bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trait discovery and editing in tomato
Authors: Rothan Christophe , Diouf Isidore , Causse Mathilde 
Published: November 2018

SummaryTomato (Solanum lycopersicum), which is used for both processing and fresh markets, is a major crop species that is the top ranked vegetable produced over the world. Tomato is also a model species for research in genetics, fruit development and disease resistance. Genetic resources available in public repositories comprise the 12 wild related species and thousands of landraces, modern cultivars and mutants. In addition, high quality genome sequences are available for cultivated tomato and for several wild relatives, hundreds of accessions have been sequenced, and databases gathering sequence data together with genetic and phenotypic data are accessible to the tomato community. Major breeding goals are productivity, resistance to biotic and abiotic stresses, and fruit sensorial and nutritional quality. New traits, including resistance to various biotic and abiotic stresses and root architecture, are increasingly being studied. Several major mutations and quantitative trait loci (QTLs) underlying traits of interest in tomato have been uncovered to date and, thanks to new populations and advances in sequencing technologies, the pace of trait discovery has considerably accelerated. In recent years, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing (GE) already proved its remarkable efficiency in tomato for engineering favorable alleles and for creating new genetic diversity by gene disruption, gene replacement, and precise base editing. Here, we provide insight into the major tomato traits and underlying causal genetic variations discovered so far and review the existing genetic resources and most recent strategies for trait discovery in tomato. Furthermore, we explore the opportunities offered by CRISPR/Cas9 and their exploitation for trait editing in tomato.
Improvement in Film Cooling Effectiveness Using Single and Double Rows of Holes With Adverse Compound Angle Orientations
Authors: Kannan E. , Sivamani Seralathan , Roychowdhury D. G. , Micha Premkumar T. , Hariram V. 
Published: November 2018

Abstract
Three-dimensional Reynolds-averaged Navier–Stokes equations with shear stress transport turbulence model are used to analyze the film cooling effectiveness on a flat plate having single row of film hole involving cylindrical hole (CH) and laidback hole (LBH). The CH and LBH are inclined at 35 deg to the surface with a compound angle (β) orientation ranging from favorable to adverse inclination (i.e., β = 0–180 deg) and examined at high and low blowing ratios (M = 1.25 and 0.60). CH with an adverse compound angle of 135 deg gives the highest area-averaged film cooling effectiveness in comparison with LBH configuration. Also, CH β = 135 deg film hole shows a higher lateral coolant spread. Later, double jet film cooling (DJFC) concept is studied for this CH. In all the cases, the first hole compound angle is fixed as 135 deg, and the second hole angle is varied from 135 deg to 315 deg. At high blowing ratio, the dual jet cylindrical hole (DJCH) with β = 135 deg, 315 deg gives a higher area-averaged film cooling effectiveness by around 66.50% compared to baseline CH β = 0 deg. On comparing all CH, LBH, and DJCH cases, the highest area-averaged film cooling effectiveness is obtained by CH configuration with β = 135 deg. Hence, the CH with its adverse compound angle (β = 135 deg) orientation could be an appropriate film cooling configuration for gas turbine blade cooling.
Outcomes following general anaesthesia in children with hypertrophic cardiomyopathy
Authors: Norrish Gabrielle , Forshaw Natalie , Woo Colleen , Avanis Mary Claire , Field Ella , Cervi Elena , Iguchi Akane , Kaski Juan Pablo 
Published: November 2018

BackgroundChildren with hypertrophic cardiomyopathy (HCM) have historically been considered to be high-risk candidates for general anaesthesia (GA), but there is currently a paucity of evidence regarding the safety of anaesthesia and perioperative outcomes in this population.MethodsClinical features and outcomes of all paediatric patients (<18 years) with HCM undergoing GA between 2000 and 2016 were reviewed.Results86 patients (median 12.4 years (IQR 6.5, 14.9)) underwent 164 separate GA procedures. Aetiology included non-syndromic disease (n=44, 56%), malformation syndromes (n=22, 26%), inborn error of metabolism (n=10, 12%) and neuromuscular disease (n=4, 5%). At the time of GA, mean maximal wall thickness (MWT) on echocardiography was 19 mm (SD±8 mm), 23 (14%) patients had severe left ventricular hypertrophy (MWT>30 mm) and 35 (21%) patients had a haemodynamically significant left ventricular outflow tract (LVOT) gradient (>50 mm Hg). The majority (n=143, 87%) had no perioperative complications. 20 (12%) patients had minor perioperative complications: bradycardia (n=4), hypotension (n=15) or transient ST segment changes (n=1). One (0.6% of GA procedures) patient experienced a cardiac arrest during anaesthetic induction with death occurring 3 days later. Clinical parameters (including age, MWT, LVOT gradient, systolic and diastolic dysfunction) were not associated with an increased risk of complicationsConclusionsThis is the largest published series to date of paediatric patients with HCM undergoing GA, which demonstrates that, in an expert centre, patients can be anaesthetised with a relatively low perianaesthetic mortality (0.6%) and prevalence of minor complications (12%). Future studies are required to systematically identify clinical features that may predict anaesthetic risk.
Drug preparation and administration errors during simulated paediatric resuscitations
Authors: Murugan Sashen , Parris Pano , Wells Mike 
Published: November 2018

IntroductionVery few studies have assessed drug preparation and administration errors during paediatric resuscitation. Current evidence suggests that medication errors in paediatrics are a serious problem. The aim of this study was to evaluate drug preparation and administration errors incurred during the simulated resuscitation of paediatric patients.MethodsThis was a prospective observational study performed in the emergency department of a tertiary-level hospital. Teams consisting of two emergency doctors were tasked with preparing and delivering medication during simulated emergency scenarios. Preparation processes were video recorded. All phials, syringes and administered volumes were collected and analysed to determine the accuracy of drug preparation and delivery. Deviations from intended volumes were calculated.Main resultsA total of 96 dosages were recorded from 24 participants. Most errors were identified in the withdrawal of drug phase (prior to dilution) (13 of 96 doses had a >20% error), and the administration of medication phase (20 of 96 doses had a >20% error). Overall the median time taken to deliver each drug was 79 s (IQR 59, 100 s). The largest percentage errors were seen when a large syringe was used to withdraw or administer a small volume of medication.ConclusionThe study clearly demonstrated that there were significant errors in the preparation and administration of medication. Training in the preparation and administration of paediatric medications should be available for all emergency nurses and doctors. Correct syringe choice may reduce these errors—smaller syringes should be used for withdrawing or administering smaller volumes.
Time-to-event analysis for sports injury research part 2: time-varying outcomes
Authors: Nielsen Rasmus Oestergaard , Bertelsen Michael Lejbach , Ramskov Daniel , Møller Merete , Hulme Adam , Theisen Daniel , Finch Caroline F , Fortington Lauren Victoria , Mansournia Mohammad Ali , Parner Erik Thorlund 
Published: November 2018

BackgroundTime-to-event modelling is underutilised in sports injury research. Still, sports injury researchers have been encouraged to consider time-to-event analyses as a powerful alternative to other statistical methods. Therefore, it is important to shed light on statistical approaches suitable for analysing training load related key-questions within the sports injury domain.ContentIn the present article, we illuminate: (i) the possibilities of includingtime-varying outcomesin time-to-event analyses, (ii) how to deal with a situation where different types of sports injuries are included in the analyses (ie, competing risks), and (iii) how to deal with the situation where multiple subsequent injuries occur in the same athlete.ConclusionTime-to-event analyses can handle time-varying outcomes, competing risk and multiple subsequent injuries. Although powerful, time-to-event has important requirements: researchers are encouraged to carefully considerpriorto any data collection that five injuries per exposure state or transition is needed to avoid conducting statistical analyses on time-to-event data leading to biased results. This requirement becomes particularly difficult to accommodate when a stratified analysis is required as the number of variables increases exponentially for each additional strata included. In future sports injury research, we need stratified analyses if the target of our research is to respond to the question: ‘how much change in training load is too much before injury is sustained, among athletes with different characteristics?’ Responding to this question using multiple time-varying exposures (and outcomes) requires millions of injuries. This should not be a barrier for future research, but collaborations across borders to collecting the amount of data needed seems to be an important step forward.
Sarcopenia as a predictor of all-cause mortality among older nursing home residents: a systematic review and meta-analysis
Authors: Zhang Xiaoming , Wang Conghua , Dou Qingli , Zhang Wenwu , Yang Yunzhi , Xie Xiaohua 
Published: November 2018

ObjectivesThis study aims to review the evidence of sarcopenia as a predictor of all-cause mortality among nursing home residents.DesignSystematic review and meta-analysis of observational cohort studies.Data sourcesPubMed, EMBASE and the Cochrane Library databases were searched for relevant articles.ParticipantsNursing home residents.Primary and secondary outcome measuresAll-cause mortality.Data analysisSummary-adjusted HRs or risk ratios (RRs) were calculated by fixed-effects model. The risk of bias was assessed by Newcastle-Ottawa Scale.ResultsOf 2292 studies identified through the systematic review, six studies (1494 participants) were included in the meta-analysis. Sarcopenia was significantly associated with a higher risk for all-cause mortality among nursing home residents (pooled HR 1.86, 95% CI 1.42 to 2.45, p<0.001, I2=0). In addition, the subgroup analysis demonstrated that sarcopenia was associated with all-cause mortality (pooled HR 1.87,95% CI 1.38 to 2.52, p<0.001) when studies with a follow-up period of 1 year or more were analysed; however, this was not found for studies with the follow-up period less than 1 year. Furthermore, sarcopenia was significantly associated with the risk of mortality among older nursing home residents when using bioelectrical impedance analysis to diagnosis muscle mass (pooled HR 1.88, 95% CI 1.39 to 2.53, p<0.001); whereas, it was not found when anthropometric measures were used to diagnosis muscle mass.ConclusionSarcopenia is a significant predictor of all-cause mortality among older nursing home residents. Therefore, it is important to diagnose and treat sarcopenia to reduce mortality rates among nursing home residents.PROSPERO registration numberCRD42018081668
Gut Feelings Questionnaire in daily practice: a feasibility study using a mixed-methods approach in three European countries
Authors: Barais Marie , van de Wiel Margje W J , Groell Nicolas , Dany Antoine , Montier Tristan , Van Royen Paul , Stolper Erik C F 
Published: November 2018

ObjectivesThe validated Gut Feelings Questionnaire (GFQ) is a 10-item questionnaire based on the definitions of the sense of alarm and the sense of reassurance. The purpose of the GFQ is to determine the presence or absence of gut feelings in the diagnostic reasoning of general practitioners (GPs).The aim was to test the GFQ on GPs, in real practice settings, to check whether any changes were needed to improve feasibility, and to calculate the prevalence of the GPs’ sense of alarm and sense of reassurance in three different countries.SettingPrimary care, six participating centres in Belgium, France and the Netherlands.ParticipantsWe performed a think-aloud study with 24 experienced Dutch GPs, GP trainees and medical clerks who filled in the GFQ after diagnosing each of six case vignettes. We then performed a feasibility study in two phases, using a mixed-method approach, with 42 French and Dutch GPs in the first phase and then 10 Belgian, 10 Dutch and 10 French GPs in the second phase. All GPs filled in the GFQ after each of eight consultations with patients presenting new complaints and were subsequently interviewed about the use of the GFQ.Outcome measuresGPs’ experiences on using the GFQ in real practice, more specifically the average time needed for filling in the questionnaire.The prevalence of GPs’ sense of alarm and sense of reassurance.ResultsThe modified version of the GFQ, created without altering the sense of the validated items, was easy to use in daily practice. The prevalence of the GPs’ sense of alarm occurred during 23%–31% of the included consultations.ConclusionsAfter a two-step study and several minor adaptations, the final version of the GFQ proved to be a feasible and practical tool to be used for prospective observational studies in daily practice.
Human papillomavirus vaccine uptake among young gay and bisexual men who have sex with men with a time-limited targeted vaccination programme through sexual health clinics in Melbourne in 2017
Authors: McGrath Launcelot , Fairley Christopher K , Cleere Eoin F , Bradshaw Catriona S , Chen Marcus Y , Chow Eric P F 
Published: November 2018

ObjectiveIn mid-2017, the Victorian Government funded a free time-limited human papillomavirus (HPV) vaccination catch-up programme for gay and bisexual men who have sex with men (MSM) aged up to 26 years through sexual health clinics or other immunisation centres. We aimed to examine the uptake of the HPV vaccine among young MSM attending the Melbourne Sexual Health Centre (MSHC).MethodsMSM aged ≤26 attending MSHC between 27 April 2017 and 31 December 2017 were included in the analysis. HPV vaccine uptake was calculated based on the first consultation of each patient during the period. Multivariable logistic regression was performed to examine the association between vaccine uptake and patient factors.ResultsThere were 2108 MSM aged ≤26 who attended MSHC over the study period, with 7.6% (n=161) reporting previous HPV vaccination. Of the 1947 eligible men, 1134 (58.2%, 95% CI 56.0% to 60.4%) were offered the vaccine by the clinicians, and 830 men received it on the day. The vaccine coverage among all eligible MSM was 42.6% (95% CI 40.4% to 44.9%; 830 of 1947) and among MSM who were offered the vaccine by the clinicians was 73.2% (95% CI 70.5% to 75.8%; 830 of 1134). Men with a history of genital warts (adjusted OR (aOR)=3.11, 95%CI 1.39 to 6.99) and those who had >4male partners in the last 12 months (aOR=1.38, 95% CI 1.04 to 1.85) were more likely to receive the HPV vaccine on the day. 304 men declined the vaccine; most men did not specify the reason (31.3%, n=95), while 27.3% (n=83) needed time to think.ConclusionAlthough vaccine uptake was 73.2% among those offered, the actual coverage of those eligible remained unsatisfactory (42.6%) in a sexual health clinic. This highlights a clinic-based targeted MSM programme may not reach sufficiently high vaccine coverage to provide MSM with the same vaccine benefits as heterosexuals.
Restricting tobacco sales to only pharmacies combined with cessation advice: a modelling study of the future smoking prevalence, health and cost impacts
Authors: Petrović-van der Deen Frederieke S , Blakely Tony , Kvizhinadze Giorgi , Cleghorn Christine L , Cobiac Linda J , Wilson Nick 
Published: November 2018

ObjectiveRestricting tobacco sales to pharmacies only, including the provision of cessation advice, has been suggested as a potential measure to hasten progress towards the tobacco endgame. We aimed to quantify the impacts of this hypothetical intervention package on future smoking prevalence, population health and health system costs for a country with an endgame goal: New Zealand (NZ).MethodsWe used two peer-reviewed simulation models: 1) a dynamic population forecasting model for smoking prevalence and 2) a closed cohort multi-state life-table model for future health gains and costs by sex, age and ethnicity. Greater costs due to increased travel distances to purchase tobacco were treated as an increase in the price of tobacco. Annual cessation rates were multiplied with the effect size for brief opportunistic cessation advice on sustained smoking abstinence.ResultsThe intervention package was associated with a reduction in future smoking prevalence, such that by 2025 prevalence was 17.3%/6.8% for Māori (Indigenous)/non-Māori compared to 20.5%/8.1% projected under no intervention. The measure was furthermore estimated to accrue 41 700 discounted quality-adjusted life-years (QALYs) (95% uncertainty interval (UI): 33 500 to 51 600) over the remainder of the 2011 NZ population’s lives. Of these QALYs gained, 74% were due to the provision of cessation advice over and above the limiting of sales to pharmacies.ConclusionsThis work provides modelling-level evidence that the package of restricting tobacco sales to only pharmacies combined with cessation advice in these settings can accelerate progress towards the tobacco endgame, and achieve large population health benefits and cost-savings.
FDA Approval Summary: Axicabtagene Ciloleucel for Relapsed or Refractory Large B-cell Lymphoma
Authors: Bouchkouj Najat , Kasamon Yvette L. , de Claro R. Angelo , George Bindu , Lin Xue , Lee Shiowjen , Blumenthal Gideon M. , Bryan Wilson , McKee Amy E. , Pazdur Richard 
Published: November 2018

Abstract
In October 2017, the FDA granted regular approval to axicabtagene ciloleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. Efficacy was based on complete remission (CR) rate and duration of response (DOR) in 101 adult patients with relapsed or refractory large B-cell lymphoma (median 3 prior systemic regimens) treated on a single-arm trial. Patients received a single infusion of axicabtagene ciloleucel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine. The objective response rate per independent review committee was 72% [95% confidence interval (CI), 62–81], with a CR rate of 51% (95% CI, 41–62). With a median follow-up of 7.9 months, the median DOR was not reached in patients achieving CR (95% CI, 8.1 months; not estimable, NE), whereas patients with partial remission had an estimated median DOR of 2.1 months (95% CI, 1.3–5.3). Among 108 patients evaluated for safety, serious adverse reactions occurred in 52%. Cytokine release syndrome and neurologic toxicities occurred in 94% and 87% of patients, respectively, leading to implementation of a risk evaluation and mitigation strategy.
A Multiyear Analysis of Global Precipitation Combining CloudSat and GPM Precipitation Retrievals
Authors: Hayden Lindsey , Liu Chuntao 
Published: November 2018

Abstract
Satellite-based instruments are essential to the observation of precipitation at a global scale, especially over remote regions. Each instrument has its own strengths and limitations in accurately determining the rate of precipitation at the surface. By using the complementary strengths of two instruments, a more complete analysis of global precipitation can be performed. The Global Precipitation Measurement (GPM) Core Observatory’s Dual-Frequency Precipitation Radar (DPR) is capable of measuring precipitation at high and medium precipitation rates by using Ku-band (13.6 GHz) radiation. The CloudSat satellite’s Cloud Profiling Radar (CPR) uses higher-frequency W-band (94 GHz) radiation and is therefore capable of measuring precipitation at low rates not detected by the GPM DPR. CloudSat observations from January 2007 to December 2016 and DPR observations from March 2014 to February 2018 are combined and the results examined. Since these datasets are not completely coincident, this study is conducted as a multiyear analysis. Observed precipitation from CloudSat is used starting at the lowest precipitation rates and increasing rates until the occurrence observed by GPM surpasses that of CloudSat, at which point data from GPM are used. The precipitation rate at which this change occurs contains important information on the amount of precipitation missed by each instrument and implications as to the size of the hydrometeors present. Liquid precipitation retrieval from CloudSat is not performed over land; analysis over land is produced here using the information available. By combining the two datasets, a more complete picture of precipitation occurring globally is obtained.
Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial
Authors: Fox Edward J , Markowitz Clyde , Applebee Angela , Montalban Xavier , Wolinsky Jerry S , Belachew Shibeshih , Fiore Damian , Pei Jinglan , Musch Bruno , Giovannoni Gavin 
Published: November 2018

Background: Upper extremity (UE) impairment is common with primary progressive multiple sclerosis (PPMS). Objective: This exploratory analysis examined the effects of ocrelizumab on confirmed progression (CP) and confirmed improvement (CI) in UE impairment in patients from ORATORIO. Methods: Patients with PPMS received ocrelizumab 600 mg or placebo every 24 weeks for ⩾120 weeks. The Nine-Hole Peg Test (9HPT) was administered at baseline (BL) and every 12 weeks thereafter. Prespecified exploratory endpoints included change in 9HPT time and proportion of patients with CP of ⩾20% in 9HPT. Analysis populations included intention-to-treat (ITT) patients and subgroups stratified by BL 9HPT time and Expanded Disability Status Scale. Post hoc analyses included the proportion of patients achieving more severe thresholds of CP and the proportion achieving CI in 9HPT. Results: Among ITT patients, ocrelizumab significantly reduced the change in 9HPT time over 120 weeks, the risk of CP of ⩾20% in 9HPT time for both hands and the risk of more severe 9HPT progression versus placebo. Numerical trends also favoured ocrelizumab versus placebo with respect to achieving CI. Consistent directional trends were observed in subgroup analyses. Conclusion: Ocrelizumab reduces the risk of UE disability progression and may increase the possibility of improvement versus placebo in PPMS.