A Real Options Perspective On R&D Portfolio Diversification

This paper shows that the conditionality of investment decisions in R&D has a critical impact on portfolio risk, and implies that traditional diversification strategies should be reevaluated when a portfolio is constructed. Real option theory argues that research projects have conditional or option-like risk and return properties, and are different from unconditional projects. Although the risk of a portfolio always depends on the correlation between projects, a portfolio of conditional R&D projects with real option characteristics has a fundamentally different risk than a portfolio of unconditional projects. When conditional R&D projects are negatively correlated, diversification only slightly reduces portfolio risk. When projects are positively correlated, however, diversification proves more effective than conventional tools predict.real options;portfolio analysis;research & development

Long-Term Quality of Life after Free Flap Upper Extremity Reconstruction for Traumatic Injuries

Background Microsurgical reconstruction of upper extremity injuries is often challenging, and the resulting impact on the quality of life (QoL) may be significant. However, there is a lack of knowledge on long-term patient-reported QoL. Methods In a retrospective long-term follow-up study, all consecutive patients with an upper extremity injury who had undergone a free flap reconstruction were identified and categorized into three groups based on the type of injury. Patient-reported upper extremity function and QoL were assessed using three validated questionnaires: the 36-item Short Form Health Survey (SF-36), the Disabilities of the Arm, Shoulder, and Ha

Preoperative breast MRI in management of patients with needle biopsy-proven ductal carcinoma in situ (DCIS)

Background: In 20e25% of patients with biopsy-proven DCIS underestimation occurs. Sentinel lymph node biopsy (SLNB) is offered to patients with biopsy-proven ductal carcinoma in situ (DCIS) and a high risk of occult invasive cancer. However, assessment of high risk is controversial. We aimed to improve selection of patients for SLNB with preoperative breast magnetic resonance imaging (MRI). Methods: In this prospective observational study, MRI was offered to all subsequent patients with a biopsy-

Immunomagnetic t-lymphocyte depletion (ITLD) of rat bone marrow using OX-19 monoclonal antibody

Graft versus host disease (GVHD) may be abrogated and host survival prolonged by in vitro depletion of T lymphocytes from bone marrow (BM) prior to allotransplantation. Using a mouse anti-rat pan T-lymphocyte monoclonal antibody (0×19) bound to monosized, magnetic, polymer beads, T lymphocytes were removed in vitro from normal bone marrow. The removal of the T lymphocytes was confirmed by flow cytometry. Injection of the T-lymphocyte-depleted bone marrow into fully allogeneic rats prevents the induction of GVHD and prolongs host survival. A highly efficient technique of T-lymphocyte depletion using rat bone marrow is described. It involves the binding of OX-19, a MoAb directed against all rat thy-mocytes and mature peripheral T lymphocytes, to monosized, magnetic polymer spheres. Magnetic separation of T lymphocytes after mixing the allogeneic bone marrow with the bead/OX-19 complex provides for a simple, rapid depletion of T lymphocytes from the bone marrow. In vitro studies using flow cytometry and the prevention of GVHD in a fully allogeneic rat bone marrow model have been used to demonstrate the effectiveness of the depletion procedure. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Climate change challenges for central banks and financial regulators

The academic and policy debate regarding the role of central banks and financial regulators in addressing climate-related financial risks has rapidly expanded in recent years. This Perspective presents the key controversies and discusses potential research and policy avenues for the future. Developing a comprehensive analytical framework to assess the potential impact of climate change and the low-carbon transition on financial stability seems to be the first crucial challenge. These enhanced risk measures could then be incorporated in setting financial regulations and implementing the policies of central banks

The challenges of communicating research evidence in practice: perspectives from UK health visitors and practice nurses

<p>Background: Health practitioners play a pivotal role in providing patients with up-to-date evidence and health information. Evidence-based practice and patient-centred care are transforming the delivery of healthcare in the UK. Health practitioners are increasingly balancing the need to provide evidence-based information against that of facilitating patient choice, which may not always concur with the evidence base. There is limited research exploring how health practitioners working in the UK, and particularly those more autonomous practitioners such as health visitors and practice nurses working in community practice settings, negotiate this challenge. This research provides a descriptive account of how health visitors and practice nurses negotiate the challenges of communicating health information and research evidence in practice.</p> <p>Methods: A total of eighteen in-depth telephone interviews were conducted in the UK between September 2008 and May 2009. The participants comprised nine health visitors and nine practice nurses, recruited via adverts on a nursing website, posters at a practitioner conference and through recommendation. Thematic analysis, with a focus on constant comparative method, was used to analyse the data.</p> <p>Results: The data were grouped into three main themes: communicating evidence to the critically-minded patient; confidence in communicating evidence; and maintaining the integrity of the patient-practitioner relationship. These findings highlight some of the daily challenges that health visitors and practice nurses face with regard to the complex and dynamic nature of evidence and the changing attitudes and expectations of patients. The findings also highlight the tensions that exist between differing philosophies of evidence-based practice and patient-centred care, which can make communicating about evidence a daunting task.</p> <p>Conclusions: If health practitioners are to be effective at communicating research evidence, we suggest that more research and resources need to be focused on contextual factors, such as how research evidence is negotiated, appraised and communicated within the dynamic patient-practitioner relationship.</p&gt

The effect of trastuzumab on cardiac function in patients with HER2-positive metastatic breast cancer and reduced baseline left ventricular ejection fraction

We investigated the effect of trastuzumab on cardiac function in a real‐world historic cohort of patients with HER2‐positive metastatic breast cancer (MBC) with reduced baseline left ventricular ejection fraction (LVEF). Thirty‐seven patients with HER2‐positive MBC and baseline LVEF of 40% to 49% were included. Median LVEF was 46% (interquartile range [IQR] 44%‐48%) and median follow‐up was 18 months (IQR 9‐34 months). During this period, the LVEF did not worsen in 24/37 (65%) patients, while 13/37 (35%) patients developed severe cardiotoxicity defined as LVEF 5%‐points below baseline) in 3/13 (23%) patients and irreversible (defined as absolute LVEF increase 5%‐points below baseline) in 3/13 (23%) patients. Likelihood of reversibility was numerically higher in patients who received cardio‐protective medications (CPM), including ACE‐inhibitors, beta‐blockers and angiotensine‐2 inhibitors, compared to those who did not receive any CPM (71% vs 13%, P = .091). Sixty‐five percent of patients who received trastuzumab for HER2‐positive MBC did not develop severe cardiotoxicity during a median follow‐up of 18 months, despite having a compromised baseline LVEF. If severe cardiotoxicity occurred, it was at least partly reversible in more than two‐thirds of the cases. Risks and benefits of trastuzumab use should be balanced carefully in this vulnerable population

Debating the Desirability of New Biomedical Technologies: Lessons from the Introduction of Breast Cancer Screening in the Netherlands

Health technology assessment (HTA) was developed in the 1970s and 1980s to facilitate decision making on the desirability of new biomedical technologies. Since then, many of the standard tools and methods of HTA have been criticized for their implicit normativity. At the same time research into the character of technology in practice has motivated philosophers, sociologists and anthropologists to criticize the traditional view of technology as a neutral instrument designed to perform a specific function. Such research suggests that the tools and methods of more traditional forms of HTA are often inspired by an ‘instrumentalist’ conception of technology that does not fit the way technology actually works. This paper explores this hypothesis for a specific case: the assessments and deliberations leading to the introduction of breast cancer screening in the Netherlands. After reconstructing this history of HTA ‘in the making’ the stepwise model of HTA that emerged during the process is discussed. This model was rooted indeed in an instrumentalist conception of technology. However, a more detailed reconstruction of several episodes from this history reveals how the actors already experienced the inadequacy of some of the instrumentalist presuppositions. The historical case thus shows how an instrumentalist conception of technology may result in implicit normative effects. The paper concludes that an instrumentalist view of technology is not a good starting point for HTA and briefly suggests how the fit between HTA methods and the actual character of technology in practice might be improved

Primary care nurses' experiences of how the mass media influence frontline healthcare in the UK

Background: Mass media plays an important role in communicating about health research and services to patients, and in shaping public perceptions and decisions about health. Healthcare professionals also play an important role in providing patients with credible, evidence-based and up-to-date information on a wide range of health issues. This study aims to explore primary care nurses' experiences of how mass media influences frontline healthcare.<p></p> Methods: In-depth telephone interviews were carried out with 18 primary care nurses (nine health visitors and nine practice nurses) working in the United Kingdom (UK). Interviews were recorded and transcribed. The data was analysed using thematic analysis, with a focus on constant comparative analysis.<p></p> Results: Three themes emerged from the data. First, participants reported that their patients were frequently influenced by controversial health stories reported in the media, which affected their perceptions of, and decisions about, care. This, in turn, impinged upon participants' workloads as they had to spend additional time discussing information and reassuring patients. Second, participants also recalled times in their own careers when media reports had contributed to a decline in their confidence in current healthcare practices and treatments. Third, the participants in this study suggested a real need for additional resources to support and expand their own media literacy skills, which could be shared with patients.<p></p> Conclusion: In an ever expanding media landscape with greater reporting on health, nurses working in the primary care setting face increasing pressure to effectively manage media stories that dispute current health policies and practices. These primary care nurses were keen to expand their media literacy skills to develop critical autonomy in relation to all media, and to facilitate more meaningful conversations with their patients about their health concerns and choices.<p></p&gt

Exploitation of Herpesvirus Immune Evasion Strategies to Modify the Immunogenicity of Human Mesenchymal Stem Cell Transplants

BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells residing in the connective tissue of many organs and holding great potential for tissue repair. In culture, human MSCs (hMSCs) are capable of extensive proliferation without showing chromosomal aberrations. Large numbers of hMSCs can thus be acquired from small samples of easily obtainable tissues like fat and bone marrow. MSCs can contribute to regeneration indirectly by secretion of cytokines or directly by differentiation into specialized cell types. The latter mechanism requires their long-term acceptance by the recipient. Although MSCs do not elicit immune responses in vitro, animal studies have revealed that allogeneic and xenogeneic MSCs are rejected. METHODOLOGY/PRINCIPAL FINDINGS: We aim to overcome MSC immune rejection through permanent down-regulation of major histocompatibility complex (MHC) class I proteins on the surface of these MHC class II-negative cells through the use of viral immune evasion proteins. Transduction of hMSCs with a retroviral vector encoding the human cytomegalovirus US11 protein resulted in strong inhibition of MHC class I surface expression. When transplanted into immunocompetent mice, persistence of the US11-expressing and HLA-ABC-negative hMSCs at levels resembling those found in immunodeficient (i.e., NOD/SCID) mice could be attained provided that recipients' natural killer (NK) cells were depleted prior to cell transplantation. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate the potential utility of herpesviral immunoevasins to prevent rejection of xenogeneic MSCs. The observation that down-regulation of MHC class I surface expression renders hMSCs vulnerable to NK cell recognition and cytolysis implies that multiple viral immune evasion proteins are likely required to make hMSCs non-immunogenic and thereby universally transplantable