bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity and safety of early vaccination with two doses of a combined measles-mumps-rubella-varicella vaccine in healthy Indian children from 9 months of age: a phase III, randomised, non-inferiority trial
Authors: Lalwani Sanjay , Chatterjee Sukanta , Balasubramanian Sundaram , Bavdekar Ashish , Mehta Shailesh , Datta Sanjoy , Povey Michael , Henry Ouzama 
Published: September 2015

ObjectiveThis study (NCT00969436) compared the immunogenicity and safety of measles-mumps-rubella (MMR) followed by MMR+varicella (V) vaccines to (1) 2 doses of combined MMRV and (2) MMR followed by MMRV, in Indian children.DesignPhase III, open, randomised, non-inferiority study.Setting6 tertiary care hospitals located in India.ParticipantsHealthy participants aged 9–10 months not previously vaccinated against/exposed to measles, mumps, rubella and varicella or without a history of these diseases.InterventionsParticipants were randomised (2:2:1) to receive 2 doses of either MMRV (MMRV/MMRV group) or MMR followed by MMRV (MMR/MMRV group) or MMR followed by MMR+V (MMR/MMR+V, control group) at 9 and 15 months of age. Antibody titres against measles, mumps and rubella were measured using ELISA and against varicella using an immunofluorescence assay.Main outcome measuresTo demonstrate non-inferiority of the 2 vaccination regimens versus the control in terms of seroconversion rates, defined as a group difference with a lower bound of the 95% CI >−10% for each antigen, 43 days postdose 2. Parents/guardians recorded solicited local and general symptoms for a 4-day and 43-day period after each vaccine dose, respectively.ResultsSeroconversion rates postdose 1 ranged from 87.5% to 93.2% for measles, 83.3% to 86.1% for mumps and 98.7% to 100% for rubella across the 3 vaccine groups. The seroconversion rates postdose 2 were 100% for measles, mumps and rubella and at least 95.8% for varicella across the 3 vaccine groups. Non-inferiority of MMRV/MMRV and MMR/MMRV to MMR/MMR+V was achieved for all antigens, 43 days postdose 2. The 3 vaccination regimens were generally well tolerated in terms of solicited local and general symptoms.ConclusionsThe immune responses elicited by the MMRV/MMRV and MMR/MMRV vaccination regimens were non-inferior to those elicited by the MMR/MMR+V regimen for all antigens. The 3 vaccination schedules also exhibited an acceptable safety profile in Indian children.Trial registration numberNCT00969436.
Risk of myocardial infarction (MI) and death following MI in people with chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis
Authors: Rothnie Kieran J , Yan Ruoling , Smeeth Liam , Quint Jennifer K 
Published: September 2015

ObjectivesCardiovascular disease is an important comorbidity in patients with chronic obstructive pulmonary disease (COPD). We aimed to systematically review the evidence for: (1) risk of myocardial infarction (MI) in people with COPD; (2) risk of MI associated with acute exacerbation of COPD (AECOPD); (3) risk of death after MI in people with COPD.DesignSystematic review and meta-analysis.MethodsMEDLINE, EMBASE and SCI were searched up to January 2015. Two reviewers screened abstracts and full text records, extracted data and assessed studies for risk of bias. We used the generic inverse variance method to pool effect estimates, where possible. Evidence was synthesised in a narrative review where meta-analysis was not possible.ResultsSearches yielded 8362 records, and 24 observational studies were included. Meta-analysis showed increased risk of MI associated with COPD (HR 1.72, 95% CI 1.22 to 2.42) for cohort analyses, but not in case–control studies: OR 1.18 (0.80 to 1.76). Both included studies that investigated the risk of MI associated with AECOPD found an increased risk of MI after AECOPD (incidence rate ratios, IRR 2.27, 1.10 to 4.70, and IRR 13.04, 1.71 to 99.7). Meta-analysis showed weak evidence for increased risk of death for patients with COPD in hospital after MI (OR 1.13, 0.97 to 1.31). However, meta-analysis showed an increased risk of death after MI for patients with COPD during follow-up (HR 1.26, 1.13 to 1.40).ConclusionsThere is good evidence that COPD is associated with increased risk of MI; however, it is unclear to what extent this association is due to smoking status. There is some evidence that the risk of MI is higher during AECOPD than stable periods. There is poor evidence that COPD is associated with increased in hospital mortality after an MI, and good evidence that longer term mortality is higher for patients with COPD after an MI.
Effect of zinc added to a daily small-quantity lipid-based nutrient supplement on diarrhoea, malaria, fever and respiratory infections in young children in rural Burkina Faso: a cluster-randomised trial
Authors: Somé Jérôme W , Abbeddou Souheila , Yakes Jimenez Elizabeth , Hess Sonja Y , Ouédraogo Zinéwendé P , Guissou Rosemonde M , Vosti Stephen A , Ouédraogo Jean-Bosco , Brown Kenneth H 
Published: September 2015

ObjectivePreventive zinc supplementation in the form of tablets or syrup reduces the incidence of diarrhoea and acute lower respiratory tract infections (RTI), but its effect on malaria is inconsistent. When zinc is administered with other micronutrients or foods, its effect is also uncertain. We assessed the effects of different amounts and sources of zinc on the frequency of diarrhoea, malaria, fever and RTI in young children.Design, setting and populationsThis community-based, double-blind, placebo-controlled, cluster-randomised trial of 2435 children 9 months of age was carried out between April 2010 and July 2012 in rural southwestern Burkina Faso.InterventionsParticipants were randomly assigned at the concession level to receive daily 1 of 4 interventions for 9 months: (1) 20 g small-quantity lipid-based nutrient supplement (SQ-LNS) without zinc and placebo tablet, (2) 20 g SQ-LNS with 5 mg zinc and placebo tablet, (3) 20 g SQ-LNS with 10 mg zinc and placebo tablet or (4) 20 g SQ-LNS without zinc and 5 mg zinc tablet. Participants were visited weekly in their homes for morbidity surveillance for 9 months, and those with uncomplicated diarrhoea and malaria received treatment from the study field workers in the community.Main outcomesIncidence and longitudinal prevalence of diarrhoea, malaria, fever, and lower and upper RTI by intervention group.ResultsThe incidence of diarrhoea, malaria and fever was 1.10 (±1.03 SD), 0.61 (±0.66 SD) and 1.49 (±1.12 SD) episodes per 100 child-days at risk, respectively, and did not differ by intervention group (p=0.589, p=0.856 and p=0.830, respectively). The longitudinal prevalence of acute lower RTI (0.1%; 95% IC 0.1–0.2%) and of upper RTI (7.8%; 95% IC 7.1–8.4%) did not differ among groups (p=0.234 and p=0.501, respectively).ConclusionsInclusion of 5 or 10 mg zinc in SQ-LNS and provision of 5 mg zinc dispersible tablet along with SQ-LNS had no impact on the incidence of diarrhoea, malaria and fever or the longitudinal prevalence of RTI compared with SQ-LNS without zinc in this population.Trial registration numberNCT00944281.
What would encourage help-seeking for memory problems among UK-based South Asians? A qualitative study
Authors: Mukadam Naaheed , Waugh Amy , Cooper Claudia , Livingston Gill 
Published: September 2015

ObjectivesPeople from Minority Ethnic groups tend to present late to dementia services, often in crisis. Culture-specific barriers to help-seeking seem to underlie this. We sought to determine these barriers to timely help-seeking for dementia among people from South Asian backgrounds and what the features of an intervention to overcome them would be.Study designQualitative study to delineate barriers to and facilitators of help-seeking for South Asian adults with dementia through focus groups and individual interviews.SettingCommunity settings in and around Greater London.ParticipantsTo achieve a maximum variation sample, we purposively recruited 53 English or Bengali speaking South Asian adults without a known diagnosis of dementia through community centres and snowballing.ResultsParticipants ranged in age from 18 to 83 years, were mostly female and were 60% Bangladeshi. We recruited people from different religions and occupational backgrounds and included those with experience of caring for someone with dementia as well as those without this experience. Participants identified four main barriers to timely diagnosis: barriers to help-seeking for memory problems; the threshold for seeking help for memory problems; ways to overcome barriers to help-seeking; what features an educational resource should have.ConclusionsWe have identified the features of an intervention with the potential to improve timely dementia diagnosis in South Asians. The next steps are to devise and test such an intervention.
E-cigarette marketing in UK stores: an observational audit and retailers’ views
Authors: Eadie D , Stead M , MacKintosh A M , MacDonald L , Purves R , Pearce J , Tisch C , van der Sluijis W , Amos A , MacGregor A , Haw S 
Published: September 2015

ObjectivesTo explore how e-cigarettes are being promoted at point of sale in the UK and how retailers perceive market trends.SettingFixed retail outlets subject to a ban on the display of tobacco products.ParticipantsObservational audit of all stores selling tobacco products (n=96) in 4 Scottish communities, conducted over 2 waves 12 months apart (2013–2014), and qualitative interviews with small retailers (n=25) in 4 matched communities.Primary and secondary outcome measuresThe audit measured e-cigarette display characteristics, advertising materials and proximity to other products, and differences by area-level disadvantage. Interviews explored retailers’ perceptions of e-cigarette market opportunities and risks, and customer responses.ResultsThe number of e-cigarette point-of-sale display units and number of brands displayed increased between waves. E-cigarettes were displayed close to products of interest to children in 36% of stores. Stores in more affluent areas were less likely to have external e-cigarette advertising than those in deprived areas. Although e-cigarettes delivered high profit margins, retailers were confused by the diversity of brands and products, and uncertain of the sector's viability. Some customers were perceived to purchase e-cigarettes as cessation aids, and others, particularly low-income smokers, as a cheaper adjunct to conventional tobacco.ConclusionsE-cigarette point-of-sale displays and number of brands displayed increased over 12 months, a potential cause for concern given their lack of regulation. Further scrutiny is needed of the content and effects of such advertising, and the potentially normalising effects of placing e-cigarettes next to products of interest to children.
Long-term musculoskeletal morbidity after adult burn injury: a population-based cohort study
Authors: Randall Sean M , Fear Mark W , Wood Fiona M , Rea Suzanne , Boyd James H , Duke Janine M 
Published: September 2015

ObjectiveTo investigate if adults who are hospitalised for a burn injury have increased long-term hospital use for musculoskeletal diseases.DesignA population-based retrospective cohort study using linked administrative health data from the Western Australian Data Linkage System.SubjectsRecords of 17 753 persons aged at least 20 years when hospitalised for a first burn injury in Western Australia during the period 1980–2012, and 70 758 persons who were age and gender-frequency matched with no injury admissions randomly selected from Western Australia's electoral roll.Main outcome measuresAdmission rates and cumulative length of stay for musculoskeletal diseases. Negative binomial and Cox proportional hazards regression modelling were used to generate incidence rate ratios (IRR) and HRs with 95% CIs, respectively.ResultsAfter adjustment for pre-existing health status and demographic characteristics, the burn cohort had almost twice the hospitalisation rate for a musculoskeletal condition (IRR, 95% CI 1.98, 1.86 to 2.10), and spent 3.70 times as long in hospital with a musculoskeletal diagnosis (95% CI 3.10 to 4.42) over the 33-year period, than the uninjured comparison cohort. Adjusted survival analyses of incident post-burn musculoskeletal disease admissions found significant increases for the 15-year post burn discharge period (0–6 months: HR, 95% CI 2.51, 2.04 to 3.11; 6 months–2 years: HR, 95% CI 1.77, 1.53 to 2.05; 2–15 years: HR, 95% CI 1.32, 1.23 to 1.42). Incident admission rates were significantly elevated for 20 years post-burn for minor and severe burn injury for a range of musculoskeletal diseases that included arthropathies, dorsopathies, osteopathies and soft tissue disorders.ConclusionsMinor and severe burn injuries were associated with significantly increased post-burn incident admission rates, long-term hospital use and prolonged length of stay for a range of musculoskeletal diseases. Further research is required that facilitates identification of at-risk patients and appropriate treatment pathways, to reduce the long-term morbidity associated with burns.
Three centuries (1670–1970) of appreciating physical landscapes
Authors: Hose Thomas A. 
Published: September 2015

Abstract
Although modern geotourism, as a form of sustainable geoheritage tourism, was only recognized as such in the 1990s, its roots lie in the seventeenth century and the Grand Tour with its domestic equivalents. At that time, a few elite travellers recorded their experiences of landscapes, natural wonders, quarries and mines. Such travellers’ observations were supplemented by those of the antiquarians for much of the eighteenth century; at that century's close, the first modern geologists were recording their observations. The nineteenth century witnessed an explosion in public interest and engagement with geology, and field excursions were provided by the burgeoning natural history and geology societies. By the close of the nineteenth century, the Romantic movement had successfully promoted wild landscapes to a newly expanding urban population. The development of the Grand Tour and the landscape aesthetic movements, the various influential institutions, key personalities and locations are considered insofar as they provide an overview of the background to historical geotourism. All are underpinned by a theoretical consideration of the geotourism paradigm and how geotourism historical studies can contextualize modern geotourism.
Cenozoic evolution of the Pamir and Tien Shan mountains reflected in syntectonic deposits of the Tajik Basin
Authors: Klocke M. , Voigt T. , Kley J. , Pfeifer S. , Rocktäschel T. , Keil S. , Gaupp R. 
Published: September 2015

Abstract
The NE Tajik Basin in Central Asia, compressed between the ranges of the Tien Shan in the north and the Pamir in the south, is a key region for understanding the evolution of these mountain systems. Erosion and deposition history of the NE Tajik Basin and the adjoining orogens since the late Oligocene is reflected in the sedimentary record.
The sedimentary rocks of the NE Tajik Basin are composed of thick units of proximal braided river deposits. They reflect large fluvial plains extending from the margins of the Northern Pamir and the Southern Tien Shan mountains, but are not related to the established lithostratigraphic scheme. Almost all Oligocene–Pliocene synorogenic deposits of the NE Tajik Basin were derived from the northern Pamir ranges, except upper Miocene–Recent proximal deposits close to the active margin of the Tien Shan. Initial uplift in some areas of the SW Tien Shan since the Oligocene was followed by a phase of low-energy sedimentation and a predominance of the southern source area. Since the middle Miocene, erosion of the ranges has occurred with the proximal sedimentation of coarse fluvial deposits along the northern margin of the Tajik Basin.
From DNA Damage to Nucleic Acid Sensing: A Strategy to Enhance Radiation Therapy
Authors: Deng Liufu , Liang Hua , Fu Sherry , Weichselbaum Ralph R. , Fu Yang-Xin 
Published: September 2015

Abstract
Local irradiation (IR) is widely used in the treatment of primary and metastatic tumors. However, the impact of IR on the immune response is currently being defined. Local and distant relapse after radiotherapy often occurs. The current rationale for the use of IR is based on direct cytotoxicity to cancer cells; however, recent studies have shown that reduction of tumor burden following ablative (large-dose) IR largely depends on type I IFN signaling and CD8+ T-cell response. Here, we review recent findings indicating that antitumor effects of radiation are contributed by both innate and adaptive immune responses. We focus on immune mechanisms, including cytosolic DNA sensing pathways that bridge the traditional view of IR-mediated DNA damage to DNA-sensing immune pathways. Also, we discuss how the efficacy of radiotherapy might be enhanced by targeting nucleic acid–sensing pathways. These findings highlight the mechanisms governing tumor escape from the immune response and the therapeutic potential of synergistic strategies to improve the efficacy of radiotherapy via immunotherapeutic intervention. Clin Cancer Res; 22(1); 20–25. ©2015 AACR.
Molecular Pathways: Targeting ATR in Cancer Therapy
Authors: Karnitz Larry M. , Zou Lee 
Published: September 2015

AbstractThe human ATR gene encodes a kinase that is activated by DNA damage and replication stress as a central transducer of a checkpoint signaling pathway. Once activated, ATR phosphorylates multiple substrates, including the kinase Chk1, to regulate cell-cycle progression, replication fork stability, and DNA repair. These events promote cell survival during replication stress and in cells with DNA damage. Accordingly, there has been the tantalizing possibility that ATR inhibitors would be therapeutically useful, especially if they were more effective in tumor versus normal cells. Indeed, multiple studies have demonstrated that alterations that promote tumorigenesis, such as defects in the ATM-p53 pathway, constitutive oncogene activation, and acquisition of the alternative lengthening of telomeres pathway, render tumor cells sensitive to ATR inhibitor monotherapy and/or increase the synergy between ATR inhibitors and genotoxic chemotherapies. Now, nearly two decades after the discovery of ATR, two highly selective and potent ATR inhibitors, AZD6738 and VX-970, are in early-phase clinical trials either as monotherapies or paired with a variety of genotoxic chemotherapies. These trials will generate important insights into the effects of ATR inhibition in humans and the potential role of inhibiting this kinase in the treatment of human malignancies. Clin Cancer Res; 21(21); 4780–5. ©2015 AACR.
Convergence analysis of the MCGNR algorithm for the least squares solution group of discrete-time periodic coupled matrix equations
Authors: Hajarian Masoud 
Published: September 2015

The conjugate gradient normal equations residual minimizing (CGNR) algorithm is a popular tool for solving large nonsymmetric linear systems. In this study, we propose the matrix form of the CGNR (MCGNR) algorithm to find the least squares solution group of the discrete-time periodic coupled matrix equations [Formula: see text] with periodic matrices. We prove that the MCGNR algorithm converges in a finite number of steps in the absence of round-off errors, that is, this algorithm has the finite termination property. Also we show that the norms of the residual matrices of the MCGNR algorithm decrease monotonically during its iteration, that is, this algorithm has the residual reducing property. To show the efficiency of the MCGNR algorithm, two numerical examples are presented.
Multiple sclerosis lesion formation and early evolution revisited: A weekly high-resolution magnetic resonance imaging study
Authors: Guttmann Charles RG , Rousset Matthieu , Roch Jean A , Hannoun Salem , Durand-Dubief Françoise , Belaroussi Boubakeur , Cavallari Michele , Rabilloud Muriel , Sappey-Marinier Dominique , Vukusic Sandra , Cotton François 
Published: September 2015

Background: Several magnetic resonance imaging (MRI) studies investigated the evolution of multiple sclerosis (MS) lesions to understand the pathophysiological mechanisms leading to blood-brain barrier breakdown and lesion formation. Only a few assessed the early natural history of MS lesions using short-interval longitudinal MRI. Objective: The purpose of this study was to characterize MS lesion occurrence and early evolution on high-resolution MRI acquired at weekly intervals. Methods: Active lesions were characterized on 3D fluid attenuation inversion recovery (FLAIR) and gadolinium-enhanced 3D T1-weighted MRI performed weekly (seven weeks) on five untreated patients with relapsing–remitting MS (RRMS). Results: Active lesions ( n=212) were detected in all patients. All showed contrast-enhancement on at least one time-point. Most new lesions (83.5%) were visible on FLAIR and post-contrast T1-weighted images at first detection; 11.2% showed activity on FLAIR images, one or more weeks before the appearance of contrast-enhancement; 12.5% enhanced before being apparent on FLAIR. Conclusion: Blood brain barrier disruption is a constant step in the natural history of active MS lesions, but does not always constitute the initial event. These findings are consistent with the existence of a subpopulation of lesions with an ‘inside-out’ genesis, where neurodegenerative processes might precede microglial activation, and a subsequent adaptive immune response.
Increased albumin quotient (QAlb) in patients after first clinical event suggestive of multiple sclerosis is associated with development of brain atrophy and greater disability 48 months later
Authors: Uher Tomas , Horakova Dana , Tyblova Michaela , Zeman David , Krasulova Eva , Mrazova Katerina , Seidl Zdenek , Vaneckova Manuela , Krasensky Jan , Weinstock-Guttman Bianca , Ramanathan Murali , Havrdova Eva , Zivadinov Robert 
Published: September 2015

Background: The utility of blood–brain barrier (BBB) biomarkers for clinical and magnetic resonance imaging progression in multiple sclerosis (MS) has not been extensively investigated. Objectives: To determine whether cerebrospinal fluid (CSF) measures of BBB at clinical onset predict radiological and clinical deterioration over 48 months. Methods: This longitudinal study included 182 patients after first clinical event suggestive of MS treated with weekly intramuscular interferon beta-1a. CSF and serum samples were analyzed for leukocytes, total protein, albumin, immunoglobulins, and oligoclonal bands. Optimal thresholds for the albumin quotient (QAlb) were determined. Mixed-effect model analyses, adjusted for age, gender, and treatment escalation, were used to analyze relationship between CSF measures and disease activity outcomes over 48 months of follow-up. Results: Increased QAlb at clinical onset was associated with enlargement of lateral ventricles ( p = .001) and greater whole brain ( p = .003), white matter ( p < .001), corpus callosum ( p < .001), and thalamus ( p = .003) volume loss over 48 months. Higher QAlb was associated with higher Expanded Disability Status Scale score over 48 months ( p = .002). Conclusions: Increased QAlb at clinical onset is associated with increased brain atrophy and greater disability in patients after first clinical event suggestive of MS.