bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal variants in NLRP and other maternal effect proteins are associated with multilocus imprinting disturbance in offspring
Authors: Begemann Matthias , Rezwan Faisal I , Beygo Jasmin , Docherty Louise E , Kolarova Julia , Schroeder Christopher , Buiting Karin , Chokkalingam Kamal , Degenhardt Franziska , Wakeling Emma L , Kleinle Stephanie , González Fassrainer Daniela , Oehl-Jaschkowitz Barbara , Turner Claire L S , Patalan Michal , Gizewska Maria , Binder Gerhard , Bich Ngoc Can Thi , Chi Dung Vu , Mehta Sarju G , Baynam Gareth , Hamilton-Shield Julian P , Aljareh Sara , Lokulo-Sodipe Oluwakemi , Horton Rachel , Siebert Reiner , Elbracht Miriam , Temple Isabel Karen , Eggermann Thomas , Mackay Deborah J G
Published: March 2018

Background

Genomic imprinting results from the resistance of germline epigenetic marks to reprogramming in the early embryo for a small number of mammalian genes. Genetic, epigenetic or environmental insults that prevent imprints from evading reprogramming may result in imprinting disorders, which impact growth, development, behaviour and metabolism. We aimed to identify genetic defects causing imprinting disorders by whole-exome sequencing in families with one or more members affected by multilocus imprinting disturbance.

Methods

Whole-exome sequencing was performed in 38 pedigrees where probands had multilocus imprinting disturbance, in five of whom maternal variants in NLRP5 have previously been found.

Results

We now report 15 further pedigrees in which offspring had disturbance of imprinting, while their mothers had rare, predicted-deleterious variants in maternal effect genes, including NLRP2, NLRP7 and PADI6. As well as clinical features of well-recognised imprinting disorders, some offspring had additional features including developmental delay, behavioural problems and discordant monozygotic twinning, while some mothers had reproductive problems including pregnancy loss.

Conclusion

The identification of 20 putative maternal effect variants in 38 families affected by multilocus imprinting disorders adds to the evidence that maternal genetic factors affect oocyte fitness and thus offspring development. Testing for maternal-effect genetic variants should be considered in families affected by atypical imprinting disorders.
Thrombectomy using the EmboTrap device: core laboratory-assessed results in 201 consecutive patients in a real-world setting
Authors: Brouwer Patrick A , Yeo Leonard L L , Holmberg Ake , Andersson Tommy , Kolloch Jens , KuntzeSöderqvist Åsa , Ohlsson Marcus , Holmin Staffan , Anastasios Mpotsaris , Gontu Vamsi Krishna , Bhogal Paul , Söderman Michael
Published: March 2018

Background

We studied patients treated with the EmboTrap revascularization device in a prospective registry which is core laboratory evaluated by physicians from external centers. The goal was to determine how the EmboTrap would perform under the everyday conditions of a high-volume stroke center.

Methods

We examined all patients with acute stroke treated with the Embotrap device from October 2013 to March 2017 in our center. Imaging parameters and times were adjudicated by core laboratory personnel blinded to clinical information, treating physician, and clinical outcomes. Clinical evaluation was performed by independent neurologists and entered in a national registry. Evaluated endpoints were: successful revascularization (modified Thrombolysis in Cerebral Infarction (mTICI) 2b–3) and good clinical outcomes at 3 months (modified Rankin Scale (mRS) 0–2).

Results

201 consecutive patients with a median NIH Stroke Scale (NIHSS) score of 15 (range 2–30) were included. 170 patients (84.6%) achieved mTICI 2b–3 reperfusion. The median number of attempts was 2 (range 1–10) with 52.8% of the population achieving good functional outcomes (mRS 0–2) at 3 months. On univariate analysis, good functional outcome was associated with the number of attempts, puncture-to-reperfusion time, anterior circulation occlusion, and NIHSS score. On multivariate analysis, pre-treatment NIHSS (OR 0.845 per point, 95% CI 0.793 to 0.908, P<0.001) and puncture-to-reperfusion time (OR 0.9952 per min, 95% CI 0.9914 to 0.9975, P=0.023) were associated with good functional outcomes at 3 months.

Conclusion

The Embotrap device has a high rate of successful reperfusion. Our core laboratory-audited single-center experience suggests the technical feasibility and safety of the Embotrap for first-line use in a real-world setting.
Meta-analyses in environmental and occupational health
Authors: Ioannidis John P A
Published: March 2018

Objectives

Meta-analyses are considered generally as the highest level of evidence, but concerns have been voiced about their massive, low-quality production. This paper aimed to evaluate the landscape of meta-analyses in the field of occupational and environmental health and medicine.

Methods

Using relevant search terms, all meta-analyses were searched for, but those published in 2015 were assessed for their origin, whether they included randomised trials and individual-level data and whether they had authors from the industry or consultancy firms.

Results

PubMed searches (last update February 2017) identified 1251 eligible meta-analyses in this field. There was a rapid increase over time (n=16 published in 1995 vs n=163 published in 2015). Of the 163 eligible meta-analyses published in 2015, 49 were from China, followed at a distance by the USA (n=19). Only 16 considered randomised (intervention) trials and 13 included individual-level data. Only 1 of the 150 meta-analyses had industry authors and none had consultancy firm authors. As an example of conflicting findings, 12 overlapping meta-analyses addressed mobile phones and brain cancer risk and they differed substantially in number of studies included, eligibility criteria and conclusions.

Conclusions

There has been a major increase in the publication of meta-analyses in occupational and environmental health over time, with the majority of these studies focusing on observational data, while a commendable fraction used individual-level data. Authorship is still limited largely to academic and non-profit authors. With massive production of meta-analyses, redundancy needs to be anticipated and efforts should be made to safeguard quality and protect from bias.
Effect and impact of mechanical ventilation in myotonic dystrophy type 1: a prospective cohort study
Authors: Boussaïd Ghilas , Prigent Hélène , Laforet Pascal , Raphaël Jean-Claude , Annane Djillali , Orlikowski David , Lofaso Frédéric
Published: March 2018

Few studies have assessed the impact of home ventilation in patients with myotonic dystrophy type 1 (DM1) and no specific recommendations are available. We assessed the survival associated with category of home ventilation adherence of patients with DM1 followed up at a home ventilation unit using a Cox proportional hazards model. 218 patients were included; those who refused or delayed their acceptance of non-invasive ventilation were at higher risk for severe events (invasive ventilation or death) (P=0.03). Risk of death was associated with orthopnoea (HR 2.37; 95% CI 1.17 to 4.80; P<0.02) and adherence category (100 to 90% vs >75%: HR 3.26; 95% CI 1.32 to 8.04; P<0.03). Failure to use home ventilation as prescribed may be associated with increased mortality in patients with DM1.
Occupational exposures and 20-year incidence of COPD: the European Community Respiratory Health Survey
Authors: Lytras Theodore , Kogevinas Manolis , Kromhout Hans , Carsin Anne-Elie , Antó Josep M , Bentouhami Hayat , Weyler Joost , Heinrich Joachim , Nowak Dennis , Urrutia Isabel , Martinez-Moratalla Jesús , Gullón José Antonio , Pereira-Vega Antonio , Raherison-Semjen Chantal , Pin Isabelle , Demoly Pascal , Leynaert Bénédicte , Villani Simona , Gislason Thorarinn , Svanes Cecilie , Holm Mathias , Forsberg Bertil , Norbäck Dan , Mehta Amar J , Probst-Hensch Nicole , Benke Geza , Jogi Rain , Torén Kjell , Sigsgaard Torben , Schlünssen Vivi , Olivieri Mario , Blanc Paul D , Vermeulen Roel , Garcia-Aymerich Judith , Jarvis Deborah , Zock Jan-Paul
Published: March 2018

Background

Occupational exposures have been associated with an increased risk of COPD. However, few studies have related objectively assessed occupational exposures to prospectively assessed incidence of COPD, using postbronchodilator lung function tests. Our objective was to examine the effect of occupational exposures on COPD incidence in the European Community Respiratory Health Survey.

Methods

General population samples aged 20–44 were randomly selected in 1991–1993 and followed up 20 years later (2010–2012). Spirometry was performed at baseline and at follow-up, with incident COPD defined using a lower limit of normal criterion for postbronchodilator FEV1/FVC. Only participants without COPD and without current asthma at baseline were included. Coded job histories during follow-up were linked to a Job-Exposure Matrix, generating occupational exposure estimates to 12 categories of agents. Their association with COPD incidence was examined in log-binomial models fitted in a Bayesian framework.

Findings

3343 participants fulfilled the inclusion criteria; 89 of them had COPD at follow-up (1.4 cases/1000 person-years). Participants exposed to biological dust had a higher incidence of COPD compared with those unexposed (relative risk (RR) 1.6, 95% CI 1.1 to 2.3), as did those exposed to gases and fumes (RR 1.5, 95% CI 1.0 to 2.2) and pesticides (RR 2.2, 95% CI 1.1 to 3.8). The combined population attributable fraction for these exposures was 21.0%.

Interpretation

These results substantially strengthen the evidence base for occupational exposures as an important risk factor for COPD.
Price, tax and tobacco product substitution in Zambia: findings from the ITC Zambia Surveys
Authors: Stoklosa Michal , Goma Fastone , Nargis Nigar , Drope Jeffrey , Chelwa Grieve , Chisha Zunda , Fong Geoffrey T
Published: March 2018

Background

In Zambia, the number of cigarette users is growing, and the lack of strong tax policies is likely an important cause. When adjusted for inflation, levels of tobacco tax have not changed since 2007. Moreover, roll-your-own (RYO) tobacco, a less-costly alternative to factory-made (FM) cigarettes, is highly prevalent.

Data and methods

We modelled the probability of FM and RYO cigarette smoking using individual-level data obtained from the 2012 and 2014 waves of the International Tobacco Control (ITC) Zambia Survey. We used two estimation methods: the standard estimation method involving separate random effects probit models and a method involving a system of equations (incorporating bivariate seemingly unrelated random effects probit) to estimate price elasticities of FM and RYO cigarettes and their cross-price elasticities.

Results

The estimated price elasticities of smoking prevalence are −0.20 and −0.03 for FM and RYO cigarettes, respectively. FM and RYO are substitutes; that is, when the price of one of the products goes up, some smokers switch to the other product. The effects are stronger for substitution from FM to RYO than vice versa.

Conclusions

This study affirms that increasing cigarette tax with corresponding price increases could significantly reduce cigarette use in Zambia. Furthermore, reducing between-product price differences would reduce substitution from FM to RYO. Since RYO use is associated with lower socioeconomic status, efforts to decrease RYO use, including through tax/price approaches and cessation assistance, would decrease health inequalities in Zambian society and reduce the negative economic consequences of tobacco use experienced by the poor.
Bronchial blocker‐induced bronchospasm in a dog
Authors: Mirra Alessandro , Iff Isabelle
Published: March 2018

A 12‐year‐old female labrador retriever weighing 27 kg required anaesthesia for an explorative thoracoscopy and intrathoracic mass biopsy. One lung ventilation was achieved using a bronchial blocker. After surgery, the dog was moved to the induction room with the bronchial blocker still in place. Once reconnected to an anaesthetic machine, absent capnography trace during mechanical ventilation, increased circuit pressure during manual ventilation and reduced tidal volume with subsequent haemoglobin desaturation occurred. After excluding other possible causes, bronchospasm due to direct bronchial blocker stimulation was suspected. Removal of the bronchial blocker, reintubation with a new endotracheal tube, administration of ketamine, adrenaline, isoflurane, theophylline and salbutamol led to the resolution of the clinical symptoms within four hours. No further episodes occurred. The dog was discharged in good general conditions seven days later.
Chronic pneumonia and focal bronchiectasis in a Siberian husky dog
Authors: Nerhagen Sivert , Shiel Robert E
Published: March 2018

An eight‐year‐old male Siberian husky dog was evaluated for chronic coughing. Thoracic radiography revealed a diffuse bronchointerstitial pattern and dilatation of the left cranial and left caudal lobar bronchi. Bronchoscopy confirmed marked dilatation of the primary bronchi in the left cranial and caudal lung lobes. Bronchoalveolar lavage revealed septic, neutrophilic inflammation. A diagnosis of severe, focal, cylindrical bronchiectasis secondary to chronic bronchopneumonia was made. Initially, the dog responded well to antimicrobial therapy; however, clinical signs returned after cessation of therapy and generalised bronchiectasis developed after seven months. Chronic bacterial bronchopneumonia should be considered as a cause of focal and generalised bronchiectasis in dogs.
Recruitment challenges in the profession … a chance to respond
Authors: Tufnell Chris , Ravetz Gudrun
Published: March 2018

In last week's Vet Record, we published an interview with Simon Innes, chief executive of CVS, in which he discussed vet salaries, recruitment challenges and his ambitions for the future. He criticised the RCVS and organisations that represent vets and vet nurses for not doing enough to tackle the recruitment crisis. Here, we give the RCVS and BVA the opportunity to respond to these criticisms.
Long-term population dynamics and conservation risk of migratory bull trout in the upper Columbia River basin
Authors: Kovach Ryan P. , Armstrong Jonathan B. , Schmetterling David A. , Al-Chokhachy Robert , Muhlfeld Clint C.
Published: March 2018

We used redd count data from 88 bull trout (Salvelinus confluentus) populations in the upper Columbia River basin to quantify local and regional patterns in population dynamics, including adult abundance, long-term trend, and population synchrony. We further used this information to assess conservation risk of metapopulations using eight population dynamic metrics associated with persistence. Local population abundances were generally low (<20 redds annually) and the majority of trends were either stable (85%) or declining (13%). Evidence of synchrony among populations was apparent but not related to fluvial distance between streams. Variability in annual abundances was 1.4–2.5 times lower in metapopulations than local populations, indicating moderate portfolio effects across the regional stock complex. Importantly, most metrics of conservation risk were uncorrelated with one another, emphasizing that multiple statistics describing population dynamics at various scales are needed for monitoring and assessing recovery. We provide a composite description of conservation risk based on local and regional population dynamics that can help inform conservation management decisions for bull trout and other freshwater fishes.
Simulation of astrophysical flows in isentropic approximation
Authors: Moiseenko S. G. , Bisnovatyi-Kogan G. S.
Published: March 2018

One of the difficulties of numerical simulations of cold supersonic astrophysical flows is a big difference in different types of energy. Gravitational and/or kinetic energy of the gas could be much larger than its internal energy. In such a case, it is possible to get large numerical errors in the simulations. To avoid this difficulty, conservation of entropy equation was used instead of energy conservation equation. The entropy conservation equation does not contain the gravitational and kinetic energy. The application of the isentropic set of equations is correct when the flow does not contain shocks or the amplitude of the shocks (shock wave Mach number) is not large. We estimate the violation of the energy conservation low when the “shock wave” is isentropic.
THE USE AND DETERMINANTS OF TRAINING AND DEVELOPMENT FOR CREATIVITY AND INNOVATION
Authors: MANRESA ALBA , BIKFALVI ANDREA , SIMON ALEXANDRA
Published: March 2018

Human Resource Management (HRM) practices are considered as a possible contributor to firm success. Further research is needed in this field to address how HRM practices contribute to a firm’s ability to be creative and innovative. The first objective of this paper is to map the implementation of training and development practices for creativity and innovation (TD4CI) in manufacturing and the second is to analyse the factors that most influence this implementation. The study, based on the Spanish sub-sample of the European Manufacturing Survey, demonstrates the unexhausted potential of TD4CI as a step prior to innovation. The results show that one third of the companies currently use TD4CI and that this figure is rising. Most of the firms, however, have not put these practices into place and they have no intention of doing so. Regarding the determinants that influence the studied practices, the results show that there are some significant factors, for example new products or services being introduced within the company in the previous three years, that positively affect all the practices. Other determinants are individually significant, for instance the complexity of the product. Some factors, on the other hand, such as size or single unit production, do not appear to influence any of the practices studied so far. The value of this research lies in the up-to-date, relevant figures it provides regarding the implementation and dissemination of TD4CI.
Preferential formation of a slide plane in translational submarine landslide deposits in a Pleistocene forearc basin fill exposed in east-central Japan
Authors: Utsunomiya Masayuki , Noda Atsushi , Otsubo Makoto
Published: March 2018

Tephra beds are considered to be potential failure planes for submarine landslides. Here, we report on an example of a coarse-ash/lapilli-tuff bed influencing translational slides. The studied mass-transport deposit (MTD) is intercalated in the Pleistocene forearc basin fill exposed in east-central Japan. This MTD consists of stacked siltstone blocks resulting from repeated imbricate thrusts branching from the décollement. The basal slide plane is located immediately below a pumice-rich coarse ash/lapilli-tuff bed. The material comprising the slip zone is injected into the overlying coarse-ash/lapilli-tuff bed, suggesting an upwards escape of excess porewater that resulted from elevated pore pressure. To explain this mode of occurrence, we propose that the detachment preferentially occurred at the top and base of the coarse-ash-tuff-rich interval which appears to have been stronger relative to the adjacent silt-dominated interval. The pumiceous coarse-ash and lapilli-tuff bed behaved as a rigid plate on top of the high-pore-pressure slip zone, which sustained the translational slide on the gentle continental slope. Therefore, in translational submarine landslides, the preferential formation of a slide plane is caused by differing frictional resistances in the layered sediments.
Bulgarian tsunami on 7 May 2007: numerical investigation of the hypothesis of a submarine-landslide origin
Authors: Gusev Oleg I. , Khakimzyanov Gayaz S. , Chubarov Leonid B.
Published: March 2018

We investigate the ability of a submarine landslide to generate the tsunami waves observed on the Bulgarian coast of Black Sea on 7 May 2007. In our simulations, a landslide is presented as a quasi-deformable body moving along a curvilinear slope under action of the forces of gravity, buoyancy, water resistance and bottom friction. We employ the fully non-linear weakly dispersive model for tsunami wave simulations. The computations show that the initial landslide position on the real slope is extremely important for its dynamics and the wave generation process. We constructed some model landslides which generated similar waves to those observed. Moreover, these landslides stopped in the same region. Finally, we evaluated the significance of the frequency dispersion effects in the simulations.
Dynamics of Bacterial Gene Regulatory Networks
Authors: Shis David L. , Bennett, Matthew R. , Igoshin Oleg A.
Published: March 2018

The ability of bacterial cells to adjust their gene expression program in response to environmental perturbation is often critical for their survival. Recent experimental advances allowing us to quantitatively record gene expression dynamics in single cells and in populations coupled with mathematical modeling enable mechanistic understanding on how these responses are shaped by the underlying regulatory networks. Here, we review how the combination of local and global factors affect dynamical responses of gene regulatory networks. Our goal is to discuss the general principles that allow extrapolation from a few model bacteria to less understood microbes. We emphasize that, in addition to well-studied effects of network architecture, network dynamics are shaped by global pleiotropic effects and cell physiology.
A Large-Scale, Exome-Wide Association Study of Han Chinese Women Identifies Three Novel Loci Predisposing to Breast Cancer
Authors: Zhang Bo , Chen Men-Yun , Shen Yu-Jun , Zhuo Xian-Bo , Gao Ping , Zhou Fu-Sheng , Liang Bo , Zu Jun , Zhang Qin , Suleman Sufyan , Xu Yi-Hui , Xu Min-Gui , Xu Jin-Kai , Liu Chen-Cheng , Giannareas Nikolaos , Xia Ji-Han , Zhao Yuan , Huang Zhong-Lian , Yang Zhen , Cheng Huai-Dong , Li Na , Hong Yan-Yan , Li Wei , Zhang Min-Jun , Yu Ke-Da , Li Guoliang , Sun Meng-Hong , Chen Zhen-Dong , Wei Gong-Hong , Shao Zhi-Min
Published: March 2018

Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here, we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls). In addition to replicating known susceptibility loci (e.g., ESR1, FGFR2, and TOX3), we identify two novel missense variants in C21orf58 (rs13047478, Pmeta = 4.52 × 10−8) and ZNF526 (rs3810151, Pmeta = 7.60 × 10−9) and one new noncoding variant at 7q21.11 (P < 5 × 10−8). C21orf58 and ZNF526 possessed functional roles in the control of breast cancer cell growth, and the two coding variants were found to be the eQTL for several nearby genes. rs13047478 was significantly (P < 5.00 × 10−8) associated with the expression of genes MCM3AP and YBEY in breast mammary tissues. rs3810151 was found to be significantly associated with the expression of genes PAFAH1B3 (P = 8.39 × 10−8) and CNFN (P = 3.77 × 10−4) in human blood samples. C21orf58 and ZNF526, together with these eQTL genes, were differentially expressed in breast tumors versus normal breast. Our study reveals additional loci and novel genes for genetic predisposition to breast cancer and highlights a polygenic basis of disease development.

Significance: Large-scale genetic screening identifies novel missense variants and a noncoding variant as predisposing factors for breast cancer. Cancer Res; 78(11); 3087–97. ©2018 AACR.
Bajijiasu Ameliorates β-Amyloid-Triggered Endoplasmic Reticulum Stress and Related Pathologies in an Alzheimer’s Disease Model
Authors: Xu Ting-Ting , Zhang Yang , He Jia-Yang , Luo Dan , Luo Yi , Wang Yi-Jie , Liu Wei , Wu Jun , Zhao Wei , Fang Jiansong , Guan Li , Huang Shun , Wang Hong , Lin Li , Zhang Shi-Jie , Wang Qi
Published: March 2018

Background/Aims: Alzheimer disease (AD) is a common neurodegenerative disease that is characterized by the deposition of beta-amyloid peptide and formation of intracellular neurofibrillary tangles. Due to the failure of various clinical trials of novel drugs for AD, effective drugs for AD treatment are urgently required. Methods: In this study, we used the classic APP/PS1 mouse model to explore the neuroprotective effects of a new compound, bajijiasu, and the mechanisms involved. Behavioral tests and western blotting were performed to assess the beneficial effects of bajijiasu in APP/PS1 mice. Results: Morris water maze and Y-maze test results showed that oral administration of bajijiasu (35 mg/kg/day and 70 mg/kg/day) improved learning and memory abilities in APP/PS1 mice. Bajijiasu reduced ROS and MDA levels in both the hippocampus and cortex. Moreover, western blotting results showed that bajijiasu protected neurons from apoptosis, elevated the expression levels of neurotrophic factors, and alleviated endoplasmic reticulum stress in both the hippocampus and cortex. Conclusion: These results indicate that the mechanisms underlying the effects of bajijiasu on AD might be related to beta-amyloid-downstream pathologies, particularly endoplasmic reticulum stress.
Decreased cAMP Level and Decreased Downregulation of β
1
‐Adrenoceptor Expression in Therapeutic Hypothermia‐Resuscitated Myocardium Are Associated With Improved Post‐Resuscitation Myocardial Function
Authors: Wang Wei , Hua Tianfeng , Li Hao , Wu Xiaobo , Bradley Jennifer , Peberdy Mary Ann , Ornato Joseph P. , Tang Wanchun
Published: March 2018

Background

Epinephrine administered during cardiopulmonary resuscitation (CPR) is associated with severe post‐resuscitation myocardial dysfunction. We previously demonstrated that therapeutic hypothermia reduced the severity of post‐resuscitation myocardial dysfunction caused by epinephrine; however, the relationship between myocardial adrenoceptor expression and myocardial protective effects by hypothermia remains unclear.

Methods and Results

Rats weighing between 450 and 550 g were randomized into 5 groups: (1) normothermic placebo, (2) normothermic epinephrine, (3) hypothermic placebo, (4) hypothermic epinephrine, and (5) sham (not subject to cardiac arrest and resuscitation). Ventricular fibrillation was induced and untreated for 8 minutes for all other groups. Hypothermia was initiated coincident with the start of
CPR
and maintained at 33±0.2°C for 4 hours. Placebo or epinephrine was administered 5 minutes after the start of
CPR
and 3 minutes before defibrillation. Post‐resuscitation ejection fraction was measured hourly for 4 hours then hearts were harvested. Epinephrine increased coronary perfusion pressure during
CPR
(27±6 mm Hg versus 21±2 mm Hg
P
<0.05). Post‐resuscitation myocardial function was impaired in the normothermic epinephrine group compared with other groups. The concentration of myocardial
cAMP
doubled in the normothermic epinephrine group (655.06±447.63 μmol/L) compared with the hypothermic epinephrine group (302.51±97.98 μmol/L;
P
<0.05). Myocardial β
1
‐adrenoceptor expression decreased with normothermia cardiac arrest but not with hypothermia regardless of epinephrine.

Conclusions

Epinephrine, administered during normothermic
CPR
, increased the severity of post‐resuscitation myocardial dysfunction. This adverse effect was inhibited by intra‐arrest hypothermia resuscitation. Declined
cAMP
with more preserved β
1
‐adrenoceptors in hypothermia‐resuscitated myocardium is associated with improved post‐resuscitated myocardial function in vivo.
Modeling Short QT Syndrome Using Human‐Induced Pluripotent Stem Cell–Derived Cardiomyocytes
Authors: El‐Battrawy Ibrahim , Lan Huan , Cyganek Lukas , Zhao Zhihan , Li Xin , Buljubasic Fanis , Lang Siegfried , Yücel Gökhan , Sattler Katherine , Zimmermann Wolfram‐Hubertus , Utikal Jochen , Wieland Thomas , Ravens Ursula , Borggrefe Martin , Zhou Xiao‐Bo , Akin Ibrahim
Published: March 2018

Background

Short
QT
syndrome (
SQTS
), a disorder associated with characteristic ECG
QT
‐segment abbreviation, predisposes affected patients to sudden cardiac death. Despite some progress in assessing the organ‐level pathophysiology and genetic changes of the disorder, the understanding of the human cellular phenotype and discovering of an optimal therapy has lagged because of a lack of appropriate human cellular models of the disorder. The objective of this study was to establish a cellular model of
SQTS
using human‐induced pluripotent stem cell–derived cardiomyocytes (hi
PSC
‐
CM
s).

Methods and Results

This study recruited 1 patient with short
QT
syndrome type 1 carrying a mutation (N588K) in
KCNH
2 as well as 2 healthy control subjects. We generated hi
PSC
s from their skin fibroblasts, and differentiated hi
PSC
s into cardiomyocytes (hi
PSC
‐
CM
s) for physiological and pharmacological studies. The hi
PSC
‐
CM
s from the patient showed increased rapidly activating delayed rectifier potassium channel current (

I
K

r
) density and shortened action potential duration compared with healthy control hi
PSC
‐
CM
s. Furthermore, they demonstrated abnormal calcium transients and rhythmic activities. Carbachol increased the arrhythmic events in
SQTS
but not in control cells. Gene and protein expression profiling showed increased
KCNH
2 expression in
SQTS
cells. Quinidine but not sotalol or metoprolol prolonged the action potential duration and abolished arrhythmic activity induced by carbachol.

Conclusions

Patient‐specific hi
PSC
‐
CM
s are able to recapitulate single‐cell phenotype features of
SQTS
and provide novel opportunities to further elucidate the cellular disease mechanism and test drug effects.
Characteristics of Phrenic Nerve Injury During Pulmonary Vein Isolation Using a 28‐mm Second‐Generation Cryoballoon and Short Freeze Strategy
Authors: Miyazaki Shinsuke , Kajiyama Takatsugu , Watanabe Tomonori , Hada Masahiro , Yamao Kazuya , Kusa Shigeki , Igarashi Miyako , Nakamura Hiroaki , Hachiya Hitoshi , Tada Hiroshi , Hirao Kenzo , Iesaka Yoshito
Published: March 2018

Background

The reported incidence of phrenic nerve injury (
PNI
) varies owing to different definitions, balloon generations, balloon size, freezing regimen, and protective maneuvers. We evaluated the incidence, predictors, and outcome of
PNI
during cryoballoon pulmonary vein isolation in a large population.

Methods and Results

Five hundred fifty atrial fibrillation patients underwent
pulmonary vein isolation
using one 28‐mm second‐generation cryoballoon and single 3‐minute freeze strategy under diaphragmatic compound motor action potential (
CMAP
) monitoring. A total of 34 (6.2%) patients experienced
PNI
during the right superior and inferior
pulmonary vein
ablation in 30 and 4 patients, respectively. Applications were interrupted using double‐stop techniques after 136 [104–158] second applications, and a
pulmonary vein isolation
was already achieved in all but one case. The baseline
CMAP
amplitude and timing of deflation (
CMAP
def
) were 0.75±0.30 and 0.17±0.17 mV, respectively. Persistent
atrial fibrillation
, larger
right superior pulmonary vein
ostia, and deeper balloon positions were associated with higher incidences of
PNI
. The
CMAP
def
predicted a
PNI
recovery delay, and the best cutoff value for predicting
PNI
recovery by the next day was 0.20 mV (sensitivity 57.1%, specificity 100%). Among 6 patients undergoing second procedures 8.5 (6.7–15.0) months later, the right superior pulmonary vein was durable in 3 with >120 second applications. Despite active balloon deflation, no significant
pulmonary vein
stenosis was observed in 15
right superior pulmonary vein
s evaluated 6 (5–9) months later. No patients had symptoms, and the
PNI
recovered 1 day and 1 month postprocedure in 21 and 4 patients, respectively.

Conclusions

PNI
resulting from cryoballoon ablation was reversible. The double‐stop technique is safe, and immediate active deflation following a
CMAP
decrease appears to be essential for faster
PNI
recovery.
Relation of Insulin Resistance to Longitudinal Changes in Left Ventricular Structure and Function in a General Population
Authors: Cauwenberghs Nicholas , Knez Judita , Thijs Lutgarde , Haddad Francois , Vanassche Thomas , Yang Wen‐Yi , Wei Fang‐Fei , Staessen Jan A. , Kuznetsova Tatiana
Published: March 2018

Background

Population data on the longitudinal changes of left ventricular (
LV
) structure and function in relation to insulin resistance are sparse. Therefore, we assessed in a general population whether hyperinsulinemia predicts longitudinal changes in
LV
and arterial characteristics.

Methods and Results

In 627 participants (mean age 50.7 years, 51.4% women), we assessed echocardiographic indexes of
LV
structure and function and carotid‐femoral pulse wave velocity by applanation tonometry at baseline and after 4.7 years. We regressed longitudinal changes in these indexes on baseline insulin and its change during follow‐up, and reported standardized effect sizes as a percentage of the
SD
of
LV
changes associated with a doubling of insulin. After adjustment, higher baseline insulin predicted a greater temporal increase in
LV
mass index (effect size: +15.1%) and E/e′ ratio (+22.1%), and a greater decrease in e′ peak and longitudinal strain (−11.2% to −17.1%). A greater increase in insulin during follow‐up related to a greater increase in LV mass index (+10.7%) and decline in ejection fraction and longitudinal strain (−11.4% to −15.7%). Participants who became or remained insulin resistant during follow‐up experienced worse changes in longitudinal strain, E/e′, and LV mass index as compared with participants who did not develop or had improved insulin resistance over time (
P
≤0.033). Moreover, multivariable‐adjusted increase in pulse wave velocity was higher in participants with diabetes mellitus than in participants without diabetes mellitus (+1.46 m/s versus +0.71 m/s;
P
=0.039).

Conclusions

Hyperinsulinemia at baseline and during follow‐up predicted worsening of
LV
function and remodeling over time. Our findings underline the importance of management of insulin resistance.
Body Marks in Jewish Sources: From Biblical to Post-Talmudic Times
Authors: Bar-Ilan Meir
Published: March 2018

During the course of two millennia, Jews imprinted signs and scripts on their bodies. Although the Bible prohibits tattooing (Lev. 19:28), some Jews wrote the Lord’s Name on their body, probably with ink. Here we examine evidence for this practice: Ezekiel 9:4–6, Cain’s Mark (Gen. 4:15), Isa. 44:5, Exod. 28:36, and 39:30, where examples of setting the Lord’s Name on one’s arm or forehead are delineated. This practice may have originated among priests (see Num. 6:22–27, which we argue is to be read literally and not as a metaphor) and only later was imitated by the laity. Thus, priests blessed orally and committed their blessing into a bodily inscription on the people they blessed. The Talmud also contains evidence that some Jews had the Lord’s Name written on their bodies in ink, and Hekhalot literature contains two detailed descriptions of how people were inscribed with God’s Name, in a kind of rite-of-passage. Other texts (e.g., Rev. 19:16; Gal. 6:17) provide additional evidence that Jews in antiquity inscribed the Lord’s Name on their bodies.
“I bear the burden of treating the gentiles”: Jewish Halakhic Authorities’ Attitudes towards Treating Muslims in the 12th–18th Centuries
Authors: Shemesh Abraham Ofir
Published: March 2018

The paper focuses on the religious, social, and historical aspects of the ancient Jewish prohibition against treating non-Jews. It discusses the attitude of rabbinic authorities towards providing medical service to Muslims in medieval and pre-modern times. It points out that circumstances did not enable the public to fulfill these instructions to the letter, and therefore many halakhic authorities in the post-Talmudic period dispensed with the prohibition almost completely. The question of treating Muslims was discussed by halakhic authorities in both Christian and Muslim countries. Stricter views were voiced concerning the treatment of Christians, but the dispensation to treat Muslims and deliver their babies was more pronounced. Halakhic authorities claimed that the original prohibition regarded idolaters, while Muslims do not engage in idolatry. Another major claim supporting the concession was a concern for animosity and harassment within the non-Jewish environment.
Could Science be Interestingly Different?
Authors: Virmajoki Veli
Published: March 2018

In this paper, I investigate the issue of the contingency and inevitability of science. First, I point out valuable insights from the existing discussion about the issue. I then formulate a general framework, built on the notion of contrastive explanation and counterfactuals, that can be used to approach questions of contingency of science. I argue, with an example from the existing historiography of science, that this framework could be useful to historians of science. Finally, I argue that this framework shows the existing views on historical contingency and counterfactuals in a new light. The framework also shows the value of existing historiography in philosophical debates.
Constructions as Triads of Form, Function, and Agency: An Agentive Cognitive Construction Grammar Study of English Modals
Authors: Torres-Martínez Sergio
Published: March 2018

The present article introduces anagentive cognitive construction grammarapproach to the analysis of English central modals. One of the premises of the new theory is that speaker meaning cannot be captured by looking at form-function relations only but through the integration of additional conceptual layers such as agency, embodiment, and argument structure construction. This theoretical turn is supported empirically by a corpus study aimed at identifying specific modal constructions in the 520 million wordCorpus of Contemporary American English. The results show that(i) English modals are reliably identifiable as constructions at a clausal level, and(ii) that, depending on the type of agency (motional or stative), modal constructions can be divided into two main categories, namelymodal agentive constructionsandmodal referential constructions. The results also support the idea that modal constructions are triadic, that is, that they display symbolic form-function relations based on iconic-indexical, and speaker-driven processes (all of which are possible thanks to the conceptualizer’s possession of the concept of objective truth). These constructions provide conceptualizers with the mental schemas necessary to construe meaning across mental spaces.
Analysing Visual Imagery: Connecting Semiotic and Cognitive Perspectives
Authors: Wong May L-Y
Published: March 2018

This article provides an exploratory study of a new analytical approach to examining visual imagery in relation to the underlying cognitive processes involved. The analytical approach combines social semiotic theory of representation with cognitive-linguistic studies on blending or conceptual integration. The author’s thesis is that visual-analytic tools suggested by the social semiotic approach perfectly complements the inward cognition of an image-viewer, a synergy which has rarely been envisaged by scholars from both disciplines. From this perspective, visual analysis is seen as both semiotically and cognitively relevant. The interdisciplinary approach developed in the article hopes to present new perspectives on the ways images are analysed and interpreted.
A Challenge to Conventional Wisdom: Locating Agency in Angola’s and Ghana’s Economic Engagements with China
Authors: Chipaike Ronald , Bischoff Paul Henri
Published: March 2018

This article makes the point that African states with significant strategic resources and democratic governance systems bargain better in economic and development assistance engagements with China and other partners. In democratic African states, non-state actors play critical complementary roles to the state, leading to multi-faceted forms of African agency. For non-democratic states, a significant limiting factor in their agency is the lack of working relationships between the state and non-state actors. Concomitantly, such states find themselves with weak bargaining and negotiating capacities. If African agency is to be assertive, then state and non-state actors should work together when engaging external partners.
Understanding Luxury Shopping Destination Preference Using Conjoint Analysis and Traditional Item-Based Measurement
Authors: Hung Kam , Guillet Basak Denizci , Zhang Hanqin Qiu
Published: March 2018

This study analyses the destination preferences of mainland Chinese tourists within the context of luxury shopping, and compares the traditional item-based method and conjoint analysis to understand their preference. The methods comparison reveals the role of trade-off in consumers’ decision making, which is seldom considered in tourism research. Conjoint analysis was also found to create more apparent patterns of travelers’ preference. Theoretically, the attributes of a luxury shopping destination are developed from scratch with a mixed methods approach. The key attributes are identified with rigorous procedures to represent the main preferences of Chinese travelers in choosing a destination for luxury shopping. This is the first attempt to compare conjoint analysis with the traditional approach in one study with empirical data to reflect the role of trade-off in tourist decision making. Practically, the results suggest some caution in the development of luxury shopping destination.
From “Ridiculous” to “Glad to Have Helped”: Debriefing News Delivery and Improved Reactions to Science in Milgram’s “Obedience” Experiments
Authors: Turowetz Jason , Hollander Matthew M.
Published: March 2018

Commentators on Milgram’s classic and controversial experiments agree that better integration of theories of “obedience to authority” with current archival research on participants’ viewpoints is essential in explaining compliance. Using conversation analysis, we examine an archived data source that is largely overlooked by the Milgram literature, yet crucial for understanding the interactional organization of participants’ displayed perspectives. In hundreds of interviews conducted immediately after each experiment, participants received one of two types of debriefing: deceptive or full. Analyzing 56 full debriefings from three experimental conditions, we find they featured interactional structuring as news delivery sequences and that debriefing news could transform initially ambivalent or negative assessments of the experiment into positive ones. Such findings reveal limitations of engaged followership, the currently dominant theory of “obedience.” Following discussion of improved assessments’ relevance to public attitudes toward science, we conclude that multiple social psychological processes were at work in producing Milgram’s results.
Testing the Predictive Validity of the Hendrich II Fall Risk Model
Authors: Jung Hyesil , Park Hyeoun-Ae
Published: March 2018

Cumulative data on patient fall risk have been compiled in electronic medical records systems, and it is possible to test the validity of fall-risk assessment tools using these data between the times of admission and occurrence of a fall. The Hendrich II Fall Risk Model scores assessed during three time points of hospital stays were extracted and used for testing the predictive validity: (a) upon admission, (b) when the maximum fall-risk score from admission to falling or discharge, and (c) immediately before falling or discharge. Predictive validity was examined using seven predictive indicators. In addition, logistic regression analysis was used to identify factors that significantly affect the occurrence of a fall. Among the different time points, the maximum fall-risk score assessed between admission and falling or discharge showed the best predictive performance. Confusion or disorientation and having a poor ability to rise from a sitting position were significant risk factors for a fall.
‘Broadcast to mark Holocaust Memorial Day’: Mass-mediated Holocaust commemoration on British television and radio
Authors: Richardson John E
Published: March 2018

This article examines the various programmes that British television and radio broadcast to mark Holocaust Memorial Day, between 2002 and 2016. Adopting a content analytic methodology, I quantified the broadcast schedules of 15 successive Holocaust Memorial Days, as recorded in archived copies of the Radio Times. My analysis reveals significant variations in mass-mediated Holocaust commemoration. Principally, I found a decrease in programming, despite a significant increase in the number of television channels; a tendency towards ‘anniversarism’ in the form and frequency of broadcast programmes; a stress on Auschwitz, as metonym of the Holocaust, and on survivors, children and music; and that commercial channels were significantly more likely to broadcast documentaries (and repeats) than the BBC’s more varied and original outputs. These variations appear to be the result of three interlinked factors: First, a sense that the audience had grown weary of World War II commemoration, following saturation broadcasting of anniversaries in 2004 to 2005; changes in the management and programming priorities of key broadcasters, particularly the BBC; and that Holocaust Memorial Day has not yet become an established day for broadcasters in the nation’s commemorative calendar.
A Two-Step Markov Processes Approach for Parameterization of Cancer State-Transition Models for Low- and Middle-Income Countries
Authors: Gopalappa Chaitra , Guo Jiachen , Meckoni Prashant , Munkhbat Buyannemekh , Pretorius Carel , Lauer Jeremy , Ilbawi André , Bertram Melanie
Published: March 2018

Implementation of organized cancer screening and prevention programs in high-income countries (HICs) has considerably decreased cancer-related incidence and mortality. In low- and middle-income countries (LMICs), screening and early diagnosis programs are generally unavailable, and most cancers are diagnosed in late stages when survival is very low. Analyzing the cost-effectiveness of alternative cancer control programs and estimating resource needs will help prioritize interventions in LMICs. However, mathematical models of natural cancer onset and progression needed to conduct the economic analyses are predominantly based on populations in HICs because the longitudinal data on screening and diagnoses required for parameterization are unavailable in LMICs. Models currently used for LMICs mostly concentrate on directly calculating the shift in distribution of cancer diagnosis as an evaluative measure of screening. We present a mathematical methodology for the parameterization of natural cancer onset and progression, specifically for LMICs that do not have longitudinal data. This full onset and progression model can help conduct comprehensive analyses of cancer control programs, including cancer screening, by considering both the positive impact of screening as well as any adverse consequences, such as over-diagnosis and false-positive results. The methodology has been applied to breast, cervical, and colorectal cancers for 2 regions, under the World Health Organization categorization: Eastern Sub-Saharan Africa (AFRE) and Southeast Asia (SEARB). The cancer models have been incorporated into the Spectrum software and interfaced with country-specific demographic data through the demographic projections (DemProj) module and costing data through the OneHealth tool. These software are open-access and can be used by stakeholders to analyze screening strategies specific to their country of interest.