bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility and Acceptability of Methods to Collect Follow-Up Information From Parents 12 Months After Their Child’s Emergency Admission to Pediatric Intensive Care*
Authors: Pulham Rachel Anne , Wray Jo , Feinstein Yael , Brown Katherine , Pierce Christine , Nadel Simon , Pathan Nazima , Garralda Elena , Ramnarayan Padmanabhan 
Published: February 2019

Objectives:
To evaluate the feasibility and acceptability of different methods of collecting follow-up data from parents 12 months after their child’s emergency admission to a PICU.

Design:
Mixed-methods explanatory sequential design.

Setting:
One regional PICU transport service and three PICUs in England.

Patients:
Children undergoing emergency transport to PICU recruited to an ongoing biomarker study whose parents consented to be contacted for follow-up 12 months after PICU admission.

Interventions:
None.

Measurements and Main Results:
Parents or guardians who consented were asked to complete three questionnaires about their child’s functional status, quality of life, and behavior 12 months after PICU admission. Parents were given a choice about method of questionnaire completion: postal, online, or telephone interview and also asked for telephone feedback about the process and the reasons for their choice. Of 486 parents who consented to be contacted at 12 months, 232 were successfully contacted. Consent to receive questionnaires was obtained in 218 of 232 (94%). Of the 218 parents, 102 (47%) chose to complete questionnaires online (with 77% completion rate), 91 (42%) chose to complete postal questionnaires (48% completion rate), and 25 (11%) chose to complete questionnaires by telephone interview (44% completion rate).

Conclusions:
Parents expressed different preferences for follow-up questionnaire completion. Response rates varied by completion method. Understanding and catering for parental preferences is an important factor in maximizing response rates for follow-up studies in intensive care.
Improving perioperative pain management: a preintervention and postintervention study in 7 developing countries
Authors: Zaslansky Ruth , Chapman C. Richard , Baumbach Philipp , Bytyqi Adem , Castro Lopes José M. , Chetty Sean , Kopf Andreas , Li Li , Ern Ming Lim , Olawoye Olayinka , Rizza Parico Jane , Soyannwo Olaitan , Stamenkovic Dusica , Wang Hongwei , Meissner Winfried 
Published: February 2019

Abstract

Introduction:
The burden of untreated postoperative pain is high.

Objective:
This study assessed feasibility of using quality improvement (QI) tools to improve management of perioperative pain in hospitals in multiple developing countries.

Methods:
The International Pain Registry and Developing Countries working groups, from the International Association for the Study of Pain (IASP), sponsored the project and PAIN OUT, a QI and research network, coordinated it, and provided the research tools. The IASP published a call about the project on its website. Principal investigators (PIs) were responsible for implementing a preintervention and postintervention study in 1 to 2 surgical wards in their hospitals, and they were free to choose the QI intervention. Trained surveyors used standardized and validated web-based tools for collecting findings about perioperative pain management and patient reported outcomes (PROs). Four processes and PROs, independent of surgery type, assessed effectiveness of the interventions.

Results:
Forty-three providers responded to the call; 13 applications were selected; and PIs from 8 hospitals, in 14 wards, in 7 countries, completed the study. Interventions focused on teaching providers about pain management. Processes improved in 35% and PROs in 37.5% of wards.

Conclusions:
The project proved useful on multiple levels. It offered PIs a framework and tools to perform QI work and findings to present to colleagues and administration. Management practices and PROs improved on some wards. Interpretation of change proved complex, site-dependent, and related to multiple factors. PAIN OUT gained experience coordinating a multicentre, international QI project. The IASP promoted research, education, and QI work.
Liver Enzyme Elevation in Pregnant Women Receiving Antiretroviral Therapy in the ANRS-French Perinatal Cohort
Authors: Sibiude Jeanne , Warszawski Josiane , Tubiana Roland , Le Chenadec Jérôme , Meier Françoise , Faye Albert , Blanche Stéphane , Mandelbrot Laurent ,   the ANRS-French Perinatal Cohort Study Group
Published: February 2019

Background:
High rates of liver enzyme elevation (LEE) in women receiving antiretroviral treatment (ART) during pregnancy have been reported, but causes remain unclear. We estimated the prevalence and risk factors of LEE in a national prospective multicenter cohort.

Methods:
We studied 5748 pregnant women living with HIV enrolled in the French Perinatal Cohort 2005–2014, treated with ART, with no active hepatitis B or C coinfection. Adjusted hazard ratio (aHR) was estimated using Cox models with ART as time-dependent variable, separately for women on ART at conception and those initiating ART during pregnancy.

Results:
LEE (grade ≥ 1) was observed in 16.7%, grade 3–4 in 2%. Among women with LEE, 6.7% had pre-eclampsia, 9.8% intrahepatic cholestasis of pregnancy, and 1.4% other identified medical causes. Most LEEs (82.2%) were unexplained. In women with unexplained LEE, LEE was the reason for hospitalization in 51 (6%) women, cesarean section in 13 (2%), induction of labor in 3 (0.4%), and change in ART regimen in 49 (6%) women. Unexplained LEE was associated with higher risk of preterm births, P < 0.001. Among women on ART at conception, the risk of unexplained LEE was lower with NNRTI-based regimens than with PI-based regimens: aHR = 0.5 (0.3–0.7), with no difference among the PI drugs. Most women initiating ART during pregnancy were on a PI-based regimen (89%). Among them, LEE was less frequent for women on nelfinavir vs. lopinavir/r [aHR = 0.4 (0.2–0.8)].

Conclusions:
Rates of LEE among pregnant women living with HIV are high and impact obstetrical care management. The possible role of PIs needs further investigation.
Ensuring Sustainability for UK Burns Services
Authors: Brady Chevonne , Edmondson Sarah-Jayne , Murray Alexandra 
Published: February 2019

Introduction
Workforce planning is an essential component of organizing any health service. Centralization of burns services pools expertise, although trainees can struggle to achieve adequate exposure to burns training. We aim to review current staffing levels and predict the future consultant numbers required for UK services to remain staffed with appropriately trained surgeons.

Methods
We have compiled a database of all UK burns consultants. Basic demographic data, such as age and sex, were collated. Projected UK population data have been used to estimate whether the number of patients under the care of the UK burns network will change in the coming years. Access to burns fellowship training has also been factored in.

Results
There are 34 burns facilities in the United Kingdom and 86 burns consultants. On average, these consultants are 13 years from retirement age. 22 will reach this age within the next decade. During this time, the UK population is expected to increase by 10%, translating to approximately another 6 consultant posts. Since there are only 2 UK recognized burns fellowships, many of the required consultants will have to seek training abroad.

Conclusions
Workforce planning is essential to avoid a short fall in the number of upcoming burns consultants. Plans must be in place to anticipate additional workload with a 10% population rise. With the current struggles of NHS funding, a comprehensive review of burns workforce planning should be undertaken to ensure that sufficient numbers of trainees are completing appropriate burns-specific training and are ready to fill these posts.
Increased Gastrointestinal Surgical Hospital Burden After Laparoscopic Gastric Bypass for Obesity
Authors: Neermark Søren , Tolstrup Janne Schurmann , Becker Povl Ulrik , Bay-Nielsen Morten , Fromholt-Larsen Jens , Thygesen Lau Caspar , Bisgaard Thue 
Published: February 2019

Objective:
To study long-term gastrointestinal surgical hospital burden (hospital readmissions and gastrointestinal surgical procedures) after laparoscopic gastric bypass.

Background:
Little is known about gastrointestinal surgical hospital burden after laparoscopic gastric bypass.

Methods:
Danish patients undergoing laparoscopic gastric bypass (BMI >35–50) from January 1, 2005 to December 31, 2013 were included (100% follow-up). The nonsurgical reference group were individuals with BMI of ≥ 30 drawn from The Danish National Health Surveys from 2005 to 2013. The primary outcome was gastrointestinal surgical hospital burden. Secondary outcome was mortality. Age, body mass index (BMI), gender, and calendar time (time of surgery and nonsurgical survey), diabetes status was adjusted for in a multivariate Poisson regression model.

Results:
13,582 bariatric surgical patients and 45,948 reference individuals were included with a mean follow-up time of 4.7 years (SD 2.4). The incidence rate ratio (IRR) for hospital re-re-admission was 2.17 higher in the intervention group (95% CI 2.04–2.31). Sensitivity analysis showed that patients operated before 2010 had a higher incidence for re-re-admission than after. IRR for surgical gastrointestinal procedures was 6.56 (CI 6.15–6.99) and 3.04 (CI 3.51–4.17) after 1 and 5 years for the intervention group compared with the reference group. Surgery for internal hernia was the most common abdominal procedure. The mortality odds ratio was 0.84 (CI 0.65–0.96).

Conclusions:
Gastrointestinal surgical hospital burden was significantly higher in the first 5 years after gastric bypass compared with a matched nonsurgical reference group of obese citizens
Total Lesion Glycolysis Assessment Identifies a Patient Fraction With a High Cure Rate Among Esophageal Adenocarcinoma Patients Treated With Definitive Chemoradiation
Authors: Harada Kazuto , Wu Carol C. , Wang Xuemei , Mizrak Kaya Dilsa , Amlashi Fatemeh G. , Iwatsuki Masaaki , Blum Murphy Mariela A. , Maru Dipen M. , Weston Brian , Lee Jeffrey H. , Rogers Jane E. , Thomas Irene , Shanbhag Namita , Bhutani Manoop S. , Hofstetter Wayne L. , Nguyen Quynh-Nhu , Ajani Jaffer A. 
Published: February 2019

Objective:
We aimed to determine whether tumor metabolism could be prognostic of cure in L-EAC patients who receive definitive chemoradiation.

Summary Background Data:
Patients with inoperable localized esophageal adenocarcinoma (L-EAC) often receive definitive chemoradiation; however, biomarkers and/or imaging variables to prognosticate cure are missing.

Methods:
Two hundred sixty-six patients with L-EAC who had chemoradiation but not surgery were analyzed from the prospectively maintained EAC databases in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center (Texas, USA) between March 2002 and April 2015. Maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) from the positron emission tomography data were evaluated.

Results:
Of 266 patients, 253 (95%) were men; the median age was 67 years (range 20–91 yrs) and 153 had poorly differentiated L-EAC. The median SUVmax was 10.3 (range 0–87) and the median TLG was 85.7 (range 0–3227). Both SUVmax and TLG were higher among those with: tumors >5 cm in length, high clinical stage, and high tumor and node categories by TNM staging (all P < 0.0001). Of 234 patients evaluable for cure, 60 (25.6%) achieved cure. In the multivariable logistic regression model, low TLG (but not low SUVmax) was associated with cure (continuous TLG value: odds ratio 0.70, 95% confidence interval (CI) 0.54–0.92). TLG was quantified into 4 quartile categorical variables; first quartile (Q1; <32), second quartile (Q2; 32.0–85.6), third quartile (Q3; 85.6–228.4), and fourth quartile (Q4; >228.4); the cure rate was only 10.3% in Q4 and 5.1% in Q3 but increased to 28.8% in Q2, and 58.6% in Q1. The cross-validation resulted in an average accuracy of prediction score of 0.81 (95% CI, 0.75–0.86).

Conclusions:
In this cross-validated model, 59% of patients in the 1st quartile were cured following definitive chemoradiation. Baseline TLG could be pursued as one of the tools for esophageal preservation.
Neuropathology-driven Whole-genome Sequencing Study Points to Novel Candidate Genes for Healthy Brain Aging
Authors: Alexander John , Ströbel Thomas , Georgitsi Marianthi , Hönigschnabl Selma , Reiner Angelika , Fischer Peter , Tsifintaris Margaritis , Paschou Peristera , Kovacs Gabor G. 
Published: February 2019

Purpose:
Understanding the healthy brain aging process is key to uncover the mechanisms that lead to pathologic age-related neurodegeneration, including progression to Alzheimer disease (AD). We aimed to address the issue of pathologic heterogeneity that often underlies a clinical AD diagnosis.

Methods:
We performed a deep whole-genome sequencing study aiming to identify variants that are associated specifically with healthy brain aging.

Patients:
We examined samples from the community-based longitudinal Vienna Transdanubian Aging study comparing neuropathologically “healthy” aging in individuals above 80 years of age with pure AD patients of the same age.

Results:
Focusing on potentially functional variants, we discovered a single variant (rs10149146) that lies on the autophagy-associated TECPR2 gene and was carried by 53.6% of the “healthy” brain elderly individuals (15/28). An additional nonsynonymous variant on the CINP gene (encoding a cell cycle checkpoint protein) was also found in 46% of healthy controls. Both variants are absent from all AD cases. TECPR2 and CINP appear to be “partner” genes in terms of regulation and their associated transcription factors have been previously implicated in AD and neurodegeneration.

Conclusions:
Our study underlines the strength of neuropathology-driven definitions in genetic association studies and points to a potentially neuroprotective effect of key molecules of autophagy and cell cycle control.
A stochastic model for error correction of kinetochore-microtubule attachments and its coupling to the spindle assembly checkpoint
Authors: Banerjee Anand , Adames Neil , Peccoud Jean , Tyson John J. 
Published: February 2019

AbstractTo divide replicated chromosomes equally between daughter cells kinetochores must attach to microtubules emanating from opposite poles of the mitotic spindle. Two mechanisms, namely, error correction and ‘spindle assembly checkpoint’ work together to facilitate this process. The error correction mechanism recognizes and detaches erroneous kinetochore-microtubule attachments, and the spindle assembly checkpoint delays the onset of anaphase until all the kinetochores are properly attached. Kinases and phosphatases at the kinetochore play a key role in proper functioning of these two mechanisms. Here we present a stochastic model to study how the opposing activities of kinases and phosphatases at the kinetochore affect error correction of kinetochore-microtubule attachments and checkpoint signaling in budding yeast, Saccharomyces cerevisiae. We show that error correction and biorientation of chromosomes occurs efficiently when the ratio between kinase activity of Ipl1 and the activity of an opposing phosphatase is a constant (balance point), and derive an approximate analytical formula that defines the balance point. Analysis of the coupling of the spindle assembly checkpoint signal to error correction shows that its strength remains high when the Ipl1 activity is equal to (or larger than) the value specified by the balance point, and the activity of another kinase, Mps1, is much larger (approximately 30 times larger) than its opposing phosphatase (PP1). We also find that the geometrical orientation of sister chromatids does not significantly improve the probability of their reaching biorientation, which depends entirely on Ipl1-dependent microtubule detachment.Author summaryThe kinetochore, the master regulator of chromosome segregation, integrates signals from different chromosome attachment states to generate an appropriate response, like the destabilization of erroneous kinetochore-microtubule attachments, stabilization of correct attachments, maintenance of the spindle assembly checkpoint signal until all kinetochores are properly attached, and finally silencing of checkpoint when biorientation is achieved. At a molecular level the job is carried out by kinases and phosphatases. The complexity of the interactions between these kinases and phosphatases makes intuitive analysis of the control network impossible, and a systems-level model is needed to put experimental information together and to generate testable hypotheses. Here we present such a model for the process of error correction and its coupling to the spindle assembly checkpoint in budding yeast. Using the model, we characterize the balance between kinase and phosphatase activities required for removing erroneous attachments and then establishing correct stable attachments between kinetochore and microtubule. We also analyze how the balance affects the strength of the spindle assembly checkpoint signal.
Information and genetic counselling for psychiatric risks in children with rare disorders
Authors: Cuthbert Andrew , Challenger Aimee , Hall Jeremy , den Bree Marianne BM van 
Published: February 2019

AbstractBackground:The diagnosis of developmental disorders is being transformed by advances in whole genome technologies. However, continuing uncertainties about the individual risks and potential severity of psychiatric impacts attributed to causal genomic variants limits the availability of comprehensive family-oriented information. In addition, there is insufficient evidence about how the parents of children with developmental disorders comprehend the facts and implications of their diagnosis through genetic counselling, nor how they gather developmental and mental health information to guide their understanding.Methods:Parents of children (aged 0–17 years) referred to paediatric genetics services completed an anonymous online 46-item survey about: (i) the experience of attending services to receive their child’s genetic diagnosis, and (ii) the availability, quality and helpfulness of information about psychiatric and neurodevelopmental conditions associated with genomic disorders.Findings:Two-hundred and eighty-six families (199 UK and 87 USA) completed the survey. One-in-three UK and one-in-five US respondents were dissatisfied with how their child’s genetic diagnosis was communicated. Satisfaction was predicted by face-to-face communication (odds ratio 2·91 [95% CI 1·43–5·94]; p=0·003); results being presented by genetics specialists (2·97 [1·41–6·26]; p=0·004); receiving clear explanations (5·14 [2·58– 10·26]; p<0·001); receiving support (2·99 [1·21–7·36], p=0·017); and male gender of the tested child (2·56 [1·28–5·14]; p=0·008). Compared to health-related information on developmental delay or intellectual disability, parents were more likely to obtain information about psychiatric manifestations from non-professional lay sources than from clinical specialists (p<0·001). This was particularly evident for families in the UK compared to the USA (p<0·001). Parents considered information from rare disorder support groups to be more helpful than from genetics specialists (odds ratio 11·0 [95% CI 5·08–86·75]; p<0·001), or paediatricians (11·0 [1·42–85·20]; p=0·006), or internet sites (15·5 [3·71–64·77]; p<0·001), which in turn proved more helpful than information provided by geneticists (2·5 [1·44–4·31]; p=0·001).Interpretation:Psychiatric comorbidity is a common feature of rare genomic disorders, but the paucity of suitable information available from clinical specialists suggests families are not optimally informed about these challenges. Wider implementation of genomic testing in general medicine should include adequate training in genetic counselling to ensure best practice in communicating and explaining complex test results supported by comprehensive, family-oriented information.Funding:The Waterloo Foundation: Changing Minds Programme (506296); The Medical Research Council (MRC) Research Grant: Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment (MR/N022572/1).
An RNA-binding protein secreted byListeria monocytogenesactivates RIG-I signaling
Authors: Pagliuso Alessandro , Tham To Nam , Allemand Eric , Robertin Stevens , Dupuy Bruno , Bertrand Quentin , Bécavin Christophe , Koutero Mikael , Najburg Valérie , Nahori Marie-Anne , Stavru Fabrizia , Dessen Andréa , Muchard Christian , Lebreton Alice , Komarova Anastassia V. , Cossart Pascale 
Published: February 2019

SummaryRecent studies have reported on the presence of bacterial RNA within or outside extracellular membrane vesicles, possibly as ribonucleoprotein complexes. Proteins that bind and stabilize bacterial RNAs in the extracellular environment have not been reported. Here, we show that the bacterial pathogenListeria monocytogenessecretes a small RNA binding protein that we named Zea. We show that Zea binds and stabilizes a subset ofL. monocytogenesRNAs causing their accumulation in the extracellular medium. Furthermore, Zea binds RIG-I, the vertebrate non-self-RNA innate immunity sensor and potentiates RIG-I-signaling leading to interferon β production. By performingin vivoinfection, we finally show that Zea modulatesL. monocytogenesvirulence. Together, this study reveals that bacterial extracellular RNAs and RNA binding proteins can affect the host-pathogen crosstalk.
Design, construction and characterisation of a novel nanovibrational bioreactor and cultureware for osteogenesis
Authors: Campsie Paul , Childs Peter G. , Robertson Shaun N. , Cameron Kenny , Hough James , Salmerón-Sánchez Manuel , Tsimbouri Monica P. , Vichare Parag , Dalby Matthew J. , Reid Stuart 
Published: February 2019

ABSTRACTIn regenerative medicine, techniques which control stem cell lineage commitment are a rapidly expanding field of interest. Recently, nanoscale mechanical stimulation of mesenchymal stem cells (MSCs) has been shown to activate mechanotransduction pathways stimulating osteogenesis in 2D and 3D culture. This has the potential to revolutionise bone graft procedures by creating cellular graft material from autologous or allogeneic sources of MSCs without using chemical induction. With the increased interest in mechanical stimulation of cells and huge potential for clinical use, it is apparent that researchers and clinicians require a scalable bioreactor system that provides consistently reproducible results with a simple turnkey approach. A novel bioreactor system is presented that consists of: a bioreactor vibration plate, calibrated and optimised for nanometre vibrations at 1 kHz, a power supply unit, which supplies a 1 kHz sine wave signal necessary to generate approximately 30 nm of vibration amplitude, and custom 6-well cultureware with toroidal shaped magnets incorporated in the base of each well for conformal attachment to the bioreactor’s magnetic vibration plate. The cultureware and vibration plate were designed using finite element analysis to determine the modal and harmonic responses, and validated by interferometric measurement. This helps ensure that the vibration plate and cultureware, and thus collagen and MSCs, all move as a rigid body, avoiding large deformations close to the resonant frequency of the vibration plate and vibration damping beyond the resonance. Assessment of osteogenic protein expression was performed to confirm differentiation of MSCs after initial biological experiments with the system, as well as atomic force microscopy of the 3D gel constructs during vibrational stimulation to verify that strain hardening of the gel did not occur. This shows that cell differentiation was the result of the nanovibrational stimulation provided by the bioreactor alone, and that other cell differentiating factors, such as stiffening of the collagen gel, did not contribute.