Upscaling in the sharing economy: insights from the UK

Aimed at academics, private businesses, investors and public sector bodies, this report develops a typology of upscaling models in the sharing economy across three key sectors: accommodation, transportation, and professional and personal services

Commissioning measurements on an Elekta Unity MR-Linac

Magnetic resonance-guided radiotherapy technology is relatively new and commissioning publications, quality assurance (QA) protocols and commercial products are limited. This work provides guidance for implementation measurements that may be performed on the Elekta Unity MR-Linac (Elekta, Stockholm, Sweden). Adaptations of vendor supplied phantoms facilitated determination of gantry angle accuracy and linac isocentre, whereas in-house developed phantoms were used for end-to-end testing and anterior coil attenuation measurements. Third-party devices were used for measuring beam quality, reference dosimetry and during treatment plan commissioning; however, due to several challenges, variations on standard techniques were required. Gantry angle accuracy was within 0.1°, confirmed with pixel intensity profiles, and MV isocentre diameter was < 0.5 mm. Anterior coil attenuation was approximately 0.6%. Beam quality as determined by TPR20,10 was 0.705 ± 0.001, in agreement with treatment planning system (TPS) calculations, and gamma comparison against the TPS for a 22.0 × 22.0 cm2 field was above 95.0% (2.0%, 2.0 mm). Machine output was 1.000 ± 0.002 Gy per 100 MU, depth 5.0 cm. During treatment plan commissioning, sub-standard results indicated issues with machine behaviour. Once rectified, gamma comparisons were above 95.0% (2.0%, 2.0 mm). Centres which may not have access to specialized equipment can use in-house developed phantoms, or adapt those supplied by the vendor, to perform commissioning work and confirm operation of the MRL within published tolerances. The plan QA techniques used in this work can highlight issues with machine behaviour when appropriate gamma criteria are set

Western Diet-Fed, Aortic-Banded Ossabaw Swine: A Preclinical Model of Cardio-Metabolic Heart Failure.

The development of new treatments for heart failure lack animal models that encompass the increasingly heterogeneous disease profile of this patient population. This report provides evidence supporting the hypothesis that Western Diet-fed, aortic-banded Ossabaw swine display an integrated physiological, morphological, and genetic phenotype evocative of cardio-metabolic heart failure. This new preclinical animal model displays a distinctive constellation of findings that are conceivably useful to extending the understanding of how pre-existing cardio-metabolic syndrome can contribute to developing HF

The effects of knock-down resistance mutations and alternative splicing on voltage-gated sodium channels in Musca domestica and Drosophila melanogaster

© 2020 Elsevier Ltd Voltage-gated sodium channels (VGSCs) are a major target site for the action of pyrethroid insecticides and resistance to pyrethroids has been ascribed to mutations in the VGSC gene. VGSCs in insects are encoded by only one gene and their structural and functional diversity results from posttranscriptional modification, particularly, alternative splicing. Using whole cell patch clamping of neurons from pyrethroid susceptible (wild-type) and resistant strains (s-kdr) of housefly, Musca domestica, we have shown that the V50 for activation and steady state inactivation of sodium currents (INa+) is significantly depolarised in s-kdr neurons compared with wild-type and that 10 nM deltamethrin significantly hyperpolarised both of these parameters in the neurons from susceptible but not s-kdr houseflies. Similarly, tail currents were more sensitive to deltamethrin in wild-type neurons (EC15 14.5 nM) than s-kdr (EC15 133 nM). We also found that in both strains, INa+ are of two types: a strongly inactivating (to 6.8% of peak) current, and a more persistent (to 17.1% of peak) current. Analysis of tail currents showed that the persistent current in both strains (wild-type EC15 5.84 nM) was more sensitive to deltamethrin than was the inactivating type (wild-type EC15 35.1 nM). It has been shown previously, that the presence of exon l in the Drosophila melanogaster VGSC gives rise to a more persistent INa+ than does the alternative splice variant containing exon k and we used PCR with housefly head cDNA to confirm the presence of the housefly orthologues of splice variants k and l. Their effect on deltamethrin sensitivity was determined by examining INa+ in Xenopus oocytes expressing either the k or l variants of the Drosophila para VGSC. Analysis of tail currents, in the presence of various concentrations of deltamethrin, showed that the l splice variant was significantly more sensitive (EC50 42 nM) than the k splice variant (EC50 866 nM). We conclude that in addition to the presence of point mutations, target site resistance to pyrethroids may involve the differential expression of splice variants

Exploratory study of consumer issues in online peer-to-peer platform markets: final report

This is a report published by the European Commission. For re-use please see the publisher's terms and conditions.This study explores consumer issues in five online peer to peer platform markets: (Re)sale of Goods; Sharing/renting of goods, Sharing/renting accommodation; Sharing/hiring rides; and Odd jobs. The study estimates that 191m citizens across the EU-28 spend EUR 27.9 billion per year on online P2P platforms. Of this total, an estimated EUR 10.61 billion consists of platform revenues and revenues of third parties. The study defines three main peer-to-peer platform business models: (a) hosting of listings where platforms do not get involved in the peer to peer transaction (b) active management of transactions where platforms foster trust among peers to facilitate a larger number of transactions and (c) platform governed peer transactions where the platform sets one or more contractual terms for the peer-to-peer transaction and exercises control over the performance of the transaction. The study identifies five key consumer issues that emerge from this new kind of economy: (1) transparency and clarity regarding the nature of transactions concluded through online P2P platforms, applicable consumer rights and obligations, the applicable legal framework and its enforcement; (2) reliability of peer review and rating systems and accuracy of identity information provided on the platform; (3) discrepancy between exclusion of platform responsibility and liability for the performance of online P2P transactions and platform practices; (4) access to redress for peer consumers and peer providers; and (5) data use and data protection issues.This report was produced under the EU Consumer Programme (2014-2020) in the frame of a service contract with the Consumers, Health, Agriculture and Food Executive Agency (Chafea) acting under the mandate from the European Commission.Published versio

Breast cancer risk factors in relation to breast density (United States)

OBJECTIVES: Evaluate known breast cancer risk factors in relation to breast density. METHODS: We examined factors in relation to breast density in 144,018 New Hampshire (NH) women with at least one mammogram recorded in a statewide mammography registry. Mammographic breast density was measured by radiologists using the BI-RADS classification; risk factors of interest were obtained from patient intake forms and questionnaires. RESULTS: Initial analyses showed a strong inverse influence of age and body mass index (BMI) on breast density. In addition, women with late age at menarche, late age at first birth, premenopausal women, and those currently using hormone therapy (HT) tended to have higher breast density, while those with greater parity tended to have less dense breasts. Analyses stratified on age and BMI suggested interactions, which were formally assessed in a multivariable model. The impact of current HT use, relative to nonuse, differed across age groups, with an inverse association in younger women, and a positive association in older women (p < 0.0001 for the interaction). The positive effects of age at menarche and age at first birth, and the inverse influence of parity were less apparent in women with low BMI than in those with high BMI (p = 0.04, p < 0.0001 and p = 0.01, respectively, for the interactions). We also noted stronger positive effects for age at first birth in postmenopausal women (p = 0.004 for the interaction). The multivariable model indicated a slight positive influence of family history of breast cancer. CONCLUSIONS: The influence of age at menarche and reproductive factors on breast density is less evident in women with high BMI. Density is reduced in young women using HT, but increased in HT users of age 50 or more

A through-life costing methodology for use in product-service-systems

Availability-based contracts which provide customers with the use of assets such as machines, ships, aircraft platforms or subsystems like engines and avionics are increasingly offered as an alternative to the purchase of an asset and separate support contracts. The cost of servicing a durable product can be addressed by Through-life Costing (TLC). Providers of advanced services are now concerned with the cost of delivering outcomes that meet customer requirements using combinations of assets and activities via a Product Service System (PSS). This paper addresses the question: To what extent are the current approaches to TLC methodologically appropriate for costing the provision of advanced services, particularly availability, through a PSS? A novel methodology for TLC is outlined addressing the challenges of PSS cost assessment with regard to 'what?' (cost object), 'why/to what extent?' (scope and boundaries), and 'how?' (computations). The research provides clarity for those seeking to cost availability in a performance-orientated contractual setting and provides insight to the measures that may be associated with it. In particular, a reductionist approach that focuses on one cost object at a time is not appropriate for a PSS. Costing an advanced service delivered through a PSS is a problem of attributing the value of means to the economic activities carried out for specific ends to be achieved. Cost results from the interplay between monetary and non-monetary metrics, and uncertainties thereof. Whilst seeking to ensure generality of the findings, the application of TLC examined here is limited to a military aircraft platform and subsystems. © 2014 Elsevier B.V. All rights reserved

Alternative Splicing in the Differentiation of Human Embryonic Stem Cells into Cardiac Precursors

The role of alternative splicing in self-renewal, pluripotency and tissue lineage specification of human embryonic stem cells (hESCs) is largely unknown. To better define these regulatory cues, we modified the H9 hESC line to allow selection of pluripotent hESCs by neomycin resistance and cardiac progenitors by puromycin resistance. Exon-level microarray expression data from undifferentiated hESCs and cardiac and neural precursors were used to identify splice isoforms with cardiac-restricted or common cardiac/neural differentiation expression patterns. Splice events for these groups corresponded to the pathways of cytoskeletal remodeling, RNA splicing, muscle specification, and cell cycle checkpoint control as well as genes with serine/threonine kinase and helicase activity. Using a new program named AltAnalyze (http://www.AltAnalyze.org), we identified novel changes in protein domain and microRNA binding site architecture that were predicted to affect protein function and expression. These included an enrichment of splice isoforms that oppose cell-cycle arrest in hESCs and that promote calcium signaling and cardiac development in cardiac precursors. By combining genome-wide predictions of alternative splicing with new functional annotations, our data suggest potential mechanisms that may influence lineage commitment and hESC maintenance at the level of specific splice isoforms and microRNA regulation

Ensuring competency in end-of-life care: controlling symptoms

BACKGROUND: Palliative medicine is assuming an increasingly important role in patient care. The Education for Physicians in End-of-life Care (EPEC) Project is an ambitious program to increase core palliative care skills for all physicians. It is not intended to transmit specialty level competencies in palliative care. METHOD: The EPEC Curriculum was developed to be a comprehensive syllabus including trainer notes, multiple approaches to teaching the material, slides, and videos of clinical encounters to trigger discussion are provided. The content was developed through a combination of expert opinion, participant feedback and selected literature review. Content development was guided by the goal of teaching core competencies not included in the training of generalist and non-palliative medicine specialist physicians. RESULTS: Whole patient assessment forms the basis for good symptom control. Approaches to the medical management of pain, depression, anxiety, breathlessness (dyspnea), nausea/vomiting, constipation, fatigue/weakness and the symptoms common during the last hours of life are described. CONCLUSION: While some physicians will have specialist palliative care services upon which to call, most in the world will need to provide the initial approaches to symptom control at the end-of-life