an attempt to solve such issues and to begin to define the infrastructure of a distributed national item bank service, the Item Bank Infrastructure Study (IBIS) brought together individuals and institutions in the UK with key expertise in areas relating to item banks. The study was funded by JISC under the Exchange for Learning (X4L) Programme with financial contributions from three of the exam boards involved – Edexcel, the Scottish Qualifications Authority (SQA) and the University of Cambridge Local Examination Syndicate (UCLES). This paper extracts the key points and conclusions from the full report which can be downloaded from www.toia.ac.uk/ibis. An accompanying paper in these proceedings, Conceptualising Item Banks, defines items, item pools and item banks, and outlines the main components of a possible distributed item bank service
Improving outcomes in advanced malignant melanoma: Update on systemic therapy
No full textMalignant melanoma continues to increase in incidence throughout the developed world. Surgery remains the cornerstone of curative treatment and the use of adjuvant systemic therapy has provoked much debate. Metastatic disease is incurable in most patients. While combination chemotherapy or biochemotherapy may be considered in certain circumstances, it is now clear that single-agent chemotherapy remains the mainstay of treatment for the majority of patients. A number of new agents and novel approaches are under evaluation and show promise. The pro-apoptotic agent oblimersen has shown improved progression-free survival and response rate, although not overall survival, when combined with dacarbazine compared with dacarbazine alone. The BRaf inhibitor sorafenib (BAY 43-9006) has produced encouraging results when administered with chemotherapy and is now being assessed in randomised studies. Thalidomide in combination with chemotherapy is well tolerated and shows a trend towards increased clinical efficacy compared with chemotherapy alone. Other anti-angiogenic drugs, such as bevacizumab, are being investigated in trials. Results with tumour vaccines have been mixed and several large trials are ongoing. This paper discusses recent pivotal studies and promising new agents in systemic therapy for advanced malignant melanoma. © 2005 Adis Dato Information BV. Alt rights reserved
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