bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the clinical practice of aminoglycoside use in paediatric patients in Kenya: findings and implications for lower-middle income countries
Authors: Onyango Elias Joseph , Okalebo Faith , Oluka Margaret , Kinuthia Rosaline , Achieng Loice , Godman Brian , Kurdi Amanj 
Published: December 2019

Abstract

Objectives
To evaluate the practice of aminoglycoside use/monitoring in Kenya and explore healthcare worker (HCW) perceptions of aminoglycoside monitoring to identify gaps and opportunities for future improvements, given the low therapeutic index of aminoglycosides.

Methods
This was a two-phase study whereby we reviewed patients’ medical records at Kenyatta National Hospital (October–December 2016) in Phase 1 and interviewed HCWs face to face in Phase 2. Outcome measures included describing and evaluating the practice of aminoglycoside use and monitoring and compliance to guidelines. Data were analysed using descriptive and inferential analysis.

Results
Overall, out of the 2318 patients admitted, 192 patients (8.3%) were prescribed an aminoglycoside, of which 102 (53.1%) had aminoglycoside doses that did not conform to national guidelines. Aminoglycoside-related adverse effects were suspected in 65 (33.9%) patients. Monitoring of aminoglycoside therapy was performed in only 17 (8.9%) patients, with no therapeutic drug monitoring (TDM), attributed mainly to knowledge and skill gaps and lack of resources. Out of the 28 recruited HCWs, 18 (64.3%) needed training in how to perform and interpret TDM results.

Conclusions
The practice of using and monitoring aminoglycosides was suboptimal, raising concerns around potential avoidable harm to patients. The identified gaps could form the basis for developing strategies to improve the future use of aminoglycosides, not only in Kenya but also in other countries with similar settings and resources.
The ‘mitochondrial contact site and cristae organising system’ (MICOS) in health and human disease
Authors: Eramo Matthew J , Lisnyak Valerie , Formosa Luke E , Ryan Michael T 
Published: December 2019

AbstractThe ‘mitochondrial contact site and cristae organising system’ (MICOS) is an essential protein complex that promotes the formation, maintenance and stability of mitochondrial cristae. As such, loss of core MICOS components disrupts cristae structure and impairs mitochondrial function. Aberrant mitochondrial cristae morphology and diminished mitochondrial function is a pathological hallmark observed across many human diseases such as neurodegenerative conditions, obesity and diabetes mellitus, cardiomyopathy, and in muscular dystrophies and myopathies. While mitochondrial abnormalities are often an associated secondary effect to the pathological disease process, a direct role for the MICOS in health and human disease is emerging. This review describes the role of MICOS in the maintenance of mitochondrial architecture and summarizes both the direct and associated roles of the MICOS in human disease.
The Impact of Immigration on Wage Dynamics: Evidence from the Algerian Independence War
Authors: Edo Anthony 
Published: December 2019

AbstractThis paper investigates the dynamics of wage adjustment to an exogenous increase in labor supply exploiting the sudden and unexpected inflow of repatriates to France resulting from Algerian independence in 1962. I measure the impact of this particular supply shift on the average wage of pre-existing native workers across French regions between 1962 and 1976. I find that regional wages decreased between 1962 and 1968, before returning to their pre-shock level 15 years after. I also investigate the dynamics of skill-specific wages in response to the regional penetration of repatriates and find that the wages of high and low educated native workers declined initially but fully recovered by 1976.
Music Therapists’ Perceptions of the Therapeutic Potentials Using Music When Working With Verbal Children on the Autism Spectrum: A Qualitative Analysis
Authors: Epstein Shulamit , Elefant Cochavit , Thompson Grace 
Published: December 2019

Abstract
While there are numerous descriptions of the use of music and its therapeutic potential by music therapists working with nonverbal children on the autism spectrum, only limited literature focuses on exploring how music therapists use music and perceive its therapeutic potential when working with children on the spectrum who have verbal skills. This qualitative study aimed to explore music therapists’ descriptions of the use of music and its therapeutic potential in their work with children on the autism spectrum who have verbal skills. Semi-structured interviews were conducted with six qualified music therapists from Israel and then analyzed according to the principles of interpretative phenomenological analysis (IPA). Three main themes were identified: (a) musical infrastructure, which describes how the music therapists facilitated musical experiences to support the children’s ability to regulate their arousal, attention and emotions; (b) the meeting point between musical and verbal playfulness, which reflects the music therapists’ beliefs about how musical experiences add vitality and support the development of both verbal and nonverbal imaginative play; and (c) musical responses, which describes the different ways music therapists use their voice and songs to interact musically with verbal children. The experiences described by the participants emphasize the importance of the therapist musically attuning to the child’s emotional, physiological, creative, and playful qualities, even when the child has verbal skills. These musical interactions help to create a shared experience between the child and therapist that are perceived to help the child’s different forms of regulation, continuity, and vitality within the play.
White Blood Cell Count and Risk of Incident Lung Cancer in the UK Biobank
Authors: Wong Jason Y Y , Bassig Bryan A , Loftfield Erikka , Hu Wei , Freedman Neal D , Ji Bu-tian , Elliott Paul , Silverman Debra T , Chanock Stephen J , Rothman Nathaniel , Lan Qing 
Published: December 2019

AbstractBackgroundThe contribution of measurable immunological and inflammatory parameters to lung cancer development remains unclear, particularly among never smokers. We investigated the relationship between total and differential white blood cell (WBC) counts and incident lung cancer risk overall and among subgroups defined by smoking status and sex in the United Kingdom (UK).MethodsWe evaluated 424 407 adults aged 37–73 years from the UK Biobank. Questionnaires, physical measurements, and blood were administered and collected at baseline in 2006–2010. Complete blood cell counts were measured using standard methods. Lung cancer diagnoses and histological classifications were obtained from cancer registries. Multivariable Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals of incident lung cancer in relation to quartiles (Q) of total WBC and subtype-specific counts, with Q1 as the reference.ResultsThere were 1493 incident cases diagnosed over an average 7-year follow-up. Overall, the highest quartile of total WBC count was statistically significantly associated with elevated lung cancer risk (HRQ4 = 1.67, 95% CI = 1.41 to 1.98). Among women, increased risks were found in current smokers (ncases / n = 244 / 19 464, HRQ4 = 2.15, 95% CI = 1.46 to 3.16), former smokers (ncases / n = 280 / 69 198, HRQ4 = 1.75, 95% CI = 1.24 to 2.47), and never smokers without environmental tobacco smoke exposure (ncases / n = 108 / 111 294, HRQ4 = 1.93, 95% CI = 1.11 to 3.35). Among men, stronger associations were identified in current smokers (ncase s / n = 329 / 22 934, HRQ4 = 2.95, 95% CI = 2.04 to 4.26) and former smokers (ncases / n = 358/71 616, HRQ4 = 2.38, 95% CI = 1.74 to 3.27) but not in never smokers. Findings were similar for lung adenocarcinoma and squamous cell carcinoma and were driven primarily by elevated neutrophil fractions.ConclusionsElevated WBCs could potentially be one of many important markers for increased lung cancer risk, especially among never-smoking women and ever-smoking men.
Friendships in Pediatric Brain Tumor Survivors and Non-Central Nervous System Tumor Survivors
Authors: Hocking Matthew C , Noll Robert B , Kazak Anne E , Brodsky Cole , Phillips Peter , Barakat Lamia P 
Published: December 2019

Abstract

Objective
Brain tumors during childhood may disrupt the development and maintenance of friendships due to the impact of disease- and treatment-related factors on functioning. The goal of this study was to determine if children treated for either a brain tumor or a non-central nervous system (CNS) solid tumor could name a friend and to evaluate the social information processes associated with the ability to name a friend.

Method
Youth (ages 7–14) treated for either a brain tumor (n = 47; mean age = 10.51 years) or a non-CNS solid tumor (n = 34; mean age = 11.29) completed an assessment within 6 months of the conclusion of treatment that included asking participants to name a friend and completing measures of social information processing (SIP). Rates of self-reported friendship were compared between groups and correlates of being able to name a friend were evaluated.

Results
Youth treated for a brain tumor (61.7%) were significantly less likely to name a friend compared with youth treated for a non-CNS solid tumor (85.3%). Diagnosis type (brain vs. non-CNS), relapse status, attribution style, and facial affect recognition were significant predictors of being able to name a friend or not in a logistic regression model.

Conclusions
Youth treated for a brain tumor and those who experienced a disease relapse are at risk for impairments in friendships; difficulties with SIP may increase this risk. Targeted screening and intervention efforts for children diagnosed with brain tumors and those who have relapsed could address difficulties with peers.
Perception of karrikins by plants: a continuing enigma
Authors: Yao Jiaren , Waters Mark T 
Published: December 2019

AbstractKarrikins are small butenolide molecules with the capacity to promote germination and enhance seedling establishment. Generated abiotically from partial combustion of vegetation, karrikins are comparatively rare in the environment, but studying their mode of action has been most informative in revealing a new regulatory pathway for plant development that uses the karrikin perception machinery. Recent studies suggest that the karrikin receptor protein KAI2 and downstream transcriptional co-repressors in the SMXL family influence seed germination, seedling photomorphogenesis, root morphology, and responses to abiotic stress such as drought. Based on taxonomic distribution, this pathway is ubiquitous and likely to be evolutionarily ancient, originating prior to land plants. However, we still do not have a good grasp on how karrikins actually activate the receptor protein, and we have yet to discover the assumed endogenous ligand for KAI2 that karrikins are thought to mimic. This review covers recent progress in this field, as well as current gaps in our knowledge.
Implications of the search for optical counterparts during the first six months of the Advanced LIGO’s and Advanced Virgo’s third observing run: possible limits on the ejecta mass and binary properties
Authors: Coughlin Michael W , Dietrich Tim , Antier Sarah , Bulla Mattia , Foucart Francois , Hotokezaka Kenta , Raaijmakers Geert , Hinderer Tanja , Nissanke Samaya 
Published: December 2019

ABSTRACT
GW170817 showed that neutron star mergers not only emit gravitational waves but also can release electromagnetic signatures in multiple wavelengths. Within the first half of the third observing run of the Advanced LIGO and Virgo detectors, there have been a number of gravitational wave candidates of compact binary systems for which at least one component is potentially a neutron star. In this article, we look at the candidates S190425z, S190426c, S190510g, S190901ap, and S190910h, predicted to have potentially a non-zero remnant mass, in more detail. All these triggers have been followed up with extensive campaigns by the astronomical community doing electromagnetic searches for their optical counterparts; however, according to the released classification, there is a high probability that some of these events might not be of extraterrestrial origin. Assuming that the triggers are caused by a compact binary coalescence and that the individual source locations have been covered during the EM follow-up campaigns, we employ three different kilonova models and apply them to derive possible constraints on the matter ejection consistent with the publicly available gravitational-wave trigger information and the lack of a kilonova detection. These upper bounds on the ejecta mass can be related to limits on the maximum mass of the binary neutron star candidate S190425z and to constraints on the mass-ratio, spin, and NS compactness for the potential black hole–neutron star candidate S190426c. Our results show that deeper electromagnetic observations for future gravitational wave events near the horizon limit of the advanced detectors are essential.
A parallel-GPU code for asteroid aggregation problems with angular particles
Authors: Ferrari Fabio , Lavagna Michèle , Blazquez Emmanuel 
Published: December 2019

ABSTRACTThe paper presents a numerical implementation of the gravitational N-body problem with contact interactions between non-spherically shaped bodies. The work builds up on a previous implementation of the code and extends its capabilities. The number of bodies handled is significantly increased through the use of a CUDA/GPU-parallel octree structure. The implementation of the code is discussed and its performance is compared against direct N2 integration. The code features both smooth (force-based) and non-smooth (impulse-based) methods, as well as a visco-elastic non-smooth method, to handle contact interaction between bodies. The numerical problem of simulating ‘rubble-pile’ asteroid gravitational aggregation processes is addressed. We discuss the features of the problem and derive criteria to set up the numerical simulation from the dynamical constraints of the combined gravitational–collisional problem. Examples of asteroid aggregation scenarios that could benefit from such implementation are finally presented.
The ACCELERATION programme: I. Cosmology with the redshift drift
Authors: Cooke Ryan 
Published: December 2019

ABSTRACT
Detecting the change of a cosmological object’s redshift due to the time evolution of the Universal expansion rate is an ambitious experiment that will be attempted with future telescope facilities. In this paper, we describe the ACCELERATION programme, which aims to study the properties of the most underdense regions of the Universe. One of the highlight goals of this programme is to prepare for the redshift drift measurement. Using the EAGLE cosmological hydrodynamic simulations, we estimate the peculiar acceleration of gas in galaxies and the Lyα forest. We find that star-forming ‘cold neutral gas’ exhibits large peculiar acceleration due to the high local density of baryons near star-forming regions. We conclude that absorption by cold neutral gas is unlikely to yield a detection of the cosmological redshift drift. On the other hand, we find that the peculiar accelerations of Lyα forest absorbers are more than an order of magnitude below the expected cosmological signal. We also highlight that the numerous low H i column density systems display lower peculiar acceleration. Finally, we propose a new ‘Lyα cell’ technique that applies a small correction to the wavelength calibration to secure a relative measurement of the cosmic drift between two unrelated cosmological sources at different redshifts. For suitable combinations of absorption lines, the cosmological signal can be more than doubled, while the affect of the observer peculiar acceleration is mitigated. Using current data of four suitable Lyα cells, we infer a limit on the cosmological redshift drift to be $\dot{v}_{\rm obs}\lt 65~{\rm m~s}^{-1}~{\rm yr}^{-1}$ (2σ).
Post-transplantation plasma malondialdehyde is associated with cardiovascular mortality in renal transplant recipients: a prospective cohort study
Authors: Yepes-Calderón Manuela , Sotomayor Camilo G , Gans Rijk O B , Berger Stefan P , Leuvenink Henri G D , Tsikas Dimitrios , Rodrigo Ramón , Navis Gerjan J , Bakker Stephan J L 
Published: December 2019

Abstract

Background
In renal transplant recipients (RTRs), cardiovascular mortality is the most common cause of long-term renal graft loss. Oxidative stress (OS) has been associated with cardiovascular disease and is known to be enhanced in RTRs. We aimed to prospectively investigate whether the concentration of the OS biomarker malondialdehyde (MDA) is associated with long-term risk of cardiovascular mortality in a large cohort of RTRs.

Methods
The plasma MDA concentration was measured using the thiobarbituric acid reaction assay in 604 extensively phenotyped RTRs with a functioning allograft for ≥1 year. The association between MDA and cardiovascular mortality was assessed using Cox proportional hazard regression analyses in the overall cohort and within subgroups according to significant effect modifiers.

Results
Median circulating MDA concentration at baseline was 5.38 [interquartile range (IQR) 4.31–6.45] μmol/L. During a follow-up period of 6.4 (IQR 5.6–6.8) years, 110 (18%) RTRs died, with 40% of deaths due to cardiovascular causes. MDA concentration was significantly associated with the risk for cardiovascular mortality {hazard ratio [HR] 1.31 [95% confidence interval (CI) 1.03–1.67] per 1-SD increment}, independent of adjustment for potential confounders, including renal function, immunosuppressive therapy, smoking status and blood pressure. The association between MDA concentration and the risk for cardiovascular mortality was stronger in RTRs with relatively lower plasma ascorbic acid concentrations [≤42.5 µmol/L; HR 1.79 (95% CI 1.30–2.48) per 1-SD increment] or relatively lower estimated glomerular filtration rates [≤45 mL/min/1.73 m2; HR 2.09 (95% CI 1.45–3.00) per 1-SD increment].

Conclusions
Circulating MDA concentration is independently associated with long-term risk for cardiovascular mortality, particularly in RTRs with relatively lower ascorbic acid concentrations or renal function. Further studies are warranted to elucidate whether OS-targeted interventions could decrease cardiovascular mortality in RTRs.
EGFR mutations are associated with response to depatux-m in combination with temozolomide and result in a receptor that is hypersensitive to ligand
Authors: Hoogstrate Youri , Vallentgoed Wies , Kros Johan M , de Heer Iris , de Wit Maurice , Eoli Marica , Sepulveda Juan Manuel , Walenkamp Annemiek M E , Frenel Jean-Sebastien , Franceschi Enrico , Clement Paul M , Weller Micheal , van Royen Martin E , Ansell Peter , Looman Jim , Bain Earle , Morfouace Marie , Gorlia Thierry , Golfinopoulos Vassilis , van den Bent Martin , French Pim J 
Published: December 2019

AbstractBackgroundThe randomized phase II INTELLANCE-2/EORTC_1410 trial on EGFR-amplified recurrent glioblastomas showed a trend towards improved overall survival when patients were treated with depatux-m plus temozolomide compared with the control arm of alkylating chemotherapy only. We here performed translational research on material derived from this clinical trial to identify patients that benefit from this treatment.MethodsTargeted DNA-sequencing and whole transcriptome analysis was performed on clinical trial samples. High-throughput, high-content imaging analysis was done to understand the molecular mechanism underlying the survival benefit.ResultsWe first define the tumor genomic landscape in this well-annotated patient population. We find that tumors harboring EGFR single-nucleotide variations (SNVs) have improved outcome in the depatux-m + TMZ combination arm. Such SNVs are common to the extracellular domain of the receptor and functionally result in a receptor that is hypersensitive to low-affinity EGFR ligands. These hypersensitizing SNVs and the ligand-independent EGFRvIII variant are inversely correlated, indicating two distinct modes of evolution to increase EGFR signaling in glioblastomas. Ligand hypersensitivity can explain the therapeutic efficacy of depatux-m as increased ligand-induced activation will result in increased exposure of the epitope to the antibody–drug conjugate. We also identified tumors harboring mutations sensitive to “classical” EGFR tyrosine-kinase inhibitors, providing a potential alternative treatment strategy.ConclusionsThese data can help guide treatment for recurrent glioblastoma patients and increase our understanding into the molecular mechanisms underlying EGFR signaling in these tumors.
The effect and safety of exercise therapy in patients with systemic sclerosis: a systematic review
Authors: Liem Sophie I E , Vliet Vlieland Theodora P M , Schoones Jan W , de Vries-Bouwstra Jeska K 
Published: December 2019

Abstract
Given the shortcomings of previous literature reviews evaluating the effect and safety of exercise therapy in SSc, we aimed to carry out a systematic review of the literature specifically on this topic. A structured search strategy was performed in Medline (via PubMed) and other electronic databases from 1990 to 3 September 2019. Randomized controlled trials, observational designs, conference abstracts and trial registrations were included if they concerned SSc patients ≥18 years of age, exercise therapy and reported outcomes related to physical functioning. Nine articles were included. Four randomized controlled trials compared (a) hand exercises, (b) orofacial exercises, (c) aerobic exercises or (d) aerobic exercises plus resistance training with no exercise, demonstrating effects on hand function (a), maximum mouth opening (b), peak oxygen uptake (c + d) and quality of life. All five observational studies concerning hand, orofacial, aerobic and/or strengthening exercises reported improvements of hand function, mouth opening, aerobic capacity and/or muscle strength. In conclusion, the evidence on the effect and safety of exercise therapy in SSc is scanty.
A singular analysis—attribution of illegality following Singularis v Daiwa
Authors: de Lacey Joseph 
Published: December 2019

Abstract
This article considers the Supreme Court’s judgment in Singularis Holdings Ltd (In Official Liquidation) v Daiwa Capital Markets Europe Ltd [2019] UKSC 50. In particular, it examines the court’s ruling in relation to attribution of illegality. This clarifies that, when determining if the knowledge and actions of a director are to be attributed to a company, the answer is to be found in a consideration of the context and purpose for which the attribution is relevant, and not in the identification of the “directing mind and will” of the company.