MUKtwelve protocol: a phase II randomised, controlled, open, parallel group, multicentre trial of selinexor, cyclophosphamide and prednisolone (SCP) versus cyclophosphamide and prednisolone (CP) in patients with relapsed or refractory multiple myeloma.

INTRODUCTION: Multiple myeloma is a malignancy of plasma cells with around 6000 new cases per year in the UK. Cyclophosphamide plus prednisolone is considered a standard of care for disease and symptom control in the advanced relapsed or refractory myeloma setting within the UK NHS. The selective nuclear export inhibitor, selinexor, has been relatively well tolerated in previous clinical trials and offers promise when used in combination with a wide range of other anti-cancer treatments. Here, we investigate if the addition of selinexor can improve responses to cyclophosphamide plus prednisolone without adding prohibitive toxicity. METHODS AND ANALYSIS: MUKtwelve is a UK-based, randomised, controlled, open, parallel group, multicentre phase II trial designed to evaluate clinical efficacy of selinexor in combination with cyclophosphamide and prednisolone (SCP) in patients with relapsed or refractory multiple myeloma. A calibration arm will receive cyclophosphamide and prednisolone alone (CP). Participants who experience disease progression on the CP arm may, if eligible, receive SCP.The MUKtwelve trial results will be the first to assess clinical efficacy of selinexor with low-dose CP in relapsed/refractory multiple myeloma. It is widely accepted that the relapsing-remitting nature of the disease is accompanied by cellular changes that often result in the requirement for novel agents and drug combinations to regain disease control. Patients also often experience cumulative toxicities throughout their treatments, limiting the treatment intensity that can be given at relapse. Thus, there is a need for novel effective combination therapies with acceptable toxicity profiles. ETHICS AND DISSEMINATION: Ethics approval is obtained. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN15028850

Impact of culture towards disaster risk reduction

Number of natural disasters has risen sharply worldwide making the risk of disasters a global concern. These disasters have created significant losses and damages to humans, economy and society. Despite the losses and damages created by disasters, some individuals and communities do not attached much significance to natural disasters. Risk perception towards a disaster not only depends on the danger it could create but also the behaviour of the communities and individuals that is governed by their culture. Within this context, this study examines the relationship between culture and disaster risk reduction (DRR). A comprehensive literature review is used for the study to evaluate culture, its components and to analyse a series of case studies related to disaster risk. It was evident from the study that in some situations, culture has become a factor for the survival of the communities from disasters where as in some situations culture has acted as a barrier for effective DRR activities. The study suggests community based DRR activities as a mechanism to integrate with culture to effectively manage disaster risk

Representing complex data using localized principal components with application to astronomical data

Often the relation between the variables constituting a multivariate data space might be characterized by one or more of the terms: ``nonlinear'', ``branched'', ``disconnected'', ``bended'', ``curved'', ``heterogeneous'', or, more general, ``complex''. In these cases, simple principal component analysis (PCA) as a tool for dimension reduction can fail badly. Of the many alternative approaches proposed so far, local approximations of PCA are among the most promising. This paper will give a short review of localized versions of PCA, focusing on local principal curves and local partitioning algorithms. Furthermore we discuss projections other than the local principal components. When performing local dimension reduction for regression or classification problems it is important to focus not only on the manifold structure of the covariates, but also on the response variable(s). Local principal components only achieve the former, whereas localized regression approaches concentrate on the latter. Local projection directions derived from the partial least squares (PLS) algorithm offer an interesting trade-off between these two objectives. We apply these methods to several real data sets. In particular, we consider simulated astrophysical data from the future Galactic survey mission Gaia.Comment: 25 pages. In "Principal Manifolds for Data Visualization and Dimension Reduction", A. Gorban, B. Kegl, D. Wunsch, and A. Zinovyev (eds), Lecture Notes in Computational Science and Engineering, Springer, 2007, pp. 180--204, http://www.springer.com/dal/home/generic/search/results?SGWID=1-40109-22-173750210-

Effects of ocean acidification on invertebrate settlement at volcanic CO<inf>2</inf> vents

We present the first study of the effects of ocean acidification on settlement of benthic invertebrates and microfauna. Artificial collectors were placed for 1 month along pH gradients at CO2 vents off Ischia (Tyrrhenian Sea, Italy). Seventy-nine taxa were identified from six main taxonomic groups (foraminiferans, nematodes, polychaetes, molluscs, crustaceans and chaetognaths). Calcareous foraminiferans, serpulid polychaetes, gastropods and bivalves showed highly significant reductions in recruitment to the collectors as pCO2 rose from normal (336-341 ppm, pH 8.09-8.15) to high levels (886-5,148 ppm) causing acidified conditions near the vents (pH 7.08-7.79). Only the syllid polychaete Syllis prolifera had higher abundances at the most acidified station, although a wide range of polychaetes and small crustaceans was able to settle and survive under these conditions. A few taxa (Amphiglena mediterranea, Leptochelia dubia, Caprella acanthifera) were particularly abundant at stations acidified by intermediate amounts of CO2 (pH 7. 41-7.99). These results show that increased levels of CO2 can profoundly affect the settlement of a wide range of benthic organisms. © 2010 Springer-Verlag

The effect of protective covers on pollinator health and pollination service delivery

Protective covers (i.e., glasshouses, netting enclosures, and polytunnels) are increasingly used in crop production to enhance crop quality, yield, and production efficiency. However, many protected crops require insect pollinators to achieve optimal pollination and there is no consensus about how best to manage pollinators and crop pollination in these environments. We conducted a systematic literature review to synthesise knowledge about the effect of protective covers on pollinator health and pollination services and identified 290 relevant studies. Bees were the dominant taxon used in protected systems (90%), represented by eusocial bees (e.g., bumble bees (Bombus spp.), honey bees (Apis spp.), stingless bees (Apidae: Meliponini)) and solitary bees (e.g., Amegilla spp., Megachile spp., and Osmia spp.). Flies represented 9% of taxa and included Calliphoridae, Muscidae, and Syrphidae. The remaining 1% of taxa was represented by Lepidoptera and Coleoptera. Of the studies that assessed pollination services, 96% indicate that pollinators were active on the crop and/or their visits resulted in improved fruit production compared with flowers not visited by insects (i.e., insect visits prevented, or flowers were self- or mechanically pollinated). Only 20% of studies evaluated pollinator health. Some taxa, such as mason or leafcutter bees, and bumble bees can function well in covered environments, but the effect of covers on pollinator health was negative in over 50% of the studies in which health was assessed. Negative effects included decreased reproduction, adult mortality, reduced forager activity, and increased disease prevalence. These effects may have occurred as a result of changes in temperature/humidity, light quality/quantity, pesticide exposure, and/or reduced access to food resources. Strategies reported to successfully enhance pollinator health and efficiency in covered systems include: careful selection of bee hive location to reduce heat stress and improve dispersal through the crop; increased floral diversity; deploying appropriate numbers of pollinators; and manipulation of flower physiology to increase attractiveness to pollinating insects. To improve and safeguard crop yields in pollinator dependent protected cropping systems, practitioners need to ensure that delivery of crop pollination services is compatible with suitable conditions for pollinator health

Measuring uncertainty and assessing its predictive power in the euro area

Expectations and uncertainty play a key role in economic behavior. This paper deals with both, expectations and uncertainty derived from the European Central Bank Survey of Professional Forecasters. Given the strong turbulences that the euro area macroeconomic indicators observe since 2007, the aim of the paper is to check whether there is any room for improvement of the consensus forecast accuracy for GDP growth and inflation when accounting for uncertainty. We propose a new measure of uncertainty, alternative to the ad hoc equal weights commonly used, based on principal components. We test the role of uncertainty in forecasting macroeconomic performance in the euro area between 2005 and 2015. We also check the role of surprises in the considered forecasting sampleMinisterio de Economía y CompetitividadFinancial support from the Spanish Ministry of Economy and Competitiveness, project numbers ECO2015-70331-C2-1-R, ECO2015-66593-P and ECO2014-56676C2-2-P and Universidad de Alcalá is acknowledged

Evaluation of the psychometric properties of the London Measure of Unplanned Pregnancy in Brazilian Portuguese

Background: Estimates of unplanned pregnancy worldwide are of concern, especially in low and middle-income countries, including Brazil. Although the contraceptive prevalence rate is high in Brazil, almost half of all pregnancies are reported as unintended. The only source of nationally representative data about pregnancy intention is the Demographic and Health Survey, as with many other countries. In more recent years, however, it has been realized that concept of unintended pregnancy is potentially more complex and requires more sophisticated measurement strategies, such as the London Measure of Unplanned Pregnancy (LMUP). The LMUP has been translated and validated in other languages, but not Portuguese yet. In this study, we evaluate the psychometric properties of the LMUP in the Portuguese language, Brazilian version. Methods: A Brazilian Portuguese version of the LMUP was produced via translation and back-translation. After piloting, the mode of administration was changed from self-completion to interviewer-administration. The measure was field tested with pregnant, postpartum, and postabortion women recruited at maternity and primary health care services in Sao Paulo city. Reliability (internal consistency) was assessed using Cronbach’s alpha and item-total correlations. Construct validity was assessed using principal components analysis and hypothesis testing. Scaling was assessed with Mokken analysis. Results: 759 women aged 15–44 completed the Brazilian Portuguese LMUP. There were no missing data. The measure was acceptable and well targeted. Reliability testing demonstrated good internal consistency (alpha = 0.81, all item-rest correlations >0.2). Validity testing confirmed that the measure was unidimensional and that all hypotheses were met: there were lower LMUP median scores among women in the extreme age groups (p<0.001), among non-married women (p<0.001) and those with lower educational attainment (p<0.001). The Loevinger H coefficient was 0.60, indicating a strong scale. Conclusion: The Brazilian Portuguese LMUP is a valid and reliable measure of pregnancy planning/intention that is now available for use in Brazil. It represents a useful addition to the public health research and surveillance toolkit in Brazil

Reservoir stress path and induced seismic anisotropy: Results from linking coupled fluid-flow/geomechanical simulation with seismic modelling

We present a workflow linking coupled fluid-flow and geomechanical simulation with seismic modelling to predict seismic anisotropy induced by nonhydrostatic stress changes. We generate seismic models from coupled simulations to examine the relationship between reservoir geometry, stress path and seismic anisotropy. The results indicate that geometry influences the evolution of stress, which leads to stress-induced seismic anisotropy. Although stress anisotropy is high for the small reservoir, the effect of stress arching and the ability of the side-burden to support the excess load limit the overall change in effective stress and hence seismic anisotropy. For the extensive reservoir, stress anisotropy and induced seismic anisotropy are high. The extensive and elongate reservoirs experience significant compaction, where the inefficiency of the developed stress arching in the side-burden cannot support the excess load. The elongate reservoir displays significant stress asymmetry, with seismic anisotropy developing predominantly along the long-edge of the reservoir. We show that the link between stress path parameters and seismic anisotropy is complex, where the anisotropic symmetry is controlled not only by model geometry but also the nonlinear rock physics model used. Nevertheless, a workflow has been developed to model seismic anisotropy induced by non-hydrostatic stress changes, allowing field observations of anisotropy to be linked with geomechanical models