183 research outputs found

    What’s in a Name? Parents’ and Healthcare Professionals’ Preferred Terminology for Pathogenic Variants in Childhood Cancer Predisposition Genes

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    Current literature/guidelines regarding the most appropriate term to communicate a cancer-related disease-causing germline variant in childhood cancer lack consensus. Guidelines also rarely address preferences of patients/families. We aimed to assess preferences of parents of children with cancer, genetics professionals, and pediatric oncologists towards terminology to describe a disease-causing germline variant in childhood cancer. Using semi-structured interviews we asked participants their most/least preferred terms from; ‘faulty gene,’ ‘altered gene,’ ‘gene change,’ and ‘genetic variant,’ analyzing responses with directed content analysis. Twenty-five parents, 6 genetics professionals, and 29 oncologists participated. An equal number of parents most preferred ‘gene change,’ ‘altered gene,’ or ‘genetic variant’ (n = 8/25). Parents least preferred ‘faulty gene’ (n = 18/25). Half the genetics professionals most preferred ‘faulty gene’ (n = 3/6); however this was least preferred by the remaining genetics professionals (n = 3/6). Many oncologists most preferred ‘genetic variant’ (n = 11/29) and least preferred ‘faulty gene’ (n = 19/29). Participants across all groups perceived ‘faulty gene’ as having negative connotations, potentially placing blame/guilt on parents/children. Health professionals described challenges selecting a term that was scientifically accurate, easily understood and not distressing to families. Lack of consensus highlights the need to be guided by families’ preferred terminology, while providing accurate explanations regarding implications of genetic findings

    Consumer Stockpiling and Sales Promotions

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    In retailing markets of storable goods, consumer behavior is typically characterized by stockpiling. While existing research has developed rich models for such strategic consumer behavior, little is known about how sellers should ideally respond to it. In this paper, we provide insights into how frequency and depth of promotions affect consumer purchases and seller revenues in the long run. We show an application to the U.S. market for laundry detergent. We use estimates from a structural dynamic demand model to simulate different pricing policies and find that in the detergent market, an increase in promotion depth is more effective than a change in promotion length. Our results suggest that this finding can be translated to markets with a large heterogeneity in storage costs and steady consumption rates

    An overlooked play? Structure, stratigraphy and hydrocarbon prospectivity of the Carboniferous in the East Irish Sea–North Channel basin complex

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    Seismic mapping of key Paleozoic surfaces in the East Irish Sea–North Channel region has been incorporated into a review of hydrocarbon prospectivity. The major Carboniferous basinal and inversion elements are identified, allowing an assessment of the principal kitchens for hydrocarbon generation and possible migration paths. A Carboniferous tilt-block is identified beneath the central part of the (Permian–Mesozoic) East Irish Sea Basin (EISB), bounded by carbonate platforms to the south and north. The importance of the Bowland Shale Formation as the key source rock is reaffirmed, the Pennine Coal Measures having been extensively excised following Variscan inversion and pre-Permian erosion. Peak generation from the Bowland source coincided with maximum burial of the system in late Jurassic–early Cretaceous time. Multiphase Variscan inversion generated numerous structural traps whose potential remains underexplored. Leakage of hydrocarbons from these into the overlying Triassic Ormskirk Sandstone reservoirs is likely to have occurred on a number of occasions, but currently unknown is how much resource remains in place below the Base Permian Unconformity. Poor permeability in the Pennsylvanian strata beneath the Triassic fields is a significant risk; the same may not be true in the less deeply buried marginal areas of the EISB, where additional potential plays are present in Mississippian carbonate platforms and latest Pennsylvanian clastic sedimentary rocks. Outside the EISB, the North Channel, Solway and Peel basins also contain Devonian and/or Carboniferous rocks. There have, however, been no discoveries, largely a consequence of the absence of a high-quality source rock and a regional seal comparable to the Mercia Mudstone Group and Permian evaporites of the Cumbrian Coast Group in the EISB

    A Perspective of Coagulation Dysfunction in Multiple Sclerosis and in Experimental Allergic Encephalomyelitis

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    A key role of both coagulation and vascular thrombosis has been reported since the first descriptions of multiple sclerosis (MS). Subsequently, the observation of a close concordance between perivascular fibrin(ogen) deposition and the occurrence of clinical signs in experimental allergic encephalomyelitis (EAE), an animal model of MS, led to numerous investigations focused on the role of thrombin and fibrin(ogen). Indeed, the activation of microglia, resident innate immune cells, occurs early after fibrinogen leakage in the pre-demyelinating lesion stage of EAE and MS. Thrombin has both neuroprotective and pro-apoptotic effects according to its concentration. After exposure to high concentrations of thrombin, astrocytes become reactive and lose their neuroprotective and supportive functions, microglia proliferate, and produce reactive oxygen species, IL-1β, and TNFα. Heparin inhibits the thrombin generation and suppresses EAE. Platelets play an important role too. Indeed, in the acute phase of the disease, they begin the inflammatory response in the central nervous system by producing of IL-1alpha and triggering and amplifying the immune response. Their depletion, on the contrary, ameliorates the course of EAE. Finally, it has been proven that the use of several anticoagulant agents can successfully improve EAE. Altogether, these studies highlight the role of the coagulation pathway in the pathophysiology of MS and suggest possible therapeutic targets that may complement existing treatments

    Overview of the 21CXRM Palaeozoic Project : a regional petroleum systems analysis of the offshore Carboniferous and Devonian of the UKCS

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    This report gives an overview of the 21CXRM Palaeozoic Project background, scope and products (Sections 1-3). It explains how the component reports and datasets of the project fit together. Overview technical information (e.g. key diagrams and charts applicable across the reports for each area) is reproduced in Sections 6 and 7 for reference, particularly as background for users of the specialist reports. A visual representation of the regional coverage and quantity of digital Palaeozoic Project products is given in Figure 1

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Inference of Consumer Consideration Sets

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    When consumers face a large number of alternatives, they tend to simplify the decision problem by reducing the number of available alternatives to a subset of relevant alternatives, i.e. a consideration set. Since consideration sets are typically unobserved, most studies in the demand literature have to assume a consideration model. If these consideration models are misspecified, the demand estimates can be biased. In this paper, we develop an approach to formally test any two competing models of consideration against one another in order to determine which model fits the data best. Our test follows the intuition of a menu approach and uses supplemental data on marginal cost-shifters to construct overidentifying restrictions. We show an application to German retailing of coffee and milk. We find that consideration sets are fundamentally different for coffee and milk, and relate our findings to differences in demand and supply conditions of the two product categories

    A randomized controlled trial of a decision aid for women considering genetic testing for breast and ovarian cancer risk

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    PURPOSE: To measure the effectiveness of a tailored decision aid (DA) designed to help women make informed decisions about genetic testing for breast/ovarian cancer risk. METHODS: A total of 145 women were randomized to receive the DA or a control pamphlet at the end of their first genetic counseling consultation. Of these, 120 (82.8%) completed two questionnaires, 1 week and 6 months post-consultation. RESULTS: While the DA had no effect on informed choice, post-decisional regret or actual genetic testing decision, the trial showed that women who received the DA had higher knowledge levels and felt more informed about genetic testing than women who received the control pamphlet (chi(2)(2) = 6.82; P = 0.033; chi(2)(1) = 4.86; P = 0.028 respectively). The DA also helped women who did not have blood drawn at their first consultation to clarify their values with regards to genetic testing (chi(2)(1) = 5.27; P = 0.022). Women who received the DA were less likely to share the information with other family members than women in the control condition (chi(2)(1) = 8.78; P = 0.003). CONCLUSIONS: Decision aids are an effective decision-support strategy for women considering genetic testing for breast/ovarian cancer risk, and are most effective before the patient has made a decision, which is generally at the point of having blood drawn
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