bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the Relationship of Inotuzumab Ozogamicin Exposure With Efficacy and Safety End Points in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia
Authors: Chen Joseph , Haughey May , Vandendries Erik , DeAngelo Daniel J. , Kantarjian Hagop M. , Ruiz‐Garcia Ana 
Published: August 2020

Inotuzumab ozogamicin (InO), an anti‐CD22 monoclonal antibody conjugated to calicheamicin, is approved in Europe and the United States for treatment of adults with relapsed or refractory acute lymphoblastic leukemia (ALL). Population analyses were performed to evaluate the relationship between InO exposure and efficacy and safety end points in patients with ALL. The probability of achieving complete remission/complete remission with incomplete hematologic recovery (CR/CRi) and minimal residual disease (MRD)‐negativity for InO relative to chemotherapy was also investigated. Data from study 1010 (NCT01363297) and INO‐VATE (NCT01564784) were pooled for exposure–response (InO, n = 234) and treatment–response (InO, n = 234; chemotherapy, n = 143) analyses. The analyses demonstrated that InO exposure was significantly correlated with achieving CR/CRi and MRD‐negativity, as well as with hepatic event adjudication board‐reported veno‐occlusive disease/sinusoidal obstruction. Patients with ALL treated with InO had significantly greater odds of achieving CR/CRi (7‐times higher) and MRD‐negativity (13‐times higher) than those receiving chemotherapy.
Knowledge, attitudes, and beliefs regarding molar incisor hypomineralization (MIH) amongst German dental students
Authors: Elhennawy Karim , Anang Mostafa , Splieth Christian , Bekes Katrin , Manton David John , Hedar Zen , Krois Joachim , Jost‐Brinkmann Paul‐Georg , Schwendicke Falk 
Published: August 2020

AbstractBackgroundKnowledge of molar incisor hypomineralization (MIH) has relevance for paediatric dentists.AimTo assess final‐year German dental students’ knowledge, attitudes, and beliefs regarding MIH.Materials and methodsA previously validated questionnaire was posted to the 31 German dental schools. Demographic covariates as well as knowledge regardingdiagnosis and prevalence, and attitudes and beliefs around aetiology and management were collected.ResultsTwenty‐two (71%) dental schools responded and a total of 877 students participated. Most (97%) were familiar with MIH and 88% were aware of the diagnostic criteria for MIH; however, only 42% knew how to implement them. One‐third were able to identify MIH and 16% reported diagnostic confidence when doing so; 90% assumed the MIH prevalence to be <10%. Two‐thirds of the respondents implicated genetic components as the main aetiological factor of MIH. Resin composite (60%) and preformed metal crowns (46%) were the dental materials most often suggested for restorative management. Almost all (98%) respondents were interested in receiving more clinical training.ConclusionGerman students were familiar with MIH; however, they reported low levels of knowledge and confidence regarding its prevalence and diagnosis. Standardized nationwide, up‐to‐date curricula should be implemented to educate future dentists in Germany.
Use of dementia care mapping in the care for older people with intellectual disabilities: A mixed‐method study
Authors: Schaap Feija D. , Dijkstra Geke J. , Reijneveld Sijmen A. , Finnema Evelyn J. 
Published: August 2020

AbstractBackgroundThe ageing of people with intellectual disabilities, with associated morbidity like dementia, calls for new types of care. Person‐centred methods may support care staff in providing this, an example being Dementia Care Mapping (DCM). DCM has been shown to be feasible in ID‐care. We examined the experiences of ID‐professionals in using DCM.MethodsWe performed a mixed‐methods study, using quantitative data from care staff (N = 136) and qualitative data (focus‐groups, individual interviews) from care staff, group home managers and DCM‐in‐intellectual disabilities mappers (N = 53).ResultsDCM provided new insights into the behaviours of clients, enabled professional reflection and gave new knowledge and skills regarding dementia and person‐centred care. Appreciation of DCM further increased after the second cycle of application.ConclusionDCM is perceived as valuable in ID‐care. Further assessment is needed of its effectiveness in ID‐care with respect to quality of care, staff‐client interactions and job performance.
Long non‐coding RNA MALAT1 targeting STING transcription promotes bronchopulmonary dysplasia through regulation of CREB
Authors: Chen Jia‐He , Feng Dan‐Dan , Chen Yu‐Fei , Yang Cai‐Xia , Juan Chen‐Xia , Cao Qian , Chen Xi , Liu Shuang , Zhou Guo‐Ping 
Published: August 2020

AbstractBronchopulmonary dysplasia (BPD) is a severe complication of preterm infants characterized by increased alveolarization and inflammation. Premature exposure to hyperoxia is believed to be a key contributor to the pathogenesis of BPD. No effective preventive or therapeutic agents have been created. Stimulator of interferon gene (STING) is associated with inflammation and apoptosis in various lung diseases. Long non‐coding RNA MALAT1 has been reported to be involved in BPD. However, how MALAT1 regulates STING expression remains unknown. In this study, we assessed that STING and MALAT1 were up‐regulated in the lung tissue from BPD neonates, hyperoxia‐based rat models and lung epithelial cell lines. Then, using the flow cytometry and cell proliferation assay, we found that down‐regulating of STING or MALAT1 inhibited the apoptosis and promoted the proliferation of hyperoxia‐treated cells. Subsequently, qRT‐PCR, Western blotting and dual‐luciferase reporter assays showed that suppressing MALAT1 decreased the expression and promoter activity of STING. Moreover, transcription factor CREB showed its regulatory role in the transcription of STING via a chromatin immunoprecipitation. In conclusion, MALAT1 interacts with CREB to regulate STING transcription in BPD neonates. STING, CREB and MALAT1 may be promising therapeutic targets in the prevention and treatment of BPD.
Boundary Layer Ingestion Propulsion: A Review on Numerical Modeling
Authors: Menegozzo Luca , Benini Ernesto 
Published: August 2020

Abstract
The present paper focuses on the numerical modeling approaches adopted in boundary layer ingestion (BLI) studies. Three driving aircraft concepts have been identified, namely propulsive fuselage concept (PFC), rear engines concept (REC), and distributed fans concept (DFC). The affiliation to relevant research projects has been considered. Specifically, European projects DisPURSAL and CENTRELINE, NASA projects STARC-ABL, D8, and N3-X, as well as ONERA projects NOVA and DRAGON have been examined, together with other significant works. The methodologies adopted by the reviewed analyses have been investigated and summarized for each concept, in order to assess the main trends of BLI modeling strategies.
Detection of SARS-CoV-2 IgG Targeting Nucleocapsid or Spike Protein by Four High-Throughput Immunoassays Authorized for Emergency Use
Authors: Prince Harry E. , Givens Tara S. , Lapé-Nixon Mary , Clarke Nigel J. , Schwab Dale A. , Batterman Hollis J. , Jones Robert S. , Meyer William A. , Kapoor Hema , Rowland Charles M. , Haji-Sheikhi Farnoosh , Marlowe Elizabeth M. 
Published: August 2020

A total of 1,200 serum samples that were tested for SARS-CoV-2 IgG antibody using the Abbott Architect immunoassay targeting the nucleocapsid protein were run in 3 SARS-CoV-2 IgG immunoassays targeting spike proteins (DiaSorin Liaison, Ortho Vitros, and Euroimmun). Consensus-positive and consensus-negative interpretations were defined as qualitative agreement in at least 3 of the 4 assays. Agreement of the 4 individual assays with a consensus-negative interpretation (
n
= 610) ranged from 96.
School absence and achievement in children with isolated orofacial clefts
Authors: Fitzsimons Kate J , Deacon Scott A , Copley Lynn P , Park Min Hae , Medina Jibby , van der Meulen Jan H 
Published: August 2020

ObjectivesTo examine school absence and academic achievement among 7-year-old children with isolated orofacial clefts in England.DesignAnalysis of educational data linked to national cleft registry and administrative hospital data.SettingEnglish state schools.Patients3523 children with isolated clefts aged 7 years between 2006 and 2014.Main outcome measuresAnnual school absence and reaching the national ‘expected level’ according to teacher-assessed academic achievement.ResultsChildren with isolated clefts had higher mean annual school absence (10.5 days) than their peers in the national population (8.9 days). Total absence was higher in children with a cleft lip and palate (CLP; 11.3 days) or with a cleft palate only (CPO; 10.5 days) than in children with a cleft lip only (CLO; 9.5 days). The percentage reaching the expected academic level decreased with increasing school absence (from 77.4% (923/1192) with annual school absence ≤5 days to 43.4% (193/445) with annual school absence >20 days). However, differences in school absence did not explain that children with CPO (65.9% reaching expected level) or CLP (66.1% reaching expected level) had poorer levels of academic achievement than children with CLO (73.5% reaching expected level). Children with a cleft were twice as often recognised as having special education needs (40.5%) than their peers (21.6%).ConclusionsSchool absence and cleft type are both independently associated with school attainment at 7 years. Children with an isolated cleft, especially when the palate is involved, and those with high levels of school absence may benefit from increased support addressing their educational needs.
P39 Pharmacy preparations for the birth of twins to an ebola survivor
Authors: Marra Fiona , Robertson Gayle , Gallagher Joanne , Mulholland Peter 
Published: August 2020

BackgroundA 43 year old patient previously treated for re-activation of Ebola Virus Disease1 presented to hospital with a twin pregnancy. As a conservative precaution, Remdesivir was obtained for potential use in the mother and the neonates.MethodAll literature was reviewed on the drug in trial and restricted license, along with drugs previously administered in this patient. The recommendation was made to consider Remdesivir and Favipiravir. The patient had received Remdesivir with probable benefit in the past. As the drug is unlicensed, the clinical team from Gilead, California were closely involved. Details of drug dosage and side effects were provided following a non-disclosure agreement. Preparations were made for an import licence following approval by NHS Greater Glasgow and Clyde health board and the Medicines and Healthcare products Regulatory Agency to import the product from California into the UK.Temperature monitored storage was arranged in advance and the drug appropriately stored. The pharmacy manual was supplied by Gilead and worksheets were prepared in advance.2 A small team of out of hours aseptic pharmacists and technicians were briefed in order to facilitate immediate supply if required. Based on published data, there were no known drug interactions and no contra-indications to breastfeeding.3OutcomeIn the weeks leading up to the delivery the infectious diseases pharmacist, aseptic lead pharmacist and neonatal pharmacist were on call for that period to then cascade requirements down to other pharmacy staff, if required out of hours. The twins were delivered safely with no issues for the neonates or the mother.ReferencesJacobs M, et al. Late Ebola virus relapse causing meningoencephalitis: a case report, Lancet 2016;388:498–503GS-5734 for Injection Pharmacy Manual rev 2.1, Gilead Sciences Inc, Foster City CA94404WHO R&D Blueprint – Ad-hoc Expert Consultation on clinical trials for Ebola Therapeutics, http://www.who.int/ebola/drc-2018/summaries-of-evidence-experimental-therapeutics.pdf?ua=1 accessed 20th May 2019
SP5 Tenfold medication errors in children – Welsh paediatric surveillance unit study 2017–9
Authors: Tse Yincent , Tuthill David 
Published: August 2020

AimsTo establish the incidence and characteristics of tenfold or greater and a tenth or less medication errors in children <16 years in Wales to help inform patient safety on a population level.MethodPopulation-based incidence study in Wales, UK, from June 2017 - May 2019 (24 months). Cases were reported from paediatricians and hospital pharmacists using the monthly Welsh Paediatric Surveillance Unit (WPSU).Results46 confirmed incidents in 44 children from 63 notifications were identified. Cases came from 8 hospitals in Wales with 29 (63%) from the sole tertiary hospital. Median age was 1.7 (range 1 week to 15) years and weight 10 kg (0.6 to 59).39 (85%) were overdosing (up to 1000x fold error) and 7 underdosing. 40 different medications were involved, 16 (37%) intravenous. Of 29 cases involving enteral medication, 26 (90%) were liquid formulations. Three cases were discharge medication prescribed or dispensed incorrectly and administrated at home. Stage of errors were primarily in prescribing 37 (80%), administration 7 (16%) and dispensing 2 (4%).18 (42%) cases reached the patient, 10 from prescribing. Seven cases were spotted after multiple doses were given. Six errors resulted in harm, three which required intensive care treatment. No deaths or permanent disabilities were reported. Half (23/46) of all errors reported and two-thirds (12/18) of cases that reached the child occurred in <10 kg children.Several human factor themes were identified: Prescribing confusion between gram milligram and microgram (none reached patient, n=7), confusing between mg and mg/kg (n=6 including 3 underdosing errors), leading zero errors (e.g. 0.1 vs 0.001 mg, n=6) and prescribing reconciliation errors where admitting doctor attempted to prescribe chronic medication in mg by reversing calculating liquid dosage expressed in mL (n=4).During this study period 164,000 hospital admissions occurred in children <16 years in Wales. Our data estimates a tenfold error incidence of 1:3600 paediatric admissions, with drug reaching the child in 1:9000 admissions.ConclusionIn this unique first ever population surveillance study, tenfold errors in children occurred at every stage of medication process and in the full range of care settings. Errors found were very different from those obtained from tertiary hospital single centre study and UK National Reporting and Learning System (NRLS). Strategies for error reduction will be more productive if designed across a whole national healthcare system.
P63 Do paediatricians recognise childhood obesity?
Authors: Ferguson Elspeth , Hannah Claire , Stewart Emily 
Published: August 2020

AimThe obesity epidemic in England is growing, with 22% of 4 and 5 year olds and 34% of 10 and 11 year olds being overweight or obese.1 With obesity being linked to several different illnesses including type 2 diabetes and hypertension, it is vital that clinicians are recognising obesity among children as early as possible.This study aims to:Carry out an audit of identification of obesity in paediatric outpatients to determine whether paediatricians are effectively identifying overweight and obese children, and whether practice conforms to standards in medical guidelines.Explore the barriers to discussing overweight and obesity with parents.Carry out a prescription audit and compare against current medical guidelines.2MethodA retrospective review of all new medical patients seen during a one-week period in July was used to determine their weight status and whether they had correctly been identified by clinicians. A short questionnaire was distributed to all clinics at the chosen hospital during a one-week period in October to determine reasons why clinicians may not choose to discuss obesity with patients and their families. A prescription audit was carried out examining the drug cards of all new overweight and obese patients admitted to wards in the chosen hospital to determine if drug doses had been correctly adjusted for weight.Results21% (21) patients in the retrospective audit were classified as either overweight or obese. 28.6% of 4 and 5-year olds were found to be either overweight or obese and 14.3% of 10 and 11-year olds. Only 3 of the 21 overweight or obese patients had been recognised as overweight or obese by clinicians in their notes. The questionnaire found that the most common reasons for not discussing overweight and obesity with patients and their families was concerns about maintaining doctor/patient and doctor/parent relationships. Other reasons given were that there was not enough time in clinic appointments or that the family was already aware. Four overweight or obese patients had been prescribed drugs based on their actual weight rather than ideal weight and therefore had received an overdose. All doses for these patients were adjusted accordingly and re-prescribed in line with trust guidelines.ConclusionsThe results of our study indicate that there is need for regular height and weight checks for all paediatric patients to ensure correct identification and management of overweight and obese children. Ways of doing this may involve more regular height measurements and providing guidelines for medical professionals in how to breech the topic of weight with patients and carers. The results of our pharmacy audit indicate that some overweight and obese children are being prescribed inappropriate doses of medication with clearly shows that there is need for more monitoring of prescribing practices in overweight and obese patients.ReferencesPublic Health England. 2017. Health matters: obesity and the food environment.Trust guidelines. 2017. Drug adjustments in obese patients.
Assessment and improvement of junior doctor handover in the emergency department
Authors: Sykes Mark , Garnham Jack , Kostelec Pablo Martin , Hall Hazel , Mitra Anu 
Published: August 2020

IntroductionEffective handover between junior doctors is widely accepted as essential for patient safety. The British Medical Association in association with the National Health Service (NHS) National Patient Safety Agency and NHS Modernisation Agency have produced clear guidance regarding the contents and setting for a safe and efficient handover. We aimed to understand current junior doctor’s opinions on the handover process in a London emergency department (ED), with subsequent assessment, and any necessary improvement, of handover practices within the department.MethodsIn a London ED, a baseline survey was completed by the senior house officer (SHO) cohort to gauge current opinions of the existing handover process. Concurrently, a blinded prospective audit of handover practises was conducted. Multiple improvement strategies were subsequently implemented and assessed via Plan–Do–Study–Act (PDSA) cycles. A standard operating procedure was initially introduced and ‘rolled out’ throughout the department. This intervention was followed by development of an electronic handover note to ease completion of a satisfactory handover. Additional surveys were conducted to continually assess SHO opinion on how the handover process was developing. The final improvement strategy was formal handover teaching at the SHO induction.ResultsBaseline audit and SHO survey highlighted several opportunities for improvement. 5 handover components were deemed essential: (1) documented handover note; (2) doctor’s names; (3) history of presenting complaint; (4) ED actions; and (5) ongoing plan. The frequency of these components saw significant improvement by completion of the final PDSA. Following SHO rotation, all of the essential components fell, only to recover after the next improvement strategy.ConclusionsJunior doctors in a London ED were not satisfied with the current SHO handover process, and handover practices were not adequate. While the rotational nature of the SHO cohort makes sustained change challenging, implementation of thoughtful and realistic improvement strategies can significantly improve handover quality.
Microsatellite frameshift variants inSGO1of gastric cancer are not always associated with MSI status
Authors: Sugiyama Tomohiro , Iwaizumi Moriya , Taniguchi Terumi , Suzuki Satoshi , Tani Shinya , Yamade Mihoko , Hamaya Yasushi , Osawa Satoshi , Furuta Takahisa , Miyajima Hiroaki , Ohta Tsutomu , Baba Satoshi , Sugimura Haruhiko , Maekawa Masato , Sugimoto Ken 
Published: August 2020

AimsAlthough frameshift variants in the microsatellite area of shugoshin 1 (SGO1) have been reported in the context of microsatellite instability-high (MSI-H)/deficient mismatch repair gastrointestinal cancer, most have been evaluated only in early stage I–III patients, and only two of its five microsatellite regions have been evaluated. Therefore, we investigated the frequency and MSI status of microsatellite frameshift variants in gastric cancer cases, including stage IV.MethodsIn a total of 55 cases, 30 gastric cancer resection and 25 non-resection cases, DNA was extracted from both tumour and normal parts and PCR was performed. The variant was confirmed by TA cloning, and MSI was evaluated using GeneMapper software.ResultsA frameshift variant of c.973delA was observed in 16 of the 45 evaluable cases. Its frequency was 35.6%. Of the 25 cases that could be assessed for MSI status, two cases of MSI-H were associated with the c.973delASGO1variant. However, c.973delASGO1variant was also observed in four cases of microsatellite stable.ConclusionOur study shows thatSGO1frameshift variants are not always associated with MSI status.
Parton-shower effects in Higgs production via vector-boson fusion
Authors: Jäger Barbara , Karlberg Alexander , Plätzer Simon , Scheller Johannes , Zaro Marco 
Published: August 2020

AbstractWe present a systematic investigation of parton-shower and matching uncertainties of perturbative origin for Higgs-boson production via vector-boson fusion. To this end we employ different generators at next-to-leading order QCD accuracy matched with shower Monte Carlo programs, , and , and a next-to-next-to-leading order QCD calculation. We thoroughly analyse the intrinsic sources of uncertainty within each generator, and then compare predictions among the different tools using the respective recommended setups. Within typical vector-boson fusion cuts, the resulting uncertainties on observables that are accurate to next-to-leading order are at the 10% level for rates and even smaller for shapes. For observables sensitive to extra radiation effects uncertainties of about 20% are found. We furthermore show how a specific recoil scheme is needed when is employed, in order not to encounter unphysical enhancements for these observables. We conclude that for vector-boson fusion processes an assessment of the uncertainties associated with simulation at next-to-leading order matched to parton showers based only on the variation of renormalisation, factorisation and shower scales systematically underestimates their true size.