bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health promotion by International Olympic Sport Federations: priorities and barriers
Authors: Mountjoy Margo , Junge Astrid , Budgett Richard , Doerr Dominik , Leglise Michel , Miller Stuart , Moran Jane , Foster Jeremy 
Published: March 2019

ObjectiveTo identify changes in International Federations’ priorities and the barriers to implementing athlete and global health initiatives. Results should influence the work of the International Federation medical committees, the IOC and the Association of Summer Olympic International Federation.MethodsThe 28 Summer and 7 Winter International Federations participating in the most recent Olympic Games (2016; 2018) were surveyed to (i) identify the importance of 27 health topics, (ii) assess their progress on implementation health-related programmes and (iii) the barriers to implementation of these programmes. We compared International Federations’ activities in 2016 and 2017.ResultsThe response rate was 83%. Health topics which most International Federations regarded as important and in which the International Federations felt insufficiently active were ‘team physician certification’, ‘prevention of harassment and abuse’, ‘eating disorders/disordered eating’, ‘mental health’ and ‘injury surveillance’. Compared with 2016, there was a decrease in International Federations’ activities in ‘injury surveillance’, ‘nutritional supplements’ and ‘hyperandrogenism’. The main barrier to implementing health-related programmes was ‘International Federation political support/willingness’, followed by ‘knowledge’. ‘Time’ and ‘coach support’ were more often reported than ‘finances’, or ‘IOC or Association of Summer Olympic International Federations partnership’.ConclusionIf International Federations are going to promote health of athletes and global health promotion through physical activity (sport), International Federation leadership must change their focus and provide greater political support for related initiatives. Improving coach and athlete knowledge of the health issues could also facilitate health programme delivery. Time constraints could be mitigated by sharing experiences among the International Federations, Association of Summer Olympic International Federations and the IOC. International Federations should focus on those health-related topics that they identified as being important, yet rate as having insufficient activity.
Major incident triage and the evaluation of the Triage Sort as a secondary triage method
Authors: Vassallo James , Smith Jason 
Published: March 2019

IntroductionA key principle in the effective management of major incidents is triage, the process of prioritising patients on the basis of their clinical acuity. In many countries including the UK, a two-stage approach to triage is practised, with primary triage at the scene followed by a more detailed assessment using a secondary triage process, the Triage Sort. To date, no studies have analysed the performance of the Triage Sort in the civilian setting. The primary aim of this study was to determine the performance of the Triage Sort at predicting the need for life-saving intervention (LSI).MethodsUsing the Trauma Audit Research Network (TARN) database for all adult patients (>18 years) between 2006 and 2014, we determined which patients received one or more LSIs using a previously defined list. The first recorded hospital physiology was used to categorise patient priority using the Triage Sort, National Ambulance Resilience Unit (NARU) Sieve and the Modified Physiological Triage Tool-24 (MPTT-24). Performance characteristics were evaluated using sensitivity and specificity with statistical analysis using a McNemar’s test.Results127 233patients (58.1%) had complete data and were included: 55.6% men, aged 61.4 (IQR 43.1–80.0 years), ISS 9 (IQR 9–16), with 24 791 (19.5%) receiving at least one LSI (priority 1). The Triage Sort demonstrated the lowest accuracy of all triage tools at identifying the need for LSI (sensitivity 15.7% (95% CI 15.2 to 16.2) correlating with the highest rate of under-triage (84.3% (95% CI 83.8 to 84.8), but it had the greatest specificity (98.7% (95% CI 98.6 to 98.8).ConclusionWithin a civilian trauma registry population, the Triage Sort demonstrated the poorest performance at identifying patients in need of LSI. Its use as a secondary triage tool should be reviewed, with an urgent need for further research to determine the optimum method of secondary triage.
Targeted next-generation sequencing detects rare genetic events in pheochromocytoma and paraganglioma
Authors: Ben Aim Laurène , Pigny Pascal , Castro-Vega Luis Jaime , Buffet Alexandre , Amar Laurence , Bertherat Jérôme , Drui Delphine , Guilhem Isabelle , Baudin Eric , Lussey-Lepoutre Charlotte , Corsini Carole , Chabrier Gérard , Briet Claire , Faivre Laurence , Cardot-Bauters Catherine , Favier Judith , Gimenez-Roqueplo Anne-Paule , Burnichon Nelly 
Published: March 2019

BackgroundKnowing the genetic status of patients affected by paragangliomas and pheochromocytomas (PPGL) is important for the guidance of their management and their relatives. Our objective was to improve the diagnostic performances of PPGL genetic testing by next-generation sequencing (NGS).MethodsWe developed a custom multigene panel, which includes 17 PPGL genes and is compatible with both germline and tumour DNA screening. The NGS assay was first validated in a retrospective cohort of 201 frozen tumour DNAs and then applied prospectively to 623 DNAs extracted from leucocytes, frozen or paraffin-embedded PPGL tumours.ResultsIn the retrospective cohort, the sensitivity of the NGS assay was evaluated at 100% for point and indels mutations and 86% for large rearrangements. The mutation rate was re-evaluated from 65% (132/202) to 78% (156/201) after NGS analysis. In the prospective cohort, NGS detected not only germline and somatic mutations but also co-occurring variants and mosaicism. A mutation was identified in 74% of patients for whom both germline and tumour DNA were available.ConclusionThe analysis of 824 DNAs from patients with PPGL demonstrated that NGS assay significantly improves the performances of PPGL genetic testing compared with conventional methods, increasing the rate of identified mutations and identifying rare genetic mechanisms.
Zebrafish model of amyloid light chain cardiotoxicity: regeneration versus degeneration
Authors: Mishra Shikha , Joshi Shaurya , Ward Jennifer E. , Buys Eva P. , Mishra Deepak , Mishra Deepa , Morgado Isabel , Fisch Sudeshna , Lavatelli Francesca , Merlini Giampaolo , Dorbala Sharmila , MacRae Calum A. , Liao Ronglih 
Published: March 2019

Cardiac dysfunction is the most frequent cause of morbidity and mortality in amyloid light chain (AL) amyloidosis caused by a clonal immunoglobulin light chain (LC). Previously published transgenic animal models of AL amyloidosis have not recapitulated the key phenotype of cardiac dysfunction seen in AL amyloidosis, which has limited our understanding of the disease mechanisms in vivo, as well as the development of targeted AL therapeutics. We have developed a transgenic zebrafish model in which a λ LC derived from a patient with AL amyloidosis is conditionally expressed in the liver under the control of the Gal4 upstream activation sequence enhancer system. Circulating LC levels of 125 µg/ml in these transgenic zebrafish are comparable to median pathological serum LC levels. Functional analysis links abnormal contractile function with evidence of cellular and molecular proteotoxicity in the heart, including increased cell death and autophagy. However, despite pathological and functional phenotypes analogous to human AL, the lifespan of the transgenic fish is comparable to control fish without the expressed AL-LC transgene. Nuclear labeling experiments suggest increased cardiac proliferation in the transgenic fish, which can be counteracted by treatment with a small molecule proliferation inhibitor leading to increased zebrafish mortality because of cardiac apoptosis and functional deterioration. This transgenic zebrafish model provides a platform to study underlying AL disease mechanisms in vivo further.NEW & NOTEWORTHY Heart failure is a major cause of mortality in amyloid light (AL) amyloidosis, yet it has been difficult to model in animals. We report the generation of a transgenic zebrafish model for AL amyloidosis with pathological concentration of circulating human light chain protein that results in cardiac dysfunction. The light chain toxicity triggers regeneration in the zebrafish heart resulting in functional compensation early in life, but with age develops into cardiac dysfunction.
Streamlining Detection of Fusion Genes in Colorectal Cancer: Having “Faith” in Precision Oncology in the (Tissue) “Agnostic” Era
Authors: Valeri Nicola 
Published: March 2019

Abstract
The FDA recently granted tissue-agnostic approval for the first-in-class TRK inhibitor larotrectinib for patients whose tumors harbor fusions in neurotrophic receptor tyrosine kinases. These fusion genes have a frequency of less than 1% in unselected patients with colorectal cancer. Using a multiomics approach and a clinically annotated cohort of patients with colorectal cancer, Cocco and colleagues showed that patients with sporadic, RAS/BRAF wild-type, mismatch repair–deficient colorectal cancer tumors with MLH1 promoter methylation present fusions in kinase genes in 42% of cases and suggested a diagnostic framework to improve the selection of patients eligible for gene fusion testing.
See related article by Cocco et al., p. 1047
Rationale for Raising Current Clinical Practice Guideline Target for Serum 25-Hydroxyvitamin D in Chronic Kidney Disease
Authors: Strugnell Stephen A. , Sprague Stuart M. , Ashfaq Akhtar , Petkovich Martin , Bishop Charles W. 
Published: March 2019

<b><i>Background:</i></b> Vitamin D repletion is recommended for secondary hyperparathyroidism (SHPT) and associated vitamin D insufficiency (VDI) in chronic kidney disease (CKD), but optimal levels of serum total 25-hydroxyvitamin D remain undefined. Clinical practice guidelines target sufficiency, whereas recent data indicate that higher levels are required to control the elevation of intact parathyroid hormone (iPTH) as CKD advances. This secondary analysis of 2 randomized controlled trials seeks to identify the minimum level of mean serum 25-hydroxyvitamin D required to control SHPT arising from VDI in stage 3 or 4 CKD. <b><i>Methods:</i></b> Adult subjects (<i>n</i> = 429) with SHPT, VDI, and stage 3 or 4 CKD were stratified by stage and treated daily with either extended-release calcifediol (ERC) or placebo in 2 identical, parallel, randomized, double-blind studies. After treatment for 26 weeks, all subjects were ranked by the level of serum total 25-hydroxyvitamin D and divided into quintiles in order to examine the relationships between the degree of vitamin D repletion and the associated changes in plasma iPTH, serum bone turnover markers, calcium, phosphorus, intact fibroblast growth factor 23 (FGF23) and vitamin D metabolites, estimated glomerular filtration rate (eGFR), and urine calcium:creatinine (Ca:Cr) ratio. <b><i>Results:</i></b> Progressive increases in serum 1,25-dihydroxyvitamin D and reductions in plasma iPTH and serum bone turnover markers were observed as mean posttreatment serum 25-hydroxyvitamin D rose from 13.9 ng/mL (in Quintile 1) to 92.5 ng/mL (in Quintile 5), irrespective of CKD stage. Mean serum calcium, phosphorus and FGF23, eGFR, and urine Ca:Cr ratio (collectively “safety parameters”) did not significantly change from Quintile 1. Suppression of iPTH and bone turnover markers was not observed until serum 25-hydroxyvitamin D rose to at least 50.8 ng/mL (Quintile 3). <b><i>Conclusion:</i></b> ERC therapy produced exposure-dependent reductions in plasma iPTH and bone turnover markers only when mean serum total 25-hydroxyvitamin D reached at least 50.8 ng/mL, indicating that current targets for vitamin D repletion therapy in CKD are too low. Gradual elevation of mean serum 25-hydroxyvitamin D to 92.5 ng/mL was not associated with significant adverse changes in safety parameters.
Doxorubicin Exposure Causes Subacute Cardiac Atrophy Dependent on the Striated Muscle–Specific Ubiquitin Ligase MuRF1
Authors: Willis Monte S. , Parry Traci L. , Brown David I. , Mota Roberto I. , Huang Wei , Beak Ju Youn , Sola Michael , Zhou Cynthia , Hicks Sean T , Caughey Melissa C. , D’Agostino Ralph B. , Jordan Jennifer , Hundley W. Gregory , Jensen Brian C. 
Published: March 2019

Background
Anthracycline chemotherapeutics, such as doxorubicin, are used widely in the treatment of numerous malignancies. The primary dose-limiting adverse effect of anthracyclines is cardiotoxicity that often presents as heart failure due to dilated cardiomyopathy years after anthracycline exposure. Recent data from animal studies indicate that anthracyclines cause cardiac atrophy. The timing of onset and underlying mechanisms are not well defined, and the relevance of these findings to human disease is unclear.

Methods and Results

Wild-type mice were sacrificed 1 week after intraperitoneal administration of doxorubicin (1–25 mg/kg), revealing a dose-dependent decrease in cardiac mass (
R
2
=0.64;
P
<0.0001) and a significant decrease in cardiomyocyte cross-sectional area (336±29 versus 188±14 µm
2
;
P
<0.0001). Myocardial tissue analysis identified a dose-dependent upregulation of the ubiquitin ligase, MuRF1 (muscle ring finger-1; R
2
=0.91;
P
=0.003) and a molecular profile of muscle atrophy. To investigate the determinants of doxorubicin-induced cardiac atrophy, we administered doxorubicin 20 mg/kg to mice lacking MuRF1 (MuRF1
−/−
) and wild-type littermates. MuRF1
−/−
mice were protected from cardiac atrophy and exhibited no reduction in contractile function. To explore the clinical relevance of these findings, we analyzed cardiac magnetic resonance imaging data from 70 patients in the DETECT-1 cohort and found that anthracycline exposure was associated with decreased cardiac mass evident within 1 month and persisting to 6 months after initiation.

Conclusions
Doxorubicin causes a subacute decrease in cardiac mass in both mice and humans. In mice, doxorubicin-induced cardiac atrophy is dependent on MuRF1. These findings suggest that therapies directed at preventing or reversing cardiac atrophy might preserve the cardiac function of cancer patients receiving anthracyclines.
Periprocedural Outcomes According to Timing of Clopidogrel Loading Dose in Patients Who Did Not Receive P2Y
12
Inhibitor Pretreatment
Authors: Abtan Jeremie , Ducrocq Gregory , Steg Philippe Gabriel , Stone Gregg W. , Mahaffey Kenneth W. , Gibson C. Michael , Hamm Christian W. , Price Matthew J. , Prats Jayne , Deliargyris Efthymios N. , White Harvey D. , Harrington Robert A. , Bhatt Deepak L. ,   on behalf of the CHAMPION PHOENIX Investigators
Published: March 2019

Background:

In patients undergoing percutaneous coronary intervention (PCI), who did not receive P2Y
12
inhibitor pretreatment, the optimal timing of P2Y
12
inhibitor loading dose remains debated. We sought to examine whether the choice of administration of the clopidogrel loading dose before or after the start of PCI had an impact on periprocedural complications, including bleeding.

Methods and Results:

The CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention) double-blind randomized trial compared cangrelor with clopidogrel loading dose at the time of PCI. Pretreatment with clopidogrel before randomization was not permitted per protocol. In the clopidogrel-only group (n=5438), a loading dose was given before (early load [EL]) or after the start of PCI (late load [LL]) according to physician choice. Overall, 3442 (63.3%) patients had EL and 1997 LL (36.7%). Median times were 5 minutes before and 20 minutes after the start of PCI, respectively. EL was more frequently used among patients with ST-segment–elevation myocardial infarction (84.4%) and non–ST-segment–elevation acute coronary syndromes (71.5%) than in stable patients (53.7%). At 48 hours, rates of the primary outcome of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis were similar (6.0% versus 5.4%) for EL versus LL, respectively (odds ratio [OR], 1.11 [95% CI, 0.87–1.41];
P
=0.41), and remained so after adjustment for potential confounders, including clinical presentation (OR [95% CI], 1.39 [0.90–2.15];
P
=0.14). Compared with clopidogrel, cangrelor consistently reduced the primary outcome in both EL (4.8% versus 6.0%; OR [95% CI], 0.80 [0.64–0.98]) and LL (4.3% versus 5.4%; OR [95% CI], 0.79 [0.59–1.06]; interaction
P
=0.99). Global Use of Strategies to Open Occluded Coronary Arteries severe/moderate bleeding rates were similar between treatment arms for both EL (OR [95% CI], 1.24 [0.58–2.66]) and LL (OR [95% CI], 2.53 [0.98–6.54]; interaction
P
=0.25).

Conclusions:
In a nonrandomized comparison of patients with clopidogrel loading before or after the start of PCI, the rates of periprocedural PCI complications, including bleeding, were similar, as were the benefits of cangrelor, regardless of the timing.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01156571.
Risk-Benefit Profile of Longer-Than-1-Year Dual-Antiplatelet Therapy Duration After Drug-Eluting Stent Implantation in Relation to Clinical Presentation
Authors: Palmerini Tullio , Bruno Antonio G. , Gilard Martine , Morice Marie-Claude , Valgimigli Marco , Montalescot Gilles , Collet Jean-Philippe , Della Riva Diego , Bacchi-Reggiani Maria Letizia , Steg Philippe Gabriel , Diallo Abdourahmane , Vicaut Eric , Helft Gerard , Nakamura Masato , Généreux Philippe , Vahl Torsten P. , Stone Gregg W. 
Published: March 2019

Background:
We sought to determine whether the risks and benefits of prolonging dual-antiplatelet therapy (DAPT) beyond 1 year after drug-eluting stent implantation depend on clinical presentation in a meta-analysis of randomized controlled trials.

Methods and Results:

Randomized controlled trials comparing ≤1- versus >1-year DAPT after drug-eluting stent placement were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. The primary efficacy end point was myocardial infarction, whereas the primary safety end point was major bleeding. Net clinical benefit was defined as the composite of myocardial infarction or major bleeding. Outcomes were analyzed according to patient presentation with stable ischemic heart disease versus acute coronary syndromes. The meta-analysis included 6 trials with a total of 21 457 patients, including 14 132 with stable ischemic heart disease and 7325 with acute coronary syndrome. After a median follow-up of 19.5 months, ≤1-year DAPT was associated with higher rates of myocardial infarction compared with >1-year DAPT (hazard ratio [HR], 1.63; 95% CI, 1.37–1.95), with no interaction apparent between treatment effect and clinical presentation. Shorter DAPT was associated with reduced rates of major bleeding compared with longer DAPT (HR, 0.64; 95% CI, 0.42–0.99) with no significant interaction between treatment effect and clinical presentation. However, a net clinical benefit of >1-year DAPT was present in patients with acute coronary syndrome (HR of shorter versus longer DAPT, 1.59; 95% CI, 1.24–2.02) but not in those with stable ischemic heart disease (HR, 1.15; 95% CI, 0.89–1.51;
P
interaction
=0.04). Shorter DAPT was also associated with lower rates of noncardiac mortality compared with longer DAPT (HR, 0.71; 95% CI, 0.52–0.96), with no significant interaction between treatment effect and clinical presentation (
P
interaction
=0.12).

Conclusions:
Compared with ≤1-year DAPT, >1-year DAPT reduces the risk of myocardial infarction but increases the risk of major bleeding and noncardiac mortality. A net clinical benefit of extended DAPT was apparent for patients with acute coronary syndrome but not for those with stable ischemic heart disease.
RETHINKING THE PRISONER’S DILEMMA GAME WITHIN THE FRAMEWORK OF THE PREBISCH-SINGER HYPOTHESIS
Authors: ÖZEKİN Ayça 
Published: March 2019

In recent years, the increasing criticism of the
assumptions of Orthodox economic theories has increased the interest in studies
that produce heterodox economics theories. In this context, by criticizing the
assumptions of orthodox economics, heterodox economics has produced new studies
in areas such as international economic theories in which these assumptions are
essential. These theories within heterodox economics are appropriate to be
analyzed with computable methods such as network models and agent-based
modeling because of their features of being adaptable to flexible assumptions
and not including certainty. At this point, game theory is one of the methods
that can be used alone or as an aid to the analysis methods mentioned. This
study aims to contribute to the development of empirical analysis methods in a
flexible structure in which the flexible assumptions of heterodox economics can
be adapted. For this purpose, the game theory, which is purified from the
assumptions of orthodox economics theories with the development of new
Heterodox economics schools, such as the evolutionary game theory and
behavioral game theory, will be used as a tool.
In the context of this study, "the prisoner's dilemma game gain matrix,"
which is used for the expression of international trade in the practice to be
performed, will be rearranged according to the claim of the Prebisch-Singer
hypothesis. By this means, it will also be
shown how to utilize game theory more broadly as a behavioral rule for
computational methods in newly developed empirical analyses for heterodox
economics theories.
TÜRKİYE ULUSAL VARLIK FONUNA İLİŞKİN BİR DEĞERLENDİRME
Authors: BEKEN Hikmet Gülçin , BALTACI Nuri 
Published: March 2019

Dünyadaki örnekleri daha öncelerde kurulmuş olsa da, Ulusal Varlık Fonu(UVF) Türkiye için oldukça yeni bir oluşum olarak karşımıza çıkmaktadır. Pek çok farklı amacı benimseyerek oluşturulan UVF’ler hem kurucu ülkeler hem de ev sahibi ülkeler üzerinden küresel sistemin işleyişini önemli ölçüde etkilemektedir. Politik iktisat içerisinde yeni bir aktör olarak kendine yer bulan UVF’ler; devlet, piyasa ve güç ilişkilerinde yaşanan değişim ve dönüşümde belirleyici olmaktadır. Mevcut UVF’ler ve Türkiye Ulusal Varlık Fonu üzerinden sağladıkları fayda ve ortaya çıkardıkları maliyetlere bu çalışmada yer verilecektir.
Ontology and Meteorology in Hippocrates’ On Regimen
Authors: Enache Cătălin 
Published: March 2019

Abstract
The paper discusses the ontology and the meteorology of Hippocrates’ On Regimen. The first part presents the elemental theory of fire and water which is based on the elemental powers movement and nutrition, and on the elemental properties warm, cold, wet, and dry. The main claim in this part is that the dualist theory of elements was meant by the Hippocratic author as a comprehensive explanation of the world. The second part presents the metaphysical foundations of meteorology. In On Regimen, natural environment has a considerable impact on human health; the theoretical basis of this interaction is given by the power of nature to transfer its elemental properties to living beings and man.
Lucretius on the Divine
Authors: Eckerman Chris 
Published: March 2019

Abstract
I provide a new interpretation of DRN 3.17-30 and 6.68-79, reading 3.17-30 in relation to Epicurus’ teachings on the mental construction of gods and 6.68-79 in relation to popular religion. I also review 5.1161-1193, discussing the evidence that the passage provides for the idealist and realist theses.