bluuebunny/crossref_metadata_2025 huggingface dataset:
Procedural safety and long‐term follow‐up after pacemaker implantation in nonagenarians
Authors: Dang Duc , Galand Vincent , Loirat Aurélie , Auffret Vincent , Behar Nathalie , Mabo Philippe , Daubert Jean‐Claude , Leclercq Christophe , Martins Raphaël P.
Published: September 2018

Background

The rate of pacemaker (PM) implantations is constantly growing. Since life expectancy of the population is projected to increase, a large number of nonagenarian patients will need PM implantation. We aimed at analyzing short‐ and long‐term outcomes after PM implantation in nonagenarians.

Methods

Patients aged ≥90 years referred for PM implantation from 2004 to 2017 were included. The primary clinical endpoint was total mortality. Secondary endpoints included procedure‐related and in‐hospital complications.

Results

A total of 172 patients were included (92.6 ± 2.1 years, from 90.0 to 101.4 years). Procedure duration was 50.0 ± 19.7 minutes. Most of the patients had VVI devices implanted (143 pts, 83.1%) and mean hospital stay was 3.5 ± 1.5 days. Nine patients (5.2%) had short‐term device‐related complications and 29 patients (16.8%) had post‐procedural complications, non‐related to the implantation, including four leading to patients' death. During a follow‐up of 22.5 months (interquartile range: 7.3‐38.0), 94 patients (54.7%) died. Survival rates were 82.9% (95% confidence interval [CI]: 76.0‐88.0), 73.7% (95% CI: 65.7‐80.1) and 37.5% (95% CI: 27.5‐47.5) after 1, 2, and 5 years, respectively. The Charlson comorbidity index was a predictive factor of procedural complications (odds ratio = 1.33; 95% CI: 1.05‐1.69, P = 0.02) while having a complication (hazard ratio [HR] = 4.04; 95% CI: 1.79‐9.11, P = 0.001) and atrial fibrillation (HR = 1.63; 95% CI: [1.02‐2.63], P = 0.043) were predictors of post‐implantation death.

Conclusion

PM implantation in nonagenarians is safe, with a low risk of procedural complications, but many comorbidities‐related complications can occur. Caution should be taken in this old and frail population since complications significantly impact patients' survival.
Differential response of pineal microglia to surgical versus pharmacological stimuli
Authors: Ibañez Rodriguez María P. , Galiana María D. , Rásmussen Jorge A. , Freites Carlos L. , Noctor Stephen C. , Muñoz Estela M.
Published: September 2018

Microglial cells are one of the interstitial elements of the pineal gland (PG). We recently reported the pattern of microglia colonization and activation, and microglia‐Pax6+ cell interactions during normal pineal ontogeny. Here, we describe the dynamics of microglia‐Pax6+ cell associations and interactions after surgical or pharmacological manipulation. In adult rats, the superior cervical ganglia (SCG) were exposed, and either bilaterally excised (SCGx) or decentralized (SCGd). In the SCGx PGs, the density of Iba1+ microglia increased after surgery and returned to sham baseline levels 13 days later. Pineal microglia also responded to SCGd, a more subtle denervation. The number of clustered Iba1+/PCNA+/ED1+ microglia was higher 4 days after both surgeries compared to the sham‐operated group. However, the number of Pax6+/PCNA− cells and the percentage of Pax6+ cells contacted by and/or phagocytosed by microglia increased significantly only after SCGx. Separate groups of rats were treated with either bacterial lipopolysaccharides (LPS) or doxycycline (DOX) to activate or inhibit pineal microglia, respectively. Peripheral LPS administration caused an increase in the number of clustered Iba1+/PCNA+/ED1+ microglial cells, and in the percentage of Pax6+ cells associated with and/or engulfed by microglia. In the LPS‐treated PGs, we also noted an increase in the number of PCNA+ cells that were Iba1− within the microglial cell clusters. The density of Pax6+ cells did not change after LPS treatment. DOX administration did not influence the parameters analyzed. These data suggest that pineal microglia are highly receptive cells capable of rapidly responding in a differential manner to surgical and pharmacological stimuli.
Targeting metabolic vulnerabilities of cancer: Small molecule inhibitors in clinic
Authors: Tripathi Satyendra C. , Fahrmann Johannes F. , Vykoukal Jody V. , Dennison Jennifer B. , Hanash Samir M.
Published: September 2018

Background

Altered cell metabolism is an established hallmark of cancer. Advancement in our understanding of dysregulated cellular metabolism has aided drastically in identifying metabolic vulnerabilities that can be exploited therapeutically. Indeed, this knowledge has led to the development of a multitude of agents targeting various aspects of tumor metabolism.

Recent findings

The intent of this review is to provide insight into small molecule inhibitors that target tumor metabolism and that are currently being explored in active clinical trials as either preventive, stand‐alone, or adjuvant therapies for various malignancies. For each inhibitor, we outline the mechanism (s) of action, preclinical/clinical findings, and limitations. Sections are divided into three aspects based on the primary target of the small molecule inhibitor (s): those that impact (1) cancer cells directly, (2) immune cells present in the tumor microenvironment, or (3) both cancer cells and immune cells. We highlight small molecule targeting of metabolic pathways including de novo fatty acid synthesis, NAD+ biosynthesis, 2‐hydroxyglutarate biosynthesis, polyamine metabolism, the kynurenine pathway, as well as glutamine and arginine metabolism.

Conclusions

Use of small molecule inhibitors aimed at exploiting tumor metabolic vulnerabilities continues to be an active area of research. Identifying metabolic dependencies specific to cancer cells and/or constituents of the tumor microenvironment is a viable area of therapeutic intervention that holds considerable clinical potential.
Bibliographies Made Easy: A Guide to Using Citation Software to Create Bibliographies
Authors: Vivek S. , Leblanc S.
Published: September 2018

Managing references, inserting citations, and creating bibliographies take a considerable amount of our time in the academic world. Tools are now available in the form of citation software that can easily help us produce highly professional bibliographies easily. This article provides a beginners guide to such software with tips on using them effectively. © 2018 by John Wiley & Sons, Inc.
Fast Wide‐Line Solid‐State NMR on a Low‐Cost Benchtop Spectrometer
Authors: Sørensen Morten K. , Balsgart Nicholas M. , Jensen Ole , Nielsen Niels Chr. , Vosegaard Thomas
Published: September 2018

Solid‐state NMR may provide access to a wealth of information on molecular structure and dynamics. However, for many applications, the acquisition is challenged by broad resonances implying large spectral linewidths and low sensitivity. Conventionally, this is tackled by using costly and laboratory‐fixed spectrometers based on large high‐field superconducting magnets. In this Communication, we demonstrate that a range of challenging wide‐line solid‐state NMR spectra can be acquired on a robust, maintenance‐free, low‐cost benchtop/mobile NMR spectrometer with a sensitivity comparable to common high‐field instruments. The performance and versatility for recording sensitive wide‐line spectra is demonstrated through acquisition of 31P NMR of paramagnetic FePO4 and full quadupolar lineshapes of Al2O3 (27Al) and KNO3 (14N). Also, we introduce interleaved acquisition of frequency‐stepped slices providing a dramatic reduction of the required experiment time.
X‐Ray Topography Characterization of the Bridgman‐Grown Crystals of Zinc Germanium Phosphide
Authors: Kaloyan Alexander A. , Podurets Konstantin M. , Prokhorov Igor A. , Kovalenko Ekaterina S. , Bezbakh Ilya Zh. , Okunev Aleksey O. , Gribenyukov Alexander I. , Verozubova Galina A.
Published: September 2018

Samples of the Bridgman‐grown nonlinear optic crystal of ZnGeP2 are studied using the methods of topography on a laboratory source and on a synchrotron radiation source. Methods of quasi‐plane‐wave topography, white beam topography, and rocking curve topography are used. Dislocation bundles, growth striations, small‐angle boundaries, and other defects are observed. The macroscopic distribution of defects in crystals and disorientations present in the crystal are studied. The mechanism of formation of images of growth striations is discussed. Digital analysis of the growth striations is carried out to characterize the growth process.
Cyclopentyl Methyl Ether: An Elective Ecofriendly Ethereal Solvent in Classical and Modern Organic Chemistry
Authors: Azzena Ugo , Carraro Massimo , Pisano Luisa , Monticelli Serena , Bartolotta Roberta , Pace Vittorio
Published: September 2018

Solvents represent one of the major contributions to the environmental impact of fine‐chemical synthesis. As a result, the use of environmentally friendly solvents in widely employed reactions is a challenge of vast real interest in contemporary organic chemistry. Within this Review, a great variety of examples showing how cyclopentyl methyl ether has been established as particularly useful for this purpose are reported. Indeed, its low toxicity, high boiling point, low melting point, hydrophobicity, chemical stability towards a wide range of conditions, exceptional stability towards the abstraction of hydrogen atoms, relatively low latent heat of vaporization, and the ease with which it can be recovered and recycled enable its successful employment as a solvent in a wide range of synthetic applications, including organometallic chemistry, catalysis, biphasic reactions, oxidations, and radical reactions.
Migration of PLM systems to cloud
Authors: Singh Shikha , Misra Subhas Chandra
Published: September 2018

Cloud computing and cloud applications are emerging as the latest technology. Cloud applications are developing very fast and adopted by most of the firms around the globe. The cloud applications are widely accepted and considered as a notion of the digitized era, but the cloud product lifecycle management (PLM) is not adopted much in Indian firms. Cloud PLM is an upcoming cloud application, but its adoption entails various challenges. Considering this fact, the paper aims to empirically investigate the critical challenges encountered by many firms for migration to of cloud PLM. A multicriteria decision making method, grey Decision Making Trial and Evaluation Laboratory along with interpretive structural modeling are employed to identify the causal challenges and their hierarchy to cloud PLM adoption. This empirical study brings out “data security” and “trust on solution provider” as the most important and critical challenges for migration to cloud PLM adoption. The findings may act as a guide for the managers in manufacturing firms in identifying the critical challenges to utilize the benefits of cloud PLM over on‐premise PLM systems.
Cocaine adulteration with the anthelminthic tetramisole (levamisole/dexamisole): Long‐term monitoring of its intake by chiral LC–MS/MS analysis of cocaine‐positive hair samples
Authors: Madry Milena M. , Kraemer Thomas , Baumgartner Markus R.
Published: September 2018

Recent studies indicate that not only the anthelminthic levamisole but also the racemate tetramisole (R‐/S‐phenyltetraimidazothiazole, PTHIT) was found as an adulterant for cocaine. We herein report on the investigation of the prevalence of PTHIT among cocaine‐positive hair samples and the discrimination of the presence of its stereoisomers levamisole and dexamisole. Cocaine‐positive hair samples were collected in a forensic context in 2015 and mainly 2017 (n = 724). Cocaine and PTHIT concentrations have been determined by achiral liquid chromatography–tandem mass spectrometry (LC–MS/MS). For distinction of levamisole/dexamisole chiral LC–MS/MS was performed. Cocaine hair concentrations ranged from 500 (cut‐off) to approximately 800 000 pg/mg. The study demonstrates a strong prevalence of PTHIT in cocaine users' hair (87%, n = 627). PTHIT hair concentrations ranged from below LLOQ 3.5 to approximately 61 000 pg/mg (median: 260 pg/mg). Surprisingly, enantiomeric ratios of levamisole/dexamisole ranged from 0.17 to 1.34 (median: 0.63). Therefore, PTHIT‐adulterated street cocaine samples (n = 24) seized between 2013 and 2016 were tested. Samples mainly contained racemic tetramisole (87.5%), only one sample contained levamisole only and two samples contained non‐racemic PTHIT. Our experiments suggest that the presence of tetramisole in biological samples may have hitherto been underestimated. Most probably higher dexamisole than levamisole concentrations in hair specimens arise from stereoselective metabolism and/or elimination. This is particularly important in light of the different pharmacological activities of the two enantiomers and potentially different adverse effects. Toxicological interpretations in intoxication cases with adulterated cocaine should not only consider levamisole but also tetramisole and terminology in scientific contributions should be used accordingly.
Semi‐quantitative determination of designer steroids by high‐performance liquid chromatography with ultraviolet detection in the absence of reference material
Authors: Voelker Sarah E. , Lorenz Lisa M. , Litzau Jonathan J.
Published: September 2018

New designer steroids are continually being encountered in dietary supplements that claim to increase muscle mass, but quantitative analysis of such ingredients is challenging due to the availability, quality, or cost of commercial reference materials. Although standard reference material typically becomes available for these emerging compounds, laboratories often face the challenge of finding properly certified materials from accredited suppliers, due to traceability requirements. Several of these designer steroids have been isolated and identified using multiple structural elucidation tools. Structural characteristics of these compounds of interest were evaluated and molar absorptivity data was collected and compared to several readily available steroid standards using ultraviolet/visible spectroscopy. This approach was used to find suitable compounds for use as surrogate reference materials in the semi‐quantitative determination of two designer steroids, 1‐dehydroepiandrosterone (1‐androsterone) and 6β‐chloro‐4‐androsten‐17β‐ol‐3‐one (6β‐chlorotestosterone). Laboratory‐fortified matrix samples and dietary supplement samples were analyzed using this method for the estimation of 1‐androsterone and 6β‐chlorotestosterone by HPLC–UV. Assay values obtained for the estimation of 1‐androsterone in a dietary supplement sample using a prasterone or dehydroepiandrosterone (DHEA) standard curve were 100% of those obtained using a 1‐androsterone reference standard, once it became commercially available. Estimations for 6β‐chlorotestosterone in laboratory‐fortified matrix samples using a testosterone standard curve were 92%–93% of those obtained using isolated 6β‐chlorotestosterone as “reference material.”
Development of high thermal conductive epoxy composite for large current switchgear
Authors: Komiya Gen , Imai Takahiro , Miyauchi Yasuhisa
Published: September 2018

Toshiba has developed solid insulated switchgear (SIS), which insulates the main circuit with epoxy composites. The solid insulating system is able not only to use no SF6, which is a kind of global warming gas, but also to supply compact equipment. In SIS, heat generated by the current loss in the conductors is dissipated through the epoxy composite. Therefore, development of high thermal conductive epoxy composites has been desired with respect to large current class SIS such as 2500 A. In this article, epoxy composite was filled with MgO having high thermal conductivity and SiO2 having low thermal expansion coefficient. The result of temperature rise analysis of 40.5 kV–2500 A SIS demonstrated that the high thermal conductive epoxy composite reduced rising temperature by approximately 10 K compared to conventional epoxy composite.
Rationale and design of the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial
Authors: Mullens Wilfried , Verbrugge Frederik H. , Nijst Petra , Martens Pieter , Tartaglia Katrien , Theunissen Evi , Bruckers Liesbeth , Droogne Walter , Troisfontaines Pierre , Damman Kevin , Lassus Johan , Mebazaa Alexandre , Filippatos Gerasimos , Ruschitzka Frank , Dupont Matthias
Published: September 2018

Aims

Decisive evidence on the optimal diuretic agent, dosing schedule, and administration route is lacking in acute heart failure (AHF) with congestion. The Acetazolamide in Decompensated heart failure with Volume OveRload (ADVOR) trial is designed to test the hypothesis that the carbonic anhydrase inhibitor acetazolamide, a potent inhibitor of proximal tubular sodium reabsorption, improves decongestion when combined with loop diuretic therapy in AHF, potentially leading to better clinical outcomes.

Methods

The ADVOR trial is set up as a multicentre, randomized, double‐blind, placebo‐controlled study, aiming to recruit 519 patients with AHF and clinically evident volume overload. All study participants receive high‐dose intravenous loop diuretics as background therapy and are randomized towards intravenous acetazolamide at a dose of 500 mg once daily vs. placebo, stratified according to including study centre and ejection fraction (< 40% vs. ≥ 40%). The primary endpoint is successful decongestion with no more than trace oedema assessed on the third morning after hospital admission, with good diuretic efficacy defined as a urine output > 3.5 L during the first 30–48 h of decongestive treatment. Secondary endpoints include all‐cause mortality or heart failure readmission after 3 months, length of hospital stay for the index admission, and longitudinal changes in the EuroQol‐5 dimensions questionnaire.

Conclusion

ADVOR will investigate if acetazolamide combined with loop diuretic therapy improves decongestion in AHF with volume overload.
A Passerini/Michael Pathway towards Butyrolactones
Authors: Jia Shuanglong , El Kaïm Laurent
Published: September 2018

The Passerini adducts of aromatic aldehydes may act as nucleophiles in Michael additions with acrylonitrile. The reaction proceeds together with hydrolysis of the ester. The resulting γ‐hydroxynitrile may be cyclized under acidic conditions to afford a three‐steps synthesis of γ‐butyrolactones from isocyanides.
In situ free‐vibration tests on unrestrained and restrained rocking masonry walls
Authors: Giresini Linda , Sassu Mauro , Sorrentino Luigi
Published: September 2018

In the out‐of‐plane assessment of rocking walls, a relevant and yet uncertain aspect is the influence of energy dissipated during motion due to impacts and restraints, such as a floor or tie rods. Therefore, in situ rocking tests on unrestrained and restrained unreinforced masonry walls, made of composite (rubble + blockwork) masonry, were performed and analyzed. The restraint is given by steel springs of assigned stiffness, simulating a floor connected to full‐scale (4 × 1 × 0.6 m3) specimens from a dismantling building. The specimens are displaced from a static equilibrium position and released, allowing to evaluate energy dissipation. The coefficient of restitution is estimated as the square root of consecutive peak velocities of the same sign, to take into account nonhomogeneities in walls. For unrestrained walls, experimental coefficients of restitution vary between 81 and 88% of analytical ones, confirming the latter as conservative. For restrained configurations, experimental coefficients of restitution are between 74% and 83% of analytical values of unrestrained walls. Hence, an additional energy damping can be ascribed to the springs. Equivalent viscous damping ratios of a nonlinear rocking system are calculated by considering a velocity logarithmic decrement, resulting between 6% and 8% (unrestrained condition) and between 8% and 10% (restrained condition). An analytical formula is proposed for estimating the coefficient of restitution for restrained walls if the dynamic properties of the unrestrained wall and the horizontal restraint are known. Finally, the relevance of a refined estimation of energy dissipation is discussed by means of numerical time history analyses.
Effect of Anode/Cathode Operating Pressures on the Liquid Water Content and Performance of a PEM Fuel Cell
Authors: Iranzo A. , Salva J. A.
Published: September 2018

The operating pressure has a significant influence in the performance of a fuel cell, as it influences the output voltage via activation, ohmic, and mass transport losses. In this work, experiments with a 50 cm2 polymer electrolyte membrane (PEM) fuel cell with serpentine flow field have been carried out to investigate the effects of the operating pressure on the cell performance, with a particular analysis of the liquid water distribution within the cell. A comprehensive matrix of anode and cathode pressures was analyzed, varying the anode and cathode pressure from 1.25 to 2.00 bar (abs). Neutron imaging was used to determine the liquid water distributions within the cell for each operating condition and to assess the effect of the different operating pressures. Cell voltage was also monitored during the experiments and included in the analysis. A certain accumulation of liquid water was found in the cathode channels, were the overall liquid water accumulation was found to be more significant for higher pressures. This dependence on the operating pressure was more pronounced for lower current densities, and it was more significant for cathode pressure than for anode pressure.
Current approaches to dementia screening and case finding in low‐ and middle‐income countries: Research update and recommendations
Authors: Magklara Eleni , Stephan Blossom C.M. , Robinson Louise
Published: September 2018

Approximately 47 million people have dementia worldwide, with this figure, it is expected to almost triple by 2050. Most people with dementia (approximately two‐thirds) live in low‐ and middle‐income countries (LMICs). This presents a significant challenge for such countries that often have limited financial resources and less well‐developed health and social care systems. In the absence of a cure, reducing the future costs of dementia care and burden of disease may be best achieved by a greater emphasis on (1) more timely diagnosis with earlier intervention to maintain functional independence and (2) undertaking “screening” in groups at high risk of developing dementia, case finding, and using brief cognitive assessment instruments. In clinical settings, a wide range of instruments for dementia screening and diagnosis are currently available; however, few cognitive assessment tools have been developed specifically for clinical use within LMIC settings. Screening for dementia and cognitive impairment in LMICs largely relies on tools adapted from high‐income countries (HICs); these often lack validation in these settings leading to education, literacy, and cultural biases. Research is urgently needed to develop cognitive assessment tools and dementia diagnostic approaches that are appropriate and feasible for clinical use in LMIC settings.
Selective serotonin reuptake inhibitor and selective serotonin and norepinephrine reuptake inhibitor use and risk of fractures in adults: A systematic review and meta‐analysis
Authors: Khanassov Vladimir , Hu Jingyi , Reeves David , van Marwijk Harm
Published: September 2018

Objective

To evaluate the association between selective serotonin reuptake inhibitor (SSRI) and selective serotonin and norepinephrine reuptake inhibitor (SNRI) use and risk of fractures in older adults.

Methods

We systematically identified and analyzed observational studies comparing SSRI/SNRI use for depression with non‐SSRI/SNRI use with a primary outcome of risk of fractures in older adults. We searched for studies in MEDLINE, PsycINFO, Embase, DARE (Database of Abstracts or Reviews of Effects), the Cochrane Library, and Web of Science clinical trial research registers from 2011 for SSRIs and 1990 for SNRIs to November 29, 2016.

Results

Thirty‐three studies met our inclusion criteria; 23 studies were included in meta‐analysis: 9 case‐control studies and 14 cohort studies. A 1.67‐fold increase in the risk of fracture for SSRI users compared with nonusers was observed (relative risk 1.67, 95% CI 1.56‐1.79, P = .000). The risk of fracture increases with their long‐term use: within 1 year, the risk is 2.9% or 1 additional fracture in every 85 users; within 5 years, the risk is 13.4% or 1 additional fracture in every 19 users. In meta‐regression, we found that the increase in risk did not differ across age groups (odds ratio = 1.006; P = .173). A limited number of studies on SNRI use and the risk of fractures prevented us from conducting a meta‐analysis.

Conclusions

Our systematic review showed an association between risk of fracture and the use of SSRIs, especially with increasing use. Age does not increase this risk. No such conclusions can be drawn about the effect of SNRIs on the risk of fracture because of a lack of studies.
Measuring the patient experience in community mental health services for older people: A study of the Net Promoter Score using the Friends and Family Test in England
Authors: Wilberforce Mark , Poll Sarah , Langham Heather , Worden Angela , Challis David
Published: September 2018

Objectives

The research aimed to explore the value of the Net Promoter Score as a service improvement tool and an outcome measure. The study objectives were to (1) explore associations between the Net Promoter Score with patient and service‐receipt characteristics; (2) evaluate the strength of association between the Net Promoter Score and a satisfaction score; and (3) evaluate its test‐retest reliability.

Methods

A postal survey was sent to service users on caseloads of community mental health teams for older people in four localities of England. The survey collected the Net Promoter Score, a single satisfaction question, and data on socio‐demographics, clinical profile, and service receipt. Analysis used non‐parametric tests of association and exploratory least squares regression. A second survey was administered for test‐retest reliability analysis. Fieldwork concluded in April 2016.

Results

For 352 respondents, the Net Promoter Score was negatively related to age and was lowest for those still within 6 months of their initial referral. Receiving support from a psychiatrist and/or support worker was linked to higher scores. A strong but imperfect correlation coefficient with the satisfaction score indicates they evaluate related but distinct constructs. It had a reasonable test‐retest reliability, with a weighted kappa of 0.706.

Conclusions

Despite doubts over its validity in community mental health services, the Net Promoter Score may produce results of value to researchers, clinicians, service commissioners, and managers, if part of wider data collection. However, multi‐item measures would provide greater breadth and improved reliability.
Day care vs home care: Effects on functional health outcomes among long‐term care beneficiaries with dementia in Korea
Authors: Lee Tae Wha , Yim Eun Shil , Choi Hyoung Shim , Chung Jane
Published: September 2018

Objectives

First, to compare changes in cognitive function, behavioral symptoms, and physical function for Korean Long‐Term Care Insurance (LTCI) beneficiaries with dementia in day care (DC) and home care (HC) settings over 1 year. Second, to examine the association between LTCI service type and the aforementioned health outcomes.

Methods

A retrospective matched cohort study was conducted using the national data set of the National Health Insurance Service in Korea. We identified 7822 beneficiaries with dementia who received either DC or HC services consistently for 1 year from 2008 to 2009. The propensity score matching method was used, yielding 416 participants in each group. Paired samples t‐tests and logistic regression analyses were conducted.

Results

Baseline differences between the two groups are present. According to multiple regression models, DC, when compared with HC, was related to less deterioration in cognitive and physical function but was associated with less improved behavioral symptoms 1 year after the LTCI enrollment. In the comparison between matched cohorts, DC, when compared with HC, was associated with less cognitive decline, less disability progression, and similar decrease in behavioral symptoms.

Conclusions

Cognitive function and disability declined less in the DC group, compared with the HC group. Conversely, behavioral symptoms showed a similar decrease between the two groups after 1‐year follow‐up. Further research is necessary to examine key features of DC services that have helped delay functional deterioration and alleviate behavioral symptoms.
Inequalities in living well with dementia—The impact of deprivation on well‐being, quality of life and life satisfaction: Results from the improving the experience of dementia and enhancing active life study
Authors: Wu Yu‐Tzu , Clare Linda , Jones Ian Rees , Martyr Anthony , Nelis Sharon M. , Quinn Catherine , Victor Christina R. , Lamont Ruth A. , Rippon Isla , Matthews Fiona E. ,   On behalf of the Improving the experience of Dementia and Enhancing Active Life (IDEAL) study
Published: September 2018

Objectives

Area level factors, such as deprivation and urban/rural settings, have been associated with variation in local resources and services and health inequality in later life. The aim of this study is to investigate the potential impact of deprivation and urban/rural areas on capability to live well with dementia and to examine whether availability of informal carers modified the associations.

Methods

The analysis was based on a large cohort study of 1547 community‐dwelling people with dementia across Great Britain. Quality of life, life satisfaction, and well‐being were measured as indices of “living well.” Multivariate modelling was used to investigate differences in living well measures across deprivation quintiles and urban/rural areas adjusting for sociodemographic factors and number of comorbidities and stratifying by three groups: those living with a carer, those with a noncoresident carer and those without a carer.

Results

Negative dose‐response relationships between deprivation and measures of quality of life (−2.12; 95% CI: −3.52, −0.73), life satisfaction (−1.27; 95% CI: −2.70, 0.16), and well‐being (−5.24; 95% CI: −10.11, −0.36) were found in participants living with a carer. The associations were less clear in those with a noncoresident carer and those without a carer but these two groups generally reported lower scores on living well indicators than participants living with a carer. There was no urban/rural difference.

Conclusions

The findings suggest inequalities in living well with dementia according to levels of deprivation. Additional resources are needed to improve postdiagnostic care in highly deprived areas and support those who have no informal carer.
Validation of a European Cross‐Cultural Neuropsychological Test Battery (CNTB) for evaluation of dementia
Authors: Nielsen T. Rune , Segers Kurt , Vanderaspoilden Valérie , Beinhoff Ulrike , Minthon Lennart , Pissiota Anna , Bekkhus‐Wetterberg Peter , Bjørkløf Guro Hanevold , Tsolaki Magda , Gkioka Mara , Waldemar Gunhild
Published: September 2018

Background

The aims of this study were to establish the diagnostic accuracy of the European Cross‐Cultural Neuropsychological Test Battery (CNTB) for dementia in different ethnic populations in Western Europe, to examine its ability to differentiate cognitive impairment profiles for dementia subtypes, and to assess the impact of demographic variables on diagnostic properties.

Methods

The study was a Western European cross‐sectional multi‐center study. A total of 66 patients with dementia and 118 cognitively intact participants were included across six memory clinics; 93 had ethnic minority background and 91 had ethnic majority background. Tests in the CNTB cover global cognitive function, memory, language, executive functions, and visuospatial functions.

Results

Significant differences with moderate to large effect sizes were present between patients with dementia and control participants on all CNTB measures. Area under the curves (AUC) ranged from .62 to .99 with a mean AUC across all measures of .83. Comparison of ethnic minority and majority groups generally revealed higher sensitivity in the minority group but no significant difference in the mean AUC's across all measures (.84 vs78, P = .42). Comparison of impairment profiles for patients with Alzheimer's disease (AD) and non‐AD dementia revealed that AD patients were significantly more impaired on the memory domain, whereas patients with non‐AD dementia were more impaired on the executive functions domain.

Conclusions

The CNTB was found to have promising cross‐cultural diagnostic properties for evaluation of dementia in the targeted minority and majority populations and could represent a valid cross‐cultural alternative to other well‐established neuropsychological test batteries when assessing patients from these populations.
Placebo‐Controlled Randomized Trial of an Intestinal Bile Salt Transport Inhibitor for Pruritus in Alagille Syndrome
Authors: Shneider Benjamin L. , Spino Cathie , Kamath Binita M. , Magee John C. , Bass Lee M. , Setchell Kenneth D. , Miethke Alexander , Molleston Jean P. , Mack Cara L. , Squires Robert H. , Murray Karen F. , Loomes Kathleen M. , Rosenthal Philip , Karpen Saul J. , Leung Daniel H. , Guthery Stephen L. , Thomas Danny , Sherker Averell H. , Sokol Ronald J. ,   for the Childhood Liver Disease Research Network
Published: September 2018

Medically refractory, severe, cholestasis‐induced pruritus in Alagille syndrome may be improved by surgical interruption of the enterohepatic circulation. This multicenter trial (NCT02057692) tested the hypothesis that the intestinal bile acid transport inhibitor maralixibat would similarly reduce pruritus in Alagille syndrome. Thirty‐seven children with Alagille syndrome were randomly assigned to double‐blinded administration of placebo, 70, 140, or 280 µg/kg/day of maralixibat for 13 weeks. Pruritus was assessed by caregiver (itch‐reported outcome instrument [ItchRO]) and clinician report (range, 0‐4 [severe]). Liver chemistries and serum bile acids were measured. The primary outcome was the change from baseline to week 13 in ItchRO relative to placebo. In the a priori first analysis of the primary efficacy endpoint, the mean adjusted difference between participants receiving 140 or 280 µg/kg/day and placebo was –0.47 (95% confidence interval [CI], –1.14, 0.20; P = 0.16). Statistically significant decreases were observed with doses of 70 and 140 µg/kg/day (mean adjusted difference, –0.89; 95% CI, –1.70, –0.08; P = 0.032; and mean adjusted difference, –0.91; 95% CI, –1.62, –0.19; P = 0.014) but not 280 µg/kg/day (mean adjusted difference, –0.04; 95% CI, –0.94, 0.86; P = 0.44) or all doses combined (mean adjusted difference, –0.61; 95% CI, –1.24, 0.20; P = 0.055). A 1‐point reduction in pruritus was more common in maralixibat‐treated versus placebo‐treated participants (caregiver ItchRO, 65% versus 25%; P = 0.06; clinician score, 76% versus 25%; P = 0.01). There were no significant changes in liver chemistries or bile acids relative to placebo. Adverse and serious adverse events were similar between maralixibat and placebo. Conclusion: Although the prespecified primary analyses of ItchRO were not all statistically significant, the data suggest that maralixibat is safe and may reduce pruritus in Alagille syndrome.
Risk of CIN3 or worse with persistence of 13 individual oncogenic HPV types
Authors: Sand Freja Lærke , Munk Christian , Frederiksen Kirsten , Junge Jette , Iftner Thomas , Dehlendorff Christian , Kjaer Susanne K.
Published: September 2018

Human papillomavirus (HPV) is essential in cervical carcinogenesis, however, less is known about the carcinogenic potential of individual HPV types. Our aim was to examine the risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) after persistence of 13 individual oncogenic HPV types. Liquid‐based cervical samples (n = 40,399) collected in 2002–2005 were tested for HPV by hybrid capture 2 and genotyped with INNO‐LiPAv2. Persistence was defined as having the same genotype twice 1–4.5 years apart. The absolute risk of CIN3+ was estimated by the Aalen‐Johansen estimator and Cox proportional hazard regression was used to compare the rates of CIN3+ according to HPV type adjusting for age and time between HPV tests. Of 2,875 oncogenic HPV‐positive women, 874 had persistence of one or more types and 761 persisted for one oncogenic HPV type only. Persistent HPV16 infection was associated with the highest risk of CIN3+, with an 8‐year absolute risk of 55% (95% CI: 45%–66%), followed by HPV33 (33% (95% CI: 20%–50%)), HPV18 (32% (95% CI: 20%–48%)) and HPV31 (31% (95% CI: 21%–46%)). Other HPV types, including HPV52 and HPV45, were also associated with high risks. Persistent HPV56 had the lowest 8‐year absolute risk of CIN3+ (3% (95% CI: 0.4%–20%)). In Cox analyses, a similar pattern remained after adjustment for age and time between tests. Our results add knowledge about the varying carcinogenic potential of individual persistent oncogenic HPV types, which may have implications for the clinical use of HPV testing.
Application of information and communication technology for internationalization of Nigerian small‐ and medium‐sized enterprises
Authors: Gbadegeshin Saheed A. , Oyelere Solomon S. , Olaleye Sunday A. , Sanusi Ismaila T. , Ukpabi Dandison C. , Olawumi Olayemi , Adegbite Ayobami
Published: September 2018

Information and communication technology (ICT) has fundamentally transformed business transactions. While its uses have become ubiquitous in the advanced economies, emerging and developing economies are still struggling with the mode and manner of the deployment of ICT for business. Thus, this study seeks to investigate how small‐ and medium‐sized enterprises (SMEs) utilize ICT in Nigeria for business internationalization. To achieve the goal of the study, a mixed‐method was employed. A questionnaire was administered to 265 people consisting of SMEs staff, managers, and owners. Similarly, interviews were conducted with seven SME decision makers. Findings revealed that Nigerian SMEs used ICT tools, such as websites and social media platforms, for internationalization. The findings also revealed that the challenges of ICT did not affect its application by these SMEs, which contrasts with many previous studies. Furthermore, this study identified privacy concerns, internet problems, cyber insecurity, trust, and system anxiety as new challenges facing the application of ICT tools by SMEs. Similarly, the findings showed that lack of ICT competence and strategic focus of ICT applications are internal problems facing Nigerian SMEs. These findings provide insight for practitioners and academia on the internationalization of Nigeria SMEs and the application of ICT to promote business growth.
Comparison of components of the Good Behavior Game in a preschool classroom
Authors: Foley Elizabeth A. , Dozier Claudia L. , Lessor Amber L.
Published: September 2018

The Good Behavior Game (GBG) is an effective intervention package for decreasing disruptive behavior in various populations and environments. There is, however, limited research evaluating the GBG with preschoolers. Furthermore, few studies have evaluated the effects of components of the GBG, and of those that have, most have done so only after exposure to the GBG package. We evaluated the effects (a) of the GBG on disruptive behavior of preschoolers during group instruction and (b) the major components of the GBG before and after implementation of the GBG package (c) at both the group and individual level. Results suggest that the GBG package was necessary for decreasing disruptive behavior. However, after exposure to the GBG, a response‐independent contingency was effective for maintaining low levels of disruptive behavior at both the group and individual level.
Retracted: Inhibitory role of lentivirus‐mediated aquaporin‐4 gene silencing in the formation of glial scar in a rat model of traumatic brain injury
Authors: Yong Ya‐Xiong , Li Yu‐Ming , Lian Jia , Luo Chuan‐Ming , Zhong De‐Xia , Han Ke
Published: September 2018

Traumatic brain injury (TBI), an acute degenerative pathology of the central nervous system, is a leading cause of death and disability. As the glial scar is a mechanical barrier to nerve regeneration, inhibitory molecules in the forming scar and methods to overcome them have suggested molecular modification strategies to allow neuronal growth and functional regeneration. Herein, we aim to investigate the effects of aquaporin‐4 (AQP4) gene silencing on the glial scar formation after TBI by establishing rat models. After modeling, TBI rats were transfected with AQP4 small hairpin RNA [shRNA] (AQP4 gene silencing by lentiviral vector–delivered shRNA) and empty vectors, respectively. Neurological functions of the rats were evaluated after TBI. The hematoxylin and eosin staining was conducted to observe histomorphological changes in rat brain tissues. The messenger RNA (mRNA) and protein expressions of glial fibrillary acidic protein (GFAP), vimentin, fibronectin, laminin, and AQP4 were measured by reverse transcription‐quantitative polymerase chain reaction and Western blot analysis. The ratio of positive expression area was calculated, and the glial scar was observed by immunohistochemistry. At the 7th, 14th, and 28th days after TBI, TBI rats treated with AQP4 shRNA showed improved neurological function and lessened histomorphological changes. AQP4 gene silencing mediated by lentivirus decreased the mRNA and protein expressions of GFAP, vimentin, fibronectin, and laminin, the number of positive cells, the ratio of positive expression area, and the glial scar. Our study demonstrates that lentivirus‐mediated AQP4 gene silencing could inhibit the formation of glial scar after TBI, which is beneficial to the recovery of neurological function.
MiR‐218 regulated cardiomyocyte differentiation and migration in mouse embryonic stem cells by targeting PDGFRα
Authors: Xu Tingting , Liu Nuoya , Shao Ying , Huang Yujie , Zhu Danyan
Published: September 2018

MicroRNAs (miRNAs) have been identified as key players in cardiogenesis and heart pathophysiological processes. However, many miRNAs are still not recognized for their roles in cardiomyocytes differentiation. In this study, we evaluated the effects of microRNA‐218 (miR‐218) in cardiomyocyte differentiation of the mouse embryonic stem cells (ESCs) in vitro. The percentage of the beating embryoid bodies (EBs) in miR‐218 mimic‐treated cells was reduced to 32% compared with miR‐218 mimic negative control (56%) on day 5 + 3. The amplitude of the intracellular Ca2+ transients in the cardiomyocytes derived from ESCs was reduced upon miR‐218 overexpression, followed by the decreased calcium‐related proteins and cell junction proteins expressions. Besides, miR‐218 expression in ESCs was related to the directional spreading ability of EBs during differentiation. The increased expression of miR‐218 could promote the migration of ESCs in vitro, while the decreased expression of miR‐218 could inhibit the migration by the transwell experiment. Meanwhile, miR‐218 could regulate cell migration–related proteins Cdc42 and Rac1. Platelet‐derived growth factor receptor α (PDGFRα) was further confirmed to be a direct target of miR‐218 both physically and functionally by dual‐luciferase reporter assay. Our data further described that overexpression of PDGFRα rescued the miR‐218‐mediated inhibition of cardiomyocyte differentiation and restored the miR‐218‐mediated promotion of cell migration. In conclusion, miR‐218 was demonstrated to exert an inhibitory function and promoted cell migration via targeting PDGFRα during cardiomyocyte differentiation from ESCs. The current study revealed the role of miR‐218 and may provide an important hint for cardiomyocyte differentiation of ESCs and induced pluripotent stem cells.
Direct inversion of the iterative subspace with contracted planewave basis functions
Authors: Stuart Duncan W. , Mosey Nicholas J.
Published: September 2018

Ways to reduce the computational cost of periodic electronic structure calculations by using basis functions corresponding to linear combinations of planewaves have been examined recently. These contracted planewave (CPW) basis functions correspond to Fourier series representations of atom‐centered basis functions, and thus provide access to some beneficial properties of planewave (PW) and localized basis functions. This study reports the development and assessment of a direct inversion of the iterative subspace (DIIS) method that employs unique properties of CPW basis functions to efficiently converge electronic wavefunctions. This method relies on access to a PW‐based representation of the electronic structure to provide a means of efficiently evaluating matrix–vector products involving the application of the Fock matrix to the occupied molecular orbitals. These matrix–vector products are transformed into a form permitting the use of direct diagonalization techniques and DIIS methods typically employed with atom‐centered basis sets. The abilities of this method are assessed through periodic Hartree–Fock calculations of a range of molecules and solid‐state systems. The results show that the method reported in this study is approximately five times faster than CPW‐based calculations in which the entire Fock matrix is calculated. This method is also found to be weakly dependent upon the size of the basis set, thus permitting the use of larger CPW basis sets to increase variational flexibility with a minor impact on computational performance. © 2018 Wiley Periodicals, Inc.
Automated Search of Minimum Free‐Energy Path by Umbrella Integration
Authors: Mitsuta Yuki , Yamanaka Shusuke , Kawakami Takashi , Okumura Mitsutaka
Published: September 2018

The free‐energy landscape is an important factor for understanding the conformational equilibria of chemical reactions, and many techniques have been developed to calculate the potential of the mean force. Unfortunately, these methods require a previous knowledge of the system for calculations because the results depend on the reaction coordinates. In this study, we combine the scaled hypersphere search method with the umbrella integration method to obtain the transition states on free‐energy landscapes and minimum‐free‐energy paths (MFEPs). With this approach, the MFEP connections between known and unknown equilibrium points are constructed without the prior knowledge of the free‐energy landscape. The problem of reaction coordinates can be solved by using a multidimensional, fully automated interrogation of MFEPs for acquiring the potential of mean force. The efficiency of the proposed method is demonstrated by applying it to alanine dipeptide and alanine tripeptide. © 2018 Wiley Periodicals, Inc.
tsscds2018: A code for automated discovery of chemical reaction mechanisms and solving the kinetics
Authors: Rodríguez Aurelio , Rodríguez‐Fernández Roberto , A. Vázquez Saulo , L. Barnes George , J. P. Stewart James , Martínez‐Núñez Emilio
Published: September 2018

A new software, called tsscds2018, has been developed to discover reaction mechanisms and solve the kinetics in a fully automated fashion. The program employs algorithms based on Graph Theory to find transition state (TS) geometries from accelerated semiempirical dynamics simulations carried out with MOPAC2016. Then, the TSs are connected to the corresponding minima and the reaction network is obtained. Kinetic data like populations vs time or the abundancies of each product can also be obtained with our program thanks to a Kinetic Monte Carlo routine. Highly accurate ab initio potential energy diagrams and kinetics can also be obtained using an interface with Gaussian09. The source code is available on the following site: http://forge.cesga.es/wiki/g/tsscds/HomePage © 2018 Wiley Periodicals, Inc.