bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized Trial of Oral and Transdermal Rivastigmine for Postural Instability in Parkinson Disease Dementia
Authors: McDonald Jaime , Pourcher Emmanuelle , Nadeau Alexandra , Corbeil Philippe 
Published: March 2018

Objectives
The objective of this study was to compare the efficacy and safety of oral and transdermal rivastigmine for postural instability in patients with Parkinson disease dementia (PDD) who were candidates for a cholinesterase inhibitor. The primary outcome was the change in mean velocity of the center of pressure (CoP) after 6 months. Secondary outcomes included structural parameters of dynamic posturography, clinical rating scales, and adverse events requiring dose reduction.

Methods
Patients with PDD were randomized in a 1:1 ratio to oral or transdermal rivastigmine with target doses of 6 mg twice daily and 9.5 mg/10 cm2 daily, respectively. Outcomes were assessed at baseline and 6 months. Results were compared within and between groups.

Results
Nineteen patients completed the study (n = 8 oral, n = 11 transdermal). Mean daily doses of 9.4 (±1.5 mg) and 16.4 (±3.6 mg) were achieved in the oral and transdermal groups, respectively. The transdermal group demonstrated a significant 15.8% decrease in mean velocity of CoP (patch: P < 0.05; oral: 10.0% decrease, P = 0.16) in the most difficult scenario (eyes closed with sway-referenced support). There was no difference between groups (P = 0.27). For structural parameters, significant improvements were seen in the mean duration of peaks (patch) and interpeak distance (oral) in the most difficult condition. No changes were observed in clinical rating scales. Six patients experienced nonserious adverse events requiring dose reduction (n = 5 oral; n = 1 transdermal).

Conclusions
Rivastigmine may improve certain elements of postural control, notably the mean velocity of CoP. Benefits appear to be more obvious under more taxing sensory conditions.
Clusters of fatty acids in the serum triacylglyceride fraction associate with the disorders of type 2 diabetes
Authors: Johnston Luke W. , Liu Zhen , Retnakaran Ravi , Zinman Bernard , Giacca Adria , Harris Stewart B. , Bazinet Richard P. , Hanley Anthony J. 
Published: March 2018

AbstractAimsOur aim was to examine longitudinal associations of triacylglyceride fatty acid (TGFA) composition with insulin sensitivity (IS) and beta-cell function.MethodsAdults at-risk for T2D (n=477) had glucose and insulin measured from a glucose challenge at 3 time points over 6 years. The outcome variables Matsuda index (ISI), HOMA2-%S, Insulinogenic Index over HOMA-IR (IGI/IR), and Insulin Secretion-Sensitivity Index-2 (ISSI-2) were computed from the glucose challenge. Gas chromatography quantified TGFA composition from the baseline. We used adjusted generalized estimating equations (GEE) models and partial least squares (PLS) regression for the analysis.ResultsIn adjusted GEE models, four TGFA (14:0, 16:0, 14:1n-7, 16:1n-7 as mol%) had strong negative associations with IS while others (e.g. 18:1n-7, 18:1n-9, 20:2n-6, 20:5n-3) had strong positive associations. Few associations were seen for beta-cell function, except for 16:0, 18:1n-7, and 20:2n-6. PLS analysis indicated four TGFA (14:0, 16:0, 14:1n-7, 16:1n-7) that clustered together and strongly related with lower IS. These four TGFA also correlated highly (r>0.4) with clinically measured TG.ConclusionsWe found that higher proportions of a cluster of four TGFA strongly related with lower IS as well as hypertriglyceridemia, suggesting only a few fatty acids within the TGFA composition may primarily explain lipids’ role in glucose dysregulation.
A mechanosensitive RhoA pathway that protects epithelia against acute tensile stress
Authors: Acharya Bipul R , Nestor-Bergmann Alexander , Liang Xuan , Budnar Srikanth , Jensen Oliver E. , Bryant Zev , Yap Alpha S. 
Published: March 2018

AbstractAdherens junctions are tensile structures that couple epithelial cells together. Junctional tension can arise from cell-intrinsic application of contractility or from the cell-extrinsic forces of tissue movement. In all these circumstances, it is essential that epithelial integrity be preserved despite the application of tensile stress. In this study, we identify junctional RhoA as a mechanosensitive signaling pathway that responds to epithelial stress. The junctional specificity of this response is mediated by the heterotrimeric protein Gα12, which is recruited by E-cadherin and, in turn, recruits p114 RhoGEF to activate RhoA. Further, we identify Myosin VI as a key mechanosensor, based on its intrinsic capacity to anchor E-cadherin to F-actin when exposed to tensile load. Tension-activated RhoA signaling was necessary to preserve epithelial integrity, which otherwise undergoes fracture when monolayer stress is acutely increased by calyculin. Paradoxically, this homeostatic RhoA signaling pathway increases junctional actomyosin, a contractile response that might be expected to itself promote fracture. Simulations of a vertex-based model revealed that the protective effect of RhoA signaling can be explained through increased yield limit at multicellular vertices, where experiments showed p114 RhoGEF was necessary to increase E-cadherin and promote actin assembly and organization.
Exact Tests of Zero Variance Component in Presence of Multiple Variance Components with Application to Longitudinal Microbiome Study
Authors: Zhai Jing , Knox Kenneth , Twigg Homer L. , Zhou Hua , Zhou Jin J. 
Published: March 2018

SummaryIn the metagenomics studies, testing the association of microbiome composition and clinical conditions translates to testing the nullity of variance components. Computationally efficient score tests have been the major tools. But they can only apply to the null hypothesis with a single variance component and when sample sizes are large. Therefore, they are not applicable to longitudinal microbiome studies. In this paper, we propose exact tests (score test, likelihood ratio test, and restricted likelihood ratio test) to solve the problems of (1) testing the association of the overall microbiome composition in a longitudinal design and (2) detecting the association of one specific microbiome cluster while adjusting for the effects from related clusters. Our approach combines the exact tests for null hypothesis with a single variance component with a strategy of reducing multiple variance components to a single one. Simulation studies demonstrate that our method has correct type I error rate and superior power compared to existing methods at small sample sizes and weak signals. Finally, we apply our method to a longitudinal pulmonary microbiome study of human immunodeficiency virus (HIV) infected patients and reveal two interesting genera Prevotella and Veillonella associated with forced vital capacity. Our findings shed lights on the impact of lung microbiome to HIV complexities. The method is implemented in the open source, high-performance computing language Julia and is freely available at https://github.com/JingZhai63/VCmicrobiome.
Complex Structural Variants Resolved by Short-Read and Long-Read Whole Genome Sequencing in Mendelian Disorders
Authors: Sanchis-Juan Alba , Stephens Jonathan , French Courtney E , Gleadall Nicholas , Mégy Karyn , Penkett Christopher , Stirrups Kathleen , Delon Isabelle , Dewhurst Eleanor , Dolling Helen , Erwood Marie , Grozeva Detelina , Arno Gavin , Webster Andrew R , Cole Trevor , Austin Topun , Branco Ricardo Garcia ,   NIHR BioResource, Ouwehand Willem H , Raymond F Lucy , Carss Keren J 
Published: March 2018

AbstractComplex structural variants (cxSVs) are genomic rearrangements comprising multiple structural variants, typically involving three or more breakpoint junctions. They contribute to human genomic variation and can cause Mendelian disease, however they are not typically considered during genetic testing. Here, we investigate the role of cxSVs in Mendelian disease using short-read whole genome sequencing (WGS) data from 1,324 individuals with neurodevelopmental or retinal disorders from the NIHR BioResource project. We present four cases of individuals with a cxSV affecting Mendelian disease-associated genes. Three of the cxSVs are pathogenic: a de novo duplication-inversion-inversion-deletion affecting ARID1B in an individual with Coffin-Siris syndrome, a deletion-inversion-duplication affecting HNRNPU in an individual with intellectual disability and seizures, and a homozygous deletion-inversion-deletion affecting CEP78 in an individual with cone-rod dystrophy. Additionally, we identified a de novo duplication-inversion-duplication overlapping CDKL5 in an individual with neonatal hypoxic-ischaemic encephalopathy. Long-read sequencing technology used to resolve the breakpoints demonstrated the presence of both a disrupted and an intact copy of CDKL5 on the same allele; therefore, it was classified as a variant of uncertain significance. Analysis of sequence flanking all breakpoint junctions in all the cxSVs revealed both microhomology and longer repetitive sequences, suggesting both replication and homology based processes. Accurate resolution of cxSVs is essential for clinical interpretation, and here we demonstrate that long-read WGS is a powerful technology by which to achieve this. Our results show cxSVs are an important although rare cause of Mendelian disease, and we therefore recommend their consideration during research and clinical investigations.
Unraveling rice tolerance mechanisms againstSchizotetranychus oryzaemite infestation
Authors: Bufon Giseli , dos Reis Blasi Édina Aparecida , Rativa Angie Geraldine Sierra , Lamb Thainá Inês , Gastmann Rodrigo , Adamski Janete Mariza , Schwambach Joséli , Ricachenevsky Felipe Klein , Heringer Angelo Schuabb , Silveira Vanildo , Lopes Mara Cristina Barbosa , Sperotto Raul Antonio 
Published: March 2018

AbstractInfestation ofSchizotetranychus oryzae(Acari: Tetranychidae) causes great losses in rice productivity. Infestation in Puitá INTA-CL cultivar reduced the number of seeds/plant, percentage of full seeds, 1,000 seeds weight, and seed length, whereas infestation in IRGA423 increased 1,000 seeds weight and seed length. Reduction in seed weight/plant caused by infestation was higher in Puitá INTA-CL than IRGA423. Thus, Puitá INTA-CL was established as susceptible, and IRGA423 as tolerant toS. oryzaeinfestation. Photosynthetic parameters were less affected by infestation in IRGA423 than in Puitá INTA-CL. Infestation also caused accumulation of H2O2, decreased cell membrane integrity and accelerated senescence in leaves of Puitá INTA-CL, while leaves of IRGA423 presented higher levels of phenolics compounds. Using proteomic analysis, we identified proteins related to plant defense, such as jasmonate synthesis, and related to other mechanisms of tolerance such as oxidative stress, photosynthesis, and DNA structure maintenance, more abundant in IRGA423 after seven days of infestation. We detected higher levels of silicon (as amorphous silica cells) in leaves of infested IRGA423 plants compared to Puitá INTA-CL, an element previously linked to plant defense. Our data shows that IRGA423 presents tolerance toS. oryzaeinfestation, and that multiple mechanisms might be employed by this cultivar.HighlightThis is the first report evaluating the defense responses (tolerance and susceptiblity) of two contrasting rice cultivars toSchizotetranychus oryzaemite infestation.
Estimation of population divergence times from SNP data and a test for treeness
Authors: Theunert Christoph , Slatkin Montgomery 
Published: March 2018

AbstractWe present a method for estimating population divergence times from genome sequences when one individual is sampled from each population. Our method is a simplified version of one presented by Rassmussen et al. (2014) for testing for direct ancestry of an archaic genome. Our method does not require distinguishing ancestral from derived alleles or assumptions about demographic history before population divergence. We discuss the relationship of our method to two similar methods, one introduced by Green et al. (2010) and denoted by F(A | B) and the other introduced by Schlebusch et al. (2017) and called the TT method. When our method is applied to individuals from three or more populations, it provides a test of whether the population history is treelike. We illustrate the use of our method by applying it to three high-coverage archaic genomes, two Neanderthals (Vindija and Altai) and a Denisovan.
A phenomenological approach to diagnosing psychosis in autism spectrum disorder and intellectual disability: a case series
Authors: Rai Rahul , Tromans Samuel , Kapugama Chaya , Chester Verity , Gunaratna Ignatius , Langdon Peter , Alexander Regi T. 
Published: March 2018

PurposeThe diagnosis of psychosis in individuals with autism spectrum disorder (ASD) poses a unique clinical challenge. The presence of intellectual disability (ID) further complicates the diagnostic picture. Reliable and timely diagnosis of psychosis in such individuals minimises the duration of untreated psychotic symptoms and the subsequent impact on the quality of life of the patients concerned. The paper aims to discuss this issue.Design/methodology/approachThe authors present four patients with psychosis, ASD and ID, who have received care within forensic mental health and ID settings. These examples demonstrate the interaction between these conditions, as well as issues pertaining to diagnosis and management.FindingsIn all four patients, sustained use of antipsychotic medication was objectively associated with an improvement in psychotic symptoms and quality of life. In instances where autistic phenomena were accentuated upon development of psychosis, such features returned to the baseline levels evident prior to the onset of psychosis.Practical implicationsThe discussion and related case examples could improve the understanding of the possibility of psychosis in individuals with ASD and ID, and increase awareness of this diagnostic possibility among healthcare professionals.Originality/valueThis is the first published case series illustrating the challenges of diagnosing psychosis in individuals with ASD and ID.
Estimating the size of the national logistics market
Authors: Solakivi Tomi , Ojala Lauri , Lorentz Harri , Töyli Juuso , Laari Sini 
Published: March 2018

PurposeThe size of the logistics market is typically estimated from the national accounting and market data. However, this data does not take certain in-house logistics services into account and most likely underestimates the true size of the market. The purpose of this paper is to develop a method for estimating the potential size of the logistics market in terms of overall logistics expenditure and to also account for in-house services.Design/methodology/approachThe research approach involves combining longitudinal industry- and firm-level turnover data, incorporating survey data from Finland on logistics outsourcing and costs, and calculating yearly logistics expenditure and the market demand for logistics services. Descriptive statistics, weighted arithmetic means and analyses of variance are employed in the estimations.FindingsThe research suggests and demonstrates a rigorous method for estimating the size of the logistics market, including both market-based demand and in-house services.Research limitations/implicationsThe empirical data used to illustrate the result are limited to a single country. The methodology should be further validated with data from other countries. The quality of the survey data could be improved by targeting multiple informants from a single firm.Social implicationsOne outcome of the research is that policymakers will be better able to estimate the size of the logistics market on a national level. For service providers, the results provide additional information on the market potential of logistics services.Originality/valueThe novelty of the research lies in combining multiple data sources and expanding the estimation of the logistics market to include services provided in-house.
Consumer-driven e-commerce
Authors: Lim Stanley Frederick W.T. , Jin Xin , Srai Jagjit Singh 
Published: March 2018

PurposeThe purpose of this paper is to re-examine the extant research on last-mile logistics (LML) models and consider LML’s diverse roots in city logistics, home delivery and business-to-consumer distribution, and more recent developments within the e-commerce digital supply chain context. The review offers a structured approach to what is currently a disparate and fractured field in logistics.Design/methodology/approachThe systematic literature review examines the interface between e-commerce and LML. Following a protocol-driven methodology, combined with a “snowballing” technique, a total of 47 articles form the basis of the review.FindingsThe literature analysis conceptualises the relationship between a broad set of contingency variables and operational characteristics of LML configuration (push-centric, pull-centric, and hybrid system) via a set of structural variables, which are captured in the form of a design framework. The authors propose four future research areas reflecting likely digital supply chain evolutions.Research limitations/implicationsTo circumvent subjective selection of articles for inclusion, all papers were assessed independently by two researchers and counterchecked with two independent logistics experts. Resulting classifications inform the development of future LML models.Practical implicationsThe design framework of this study provides practitioners insights on key contingency and structural variables and their interrelationships, as well as viable configuration options within given boundary conditions. The reformulated knowledge allows these prescriptive models to inform practitioners in their design of last-mile distribution.Social implicationsImproved LML performance would have positive societal impacts in terms of service and resource efficiency.Originality/valueThis paper provides the first comprehensive review on LML models in the modern e-commerce context. It synthesises knowledge of LML models and provides insights on current trends and future research directions.
Value co-creation in an outsourcing arrangement between manufacturers and third party logistics providers: resource commitment, innovation and collaboration
Authors: Sinkovics Rudolf R. , Kuivalainen Olli , Roath Anthony S. 
Published: March 2018

PurposeThis paper aims to explore value co-creation between manufacturing firms and third-party logistics providers (3PLs). The specific focus is on resources and value co-creation with the aim to examine a set of relationships among the 3PL’s resource commitment, collaboration and innovation, and their performance outcomes.Design/methodology/approachSurvey data consisting of 142 UK manufacturing firms are used to study the 3PL and manufacturing customer value co-creation. The confirmatory factor model (CFA) and subsequent structural equation model were tested using EQS 6.1.FindingsThe findings show that collaboration between the manufacturers and the 3PLs mediates the relationship between resource commitment and innovation, and performance. 3PLs are becoming much more of a collaborative partner which support the idea of value co-creation strategy.Research limitations/implicationsThe study is cross-sectional; temporal evolution of value co-creation should be studied in the future.Practical implicationsWhen manufacturers and 3PLs collaborate to target efforts strategically, the 3PL’s resource commitment can be directed towards the development of new innovative approaches.Originality/valueThe study contributes to the discussion of forms of co-creation, and theoretical frameworks which would enable us to understand how customers and other actors engage with the companies in collaborative value creation activities.
Developing closed loop supply chains for environmental sustainability
Authors: Ashby Alison 
Published: March 2018

PurposeForward and reverse supply chains form a “closed loop” when managed in a coordinated way and this “cradle to cradle” responsibility has strong relevance to addressing environmental sustainability in global supply chains. The extensive outsourcing of manufacturing has created highly fragmented supply chains, which is strongly evidenced within the UK clothing industry, and it presents major environmental challenges, particularly around waste and resource use. The purpose of this paper is to investigate how a closed loop supply chain (CLSC) can be successfully developed to address environmental sustainability.Design/methodology/approachThe natural resource-based view (NRBV) acknowledges the importance of a firm’s tangible and intangible resources, as well as socially complex relationships, and provides three path-dependent strategies for achieving environmentally based competitive advantage. Via an in-depth case study of the UK-based clothing firm, the NRBV is employed as a framework for understanding the processes that a focal firm needs to engage in to develop a CLSC, and the contribution that is made by its resources and supplier relationships.FindingsThe findings illustrate the key importance of strategic resources and shared vision and principles between the focal firm and its suppliers, in order to progress from a more reactive pollution prevention strategy to a fully embedded CLSC response to environmental sustainability. The case study highlights the need to extend the current CLSC model to integrate the design function and end customer; the design function ensures that appropriate environmental practices can be implemented, and customers represent a key stakeholder as they enable the reverse flows required to maximise value and minimise waste.Originality/valueThe NRBV and its three path-dependent strategies are an established framework for understanding environmentally based competitive advantage, but has not previously been explicitly employed to investigate CLSCs. This research, therefore, provides valuable insight into the applicability of this model in the supply chain field, and the key role of tangible and intangible resources and socially complex supplier relationships in developing and achieving a CLSC.
A general approach to generate random variates for multivariate copulae
Authors: Tajvidi N. , Turlach B.A. 
Published: March 2018

SummaryWe suggest two methods for simulating from a multivariate copula in an arbitrary dimension. Although our main emphasis in this paper is on multivariate extreme value distributions, the proposed methods can be applied to any copula. The basic idea is to approximate the (unknown) density of the copula by a distribution that has a piece‐wise constant (histogram) density. This is achieved by partitioning the support of a given copula C into a large number of hyper‐rectangles and using them to generate random variates from an approximation of the copula. We suggest two methods for finding this approximation which correspond to either finding hyper‐rectangles which have equal probability mass with respect to C, or determining a partition using hyper‐squares of equal volume and finding the corresponding probability mass of each hyper‐square. We also discuss how the generated random variates can be used as proposals in a Metropolis–Hastings algorithm, when C is an absolutely continuous distribution function, to generate a sequence of random variates from C. An implementation of the proposed methodologies is provided for the statistical computing and graphics environment R in our package called SimCop.