bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement Error Correction and Sensitivity Analysis in Longitudinal Dietary Intervention Studies Using an External Validation Study
Authors: Siddique Juned , Daniels Michael J. , Carroll Raymond J. , Raghunathan Trivellore E. , Stuart Elizabeth A. , Freedman Laurence S. 
Published: February 2019

Abstract
In lifestyle intervention trials, where the goal is to change a participant's weight or modify their eating behavior, self-reported diet is a longitudinal outcome variable that is subject to measurement error. We propose a statistical framework for correcting for measurement error in longitudinal self-reported dietary data by combining intervention data with auxiliary data from an external biomarker validation study where both self-reported and recovery biomarkers of dietary intake are available. In this setting, dietary intake measured without error in the intervention trial is missing data and multiple imputation is used to fill in the missing measurements. Since most validation studies are cross-sectional, they do not contain information on whether the nature of the measurement error changes over time or differs between treatment and control groups. We use sensitivity analyses to address the influence of these unverifiable assumptions involving the measurement error process and how they affect inferences regarding the effect of treatment. We apply our methods to self-reported sodium intake from the PREMIER study, a multi-component lifestyle intervention trial.
Academic staff perspectives on technology for assessment (TfA) in higher education: A systematic literature review
Authors: Brady Mairead , Devitt Ann , Kiersey Rachel A. 
Published: February 2019

AbstractThis paper presents a systematic literature review of academic staff experiences and perceptions of adopting Technology for Assessment OF/FOR/AS Learning in Higher Education. This paper is a qualitative synthesis of 65 peer‐reviewed journal articles published between 2012 and 2017 reporting on the use of technology for assessment (TfA). The results suggest that there are some efficiencies for staff in implementing TfA but this can come with a cost at the set‐up and maintenance phases. Furthermore, results indicated that assessment design is not of foremost concern to academic staff when introducing TfA, but that a wide variety of pressures and both educational and operational drivers are present. There were inconclusive findings in relation to understandings of appropriate institutional environments and supports for TfA to flourish in higher education. There is a need for empirical research, particularly longitudinal investigations, of academic experiences of implementations of TfA to investigate sustainability of adoption. The imperative of exploring the academic staff perspective as the instigator and manager of both the technology and the student learning experience requires deep consideration as TfA adoption progresses.
The impact of cytogenetics on duration of response and overall survival in patients with relapsed multiple myeloma (long‐term follow‐up results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open‐label, phase 3 trial
Authors: Cook Gordon , Royle Kara‐Louise , O'Connor Sheila , Cairns David A. , Ashcroft A. John , Williams Cathy D. , Hockaday Anna , Cavenagh Jamie D. , Snowden John A. , Ademokun Debo , Tholouli Eleni , Andrews Vivienne E. , Jenner Matthew , Parrish Christopher , Yong Kwee , Cavet Jim , Hunter Hannah , Bird Jenny M. , Pratt Guy , Drayson Mark T. , Brown Julia M. , Morris Treen C. M. ,   the National Cancer Research Institute Haemato‐oncology Clinical Studies Group
Published: February 2019

SummaryThe Myeloma X trial (ISCRTN60123120) registered patients with relapsed multiple myeloma. Participants were randomised between salvage autologous stem cell transplantation (ASCT) or weekly cyclophosphamide following re‐induction therapy. Cytogenetic analysis performed at trial registration defined t(4;14), t(14;16) and del(17p) as high‐risk. The effect of cytogenetics on time to progression (TTP) and overall survival was investigated. At 76 months median follow‐up, ASCT improved TTP compared to cyclophosphamide (19 months (95% confidence interval [95% CI] 16–26) vs. 11 months (9–12), hazard ratio [HR]: 0·40, 95% CI: 0·29–0·56, P < 0·001), on which the presence of any single high‐risk lesion had a detrimental impact [likelihood ratio test (LRT): P = 0·011]. ASCT also improved OS [67 months (95% CI 59‐not reached) vs. 55 months (44–67), HR: 0·64, 95% CI: 0·42–0·99, P = 0·0435], with evidence of a detrimental impact with MYC rearrangement (LRT: P = 0·021). Twenty‐one (24·7%) cyclophosphamide patients received an ASCT post‐trial, median OS was not reached (95% CI: 39‐not reached) for these participants compared to 31 months (22–39), in those who did not receive a post‐trial ASCT. The analysis further supports the benefit of salvage ASCT, which may still be beneficial after second relapse in surviving patients. There is evidence that this benefit reduces in cytogenetic high‐risk patients, highlighting the need for targeted study in this patient group.
Phase I dose‐escalation study of capmatinib (INC280) in Japanese patients with advanced solid tumors
Authors: Esaki Taito , Hirai Fumihiko , Makiyama Akitaka , Seto Takashi , Bando Hideaki , Naito Yoichi , Yoh Kiyotaka , Ishihara Kae , Kakizume Tomoyuki , Natsume Kazuto , Myers Andrea , Doi Toshihiko 
Published: February 2019

Capmatinib is a highly specific, potent and selective MET inhibitor. This was an open‐label, multicenter, dose‐escalation, phase I study conducted in Japanese patients with advanced solid tumors (not selected based on their MET status). The primary objective was to determine the maximum tolerated dose (MTD) and/or highest studied dose being safe. Secondary objectives included safety, pharmacokinetics and preliminary antitumor activity. Dose escalation was guided by a Bayesian Logistic Regression Model dependent on dose‐limiting toxicities (DLT) in cycle 1. Of 44 adult Japanese patients with confirmed advanced solid tumors enrolled, 29 received capmatinib capsules (doses ranging from 100 mg once daily [q.d.] to 600 mg twice daily [b.i.d.]) and 15 received tablets (200 mg b.i.d. and 400 mg b.i.d.). DLT occurred in two patients: grade 2 suicidal ideation (600 mg b.i.d. capsule) and grade 3 depression (400 mg b.i.d. tablet). MTD was not reached. The highest studied dose determined to be safe as tablet was 400 mg b.i.d., whereas it is not yet determined for capsules. Most common adverse events suspected to be drug‐related were increased blood creatinine, nausea, decreased appetite, vomiting and diarrhea. Following repeated daily dosing up to day 15 by q.d. or b.i.d. regimen using capsules, median time to reach maximum plasma drug concentration (Tmax) was 1.0‐4.0 hours; absorption was more rapid after dosing using tablets, with median Tmax of 1.0 hour on both days 1 and 15. Eight patients had a best overall response of stable disease. These data support further clinical development of capmatinib.
Sex‐specific associations between insulin resistance and bone parameters in overweight and obese older adults
Authors: Mesinovic Jakub , McMillan Lachlan B. , Shore‐Lorenti Catherine , Zengin Ayse , De Courten Barbora , Ebeling Peter R. , Scott David 
Published: February 2019

SummaryObjectivesTo determine sex‐specific associations between insulin resistance and bone parameters measured by peripheral quantitative computed tomography in overweight and obese community‐dwelling older adults.Study designCross‐sectional study of 79 community‐dwelling overweight and obese adults (mean ± SD age 62.8 ± 7.9 years; body mass index 32.3 ± 6.1 kg/m2; 58% women).Main outcome measuresPeripheral quantitative computed tomography assessed distal radius and tibia trabecular volumetric bone mineral density (vBMD) and proximal radius and tibia cortical vBMD, periosteal circumference, endosteal circumference and stress‐strain index. The Homeostatic Model Assessment of Insulin Resistance (HOMA‐IR) score was calculated from fasting glucose and insulin values. Lean mass was assessed using dual‐energy X‐ray absorptiometry. Total minutes of moderate and vigorous physical activity (MVPA) were calculated using the Active Australia Survey.ResultsMen and women in this cohort had no significant differences in fasting glucose and insulin concentrations, HOMA‐IR values and diabetes prevalence (all P > 0.05). In women, HOMA‐IR was positively correlated with proximal radius periosteal and endosteal circumference (r = 0.331; P = 0.034 and r = 0.325; P = 0.038, respectively). These associations became nonsignificant in multivariable regression analyses; however, HOMA‐IR was negatively associated with proximal radius cortical vBMD (B = −4.79; 95% CI −8.66, −0.92) after adjusting for age, lean mass and MVPA. All associations between HOMA‐IR and bone parameters became nonsignificant in a sensitivity analysis excluding individuals with diabetes, or self‐reported use of glucose‐lowering medications. There were no associations between HOMA‐IR and bone parameters in men.ConclusionsHomeostatic Model Assessment of Insulin Resistance was negatively associated with radial cortical vBMD in overweight and obese older women, but not in men. Further studies are needed to clarify sex‐specific associations between insulin resistance and bone health in overweight and obese older adults.
Accounting for unintended consequences of resource policy: Connecting research that addresses displacement of environmental impacts
Authors: Lewison Rebecca L. , Johnson Andrew F. , Gan Jianbang , Pelc Robin , Westfall Katie , Helvey Mark 
Published: February 2019

AbstractNatural resource policies enacted to protect environmental integrity play an important role in promoting sustainability. However, when resources are shared ecologically, economically, or through a common, global interest, policies implemented to protect resource sustainability in one domain can displace, and in some cases magnify, environmental degradation to other domains. Although such displacement has been recognized as a fundamental challenge to environmental and conservation policy within some resource sectors, there has been little cross‐disciplinary and cross‐sectoral integration to address the problem. This suggests that siloed knowledge may be impeding widespread recognition of the ubiquity of displacement and the need for mitigation. Here, we connect research across multiple disciplines to promote a broader discussion and recognition of the processes and pathways that can lead to displaced impacts that countermand or undermine resource policy and outline a number of approaches that can mitigate displacement.
Food supplementation protects Magnificent frigatebird chicks against a fatal viral disease
Authors: Sebastiano Manrico , Eens Marcel , Pineau Kévin , Chastel Olivier , Costantini David 
Published: February 2019

AbstractOutbreaks of wildlife diseases are occurring at an unprecedented rate. In French Guiana, recurrent episodes of frigatebird chicks’ mortality due to a viral disease that first appeared in 2005 have recently turned into massive mortality episodes (85–95%) of chicks. One of the suggested hypotheses behind the appearance of the disease is food limitation due to the recent decline of local shrimp fishery boats on which frigatebirds rely for opportunistic feeding. We therefore experimentally fish‐supplemented frigatebird chicks with and without clinical signs of the disease. Food supplementation protected all chicks from the appearance of clinical signs of the disease and increased survival perspectives of sick chicks. These results suggest that food shortage might decrease resistance of chicks to infectious diseases and that using a specifically tailored food supplementation regime could be a complimentary tool to protect frigatebirds and other endangered birds from disease outbreaks threatening them with extinction.
Acquired neuromyotonia in children with CASPR2 and LGI1 antibodies
Authors: Surana Snehal , Kumar Ratna , Pitt Matthew , Hafner Patricia , Mclellan Ailsa , Davidson Joyce , Prabakhar Prab , Vincent Angela , Hacohen Yael , Wright Sukhvir 
Published: February 2019

Acquired neuromyotonia is a form of peripheral nerve hyperexcitability. In adults, pathogenic antibodies that target the extracellular domains of leucine‐rich glioma‐inactivated protein 1 (LGI1) and contactin‐associated protein‐like 2 (CASPR2) have been reported. We describe three paediatric patients with acquired neuromyotonia and CASPR2 and LGI1 serum antibodies. They all presented with acute‐onset myokymia and pain in the lower limbs; one patient also had muscle weakness. Electromyography was suggestive of peripheral nerve hyperexcitability. Two patients improved without immunotherapy; one treated patient remained immunotherapy‐dependent. Although not fatal, acquired paediatric neuromyotonia can be disabling. It is amenable to symptomatic treatment or may undergo spontaneous recovery. More severe cases may require rational immunotherapy.What this paper adds

The symptoms of neuromyotonia may resolve spontaneously or may require sodium channel blockers.

Patients with debilitating symptoms who are refractory to symptomatic therapy may require immunotherapy.
Relationship between fasting plasma glucose and incidence of diabetes in children and adolescents
Authors: Yang C.‐Y. , Li H.‐Y. , Sung F.‐C. , Tan E. Chia‐Hui , Wei J.‐N. , Chuang L.‐M. 
Published: February 2019

AbstractAimTo investigate the appropriate fasting plasma glucose threshold by which to define prediabetes in children and adolescents, based on its ability to predict incident paediatric diabetes.MethodsIn a nationwide survey of diabetes and renal disease conducted between 1992 and 2000 in all school‐aged children in Taiwan, those with abnormal results in repeated urine tests received further physical examination and blood tests. Students who had blood tests for at least two time points were selected for the present study (N = 12 119). The incidence of paediatric diabetes, adjusted hazard ratio and predictive power of fasting plasma glucose were analysed.ResultsThe incidence of paediatric diabetes increased with increasing fasting plasma glucose levels. Groups with fasting plasma glucose >5.6 mmol/l had a higher adjusted hazard ratio. The adjusted hazard ratio of incident diabetes for participants with higher fasting plasma glucose rose continuously when using a higher threshold for fasting plasma glucose. The area under the receiver‐operating characteristic curve for fasting plasma glucose was 0.628 for predicting paediatric diabetes. The association between fasting plasma glucose and incident paediatric diabetes and the area under the receiver‐operating characteristic curve were similar in boys and girls and were higher in the age group 12–18 years. According to receiver‐operating characteristic curve analysis, the optimal thresholds, sensitivity and specificity were 4.75 mmol/l, 65% and 51%, respectively, for those aged 6–11 years and 5.19 mmol/l, 60% and 73%, respectively, for those aged 12–18 years.ConclusionFasting plasma glucose is associated with the incidence of paediatric diabetes. The results of the present study can be used as reference data to suggest a cut‐off value to define paediatric prediabetes.
The effects of licogliflozin, a dual SGLT1/2 inhibitor, on body weight in obese patients with or without diabetes
Authors: He Yan‐Ling , Haynes William , Meyers Charles D. , Amer Ahmed , Zhang Yiming , Mahling Ping , Mendonza Anisha E. , Ma Shenglin , Chutkow William , Bachman Eric 
Published: February 2019

BACKGROUNDThere is an unmet need for a safer and more effective treatment for obesity. This study assessed the effects of licogliflozin, a dual inhibitor of sodium‐glucose co‐transporter (SGLT) 1/2, on body weight, metabolic parameters and incretin hormones in patients with type 2 diabetes mellitus (T2DM) and/or obesity.METHODSPatients with obesity (BMI, 35‐50 kg/m2) were enrolled into a 12‐week study (N = 88; licogliflozin 150 mg q.d.). Patients with T2DM were enrolled into a second, two‐part study, comprising a single‐dose cross‐over study (N = 12; 2.5 − 300 mg) and a 14‐day dosing study (N = 30; 15 mg q.d). Primary endpoints included effects on body weight, effects on glucose, safety and tolerability. Secondary endpoints included urinary glucose excretion (UGE24) and pharmacokinetics, while exploratory endpoints assessed the effects on incretin hormones (total GLP‐1, PYY3‐36, and GIP), insulin and glucagon.RESULTSTreatment with licogliflozin 150 mg q.d. for 12 weeks in patients with obesity significantly reduced body weight by 5.7% vs placebo (P < 0.001) and improved metabolic parameters such as significantly reduced postprandial glucose excursion (21%; P < 0.001), reduced insulin levels (80%; P < 0.001) and increased glucagon (59%; P < 0.001). In patients with T2DM, a single dose of licogliflozin 300 mg in the morning prior to an oral glucose tolerance test (OGTT) remarkably reduced glucose excursion by 93% (P < 0.001; incremental AUC0‐4h) and suppressed insulin by 90% (P < 0.01; incremental AUC0‐4h). Treatment with licogliflozin 15 mg q.d. for 14 days reduced 24‐hour average glucose levels by 26% (41 mg/dL; P < 0.001) and increased UGE24 to 100 g (P < 0.001) in patients with T2DM. In addition, this treatment regimen significantly increased total GLP‐1 by 54% (P < 0.001) and PYY3‐36 by 67% (P < 0.05) post OGTT vs placebo, while significantly reducing GIP levels by 53% (P < 0.001). Treatment with licogliflozin was generally safe and well tolerated. Diarrhea (increased numbers of loose stool) was the most common adverse event in all studies (90% with licogliflozin vs 25% with placebo in the 12‐week study), while a lower incidence of flatulence, abdominal pain and abdominal distension (25%‐43% with licogliflozin vs 9%‐11% with placebo in the 12‐week study) were among the other gastrointestinal events reported.CONCLUSIONLicogliflozin treatment (1‐84 days) leads to significant weight loss and favourable changes in a variety of metabolic parameters and incretin hormones. Dual inhibition of SGLT1/2 with licogliflozin in the gut and kidneys is an attractive strategy for treating obesity and diabetes.
Normal values for tissue velocity and strain rate imaging parameters of left and right atrial myocardium in normal subjects
Authors: Safir‐Mardanloo Azam , Khorsand Askari Mani , Lotfi Tokaldany Masoumeh‐ , Ashrafi Mohammad Moein , Sadeghian Hakimeh 
Published: February 2019

ObjectiveTo determine normal values for tissue velocity imaging (TVI) and strain rate imaging (SRI) in the left atrium (LA) and right atrium (RA) in normal subjects.MethodsA total of 63 healthy volunteers (50.8% male, age: 20–50 years) prospectively underwent TVI and SRI. The peak systolic velocity (TVs), strain (STs) and strain rate (SRs), peak early and late diastolic velocities (TVe and TVa), strain (STe and STa), and strain rate (SRe and SRa) were measured in the base and mid of the LA and RA walls and roofs.ResultsBy TVI, TVs and TVe of LA walls decreased significantly from basal to mid‐level and from mid to the roof. Mean Tva of LA walls reduced significantly from basal to mid‐level and to the roof. By SRI, mean STs and STe of LA walls increased remarkably from basal to mid‐level and to the roof and also mean SRs, SRe and SRa increased significantly from basal to mid‐level and to the roof. For SRe, the changes were also significant from mid‐LA wall to the roof. Mean Tvs, Tve, and Tva of the RA walls reduced significantly from base to mid and then to the RA roof. RA systolic, early, and late diastolic ST and SR increased from base to mid and to the roof.ConclusionPeak systolic and diastolic velocities of the LA and RA decreased from the base to the mid and to the roof, while systolic and diastolic ST and SR increased from the base to the mid to the roof.
Peptidomic analysis of cartilage and subchondral bone in OA patients
Authors: Gatenholm Birgitta , Gobom Johan , Skillbäck Tobias , Blennow Kaj , Zetterberg Henrik , Brittberg Mats 
Published: February 2019

AbstractBackgroundThe objective of this study was to develop a method for directly analysing osteochondral samples straight out of the operating room without cell culturing, thereby enabling identification of potential peptide biomarkers to better understand the mechanisms involved in the development of osteoarthritis and pain.Material and MethodsOsteochondral plugs from wounded and macroscopically nonwounded zones of the femur condyle were collected from six patients with manifest osteoarthritis (OA) undergoing total knee arthroplasty (TKA). The samples were demineralized and supernatant was collected and isotopically marked with Tandem Mass Tag (TMT) labelling and analysed using liquid chromatography coupled with tandem mass spectrometry LC‐MS/MS.ResultsUsing peptidomics, 6292 endogenous peptides were identified. Five hundred sixty‐six peptides (8 identified endogenous peptides) differed significantly (P‐value 0.10) from wounded zones compared to nonwounded zones.ConclusionThis pilot study shows promising results for enabling peptidomic analysis of cartilage and bone straight out of the operating room. With further refinement, peptidomics can potentially become a diagnostic tool for OA, and improve the knowledge of disease progression and genesis of pain.
Mechanistic, ecological, and evolutionary consequences of artificial light at night for insects: review and prospective
Authors: Desouhant Emmanuel , Gomes Elisa , Mondy Nathalie , Amat Isabelle 
Published: February 2019

AbstractThe alternation of light and dark periods on a daily or seasonal time scale is of utmost importance for the synchronization of physiological and behavioral processes in the environment. For the last 2 decades, artificial light at night (ALAN) has strongly increased worldwide, disrupting the photoperiod and its related physiological processes, and impacting the survival and reproduction of wild animals. ALAN is now considered as a major concern for biodiversity and human health. Here, we present why insects are relevant biological models to investigate the impact of ALAN. First the phenotypic responses to ALAN and their underpinning mechanisms are reviewed. The consequences for population dynamics, and the community composition and functioning are described in the second part. Because ALAN provides new and widespread selective pressure, we inventory evolutionary changes in response to this anthropogenic change. Finally, we identify promising future avenues, focusing on the necessity of understanding evolutionary processes that could help stakeholders consider darkness as a resource to preserve biodiversity as well as numerous ecosystem services in which insects are involved.
A review of the research literature on adult learning and employability
Authors: Midtsundstad Tove 
Published: February 2019

AbstractBecause of rising life expectancy and declining birth rates, reducing early retirement and prolonging employees’ working lives have become major goals on social policy agendas. In this context, ensuring the adaptability and employability of the existing workforce has become an important issue. The aim of this article is to conduct a review of the most recent literature on employment outcomes of adult learning. The review covers literature published in English since 2010.