bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the safety, tolerability, and pharmacokinetics of RO7049389 in healthy Chinese volunteers
Authors: Wu Xiaojie , Feng Sheng , Zhang Jing , Zhang Wenhong , Zhang Yuchen , Zhu Mingfen , Triyatni Miriam , Zhao Na , Bo Qingyan , Jin Yuyan 
Published: September 2021

AbstractThe objectives of this phase I study are to assess the safety, tolerability, and pharmacokinetics (PKs) of RO7049389 in healthy Chinese volunteers (HVs) and evaluate potential ethnic differences in the safety and PKs using data from this study and the first‐in‐human study (in which most of the HVs were non‐Asian). HVs randomly received a single dose of 200–600 mg of RO7049389 or a placebo in a single ascending dose (n = 28) or multiple doses of 200–400 mg of RO7049389 or a placebo in multiple ascending doses (n = 24). Safety and tolerability were monitored throughout the study. Serial blood samples were collected for PK analysis. RO7049389 was safe and well‐tolerated in the HVs. The time to maximum concentration ranged from 1.5 to 3.0 h, and terminal half‐life ranged from 3.66 to 14.6 h. A single dose of 200–600 mg and multiple doses of 200–400 mg exhibited nonlinear PKs. In general, the safety profiles were comparable between non‐Asian and Asian HVs, but the plasma exposure of RO7049389 in Chinese HVs was higher than that in non‐Asian HVs. The data generated from this study will provide guidance for future clinical studies on RO7049389 in Chinese/Asian patients with hepatitis B virus.
Multisite evaluation of institutional processes and implementation determinants for pharmacogenetic testing to guide antidepressant therapy
Authors: Tuteja Sony , Salloum Ramzi G. , Elchynski Amanda L. , Smith D. Max , Rowe Elizabeth , Blake Kathryn V. , Limdi Nita A. , Aquilante Christina L. , Bates Jill , Beitelshees Amber L. , Cipriani Amber , Duong Benjamin Q. , Empey Philip E. , Formea Christine M. , Hicks J. Kevin , Mroz Pawel , Oslin David , Pasternak Amy L. , Petry Natasha , Ramsey Laura B. , Schlichte Allyson , Swain Sandra M. , Ward Kristen M. , Wiisanen Kristin , Skaar Todd C. , Van Driest Sara L. , Cavallari Larisa H. , Bishop Jeffrey R. ,   for the IGNITE Pharmacogenetics Working Group
Published: September 2021

AbstractThere is growing interest in utilizing pharmacogenetic (PGx) testing to guide antidepressant use, but there is lack of clarity on how to implement testing into clinical practice. We administered two surveys at 17 sites that had implemented or were in the process of implementing PGx testing for antidepressants. Survey 1 collected data on the process and logistics of testing. Survey 2 asked sites to rank the importance of Consolidated Framework for Implementation Research (CFIR) constructs using best‐worst scaling choice experiments. Of the 17 sites, 13 had implemented testing and four were in the planning stage. Thirteen offered testing in the outpatient setting, and nine in both outpatient/inpatient settings. PGx tests were mainly ordered by psychiatry (92%) and primary care (69%) providers. CYP2C19 and CYP2D6 were the most commonly tested genes. The justification for antidepressants selected for PGx guidance was based on Clinical Pharmacogenetics Implementation Consortium guidelines (94%) and US Food and Drug Administration (FDA; 75.6%) guidance. Both institutional (53%) and commercial laboratories (53%) were used for testing. Sites varied on the methods for returning results to providers and patients. Sites were consistent in ranking CFIR constructs and identified patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and the identification of champions as most important for implementation. Sites deployed similar implementation strategies and measured similar outcomes. The process of implementing PGx testing to guide antidepressant therapy varied across sites, but key drivers for successful implementation were similar and may help guide other institutions interested in providing PGx‐guided pharmacotherapy for antidepressant management.
Neurological outcome in WDR62 primary microcephaly
Authors: Ruaud Lyse , Drunat Séverine , Elmaleh‐Bergès Monique , Ernault Anais , Guilmin Crepon Sophie ,   The MCPH Consortium, El Ghouzzi Vincent , Auvin Stéphane , Verloes Alain , Passemard Sandrine 
Published: September 2021

AimTo characterize the cortical structure, developmental, and cognitive profiles of patients with WD repeat domain 62 (WDR62)‐related primary microcephaly.MethodIn this observational study, we describe the developmental, neurological, cognitive, and brain imaging characteristics of 17 patients (six males, 11 females; mean age 12y 3mo standard deviation [SD] 5y 8mo, range 5y–24y 6mo) and identify 14 new variants of WDR62. We similarly analyse the phenotypes and genotypes of the 59 previously reported families.ResultsBrain malformations, including pachygyria, neuronal heterotopia, schizencephaly, and microlissencephaly, were present in 11 out of 15 patients. The mean full‐scale IQ of the 11 assessed patients was 51.8 (standard deviation [SD] 12.6, range 40–70). Intellectual disability was severe in four patients, moderate in four, and mild in three. Scores on the Vineland Adaptive Behavior Scales obtained from 10 patients were low for communication and motor skills (mean 38.29, SD 7.74, and 37.71, SD 5.74 respectively). The socialization score was higher (mean 47.14, SD 12.39). We found a significant difference between scores for communication and daily living skills (mean 54.43, SD 11.6; p=0.001, one‐way analysis of variance). One patient displayed progressive ataxia.InterpretationWDR62‐related cognitive consequences may be less severe than expected because 3 out of 11 of the assessed patients had only mild intellectual disability and relatively preserved abilities of autonomy in daily life. We identified progressive ataxia in the second decade of life in one patient, which should encourage clinicians to follow up patients in the long term.
Inequities in quality and safety outcomes for hospitalized children with intellectual disability
Authors: Mimmo Laurel , Harrison Reema , Travaglia Joanne , Hu Nan , Woolfenden Susan 
Published: September 2021

AimTo investigate if there are inequities in quality and safety outcomes for children with intellectual disability admitted to two tertiary paediatric hospitals.MethodA cross‐sectional study of 1367 admissions for 1018 randomly selected patients admitted for more than 23 hours to one of two tertiary children’s hospitals in Sydney, Australia (1st January–31st December 2017). Electronic medical records were manually interrogated to identify children with intellectual disability (including developmental delay). Data extracted included patient demographics, length of stay, number of admissions, and reported clinical incidents.ResultsIn total, 12.3% (n=125) of children admitted during the study period had intellectual disability, which represented 13.9% (n=190) of admissions. Sex and age at admission in children with and without intellectual disability were similar: 83 (43.7%) vs 507 (43.1%) females and 107 (56.3%) vs 670 (56.9%) males, p=0.875; median age 3 years (0–18y) vs 4 years (0–18y), p=0.122. Children with intellectual disability had significantly greater median length of stay (100.5h vs 79h, p<0.001) and cost of admission (A$11 596.38 vs A$8497.96) than their peers (p=0.001). Children with intellectual disability had more admissions with at least one incident compared to children without intellectual disability (14.7% vs 9.7%); this was not statistically significant (p=0.06).InterpretationChildren with intellectual disability experience inequitable quality and safety outcomes in hospital. Engaging children and families in clinical incident reporting may enhance understanding of safety risks for children with intellectual disability in hospital.
Sources of divergence in income in Indian states, 2001–2015
Authors: Misra Biswa Swarup , Nazlioglu Saban , Kucukkaplan Ilhan 
Published: September 2021

SummaryMotivationEmpirical studies on income convergence for India indicate that Indian states exhibit divergence in income. The literature, however, has neglected the convergence dynamics of the main sources of output. A pertinent question is whether divergence in income is due to divergence in factor inputs (capital and labour) and/or in total factor productivity (TFP) in India, a low middle‐income country with high dispersion of per capita income across its states.PurposeThis article examines the sources of income divergence in Indian states by analysing convergence in TFP, labour, and capital.Methods and approachWe test for stochastic convergence hypothesis by employing state‐level data for 19 Indian states during the period 2001–2015. Given the small sample dimension of the Indian state‐level income data, we benefit from the recent developments in non‐stationary panel data literature; and conduct novel panel stationarity and unit root tests with a fixed time dimension. We further carry out a robustness analysis to account for cross‐section dependency across the states.FindingsTFP as well as the factor inputs (labour and capital) exhibit divergence, implying persistence in income inequality across Indian states. Divergence in labour across the states reflects the fact that migration is primarily an intra‐district phenomenon. Poor investment climate in low‐income states acts as a barrier for convergence in capital. TFP and capital stock are found to be correlated, and thereby lower investment in poorer states may be responsible for divergence in TFP across the states.Policy implicationsMigration in India is primarily an intra‐district phenomenon. There is a need to study the reasons which are discouraging inter‐district and inter‐state migration for better utilization of the labour resource. Government intervention has not been adequate to improve the infrastructure position and encourage capital inflows to low‐income states. Low‐income states should improve their business climate and create support infrastructure to earn the confidence of investors. Increasing investment in low‐income states would help to increase their TFP and catch up with the high‐income states.
Pull factors for migration: The impact of migrant integration policies
Authors: Beverelli Cosimo 
Published: September 2021

AbstractThis paper investigates the impact of migrant integration policies set by destination countries on migration from 202 origins to 27 destinations during the period 2010–2018. Employing a structural gravity methodology which features international and domestic (i.e., intra‐national) migration flows, it shows that migrant integration policies, on average, positively affect cross‐border migration relative to domestic migration. Moving from the 25th percentile to the median of the variable summarizing migrant integration policies increases cross‐border relative to domestic migration by one third. Such impact is largely driven by policies on family reunion and permanent residence.
Nanosystems and exosomes as future approaches in treating multiple sclerosis
Authors: Sidoryk‐Węgrzynowicz Marta , Dąbrowska‐Bouta Beata , Sulkowski Grzegorz , Strużyńska Lidia 
Published: September 2021

AbstractMultiple sclerosis (MS) is an immune‐mediated demyelinating disease of the central nervous system which leads to neurological dysfunctions and severe disabilities. MS pathology is characterised by damage of the blood‐brain barrier and infiltration of autoreactive T cells that overactivate glial cells, thereby initiating neuroinflammation accompanied by the formation of demyelinating plaques and neurodegeneration. Clinical deficits in this multifactorial disease depend on the progression of myelin loss, the stage of inflammation, the status of axons and the activity of oligodendrocyte precursor cells (OPCs). Despite significant progress in the treatment of MS, current therapies remain limited and new approaches are highly desirable. Nanosystems based on liposomes and nanoparticles are among some of the more noteworthy therapeutic strategies being investigated. Applications of nanosystems alone or as drug carriers in animal models of MS have been found to successfully alleviate the symptoms of the disease and exert anti‐inflammatory potential. Exosomes are a specific type of nanosystem based on nanometre‐sized extracellular vesicles released by different cells which exhibit important healing features. Exosomes contain an array of anti‐inflammatory and neuroprotective agents which may contribute to modulation of the immune system as well as promoting remyelination and tissue repair. In this review, opportunities to use nanosystems against progression of MS will be discussed in context of cell‐specific pathologies associated with MS.
Potential of combined neutron and X‐ray imaging to quantify local carbon contents in soil
Authors: Koestel John , Fukumasu Jumpei , Larsbo Mats , Herrmann Anke M. , Ariyathilaka Pawala , Magdysyuk Oxana V. , Burca Genoveva 
Published: September 2021

AbstractIn this study, we investigated the potential and limitations of using joint X‐ray and time‐of‐flight (TOF) neutron imaging for mapping the 3‐dimensional organic carbon distribution in soil. This approach is viable because neutron and X‐ray beams have complementary attenuation properties. Soil minerals consist to a large part of silicon and aluminium, and elements that are relatively translucent to neutrons but attenuate X‐rays. In contrast, attenuation of neutrons is strong for hydrogen, which is abundant in soil organic matter (SOM), while hydrogen barely attenuates X‐rays. In theory, TOF neutron imaging does further more allow the imaging of Bragg edges, which correspond to d‐spacings in minerals. This could help to distinguish between SOM and clay minerals, the mineral group in soil that is most strongly associated with hydrogen atoms. We collected TOF neutron image data at the IMAT beamline at the ISIS facility and synchrotron X‐ray image data at the I12 beamline at the Diamond Light source, both located within the Rutherford Appleton Laboratory, Harwell, UK. The white beam (the full energy spectrum) neutron image clearly showed variations in neutron attenuation within soil aggregates at approximately constant X‐ray attenuations. This indicates a constant bulk density with varying organic matter and/or clay content. Unfortunately, the combination of TOF neutron and X‐ray imaging was not suited to allow for a distinction between SOM and clay minerals at the voxel scale. While such a distinction is possible in theory, it is prevented by technical limitations. One of the main reasons is that the neutron frequencies available at modern neutron sources are too large to capture the main d‐spacings of clay minerals. As a result, inference to voxel scale SOM concentrations is presently not feasible. Future improved neutron sources and advanced detector designs will eventually overcome the technical problems encountered here. On the positive side, combined X‐ray and TOF neutron imaging demonstrated abilities to identify quartz grains and to distinguish between plastics and plant seeds.Highlights
Full understanding of biogeochemical processes requires three‐dimensional (3‐D) maps of organic matter in soil (SOM).
This study investigates a novel method to map voxel‐scale SOM contents with 3‐D resolution.
The method is based a combination of X‐ray and time‐of‐flight neutron tomography.
At present, technical limitations prevent distinguishing between SOM and clay mineral contents.
More advanced neutron sources are required to overcome the encountered technical obstacles.
Recurrent febrile seizures alter intrahippocampal temporal coordination but do not cause spatial learning impairments
Authors: Kloc Michelle L. , Daglian Jennifer M. , Holmes Gregory L. , Baram Tallie Z. , Barry Jeremy M. 
Published: September 2021

AbstractObjectiveFebrile seizures (FSs) are the most common form of seizures in children. Single short FSs are benign, but FSs lasting longer than 30 min, termed febrile status epilepticus, may result in neurological sequelae. However, there is little information about an intermediary condition, brief recurrent FSs (RFSs). The goal of this study was to determine the role of RFSs on spatial learning and memory and the properties of spontaneous hippocampal signals.MethodsA hippocampus‐dependent active avoidance task was used to assess spatial learning and memory in adult rats that underwent experimental RFSs (eRFSs) in early life compared with their littermate controls. Following completion of the task, we utilized high‐density laminar probes to measure spontaneous hippocampal CA1 circuit activity under urethane anesthesia, which allowed for the simultaneous recording of input regions in CA1 associated with both CA3 and entorhinal cortex.ResultsRFSs did not result in deficits in the active avoidance spatial test, a hippocampus‐dependent test of spatial learning and memory. However, in vivo high‐density laminar electrode recordings from eRFS rats had significantly altered power and frequency expression of theta and gamma bandwidths as well as signaling efficacy along the CA1 somatodendritic axis. Thus, although eRFS modified CA1 neuronal input/output dynamics, these alterations were not sufficient to impair active avoidance spatial behavior.SignificanceThese findings indicate that although eRFSs do not result in spatial cognitive deficits in the active avoidance task, recurrent seizures do alter the brain and result in longstanding changes in the temporal organization of the hippocampus.
Chaos during the COVID‐19 outbreak: Predictors of household chaos among low‐income families during a pandemic
Authors: Johnson Anna D. , Martin Anne , Partika Anne , Phillips Deborah A. , Castle Sherri ,   The Tulsa SEED Study Team*
Published: September 2021

AbstractObjectiveThe objective of this study was to explore whether household chaos measured during the COVID‐19 pandemic is predicted by prepandemic parental and household characteristics.BackgroundThe COVID‐19 pandemic has dramatically altered children's home environments and routines due to stay‐at‐home orders, school closures, and economic shocks. These disruptions have been especially challenging for low‐income families who have limited resources and have been disproportionately affected by the pandemic. Household chaos, which captures routines, organization, stability, noise, and crowding in the home, is a documented threat to parent functioning and positive child development. The pandemic has likely exacerbated household chaos, especially for low‐income families.MethodData come from a larger, ongoing study of low‐income children and their parents in Tulsa, Oklahoma; this analysis relies on data from the subset of low‐income parents who responded to surveys when their children were in kindergarten (in 2018–2019) and during the pandemic, when their children were in first grade (n = 335). We use multivariate ordinary least squares regression models to test whether household chaos measured during the pandemic is predicted by prepandemic parental and household characteristics.ResultsPrepandemic parental depression and household chaos were significantly predictive of chaos during the pandemic, even after accounting for household demographics.ImplicationsThe current study highlights pandemic‐induced elevations in parental distress and household chaos among low‐income families. Results will provide valuable direction to policymakers, educators, and parents on how best to offset negative impacts of the COVID‐19 pandemic on family functioning and child development.
The CO2 record at the Amazon Tall Tower Observatory: A new opportunity to study processes on seasonal and inter‐annual scales
Authors: Botía Santiago , Komiya Shujiro , Marshall Julia , Koch Thomas , Gałkowski Michał , Lavric Jost , Gomes‐Alves Eliane , Walter David , Fisch Gilberto , Pinho Davieliton M. , Nelson Bruce W. , Martins Giordane , Luijkx Ingrid T. , Koren Gerbrand , Florentie Liesbeth , Carioca de Araújo Alessandro , Sá Marta , Andreae Meinrat O. , Heimann Martin , Peters Wouter , Gerbig Christoph 
Published: September 2021

AbstractHigh‐quality atmospheric CO2 measurements are sparse in Amazonia, but can provide critical insights into the spatial and temporal variability of sources and sinks of CO2. In this study, we present the first 6 years (2014–2019) of continuous, high‐precision measurements of atmospheric CO2 at the Amazon Tall Tower Observatory (ATTO, 2.1°S, 58.9°W). After subtracting the simulated background concentrations from our observational record, we define a CO2 regional signal () that has a marked seasonal cycle with an amplitude of about 4 ppm. At both seasonal and inter‐annual scales, we find differences in phase between and the local eddy covariance net ecosystem exchange (EC‐NEE), which is interpreted as an indicator of a decoupling between local and non‐local drivers of . In addition, we present how the 2015–2016 El Niño‐induced drought was captured by our atmospheric record as a positive 2σ anomaly in both the wet and dry season of 2016. Furthermore, we analyzed the observed seasonal cycle and inter‐annual variability of together with net ecosystem exchange (NEE) using a suite of modeled flux products representing biospheric and aquatic CO2 exchange. We use both non‐optimized and optimized (i.e., resulting from atmospheric inverse modeling) NEE fluxes as input in an atmospheric transport model (STILT). The observed shape and amplitude of the seasonal cycle was captured neither by the simulations using the optimized fluxes nor by those using the diagnostic Vegetation and Photosynthesis Respiration Model (VPRM). We show that including the contribution of CO2 from river evasion improves the simulated shape (not the magnitude) of the seasonal cycle when using a data‐driven non‐optimized NEE product (FLUXCOM). The simulated contribution from river evasion was found to be 25% of the seasonal cycle amplitude. Our study demonstrates the importance of the ATTO record to better understand the Amazon carbon cycle at various spatial and temporal scales.
ENTRY DECISIONS AND ASYMMETRIC COMPETITION BETWEEN NON‐PROFIT AND FOR‐PROFIT HOMES IN THE LONG‐TERM CARE MARKET
Authors: Grant Iris , Kesternich Iris , Van Biesebroeck Johannes 
Published: September 2021

AbstractDemand for long‐term care services is growing strongly. Using a rich administrative data set for Germany, we examine strategic interaction between nonprofit and for‐profit nursing homes. The estimated competitive effects imply that competition is much stronger within type, suggesting that they provide differentiated products. Over time, the entry behavior of for‐profit homes has converged to that of the more established nonprofits and between‐type competition has become stronger. Counterfactual simulations of proposed changes in government policy indicate that even moderate changes have a large impact on the fraction of markets that remain unserved or only served by a single type.
Labour and technology: Reflecting on a century of debate in the International Labour Review
Authors: HOWCROFT Debra , RUBERY Jill 
Published: September 2021

AbstractThe aim of this Centenary Issue is to assess a century of debates about the relationships between labour and technology as reflected in various relevant articles in the International Labour Review. The recent wave of interest in sociotechnical change and its implications for the future of work has led numerous commentators to claim that we are on the brink of unprecedented and seismic change. The 14 articles selected for this issue were published between 1925 and 2020 and provide a timely reflection on foundational debates that continue to resonate today.