bluuebunny/crossref_metadata_2025_split huggingface dataset:
P36 A review of aspirin discharge documentation in paediatric cardiology
Authors: Gage Susie 
Published: January 2018

The humble drug Aspirin, derived from willow bark, is widely used in paediatric cardiology. It is used for a number of different indications mainly for its antiplatelet action; a few such examples include Blalock-Taussig shunts, Glenn shunts, post ablation stroke prevention and in Kawasaki Disease.The discharge summary is a means of communicating changes to GPs, other hospitals and paediatricians within the paediatric cardiac network. The aim of the review was to assess the situation currently; whether the indication and duration of aspirin were documented on the patient’s discharge summary. This issue has been raised through our paediatric cardiac network meeting.A retrospective study was carried out. A list of all patients discharged from the paediatric cardiac ward in January & February 2016 was obtained from Medway; our electronic patient information system for admissions and discharges. Using this list of patients, Heartsuite; our electronic cardiac database, was used to find 30 patients, who were discharged on aspirin.The following data was collected on each of these discharge summaries; whether aspirin was newly started or continued, whether the indication and duration of aspirin was documented.The data was collected and of the 30 discharge summaries viewed with aspirin on discharge; 18 (60%) were newly started on aspirin and 12 (40%) were continued on aspirin, 4 (13.3%) had the indication documented and 12 (40%) had the duration documented.The paediatric cardiac patients discharged on aspirin, as shown by the results in this review show that the majority of discharge summaries do not have the indication or duration of aspirin documented. So, there was found to be inadequate documentation and communication to users in our paediatric cardiac network. With this in mind a service improvement is necessary.The improvement suggestions are two-fold. Firstly, an additional note needs to be made to the surgical operation note that can be transferred to the discharge summary. Secondly, the addition of a mandatory field on the medication section of the discharge summary for the indication and the duration of aspirin.
7 Development of a leaflet to teach children to swallow tablets
Authors: Mawson Charlotte 
Published: January 2018

AimIn paediatric pharmacy a wide range of medications are used, which are often not available in formulations suitable for children. We wanted to design a tool that would enhance our patients’ experience of medication taking as well as improving accessibility to medicines, palatability and ease of administration.MethodThe European Medicines Agency advises that ‘for chronic diseases, the acceptability of tablets in children may be improved by adequate training’.1 Among others a study has shown that almost half of two year olds could swallow a 3 mm tablet, increasing to 85% in 5 year olds.2A leaflet was suggested as the best way to teach our patients and their parents how to swallow tablets as it could be widely distributed. It was developed with a working group of paediatric clinical psychologists and a paediatric pharmacist. The leaflet aims to be encouraging and provide practical tips and advice. It offers seven different techniques for swallowing tablets which were adapted from web-based advice and previous cases. The leaflet was piloted in a small number of patients and they were given a questionnaire.ResultsTen questionnaires were returned, with patients’ ages ranging from 5 to 17. All the patients said that they would now be taking all or some of their medication as tablets. All of the techniques were tried by 2 or more patients and each technique was successful for at least 1 child. The most popular method was the ‘big gulp method’ which worked for 8 patients. This involves swirling the tablet around the mouth for 10 s with as much water as possible and then taking a large gulp until all the water and the tablet have gone.Positive feedback for the leaflet included ‘feels grown up being able to take a tablet’, taking tablets is ‘easier’ and ‘quicker’; one patient wished they had been given the leaflet sooner. Parents also fed back that ‘there was no longer a fight to take medicines’ and ‘it’s much easier for school to manage’.ConclusionThe findings have shown that this is a very successful and useful tool. It allows children and their families to take ownership of their medicine taking. To enable more patients to benefit, further engagement from multidisciplinary teams e.g. play specialists, is needed. In the long-term this leaflet could be used to proactively start patients on tablets rather than reactively, creating potential cost savings and a reduction in the use of unlicensed medicines and specials.ReferencesEuropean Medicines Agency. Guideline on pharmaceutical development of medicines for paediatric use2013. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/07/WC500147002.pdf [Accessed: 28 July 2016].Thomson SA, Tuleu C, Wong ICK, et al. Minitablets: New modality to deliver medicines to preschool-aged children. Paediatrics2009;123(2):235–238.
9 Children/young people taking long-term medicines – a survey of the experiences of community pharmacists
Authors: Aston Jeff 
Published: January 2018

AimTo identify the experiences of community pharmacists in caring for children/young people, or their parents/carers, taking long-term medicines.MethodA pre-piloted 13 point semi-structured survey, participant information leaflet, consent form and pre-paid return envelope were posted to all 354 community pharmacists who had dispensed a prescription from a single specialist paediatric hospital during November and December 2015. Community pharmacy addresses were obtained from the National Health Service Business Services Authority ePACT system. Telephone follow-up of non-responders and, if necessary, a repeat mailing was made from 3 weeks after the original return by date.Participants were asked about their experiences of undertaking a medication review with either children/young people or their parents/carers, medication-related problems presenting to them, adherence, information needs of patients/carers and what issues were reported to them from this group.The data were analysed using SPSS version 22 and NVivo version 10.ResultsA response rate of 76/354 (21.5%) was achieved. Eighteen (23.7%) respondents had undertaken a Medicines Use Review (MUR),122 (28.9%) a New Medicines Service (NMS)2 review and 16 (21.1%) had undertaken another type of medication review in a child/young person. Respondents reported that patients or their carers had presented to them with adherence issues including stopping the medicine (24, 31.6%) and changing the dose (28, 36.8%) without informing the prescriber. Patients or their carers had requested information from them about the indication (59, 77.6%), dose regime (63, 82.9%), administration (64, 84.2%) and adverse effects (58, 76.6%). Respondents also reported patients/carers experiencing difficulties obtaining further supplies of a medicine from their community pharmacy (47, 61.8%) and patients’ general practitioners declining to prescribe a medicine recommended by the patient’s hospital-based specialist (27, 35.5%).ConclusionThis study has demonstrated that children, and their carers, taking long-term medicines experience a range of issues that they present to community pharmacists. Many of these issues would fall within the purview of currently funded medication review services namely the NMS and MUR.1,2 However, the proportion of pharmacists in this study undertaking formal medication review with children or their parents/carers was low. Further work is required to demonstrate the outcomes that such a review could have in this cohort of patients.ReferencesPharmaceutical Services Negotiating Committee. MURs: The basics. What is the medicines use review and prescription intervention service? [Internet] 2016. Available from: MURs: The basics http://psnc.org.uk/services-commissioning/advanced-services/murs/murs-the-basics/ [Available: 19 May 2016].Pharmaceutical Services Negotiating Committee. New Medicines Service (NMS) [Internet] 2016. http://psnc.org.uk/services-commissioning/advanced-services/nms/ [Available: 19 May 2016].
Differentiating between biogenic and thermogenic sources of natural gas in coalbed methane reservoirs from the Illinois Basin using noble gas and hydrocarbon geochemistry
Authors: Moore Myles T. , Vinson David S. , Whyte Colin J. , Eymold William K. , Walsh Talor B. , Darrah Thomas H. 
Published: January 2018

Abstract

While coalbed methane (CBM) is a significant source of natural gas production globally, uncertainties regarding the proportions of biogenic and thermogenic natural gas in CBM reservoirs still remain. We integrate major gases, hydrocarbon composition, hydrocarbon stable isotopes and noble gases in fluids from 20 producing CBM wells to more accurately constrain the genetic source of natural gases in the eastern Illinois Basin, USA. Previous studies have indicated primarily biogenic production of methane (>99.6%) with negligible contributions from thermogenic natural gases. However, by integrating noble gases, we identify quantifiable (up to 19.2%) contributions of exogenous thermogenic gas in produced gases from the Seelyville and Springfield coal seams. Thermogenic gases are distinguished by a positive relationship between methane, ethane and helium-4, lower C
1
/C
2
+, heavier δ
13
C-CH
4
, more radiogenic noble gases (
4
He,
21
Ne*,
40
Ar*), and lower abundances of atmospherically derived gases (
20
Ne,
36
Ar). Biogenic gases displayed lighter δ
13
C-CH
4
, higher C
1
/C
2
+, higher levels of atmospheric gases and lower abundances of radiogenic noble gases. Our data suggest that natural gases from a deeper, exogenous thermogenic source likely migrated to the Pennsylvanian-aged coals at an unknown time and later mixed with biogenic methane diluting the geochemical signature of the thermogenic methane within the Springfield and Seelyville coal seams.
XIAP Regulation by MNK Links MAPK and NFκB Signaling to Determine an Aggressive Breast Cancer Phenotype
Authors: Evans Myron K. , Brown Michael C. , Geradts Joseph , Bao Xuhui , Robinson Timothy J. , Jolly Mohit Kumar , Vermeulen Peter B. , Palmer Gregory M. , Gromeier Matthias , Levine Herbert , Morse Michael A. , Van Laere Steven J. , Devi Gayathri R. 
Published: January 2018

Abstract
Hyperactivation of the NFκB pathway is a distinct feature of inflammatory breast cancer (IBC), a highly proliferative and lethal disease. Gene expression studies in IBC patient tissue have linked EGFR (EGFR/HER2)-mediated MAPK signaling to NFκB hyperactivity, but the mechanism(s) by which this occurs remain unclear. Here, we report that the X-linked inhibitor of apoptosis protein (XIAP) plays a central role in linking these two pathways. XIAP overexpression correlated with poor prognoses in breast cancer patients and was frequently observed in untreated IBC patient primary tumors. XIAP drove constitutive NFκB transcriptional activity, which mediated ALDH positivity (a marker of stem-like cells), in vivo tumor growth, and an IBC expression signature in patient-derived IBC cells. Using pathway inhibitors and mathematical models, we defined a new role for the MAPK interacting (Ser/Thr)-kinase (MNK) in enhancing XIAP expression and downstream NFκB signaling. Furthermore, targeted XIAP knockdown and treatment with a MNK inhibitor decreased tumor cell migration in a dorsal skin fold window chamber murine model that allowed for intravital imaging of local tumor growth and migration. Together, our results indicate a novel role for XIAP in the molecular cross-talk between MAPK and NFκB pathways in aggressive tumor growth, which has the potential to be therapeutically exploited.
Significance: Signaling by the MNK kinase is essential in inflammatory breast cancer, and it can be targeted to inhibit XIAP–NFκB signaling and the aggressive phenotype of this malignancy. Cancer Res; 78(7); 1726–38. ©2018 AACR.
Integrative Genomic Analysis Predicts Causative Cis-Regulatory Mechanisms of the Breast Cancer–Associated Genetic Variant rs4415084
Authors: Zhang Yi , Manjunath Mohith , Zhang Shilu , Chasman Deborah , Roy Sushmita , Song Jun S. 
Published: January 2018

Abstract
Previous genome-wide association studies (GWAS) have identified several common genetic variants that may significantly modulate cancer susceptibility. However, the precise molecular mechanisms behind these associations remain largely unknown; it is often not clear whether discovered variants are themselves functional or merely genetically linked to other functional variants. Here, we provide an integrated method for identifying functional regulatory variants associated with cancer and their target genes by combining analyses of expression quantitative trait loci, a modified version of allele-specific expression that systematically utilizes haplotype information, transcription factor (TF)–binding preference, and epigenetic information. Application of our method to a breast cancer susceptibility region in 5p12 demonstrates that the risk allele rs4415084-T correlates with higher expression levels of the protein-coding gene mitochondrial ribosomal protein S30 (MRPS30) and lncRNA RP11-53O19.1. We propose an intergenic SNP rs4321755, in linkage disequilibrium (LD) with the GWAS SNP rs4415084 (r2 = 0.988), to be the predicted functional SNP. The risk allele rs4321755-T, in phase with the GWAS rs4415084-T, created a GATA3-binding motif within an enhancer, resulting in differential GATA3 binding and chromatin accessibility, thereby promoting transcription of MRPS30 and RP11-53O19.1. MRPS30 encodes a member of the mitochondrial ribosomal proteins, implicating the role of risk SNP in modulating mitochondrial activities in breast cancer. Our computational framework provides an effective means to integrate GWAS results with high-throughput genomic and epigenomic data and can be extended to facilitate rapid functional characterization of other genetic variants modulating cancer susceptibility.
Significance: Unification of GWAS results with information from high-throughput genomic and epigenomic profiles provides a direct link between common genetic variants and measurable molecular perturbations. Cancer Res; 78(7); 1579–91. ©2018 AACR.
A Novel Method for Rapid Molecular Subgrouping of Medulloblastoma
Authors: Gómez Soledad , Garrido-Garcia Alícia , Garcia-Gerique Laura , Lemos Isadora , Suñol Mariona , de Torres Carmen , Kulis Marta , Pérez-Jaume Sara , Carcaboso Ángel M. , Luu Betty , Kieran Mark W. , Jabado Nada , Kozlenkov Alexey , Dracheva Stella , Ramaswamy Vijay , Hovestadt Volker , Johann Pascal , Jones David T.W. , Pfister Stefan M. , Morales La Madrid Andrés , Cruz Ofelia , Taylor Michael D. , Martin-Subero Jose-Ignacio , Mora Jaume , Lavarino Cinzia 
Published: January 2018

Abstract
Purpose: The classification of medulloblastoma into WNT, SHH, group 3, and group 4 subgroups has become of critical importance for patient risk stratification and subgroup-tailored clinical trials. Here, we aimed to develop a simplified, clinically applicable classification approach that can be implemented in the majority of centers treating patients with medulloblastoma.
Experimental Design: We analyzed 1,577 samples comprising previously published DNA methylation microarray data (913 medulloblastomas, 457 non-medulloblastoma tumors, 85 normal tissues), and 122 frozen and formalin-fixed paraffin-embedded medulloblastoma samples. Biomarkers were identified applying stringent selection filters and Linear Discriminant Analysis (LDA) method, and validated using DNA methylation microarray data, bisulfite pyrosequencing, and direct-bisulfite sequencing.
Results: Using a LDA-based approach, we developed and validated a prediction method (EpiWNT-SHH classifier) based on six epigenetic biomarkers that allowed for rapid classification of medulloblastoma into the clinically relevant subgroups WNT, SHH, and non-WNT/non-SHH with excellent concordance (&gt;99%) with current gold-standard methods, DNA methylation microarray, and gene signature profiling analysis. The EpiWNT-SHH classifier showed high prediction capacity using both frozen and formalin-fixed material, as well as diverse DNA methylation detection methods. Similarly, we developed a classifier specific for group 3 and group 4 tumors, based on five biomarkers (EpiG3-G4) with good discriminatory capacity, allowing for correct assignment of more than 92% of tumors. EpiWNT-SHH and EpiG3-G4 methylation profiles remained stable across tumor primary, metastasis, and relapse samples.
Conclusions: The EpiWNT-SHH and EpiG3-G4 classifiers represent a new simplified approach for accurate, rapid, and cost-effective molecular classification of single medulloblastoma DNA samples, using clinically applicable DNA methylation detection methods. Clin Cancer Res; 24(6); 1355–63. ©2018 AACR.
Intratumoral Payload Concentration Correlates with the Activity of Antibody–Drug Conjugates
Authors: Zhang Donglu , Yu Shang-Fan , Khojasteh S. Cyrus , Ma Yong , Pillow Thomas H. , Sadowsky Jack D. , Su Dian , Kozak Katherine R. , Xu Keyang , Polson Andrew G. , Dragovich Peter S. , Hop Cornelis E.C.A. 
Published: January 2018

Abstract
Antibody–drug conjugates (ADC) have become important scaffolds for targeted cancer therapies. However, ADC exposure–response correlation is not well characterized. We demonstrated that intratumor payload exposures correlated well with the corresponding efficacies of several disulfide-linked ADCs, bearing an DNA alkylating agent, pyrrolo[2,1-c][1,4]benzodiazepine-dimer (PBD), in HER2-expressing xenograft models. The correlation suggests that a threshold concentration of intratumor payload is required to support sustained efficacy and an ADC can deliver an excessive level of payload to tumors that does not enhance efficacy (“Plateau” effect). In contrast to tumor PBD concentrations, related assessments of systemic exposures, plasma stability, and drug-to-antibody ratio changes of related ADCs did not consistently rationalize the observed ADC efficacies. A minimal efficacious dose could be determined by ADC dose-fractionation studies in the xenograft models. Mechanistic investigations revealed that both linker immolation and linker disulfide stability are the key factors that determine intratumor PBD concentrations. Overall, this study demonstrates how a linker design can impact ADC efficacy and that the intratumor exposure of a payload drug as the molecular mechanism quantitatively correlate with and predict the antitumor efficacy of ADCs. Mol Cancer Ther; 17(3); 677–85. ©2018 AACR.
Aristóteles e os Índios Americanos: Um estudo do preconceito de raça no Novo Mundo (III)
Authors: Hanke Lewis 
Published: January 2018

O GRANDE DEBATE DE VALLADOLID — 1550-1551: COMO CONDUZIR UMA GUERRA JUSTA CONTRA OS INDÍGENAS AMERICANOS . O segundo problema que Sepúlveda expõe, em Demócra-tes, é como fazer uma guerra justa contra os índios. Tendo Demócrates convencido Leopoldo que as guerras podiam ser justas, a maneira pelas quais podiam ser feitas com justiça atraia agora a atenção de ambos.
Resenha de: Gênes et les foires de change de Lyon a Besançon
Authors: Paula Eurípedes Simões de 
Published: January 2018

GIOFFRE (Domenico). Gênes et les foires de change de Lyon a Besançon. Paris. S. E. V. P. E. N. École Pratique des Hautes Études. Centre de Recherches historiques. VIe section. Coleção "Affaires et gens d'affaires".
O poeta Américo Elísio, "alter ego" de José Bonifácio, homem de ciência e homem público
Authors: Amora Antônio Soares 
Published: January 2018

Situação histórica de Américo Elísio. Por incrível que possa parecer, José Bonifácio, que é, sabidamente, uma das maiores figuras do fim do século XVIII e comêço do século XIX, no campo das ciências naturais, da tecnicologia agrícola e industrial, e também um dos mais ilus-tres e atuantes homens públicos da nossa Independência —começou sua carreira intelectual' como poeta; na poesia se refugiou, mais de uma vez, das decepções e das amarguras da vida política; e ao pensar, na altura dos 60 anos, em garantir, na memória dos pósteros, o seu nome, foi em suas poesias reunidas e publicadas, em 1825, em Bordéus, que confiou.
Resenha de: Coleção Nouvelle Clio: L'histoire et ses problèmes
Authors: Novais Fernando A. 
Published: January 2018

COLEÇÃO NOUVELLE CLIO: L'HISTOIRE ET SES PROBLÈMES. Dirigida por Robert Boutruche e Paul Lemerle. Presses Universitaires de France. Paris. Godechot (Jasques). — Les Révolutions 1770-1799. Paris, 1963. (Nouvelle Clio, vol. 36). Mauro (Fréderic). — L'Expansion européenne 1600-1870. Paris, 1964. (Nouvelle Clio, vol. 27). Duroselle (J. -B.). — L'Europe de 1815 à nos jours: vie politique et relations internationales. Paris, 1964. (Nouvelle Clio, vol. 38) Fohlen (Claude). L'Amérique anglo-saxonne de 1815 ànos jours. Paris, 1965. (Nouvelle Clio, vol. 43). Delumeau (Jean). — Naissance et affirmation de la Réforme. Paris, 1965. (Nouvelle Clio, vol. 30).
A origem da Universidade de Paris (I)
Authors: Nunes Ruy Afonso da Costa 
Published: January 2018

O objetivo desta monografia é examinar a origem da Universidade de Paris . Foi no princípio do século XIII que a Universidade começou a organizar-se . Em 1200, por um privilégio outorgado por Filipe Augusto, a corporação dos professôres e dos estudantes de Paris passou a reger-se pela jurisdição eclesiástica, furtando-se dessa maneira ao fôro civil. Em 1215, Roberto de Courçon, legado pontifício, conce-deu ao studium parisiense seus primeiros estatutos oficiais . Se tais medidas constituíram o início da organização jurídica da Universidade, foram, por outro lado, o remate de um lento processo de formação . Mas, como decorreu êsse movimento germinativo da Universidade de Paris? Que condições o prepararam e que fatôres contri-buíram para sua gênese e desenvolvimento?
Fomento ultramarino e mercantilismo: a Companhia Geral do Grão-Pará e Maranhão (1755-1778)
Authors: Dias Manuel Nunes 
Published: January 2018

CONTINUAÇÃO - CAPÍTULO II No comêço da administração de Francisco Xavier de Men-donça Furtado, governador e capitão-general do Estado do Grão-Pará e Maranhão, a Amazônia ainda enfrentava os seus pro-blemas de ligação com o mundo europeu.
Resenha de: Fuentes para la História de Ibero-América conservadas en Suecia
Authors: Witter José Sebastião 
Published: January 2018

MÔRNER (Magnus) . — Fuentes para la História de Ibero-América conservadas en Suecia. Guia compilado por Magnus Mõrner. Traducción del sueco por Ester Pastor Lopes. Arquico Nacional da Suécia, Estocolmo, 1968.
Resenha de: Compêndio das eras da Província do Pará
Authors: Lapa José Roberto do Amaral 
Published: January 2018

BAENA (Antônio). — Compêndio das éras da Província do Pará, Coleção Ama- zônica. Série José Veríssimo. Universidade Federal do Pará. Belém, 1969.
Rita Lobato: a primeira médica formada no Brasil
Authors: Lobo Francisco Bruno 
Published: January 2018

O Govêrno resolveu homenagear a mulher brasileira emitindo uma série de selos postais, ,nos quais figurassem, em efígie, as pioneiras. Dentre elas foi escolhida a primeira mulher que se diplomou em medicina em uma Faculdade brasileira: A Dra. Rita Lobato de Freitas . No dia 9 de junho, aniversário de seu nascimento, o referido sêlo entrou em circulação.
História da Ciência e Metodologia
Authors: Motoyama Shozo 
Published: January 2018

Impõe-se a pergunta: "Qual é a importância da História da Ciência na formação de cientistas e educadores?" Temos duas respostas, de acôrdo com as pessoas em jôgo . Se se quer "cientistas" tecnocratas, especialistas de visão curta, homens néscios em tudo, menos na matéria da sua especialidade, a resposta é: nenhuma.
Resenha de: La société aux XIe et XIIe siécles dans la région mâconnaise
Authors: Paula Eurípedes Simões de 
Published: January 2018

DUBY (Georg:s). — La société aux XIe et XIIe siécles dans la région miiconnaise. Coleção "Bibliothèque Générale" da "École Pratique des Hautes Études. VIe Section". S.E.V.P.E.N. Paris. 1971. 525 pp. XII croquis. Preço: 68 F-71,15 Ffco. (reedição).