bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association betweenhuman leucocyte antigen-DOpolymorphisms and interferon/ribavirin treatment response in hepatitis C virus type 1 infection in Chinese population: a prospective study
Authors: Yao Yinan , Liu Mei , Zang Feng , Yue Ming , Xia Xueshan , Feng Yue , Fan Haozhi , Zhang Yun , Huang Peng , Yu Rongbin 
Published: April 2018

ObjectiveThehuman leucocyte antigen-DO(HLA-DO) gene located in theHLAnon-classical class-II region may play a role in treatment response to hepatitis C virus (HCV). This study was conducted to explore the role of single nucleotide polymorphisms (SNPs) inHLA-DOin responding to HCV therapy.SettingAll patients were recruited between January 2011 and September 2016 from the Jurong People’s Hospital, Jiangsu Province, China.ParticipantsA total of 346 chronic hepatitis C (CHC) patients who finished the 48-week pegylated interferon-alpha and ribavirin (PEG IFN-α/RBV) treatment were enrolled in this study. All patients were former remunerated blood donors. The inclusion criteria for patients were as follows: (1) treatment-naive and treated with PEG IFN-α/RBV, (2) HCV RNA was present in serum for over 6 months before treatment, (3) negative for hepatitis B (HBV) or HIV infection and (4) lacked any other hepatic diseases.All participants in this study were Chinese Han population and infected with HCV genotype 1b and treated with subcutaneous PEG IFN-α at a dose of 180 µg once a week with the addition of 800–1000 mg/d RBV according to weight orally for 48 weeks.ResultsThe SNPsHLA-DOArs1044429 andHLA-DOBrs2284191 and rs2856997 of 18 SNPs were correlated with HCV treatment response in the Chinese Han population. The dominant model indicated that patients carrying favourable genotypes at rs1044429 AA and rs2284191 AA were more likely to achieve sustained virological response (SVR) (OR 1.99, 95% CI 1.25 to 3.19; OR 2.71, 95% CI 1.58 to 4.63, respectively), while patients carrying unfavourable genotypes at rs2856997 GG were less likely to achieve SVR (OR 0.48, 95% CI 0.29 to 0.78).ConclusionGenetic variations at rs1044429, rs2284191 and rs2856997 were independent predictors of HCV treatment response in the Chinese Han population.
Association between physical activity and health-related quality of life in elderly individuals with pre-diabetes in rural Hunan Province, China: a cross-sectional study
Authors: Xu Huilan , Tang Lu , Hu Zhao , Gao Fan , Yang Yang , Qin Lulu , Luo Bang-an 
Published: April 2018

ObjectivesThere are few data on the relationship between health-related quality of life (HRQoL) and physical activity among elderly individuals with pre-diabetes. This study aimed to determine if differences existed in HRQoL between individuals with pre-diabetes who were physically active compared with those who were physically inactive in rural China.Design, setting and participantsA cross-sectional survey was conducted among the elderly (≧60 years) in rural communities in Yiyang City of China. Multistage cluster random sampling was carried out to select 42 areas, and interviews were conducted among 434 elderly individuals with pre-diabetes. Pre-diabetes was screened using an oral glucose tolerance test.Main outcome measuresThe Medical Outcomes Study 36-Item Short Form Health Survey questionnaire was used to measure HRQoL. Physical activity was assessed using the International Physical Activity Questionnaire. Multivariate analysis of covariance (MANCOVA) was used to test for differences in HRQoL between the physically active group and the inactive group.ResultsA total of 434 individuals with pre-diabetes were included in this study. The physical component summary (PCS) score of HRQoL was 42.1±10.2 and the mental component summary score was 46.4±8.9. A median total physical activity of 524 metabolic equivalent-min/week was reported. A significant MANCOVA model (Wilks’ λ=0.962,F(2,423)=8.44, P<0.001) indicated that elderly individuals with pre-diabetes who were physically active reported higher PCS scores (Mdiff=5.2, P<0.001, effective size=0.47) compared with those physically inactive after adjusting for the following covariates: age, gender, marital status, education, smoking, chronic disease, body mass index and waist:hip ratio.ConclusionsThe HRQoL of elderly individuals with pre-diabetes is poor in rural China. These findings demonstrated that elderly individuals with pre-diabetes who were physically active had higher PCS scores than those who were physically inactive. Furthermore, these results support the rationale for developing a physical activity intervention for HRQoL of individuals with pre-diabetes.Trial registration numberChiCTR-IOR-15007033; Results.
OPTIMAL and ENSURE trials-based combined cost-effectiveness analysis of erlotinib versus chemotherapy for the first-line treatment of Asian patients with non-squamous non-small-cell lung cancer
Authors: Wen Feng , Zheng Hanrui , Zhang Pengfei , Hutton David , Li Qiu 
Published: April 2018

ObjectivesErlotinib, the first generation of epidermoid growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been recommended as an essential treatment in patients with non-small-cell lung cancer (NSCLC) with EGFR mutation. Although it has improved progression-free survival (PFS), overall survival (OS) was limited and erlotinib can be expensive. This cost-effectiveness analysis compares erlotinib monotherapy with gemcitabine-included doublet chemotherapy.SettingFirst-line treatment of Asian patients with NSCLC with EGFR mutation.MethodsA Markov model was created based on the results of the ENSURE (NCT01342965) and OPTIMAL (CTONG-0802) trials which evaluated erlotinib and chemotherapy. The model simulates cancer progression and all causes of death. All medical costs were calculated from the perspective of the Chinese healthcare system.Main outcome measuresThe primary outcomes are costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs).ResultsThe combined PFS was 11.81 months and 5.1 months for erlotinib and chemotherapy, respectively, while the OS was reversed at 24.68 months for erlotinib and 26.16 months for chemotherapy. The chemotherapy arm gained 0.13 QALYs compared with erlotinib monotherapy (1.17 QALYs vs 1.04 QALYs), while erlotinib had lower costs ($55 230 vs $77 669), resulting in an ICER of $174 808 per QALY for the chemotherapy arm, which exceeds three times the Chinese GDP per capita. The most influential factors were the health utility of PFS, the cost of erlotinib and the health utility of progressed disease.ConclusionErlotinib monotherapy may be acceptable as a cost-effective first-line treatment for NSCLC compared with gemcitabine-based chemotherapy. The results were robust to changes in assumptions.Trial registration numberNCT01342965and CTONG-0802.
A protocol for a Canadian prospective observational study of decision-making on active surveillance or surgery for low-risk papillary thyroid cancer
Authors: Sawka Anna M , Ghai Sangeet , Tomlinson George , Rotstein Lorne , Gilbert Ralph , Gullane Patrick , Pasternak Jesse , Brown Dale , de Almeida John , Irish Jonathan , Chepeha Douglas , Higgins Kevin , Monteiro Eric , Jones Jennifer M , Gafni Amiram , Goldstein David P 
Published: April 2018

IntroductionLow-risk papillary thyroid cancer (PTC) is increasingly being diagnosed throughout the world; yet the mortality risk is low compared with other malignancies. Traditional management includes thyroid surgery, sometimes followed by radioactive iodine and thyroid hormone treatment. Active surveillance (AS) has been proposed as a means to reduce overtreatment of PTC. AS involves close disease follow-up, with the intention to intervene if the disease progresses, or on patient request.Methods and analysisThis is a multiphase prospective observational study. In the first phase of this study, consenting eligible adults with low-risk PTC, that is, <2 cm in maximal diameter, confined to the thyroid and not immediately adjacent to critical structures in the neck, are provided verbal and written information about PTC disease prognosis following surgery or AS. Questionnaires are administered at baseline and after the disease management decision on AS or surgery is finalised. Patients may choose either option (surgery or AS), and the primary outcome is the frequency with which either disease management option is chosen. Secondary outcomes include: rationale for the decision, role of the patient in decision-making and decision satisfaction. In the second phase of the study, consenting eligible adult patients who completed the first study phase may enrol in respective AS or surgery group follow-up studies. The following outcomes are examined 1 year after enrolment in the follow-up phase: decision regret about disease management choice (primary outcome), psychological distress, disease-specific quality of life, fear of disease progression, body image satisfaction, disease progression, crossover to surgery in the AS group, new chronic thyroid hormone use and healthcare resource utilisation.Ethics and disseminationThe University Health Network Research Ethics Board approved this study (ID 15-8942). The results will be published in an open access journal.Trial registration numberNCT03271892; Pre-results.
Improving antibiotic prescribing by general practitioners: a protocol for a systematic review of interventions involving pharmacists
Authors: Saha Sajal K , Hawes Lesley , Mazza Danielle 
Published: April 2018

IntroductionEffective antibiotic options in general practice for patients with infections are declining significantly due to antibiotic over-prescribing and emerging antibiotic resistance. To better improve antibiotic prescribing by general practitioner (GP), pharmacist–GP collaborations have been promoted under antibiotic stewardship programmes. However, there is insufficient information about whether and how pharmacists help GPs to more appropriately prescribe antibiotics. This systematic review aims to determine whether pharmacist-led or pharmacist-involved interventions are effective at improving antibiotic prescribing by GPs.Methods and analysisA systematic review of English language randomised controlled trials (RCTs), cluster RCTs, controlled before-and-after studies and interrupted time series studies cited in MEDLINE, EMBASE, EMCARE, CINAHL Plus, PubMed, PsycINFO, Cochrane Central Register of Controlled Trials and Web of Science databases will be conducted. Studies will be included if a pharmacist is involved as the intervention provider and GPs are the intervention recipients in general practice setting. Data extraction and management will be conducted using Effective Practice and Organisation of Care data abstraction tools and a template for intervention description and replication. The Cochrane and ROBINS-I risk of bias assessment tools will be used to assess the methodological quality of studies. Primary outcome measures include changes (overall, broad spectrum and guidelines concordance) of GP-prescribed antibiotics. Secondary outcomes include quality of antibiotic prescribing, delayed antibiotic use, acceptability and feasibility of interventions. Meta-analysis for combined effect and forest plots, χ2test and I2statistics for detailed heterogeneity and sensitivity analysis will be performed if data permit. Grading of Recommendations Assessment, Development and Evaluation and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidance will be used to report findings.Ethics and disseminationNo ethics approval is required as no primary, personal or confidential data are being collected in this study. The findings will be disseminated to national and international scientific sessions and published in a peer-reviewed journal.PROSPERO registration numberCRD42017078478.
Is there an association between nurse, clinical teacher and peer feedback for trainee doctors’ medical specialty choice? An observational study in Taiwan
Authors: Hsu Chih-Ming , Hsiao Cheng-Ting , Chang Li-Chun , Chang Hung-Yu 
Published: April 2018

ObjectivesThis study explored whether there is an association between medical trainees’ future specialty choices and the 360-degree feedback they receive. We hypothesised that the higher the scores that teachers, trainees and/or nurses give to postgraduate year 1s (PGY1s) in any given specialty, the more likely that they will choose that specialty for their residency.SettingThe study was conducted in a large regional teaching hospital in Taiwan.ParticipantsThe participants of this study were n=66 PGY1s who had completed their medical studies domestically or internationally and had received their PGY1 training in a single teaching hospital in southern Taiwan. Data from 990 assessments were included.Primary and secondary outcome measuresLogistic regression analyses for teachers’, nursing staff and peers’ authentic assessments of trainees were undertaken for (1) desired specialty, (2) applied specialty, (3) enrolled specialty, (4) consistency between desired and applied specialties, (5) consistency between applied and enrolled specialties and (6) consistency between desired and enrolled specialties. Alpha was set at p<0.05.ResultsNursing staff scores were significantly associated with all six dependent variables. Furthermore, teachers’ scores were significantly associated with trainees’ desired specialty and the consistency between desired and enrolled specialty. Peers’ scores were not significantly associated with any dependent variable.ConclusionsTrainees’ specialty choices are associated with scores given by nursing staff and clinical teachers. We suggest that qualitative research methods should further explore this association to ascertain whether PGY1s are consciously influenced by these scores and if so, in what way.
Enhancing the quality and safety of care through training generalist doctors: a longitudinal, mixed-methods study of a UK broad-based training programme
Authors: Bullock Alison , Webb Katie Louise , Muddiman Esther , MacDonald Janet , Allery Lynne , Pugsley Lesley 
Published: April 2018

ObjectiveChanging patient demographics make it ever more challenging to maintain the quality and safety of care. One approach to addressing this is the development of training for generalist doctors who can take a more holistic approach to care. The purpose of the work we report here is to consider whether a broad-based training programme prepares doctors for a changing health service.Setting and participantsWe adopted a longitudinal, mixed-methods approach, collecting questionnaire data from trainees on the broad-based training (BBT) programme in England (baseline n=62) and comparator trainees in the same regions (baseline n=90). We held 15 focus groups with BBT trainees and one-to-one telephone interviews with trainees post-BBT (n=21) and their Educational Supervisors (n=9).ResultsFrom questionnaire data, compared with comparator groups, BBT trainees were significantly more confident that their training would result in: wider perspectives, understanding specialty complementarity, ability to apply learning across specialties, manage complex patients and provide patient-focused care. Data from interviews and focus groups provided evidence of positive consequences for patient care from BBT trainees’ ability to apply knowledge from other specialties. Specifically, insights from BBT enabled trainees to tailor referrals and consider patients’ psychological as well as physical needs, thus adopting a more holistic approach to care. Unintended consequences were revealed in focus groups where BBT trainees expressed feelings of isolation. However, when we explored this sentiment on questionnaire surveys, we found that at least as many in the comparator groups sometimes felt isolated.ConclusionsPractitioners with an understanding of care across specialty boundaries can enhance patient care and reduce risks from poor inter-specialty communication. Internationally, there is growing recognition of the place of generalism in medical practice and the need to take a more person-centred approach. Broad-based approaches to training support the development of generalist doctors, which is well-suited to a changing health service.
Comparative effectiveness of treatments to prevent dental caries given to rural children in school-based settings: protocol for a cluster randomised controlled trial
Authors: Ruff Ryan Richard , Niederman Richard 
Published: April 2018

IntroductionDental caries is the most prevalent childhood disease in the world and can lead to infection, pain and reduced quality of life. Multiple prevention agents are available to arrest and prevent dental caries; however, little is known of the comparative effectiveness of combined treatments when applied in pragmatic settings. The aim of the presented study is to compare the benefit of silver diamine fluoride and fluoride varnish versus fluoride varnish and glass ionomer therapeutic sealants in the arrest and prevention of dental caries.Methods and analysisA longitudinal, pragmatic, cluster randomised, single-blind, non-inferiority trial will be conducted in low-income rural children enrolled in public elementary schools in New Hampshire, USA, from 2018 to 2023. The primary objective is to compare the non-inferiority of alternative agents in the arrest and prevention of dental caries. The secondary objective is to compare cost-effectiveness of both interventions. Caries arrest will be evaluated after 2 years, and caries prevention will be assessed at the completion of the study. Data analysis will follow intent to treat, and statistical analyses will be conducted using a significance level of 0.05.Ethics and disseminationThe standard of care for dental caries is office-based surgery, which presents multiple barriers to care including cost, fear and geographic isolation. The common intervention used in school-based caries prevention is dental sealants. The simplicity and affordability of silver diamine fluoride may be a viable alternative for the prevention of dental caries in high-risk children. Results can be used to inform policy for best practices in school-based oral healthcare.Trial registrationNCT03448107. Pre-results.
UK petrol retailing: competitive rivalry and the decline of the oil majors in the twentieth century
Authors: Ritson Neil H. , Byrne Ian , Cohen David A. 
Published: April 2018

Abstract
The development of the retail petroleum industry in the UK has received only sporadic attention by academics. This is curious, as the industry has vital importance to modern commerce. The industry is usually thought of as an oligarchy, with a small number of companies controlling the production and movement of products through vertical integration. However, there is evidence of change in the industry: there has been a significant number of exchanges of retailing sites between the major entities themselves, and a rise in the number and influence of competitors. These constitute both multiple retailers such as supermarket chains and, at the ‘competitive fringe’, a rise in the number of smaller independents. This paper identifies the historical changes and analyses the factors underlying them.
The history of exploration and development of the Liverpool Bay fields and the East Irish Sea Basin
Authors: Bunce J. 
Published: April 2018

Abstract
Hydrocarbon exploration in the East Irish Sea Basin began with the identification of surface oil seeps in peat beds in Lancashire, UK. This precipitated the drilling of the first onshore exploration wells. The discovery of the Formby Field in west Lancashire at the end of the 1930s triggered a wave of further drilling. Wells drilled in west Lancashire had limited success, with only minor hydrocarbon shows, whilst the production from the Formby Field was modest. Nonetheless, the invaluable geological information taken from onshore wells and the ratification of the Continental Shelf Act led to a shift in focus to the offshore and a period of significant interest in the East Irish Sea. Two key periods of oil and gas exploration activity stand out in the history of the offshore basin, the first headed by the Gas Council during the 1970s resulted in the discovery of the gas giants of Morecambe Bay, whilst the second fronted by Hamilton Oil during the 1990s heralded the discovery of oil with the Douglas and Lennox fields in Liverpool Bay. Exploration in the basin has waned during the last decade; however, to date, this mature hydrocarbon province has yielded estimated hydrocarbon reserves of over 1.8 BBOE (billion barrels of oil equivalent).
Archibald Geikie and the Ice Age controversy
Authors: Summerhayes Colin P. 
Published: April 2018

Abstract
In the early 1830s Charles Lyell was convinced that much of western Europe had been submerged during the Pleistocene by cold seas strewn with icebergs; the relicts of whose loads of rock and mud occurred on land as boulder clay and erratic blocks. Swiss scientist Louis Agassiz disagreed, considering in 1837 that these were the products of deposition by a great ice sheet. Archibald Geikie realized by 1863 that Lyell was wrong. Mountain glaciers had carved the topography of Scotland and other parts of the UK, feeding an ice sheet that left glacial erratics behind when it melted away. He hoped, in vain, to change Lyell's mind. Archibald Geikie's mantle passed to his brother James, who compiled evidence from around the world to demonstrate the correctness of his brother's thesis. It was published in 1874 just before Lyell died still arguing for the correctness of his iceberg theory, which gave us the word ‘drift’ for the unconsolidated deposits mantling the UK. Even so, by then Lyell had gone some way – no doubt partly influenced by the Geikies – to accepting that in certain instances glacial action had, indeed, moved large erratic blocks – locally even uphill, as in the Jura.
Introduction of Genetically Modified CD3ζ Improves Proliferation and Persistence of Antigen-Specific CTLs
Authors: Miyao Kotaro , Terakura Seitaro , Okuno Shingo , Julamanee Jakrawadee , Watanabe Keisuke , Hamana Hiroshi , Kishi Hiroyuki , Sakemura Reona , Koyama Daisuke , Goto Tatsunori , Nishida Tetsuya , Murata Makoto , Kiyoi Hitoshi 
Published: April 2018

Abstract
The clinical efficacy of T-cell therapies based on T cells transduced with genes encoding tumor-specific T-cell receptors (TCR-T) is related to the in vivo persistence of the T cells. To improve persistence without modifying TCR affinity, we instead modified intracellular signaling, using artificial T cell–activating adapter molecules (ATAM), generated by inserting the intracellular domain (ICD) of activating T-cell signaling moieties into CD3ζ. ATAMs with the ICD of either CD28 or 4-1BB were generated, assembled into the TCR complex as a part of CD3ζ, and enhanced downstream signaling from the supramolecular activation cluster. ATAMs were retrovirally introduced into human CMV-specific or NY-ESO-1–specific TCR-transduced CD8+ T lymphocytes, and downstream functionality was then examined. ATAM-transduced NY-ESO-1 TCR-T cells were also investigated using the U266-xenograft mouse model. ATAMs were successfully transduced and localized to the cell membrane. ATAM-transduced CMV-specific T cells retained their cytotoxic activity and cytokine production against peptide-pulsed target cells without altering antigen-specificity and showed resistance to activation-induced cell death. Upon both single and repeated stimulation, CD3ζ/4-1BB–transduced T cells had superior proliferation to the CD3ζ-transduced T cells in both the CMV-specific and the NY-ESO-1 TCR-T models and significantly improved antitumor activity compared with untransduced T cells both in vitro and in a mouse xenograft model. ATAM-transduced TCR-T cells demonstrated improved proliferation and persistence in vitro and in vivo. This strategy to control the intracellular signaling of TCR-T cells by ATAM transduction in combination with various tumor-specific TCRs may improve the efficacy of TCR-T therapy. Cancer Immunol Res; 6(6); 733–44. ©2018 AACR.