bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Properties for Laminate Composites in the Marine Environment
Authors: Zhong Luo , Libao Zhu
Published: July 2019

Dynamic properties of high strain rate and absorbing energy for laminate composites in the marine environment were studied in this paper. The high strain rate dynamic compressive tests were carried out on Split Hopkinson Pressure Bar(SHPB) experimental facility at strain rate 1800/s, 1530/s, 1230/s and 950/s. The front surface failure modes were Analyzed by optical micrographs. A fractured fibres mode was discussed in high rate compression. The stress-strain rate curves showed that, the specimen dynamic properties were better for the samples immersed in marine environment for 12 days. The energy absorption properties were test by ballistic trajectory experiment. Experimental results and penetration faces showed that, the ballistic trajectory properties with 60days of hygrothermal environment was better.
Effect of extraction process on extraction yeild, total polyphenol content and antioxidant activity of Jasminum Subtriplinerve
Authors: Anh Trieu Tuan , Hao Luu Tu , Lam Tri Duc
Published: July 2019

Jasminum Subtriplinerve Blume (Oleaceae) is herbal plants widely a tea for weight loss, stimulates milk glands. Extract product it easy used yet had little research. This study was carried out to evaluate the effect of extracting conditions such as water/material ratio, extraction temperature and extracting time on extracting yield, polyphenol content and antioxidant activity of J.subtriplinerve extract. The total phenolic compounds were determined according to the Folin-Ciocalteu method. Extraction yield (0.22g/100 g) was obtained at water/material ratio 15:1 (ml/g), 40°C and 4 hours extraction time. Under these optimized conditions, the polyphenol content of was 2640.4 μg/1g extract. And the extract can harvest 46.11 % of DPPH (30 μg/mL) at 10 000 μg/ml concentration
The thermal conductivity of the variband crystals of the Bix-Sb1-x system in the semiconductor region of the composition at the temperature of about 100 K
Authors: Bochegov V.I. , Melnikov N.A.
Published: July 2019

The previously observed experimental difference in the thermal conductivity of gradient-inhomogeneous (variband) single-crystal samples of the Bi
x
-Sb1-x
system in the case of parallel and antiparallel directions of the temperature gradients and composition in the semimetallic range of composition values (0.03 <x <0.10) under similar temperature conditions was also experimentally confirmed in other samples of this material having a composition in the interval of the semiconductor region (0.11 < x < 0.19). A theoretical model of the possible mechanism of this effect for the semiconductor region of the composition is proposed.
A Study on the Shape deviation rate of Hydroforming of Seamed tubes Based on Two Different Velocity
Authors: Liu Qin , Yang Lianfa , Wei Jun , Guo Jian , He Yulin
Published: July 2019

Due to the low price, the seamed tubes are used more and more widely in various industrial fields in recent years. The difference in material properties between the weld zone of the parent metal zone of the thin-walled seamed tubes, the deformation of the hydraulic bulging under the same conditions will also be different, thus resulting in an inconsistency in the overall bulging of the seamed tubes. In this paper, the hydraulic bulging experiment of the seamed tubes at low and medium velocity, and the shape deviation law of the seamed tubes at different velocity are obtained. In the first half of the bulging, the seamed tubes at the medium velocity drops faster than the low velocity shape deviation rate, and the medium velocity is closer to circle; in the second half of the bulging, the medium velocity is go up faster than the low velocity. The shape deviation rate is higher before the tubes are burst, but the medium velocity’s radial average bulge height is smaller than the low velocity.
Improvement And Application Of Comprehensive Weighted Allocated Method Based On Fault Rate And Design Character
Authors: Gui-xiang Shen , Lu-yao Dong , Jin-tong Liu , Shu-bin Liang , Meng-jiao Ma
Published: July 2019

In order to solve the problem of weighting factor in the maintenance comprehensive weighted allocation model based on failure rate and design characteristics. Firstly, the fuzzy comprehensive evaluation method is introduced. Secondly, the fuzzy judgment matrix is established by using the three-scale method and the weight is obtained. Then the binary fuzzy contrast is used to establish the relationship matrix of the influencing factors and the evaluation matrix is obtained. The weighting factor is calculated by the fuzzy transformation. When the failure rates vary widely, the allocation results will weak the design characteristics by relying on the failure rate. So the weighting factor should be modified to improve the rationality of the distribution result. Finally, take a machining center as an example to verify the maintenance distribution application.
Magnetic graphene oxide for efficient solid phase extraction of DEHP
Authors: Ma L , Huang J , Zhou M
Published: July 2019

DEHP (di-2-ethylhexyl phthalate) can cause negative impacts on human health, thus development of reliable analytical methods for the determination of PAEs is important.In this work, magnetic graphene oxide was synthesized and used as the sorbent for solid phase extraction of DEHP. Factors that influence the extraction efficiency of DEHP were studied. The optimum conditions, such as solution pH, extraction time, desorption time, and eluent type and volume were obtained. The analytical performance of the developed method was investigated, and it was found that the limit of detection (LOD) for DEHP was 0.35 μg/L and the related standard deviation (RSD) was 4.3 %. The proposed method was applied in the determination of DEHP in environmental water samples with recoveries of 91.6-106.5%.
The problem of measuring trait-preference correlations without disrupting them
Authors: Hosken David J , Wilson Alastair J
Published: July 2019

A key element at the heart of the Fisher–Lande–Kirkpatrick model of the sexual selection process is the genetic correlation between (male) trait and (female) preference. The strength of this association is critical in determining a population’s evolutionary trajectory, which is why estimating its magnitude is so important. In the Lande model, the trait-preference correlation is solely established and maintained by mate choice, and although it is unclear how exclusively mate choice does this in nature, the experimental designs typically employed to measure trait-preference genetic correlations could be systematically weakening estimates by not allowing free mate choice (similarly with husbandry practices). The precise impact of the problem is unknown, and possibly unknowable, but simple solutions can be applied to ensure the accuracy of trait-preference correlation estimates is maximized.
MemBlob database and server for identifying transmembrane regions using cryo-EM maps
Authors: Farkas Bianka , Csizmadia Georgina , Katona Eszter , Tusnády Gábor E , Hegedűs Tamás
Published: July 2019

The identification of transmembrane helices in transmembrane proteins is crucial, not only to understand their mechanism of action but also to develop new therapies. While experimental data on the boundaries of membrane-embedded regions are sparse, this information is present in cryo-electron microscopy (cryo-EM) density maps and it has not been utilized yet for determining membrane regions. We developed a computational pipeline, where the inputs of a cryo-EM map, the corresponding atomistic structure, and the potential bilayer orientation determined by TMDET algorithm of a given protein result in an output defining the residues assigned to the bulk water phase, lipid interface and the lipid hydrophobic core. Based on this method, we built a database involving published cryo-EM protein structures and a server to be able to compute this data for newly obtained structures.

Availability and implementation

http://memblob.hegelab.org.

Supplementary information

Supplementary data are available at Bioinformatics online.
MCMCtreeR: functions to prepare MCMCtree analyses and visualize posterior ages on trees
Authors: Puttick Mark N
Published: July 2019

The fossil record is incomplete, so molecular divergence time analysis is a crucial tool in estimating evolutionary timescales. MCMCtree contained in the PAML software provides Bayesian methods to estimate divergence times of genomic-sized sequences. Here, I present MCMCtreeR, a flexible R package to prepare time priors for MCMCtree analysis and plot time-scaled phylogenies. The package provides functions to refine parameters and visualize time-calibrated node prior distributions so that these priors accurately reflect confidence in known, usually fossil, time information. After the parameters have been chosen, the package produces output files ready for MCMCtree analysis. Following analysis, the package has tools to compare prior and posterior calibrated node age distributions and produce plots of the time-scaled phylogenies. The plotting functions allow for the inclusion of age uncertainty on time-scaled phylogenies, including the display of full posterior distributions on nodes. Options also allow for the inclusion of the geological timescale, and these plotting functions are applicable with posterior age estimates from any Bayesian divergence time estimation software.

Availability and implementation

MCMCtreeR is an R package available on CRAN (https://CRAN.R-project.org/package=MCMCtreeR). MCMCtreeR depends on the R packages ape, sn and stats4.
Sodium-glucose cotransporter 2 inhibitors for diabetic kidney disease: a primer for deprescribing
Authors: Li Jiahua , Fagbote Christopher O , Zhuo Min , Hawley Chelsea E , Paik Julie M
Published: July 2019

Chronic kidney disease (CKD) is a critical global public health problem associated with high morbidity and mortality, poorer quality of life and increased health care expenditures. CKD and its associated comorbidities are one of the most complex clinical constellations to manage. Treatments for CKD and its comorbidities lead to polypharmacy, which exponentiates the morbidity and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown remarkable benefits in cardiovascular and renal protection in patients with type 2 diabetes mellitus (T2DM). The pleiotropic effects of SGLT2is beyond glycosuria suggest a promising role in reducing polypharmacy in diabetic CKD, but the potential adverse effects of SGLT2is should also be considered. In this review, we present a typical case of a patient with multiple comorbidities seen in a CKD clinic, highlighting the polypharmacy and complexity in the management of proteinuria, hyperkalemia, volume overload, hyperuricemia, hypoglycemia and obesity. We review the cardiovascular and renal protection effects of SGLT2is in the context of clinical trials and current guidelines. We then discuss the roles of SGLT2is in the management of associated comorbidities and review the adverse effects and controversies of SGLT2is. We conclude with a proposal for deprescribing principles when initiating SGLT2is in patients with diabetic CKD.
Server-Aided Revocable Predicate Encryption: Formalization and Lattice-Based Instantiation
Authors: Ling San , Nguyen Khoa , Wang Huaxiong , Zhang Juanyang
Published: July 2019

Efficient user revocation is a necessary but challenging problem in many multi-user cryptosystems. Among known approaches, server-aided revocation yields a promising solution, because it allows to outsource the major workloads of system users to a computationally powerful third party, called the server, whose only requirement is to carry out the computations correctly. Such a revocation mechanism was considered in the settings of identity-based encryption and attribute-based encryption by Qin et al. (2015, ESORICS) and Cui et al. (2016, ESORICS ), respectively. In this work, we consider the server-aided revocation mechanism in the more elaborate setting of predicate encryption (PE). The latter, introduced by Katz et al. (2008, EUROCRYPT), provides fine-grained and role-based access to encrypted data and can be viewed as a generalization of identity-based and attribute-based encryption. Our contribution is 2-fold. First, we formalize the model of server-aided revocable PE (SR-PE), with rigorous definitions and security notions. Our model can be seen as a non-trivial adaptation of Cui et al.’s work into the PE context. Second, we put forward a lattice-based instantiation of SR-PE. The scheme employs the PE scheme of Agrawal et al. (2011, ASIACRYPT) and the complete subtree method of Naor et al. (2001, CRYPTO) as the two main ingredients, which work smoothly together thanks to a few additional techniques. Our scheme is proven secure in the standard model (in a selective manner), based on the hardness of the learning with errors problem.
Bilateral papillary muscle repositioning: successful repair of functional mitral regurgitation in dilative cardiomyopathy
Authors: Langer Frank , Kunihara Takashi , Miyahara Shunsuke , Fahrig Lisa , Blümel Maria , Klär Annika , Raddatz Alexander , Karliova Irem , Bekhit Abdelshafi , Schäfers H -J
Published: July 2019

OBJECTIVES:

Functional mitral regurgitation (FMR) in patients with non-ischaemic dilative cardiomyopathy (DCM) is associated with heart failure and poor outcome. Aggressively undersized annuloplasty as an annular solution for a ventricular problem ameliorates heart failure but may be associated with recurrent FMR and does not improve survival. We sought to analyse if moderately undersized annuloplasty with repositioning of both papillary muscles can lead to improved valve stability and outcome in patients with DCM and FMR.

METHODS:

In 66 patients with DCM-associated FMR (age 66 ± 12 years, ejection fraction 29 ± 6% and mean pulmonary artery pressure 35 ± 11 mmHg) and severe leaflet tethering (tenting height ≥10 mm) bilateral papillary muscle repositioning was added to moderately undersized ring annuloplasty (median size 30 mm). Concomitant surgery included tricuspid valve repair in 86% of patients and atrial ablation in 44%.

RESULTS:

The early mortality rate was 9%. Overall 5-year freedom from all-cause death, left ventricular assist device implantation or heart transplant was 58% (95% confidence interval 45–71%). Six patients underwent reoperation (redo repair n = 4). Reverse remodelling was observed during follow-up in 66% of patients with decreasing left ventricular end-diastolic diameters (66 ± 5 to 61 ± 12 mm; P < 0.001) and left ventricular end-systolic diameters (56 ± 9 to 51 ± 14 mm; P = 0.001). Subgroup analyses (partial versus complete ring, preoperative left ventricular end-diastolic diameters <65 mm vs left ventricular end-diastolic diameter ≥65 mm) documented similar survival rates. A competing risks regression analysis identified cerebral vascular disease (P = 0.01), use of a partial ring (P = 0.03) and absence of tricuspid valve repair (P = 0.03) as independent predictors of death.

CONCLUSIONS:

The combination of bilateral papillary muscle repositioning and moderately undersized ring annuloplasty leads to stable mid-term repair results and reverse remodelling in patients with DCM and FMR and severe leaflet tethering.
Additional frozen elephant trunk as a bailout for a misdeployed frozen elephant trunk in the false lumen in a patient with acute aortic dissection
Authors: Tamai Koichi , Hori Daijiro , Yuri Koichi , Yamaguchi Atsushi
Published: July 2019

Using a frozen elephant trunk (FET) in patients with acute aortic dissection is an effective method to induce aortic remodelling after surgery. A 40-year-old man with Stanford type A acute aortic dissection underwent emergency total arch replacement with FET. The FET was inserted into the descending aorta under direct vision. However, transoesophageal echocardiography after the deployment of the FET revealed that it was misdeployed in the false lumen. An additional FET was deployed in the true lumen to redirect the blood flow to the true lumen. The patient was discharged from the hospital without any major complications. Computed tomography 6 months after surgery revealed enhanced aortic remodelling without any signs of stent graft-induced new entry. Additional deployment of a FET into the true lumen could be an option for a misdeployed FET in the false lumen.
Aetiologies and temporal trends of atrioventricular block in young patients: a 20-year nationwide study
Authors: Rudbeck-Resdal Johnni , Christiansen Morten K , Johansen Jens B , Nielsen Jens C , Bundgaard Henning , Jensen Henrik K
Published: July 2019

Aims

To describe aetiologies and temporal trends in young patients with atrioventricular block (AVB).

Methods and results

We identified all patients in Denmark, receiving their first pacemaker because of AVB before the age of 50 years between 1996 and 2015. Medical records were reviewed and clinical information and diagnostic work-up results were obtained to evaluate the aetiology. We used Poisson regression testing for temporal trends. One thousand and twenty-seven patients were identified, median age at time of implantation was 38 (interquartile range 25–45) years, 584 (56.9%) were male. The aetiologies were complications to cardiac surgery [n = 157 (15.3%)], congenital AVB [n = 93 (9.0%)], cardioinhibitory reflex [n = 52 (5.0%)], congenital heart disease [n = 43 (4.2%)], complication to radiofrequency ablation [n = 35 (3.4%)], cardiomyopathy [n = 31 (3.0%)], endocarditis [n = 18 (1.7%)], muscular dystrophy [n = 14 (1.4%)], ischaemic heart disease [n = 14 (1.4%)], sarcoidosis [n = 11 (1.1%)], borreliosis [n = 9 (0.9%)], hereditary [n = 6 (0.6%)], side-effect to antiarrhythmics [n = 6 (0.6%)], planned His-ablation [n = 5 (0.5%)], complication to alcohol septal ablation [n = 5 (0.5%)], and other known aetiologies [n = 11 (1.1%)]. The aetiology remained unknown in 517 (50.3%) cases. While the number of patients with unknown aetiology increased during the study period (P < 0.001), we observed no significant change in the number of patients with identified aetiology (P = 0.35).

Conclusion

In a nationwide cohort, the aetiology of AVB was identified in only half the patients younger than 50 years referred for first-time pacemaker implantation. The number of patients with unknown aetiology increased during the study period. These findings indicate need for better insight into aetiologies of AVB and improved diagnostic work-up guidelines.
iMicrobe: Tools and data-driven discovery platform for the microbiome sciences
Authors: Youens-Clark Ken , Bomhoff Matt , Ponsero Alise J , Wood-Charlson Elisha M , Lynch Joshua , Choi Illyoung , Hartman John H , Hurwitz Bonnie L
Published: July 2019

Background

Scientists have amassed a wealth of microbiome datasets, making it possible to study microbes in biotic and abiotic systems on a population or planetary scale; however, this potential has not been fully realized given that the tools, datasets, and computation are available in diverse repositories and locations. To address this challenge, we developed iMicrobe.us, a community-driven microbiome data marketplace and tool exchange for users to integrate their own data and tools with those from the broader community.

Findings

The iMicrobe platform brings together analysis tools and microbiome datasets by leveraging National Science Foundation–supported cyberinfrastructure and computing resources from CyVerse, Agave, and XSEDE. The primary purpose of iMicrobe is to provide users with a freely available, web-based platform to (1) maintain and share project data, metadata, and analysis products, (2) search for related public datasets, and (3) use and publish bioinformatics tools that run on highly scalable computing resources. Analysis tools are implemented in containers that encapsulate complex software dependencies and run on freely available XSEDE resources via the Agave API, which can retrieve datasets from the CyVerse Data Store or any web-accessible location (e.g., FTP, HTTP).

Conclusions

iMicrobe promotes data integration, sharing, and community-driven tool development by making open source data and tools accessible to the research community in a web-based platform.
Does Reverse Causality Underlie the Temporal Relationship Between Depression and Crohn’s Disease?
Authors: Gaines Lawrence S , Slaughter James C , Schwartz David A , Beaulieu Dawn B , Horst Sara N , Dalal Robin L , Scoville Elizabeth A , Sandler Robert S , Kappelman Michael D
Published: July 2019

Background

Studies suggest that there is a temporal relationship between depression and Crohn’s disease (CD) activity. However, these studies assumed a unidirectional relationship and did not examine the possibility of reverse causality and the risk of a spurious association due to the overlap of symptoms underlying the depression–CD relationship. We evaluated the existence of reverse causality reflected in a possible bidirectional relationship between patient-reported CD activity and an affective–cognitive dimension of depression.

Methods

We studied 3307 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, and an affective–cognitive index of depression. Crohn’s disease status and the affective–cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We used structural equation models to evaluate whether the effect of depression on future CD activity is stronger than the effect of CD activity on future depression. We calculated the likelihood that each of these hypotheses is supported by the data and calculated the likelihood ratio to provide a relative measure of which hypothesis best accounts for the data.

Results

The results of the informative hypothesis testing showed the most support for the hypothesis stating that an affective–cognitive dimension of depression is a stronger predictor of patient-reported CD activity than the converse.

Conclusions

The hypothesis that an affective–cognitive dimension of depression predicts patient-reported exacerbation of CD is 218 times more likely to account for the data than the converse.
Inflammation and Inflammatory Cytokine Contribute to the Initiation and Development of Ulcerative Colitis and Its Associated Cancer
Authors: Yao Dianbo , Dong Ming , Dai Chaoliu , Wu Shuodong
Published: July 2019

Dysregulated inflammatory responses play a pivotal role in the initiation, development, and progression of tumors, as demonstrated by the association between ulcerative colitis and the increased risk of colon carcinoma. In this review, the underlying mechanisms for the initiation and development of ulcerative colitis and colitis-associated cancer are described, mainly focusing on the inflammation and inflammatory cytokine. Disruption of the intestinal mucosal barrier and bacterial invasion resulted in intestinal inflammation; and further TLR4/NF-κB stimulation in intestinal epithelial cells, inflammatory cell infiltration, and inflammatory cytokine release all confer survival advantages to or promote abnormal proliferation in susceptible cells. Importantly, the respective roles of TLR4/NF-κB, TNF–α, and IL-6 in intestinal epithelial cells and inflammatory cells are summarized in detail. A thorough understanding of these molecular mechanisms may help researchers and clinicians to explore novel approaches for the prevention and treatment of colitis-associated cancer.
Self-expanding apical closure device for full-percutaneous closed-chest transapical valve procedures with large-sized introducer sheaths: first study in an animal model
Authors: Hong Nanchao , Lu Yanan , Hu Hanbo , Sun Jing , Sun Kun , von Segesser Ludwig Karl , Berdajs Denis , Chen Sun , Ferrari Enrico
Published: July 2019

OBJECTIVES

Available apical occluders do not fulfil requirements for full-percutaneous transapical valve procedures with large-sized introducer sheaths. A self-expanding closure device designed for closed-chest transapical valve procedures was tested in an animal model to verify safety, efficacy and thrombogenicity.

METHODS

Large-sized 21-Fr introducer sheaths (Certitude™ system for Sapien™ valves) were percutaneously placed in the ventricles of nine 3-month old minipigs. To seal the apical access, delivery catheters carrying folded self-expanding plugs were inserted. Then, the plugs were deployed while sheaths were removed. Echocardiograms verified tamponade and cardiac function, drains were not placed and a 3-month long aspirin therapy was administered. After 6 and 9 months, animals were euthanized and organs were analysed for macroembolic lesions search. Histological analysis was also performed.

RESULTS

Nine minipigs (weight: 28±3 kg) were used for this study. Eight plugs were successfully deployed in 8 ventricles without cardiac tamponade or ventricular dysfunction (success rate: 88.9%). In a failed procedure (the animal died after 1 month of cardiac tamponade), the outer disc of the apical plug got stuck in the intercostal space and did not correctly deploy. Post-mortem analysis in 8 minipigs at 6 (n = 4) and 9 months (n = 4) confirmed full deployment and good fixation of all plugs with internal surfaces covered by new endocardium. Macroscopic analysis of myocardium and vital organs showed absence of embolic lesions. Histological analysis showed absence of significant inflammatory infiltration and thrombosis.

CONCLUSIONS

In this animal model, self-expanding closure devices sealed 21-Fr large percutaneous apical accesses without acute tamponade, thrombosis or embolization. Further tests to evaluate full-percutaneous closed-chest apical procedures are required.
Inflammatory myofibroblastic tumour in the right ventricle of a 66-year-old man
Authors: Monzón Díaz Diego , Cuerpo Caballero Gregorio , Irabien Ortiz Angela , Gonzalez Pinto Ángel
Published: July 2019

Herein, we present the case of a 66-year-old man with an inflammatory myofibroblastic tumour. An inflammatory myofibroblastic tumour is an extremely rare entity, with only 60 cases having been reported to date in the literature. The origin of this type of tumour is unknown and the treatment of choice is surgical resection. We present the surgical technique of our case and a review of the literature regarding this tumour. This is the first case described in a man above 60 years of age with a tumour located in the right ventricle.
The role of cardiovascular disease in the relationship between air pollution and incident dementia: a population-based cohort study
Authors: Ilango Sindana D , Chen Hong , Hystad Perry , van Donkelaar Aaron , Kwong Jeffrey C , Tu Karen , Martin Randall V , Benmarhnia Tarik
Published: July 2019

Background

Evidence suggests a link between air pollution and dementia. Cardiovascular disease (CVD) may be a potential determinant of dementia. This motivated us to quantify the contribution of CVD to the association between air pollution and dementia.

Methods

A cohort of Canadian-born residents of Ontario, who participated in the 1996–2003 Canadian Community Health Surveys, was followed through 2013 or until dementia diagnosis. Exposure to nitrogen dioxide (NO2) and fine particulate matter (PM2.5) was estimated with a 3-year average and 5-year lag before dementia diagnosis. Incident CVD was evaluated as a mediator. We used multi-level Cox proportional and Aalen additive hazard regression models, adjusting for individual- and neighbourhood-level risk factors to estimate associations with NO2 and PM2.5. We estimated the total, direct and indirect effects of air pollution on dementia through cardiovascular disease.

Results

This study included 34 391 older adults. At baseline, the mean age of this cohort was 59 years. The risk of dementia was moderately higher among those more exposed to NO2 (hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.99–1.19; and 100 additional cases per 100 000 [standard error (SE) <100x10-5]) and PM2.5 [(HR 1.29, 95% CI 0.99–1.64; 200 additional cases per 100 000] [SE 100x10-5]) after adjusting for covariates; however, these estimates are imprecise. A greater proportion of the relationship between PM2.5 and dementia was mediated through CVD than NO2 for both scales.

Conclusions

These results suggest some of the association between air pollution and dementia is mediated through CVD, indicating that improving cardiovascular health may prevent dementia in areas with higher exposure to air pollution.
Factorial Mendelian randomization: using genetic variants to assess interactions
Authors: Rees Jessica M B , Foley Christopher N , Burgess Stephen
Published: July 2019

Background

Factorial Mendelian randomization is the use of genetic variants to answer questions about interactions. Although the approach has been used in applied investigations, little methodological advice is available on how to design or perform a factorial Mendelian randomization analysis. Previous analyses have employed a 2 × 2 approach, using dichotomized genetic scores to divide the population into four subgroups as in a factorial randomized trial.

Methods

We describe two distinct contexts for factorial Mendelian randomization: investigating interactions between risk factors, and investigating interactions between pharmacological interventions on risk factors. We propose two-stage least squares methods using all available genetic variants and their interactions as instrumental variables, and using continuous genetic scores as instrumental variables rather than dichotomized scores. We illustrate our methods using data from UK Biobank to investigate the interaction between body mass index and alcohol consumption on systolic blood pressure.

Results

Simulated and real data show that efficiency is maximized using the full set of interactions between genetic variants as instruments. In the applied example, between 4- and 10-fold improvement in efficiency is demonstrated over the 2 × 2 approach. Analyses using continuous genetic scores are more efficient than those using dichotomized scores. Efficiency is improved by finding genetic variants that divide the population at a natural break in the distribution of the risk factor, or else divide the population into more equal-sized groups.

Conclusions

Previous factorial Mendelian randomization analyses may have been underpowered. Efficiency can be improved by using all genetic variants and their interactions as instrumental variables, rather than the 2 × 2 approach.
Effectiveness of Partial and Full Influenza Vaccination Among Children Aged <9 Years in Hong Kong, 2011–2019
Authors: Chua Huiying , Chiu Susan S , Chan Eunice L Y , Feng Shuo , Kwan Mike Y W , Wong Joshua S C , Peiris J S Malik , Cowling Benjamin J
Published: July 2019

Background

Two doses of influenza vaccination are recommended for previously unvaccinated children aged <9 years, and receipt of 1 dose is sometimes termed “partial vaccination.” We assessed the effectiveness of partial and full influenza vaccination in preventing influenza-associated hospitalization among children in Hong Kong.

Methods

Using the test-negative design we enrolled 23 187 children aged <9 years admitted to hospitals with acute respiratory illness from September 2011 through March 2019. Vaccination and influenza status were recorded. Fully vaccinated children included those vaccinated with 2 doses or, if previously vaccinated, those vaccinated with 1 dose. Partially vaccinated children included those who should have received 2 doses but only received 1 dose. We estimated vaccine effectiveness (VE) by using conditional logistic regression models matched on epidemiological week.

Results

Overall VE estimates among fully and partially vaccinated children were 73% (95% confidence interval, 69%–77%) and 31% (95% confidence interval, 8%–48%), respectively. A consistently higher VE was observed in children fully vaccinated against each influenza virus type/subtype. The effectiveness of partial vaccination did not vary by age group.

Conclusions

Partial vaccination was significantly less effective than full vaccination. Our study supports the current recommendation of 2 doses of influenza vaccination in previously unvaccinated children <9 years of age.
Effect of HIV Infection and Antiretroviral Treatment on Pregnancy Rates in the Western Cape Province of South Africa
Authors: Johnson Leigh F , Mutemaringa Themba , Heekes Alexa , Boulle Andrew
Published: July 2019

Background

Previous studies suggest that untreated human immunodeficiency virus (HIV) infection is associated with a reduced incidence of pregnancy, but studies of the effect of antiretroviral treatment (ART) on pregnancy incidence have been inconsistent.

Methods

Routine data from health services in the Western Cape province of South Africa were linked to identify pregnancies during 2007–2017 and maternal HIV records. The time from the first (index) pregnancy outcome date to the next pregnancy was modeled using Cox proportional hazards models.

Results

During 2007–2017, 1 042 647 pregnancies were recorded. In all age groups, pregnancy incidence rates were highest in women who had started ART, lower in HIV-negative women, and lowest in ART-naive HIV-positive women. In multivariable analysis, after controlling for the most recent CD4+ T-cell count, pregnancy incidence rates in HIV-positive women receiving ART were higher than those in untreated HIV-positive women (adjusted hazard ratio, 1.63; 95% confidence interval, 1.59–1.67) and those in HIV-negative women.

Conclusion

Among women who have recently been pregnant, receipt of ART is associated with high rates of second pregnancy. Better integration of family planning into HIV care services is needed.
Adaptation of the WHO Essential Medicines List for national antibiotic stewardship policy in England: being AWaRe
Authors: Budd Emma , Cramp Emma , Sharland Mike , Hand Kieran , Howard Philip , Wilson Peter , Wilcox Mark , Muller-Pebody Berit , Hopkins Susan
Published: July 2019

Objectives

Appropriate use of and access to antimicrobials are key priorities of global strategies to combat antimicrobial resistance (AMR). The WHO recently classified key antibiotics into three categories (AWaRe) to improve access (Access), monitor important antibiotics (Watch) and preserve effectiveness of ‘last resort’ antibiotics (Reserve). This classification was assessed for antibiotic stewardship and quality improvement in English hospitals.

Methods

Using an expert elicitation exercise, antibiotics used in England but not included in the WHO AWaRe index were added to an appropriate category following a workshop consensus exercise with national experts. The methodology was tested using national antibiotic prescribing data and presented by primary and secondary care.

Results

In 2016, 46/108 antibiotics included within the WHO AWaRe index were routinely used in England and an additional 25 antibiotics also commonly used in England were not included in the WHO AWaRe index. WHO AWaRe-excluded and -included antibiotics were reviewed and reclassified according to the England-adapted AWaRE index with the justification by experts for each addition or alteration. Applying the England-adapted AWaRe index, Access antibiotics accounted for the majority (60.9%) of prescribing, followed by Watch (37.9%) and Reserve (0.8%); 0.4% of antibiotics remained unclassified. There was unexplained 2-fold variation in prescribing between hospitals within each AWaRe category, highlighting the potential for quality improvement.

Conclusions

We have adapted the WHO AWaRe index to create a specific index for England. The AWaRe index provides high-level understanding of antibiotic prescribing. Subsequent to this process the England AWaRe index is now embedded into national antibiotic stewardship policy and incentivized quality improvement schemes.
Local surface plasmon resonance of gold nanoparticles as a correlative light and electron microscopy (CLEM) tag for biological samples
Authors: Haruta Tomohiro , Hasumi Keiko , Ikeda Yuta , Konyuba Yuji , Fukuda Tomohisa , Nishioka Hideo
Published: July 2019

In this study, we investigated use of local surface plasmon resonance (LSPR) of metal nanoparticles (NPs) as a correlative light and electron microscopy (CLEM) tag for biological samples. Gold NPs in ultra-thin sections for TEM revealed that LSPR could be observed by optical microscopy at sizes of 20 nm or larger. Gold NPs at sizes less than 20 nm could be observed using the gold enhancement method. Therefore, this CLEM tag could be applied to immunoelectron microscopy using this gold enhancement method.
Posture control in land plants: growth, position sensing, proprioception, balance, and elasticity
Authors: Moulia Bruno , Bastien Renaud , Chauvet-Thiry Hugo , Leblanc-Fournier Nathalie
Published: July 2019

The colonization of the atmosphere by land plants was a major evolutionary step. The mechanisms that allow for vertical growth through air and the establishment and control of a stable erect habit are just starting to be understood. A key mechanism was found to be continuous posture control to counterbalance the mechanical and developmental challenges of maintaining a growing upright structure. An interdisciplinary systems biology approach was invaluable in understanding the underlying principles and in designing pertinent experiments. Since this discovery previously held views of gravitropic perception had to be reexamined and this has led to the description of proprioception in plants. In this review, we take a purposefully pedagogical approach to present the dynamics involved from the cellular to whole-plant level. We show how the textbook model of how plants sense gravitational force has been replaced by a model of position sensing, a clinometer mechanism that involves both passive avalanches and active motion of statoliths, granular starch-filled plastids, in statocytes. Moreover, there is a transmission of information between statocytes and other specialized cells that sense the degree of organ curvature and reset asymmetric growth to straighten and realign the structure. We give an overview of how plants have used the interplay of active posture control and elastic sagging to generate a whole range of spatial displays during their life cycles. Finally, a position-integrating mechanism has been discovered that prevents directional plant growth from being disrupted by wind-induced oscillations.
Differential activity of F-box genes and E3 ligases distinguishes sexual versus apomictic germline specification in Boechera
Authors: Zühl Luise , Volkert Christopher , Ibberson David , Schmidt Anja
Published: July 2019

A comprehensive tissue type-specific transcriptional study identifies 45 genes consistently differentially expressed during Boechera sexual as compared with apomictic germline specification, suggesting their relevance for apomixis.
Nativity of lignin carbohydrate bonds substantiated by biomimetic synthesis
Authors: Giummarella Nicola , Balakshin Mikhail , Koutaniemi Sanna , Kärkönen Anna , Lawoko Martin
Published: July 2019

Direct evidence of lignin–carbohydrate linkages was found in lignin substrates isolated and synthetized mimicking their native state and overcoming any kind of harsh extraction and chemical pre-treatments.
Observable tests of self-interacting dark matter in galaxy clusters: cosmological simulations with SIDM and baryons
Authors: Robertson Andrew , Harvey David , Massey Richard , Eke Vincent , McCarthy Ian G , Jauzac Mathilde , Li Baojiu , Schaye Joop
Published: July 2019

We present bahamas-SIDM, the first large-volume, $(400 \, h^{-1} \mathrm{\, Mpc})^{3}$, cosmological simulations including both self-interacting dark matter (SIDM) and baryonic physics. These simulations are important for two primary reasons: (1) they include the effects of baryons on the dark matter distribution and (2) the baryon particles can be used to make mock observables that can be compared directly with observations. As is well known, SIDM haloes are systematically less dense in their centres, and rounder, than CDM haloes. Here, we find that that these changes are not reflected in the distribution of gas or stars within galaxy clusters, or in their X-ray luminosities. However, gravitational lensing observables can discriminate between DM models, and we present a menu of tests that future surveys could use to measure the SIDM interaction strength. We ray-trace our simulated galaxy clusters to produce strong lensing maps. Including baryons boosts the lensing strength of clusters that produce no critical curves in SIDM-only simulations. Comparing the Einstein radii of our simulated clusters with those observed in the CLASH survey, we find that at velocities around $1000 \mathrm{\, km \, s^{-1}}$ an SIDM cross-section of $\sigma /m \gtrsim 1 \, \mathrm{cm^2 \, g^{-1}}$ is likely incompatible with observed cluster lensing.
Chandra observation of a cold front in Abell 2554
Authors: Erdim M Kiyami , Hudaverdi Murat
Published: July 2019

We present the evidence for the existence of sub-structure in the cold front cluster A2554 based on a 20.14 ks Chandra observation. Using centroid shift and X-ray brightness concentration parameters, we confirm that A2554 is a dynamically disturbed system. We detect two dominant structures: a main cluster at z = 0.1108 and a foreground northern sub-structure at z = 0.1082. The analysis reveals an X-ray surface brightness edge at r ≃ 60 h−1 kpc from the cluster core. The thermodynamical profiles across the edge are ruling out the shock scenario. The temperature jump (from ∼6 keV to ∼10 keV), and pressure equilibrium (P0/P1 = 1.01 ± 0.23) across the edge, are consistent with the definition of a cold front with a Mach number $\mathcal {M}_1=0.94^{+0.13}_{-0.17}$. We also observed a weak bow-shock at ∼100 kpc in front of the cold cloud, corresponding an upper limit to the Mach number $\mathcal {M}_1$ ∼1.1. If the northern sub-structure was not related to the cold front, we conclude that the transonic motion of the cloud is caused by a merger, which was weak or occurred long ago.
Validation of the LACE Index (Length of Stay, Acuity of Admission, Comorbidities, Emergency Department Use) in the Adult Neurosurgical Patient Population
Authors: Linzey Joseph R , Nadel Jeffrey L , Wilkinson D Andrew , Rajajee Venkatakrishna , Daou Badih J , Pandey Aditya S
Published: July 2019

BACKGROUND

The LACE index (Length of stay, Acuity of admission, Comorbidities, Emergency department use) quantifies the risk of mortality or unplanned readmission within 30 d after hospital discharge. The index was validated originally in a large, general population and, subsequently, in several specialties, not including neurosurgery.

OBJECTIVE

To determine if the LACE index accurately predicts mortality and unplanned readmission of neurosurgery patients within 30 d of discharge.

METHODS

We performed a retrospective, cohort study of consecutive neurosurgical procedures between January 1 and September 29, 2017 at our institution. The LACE index and other clinical data were abstracted. Data analysis included univariate and multivariate logistic regressions.

RESULTS

Of the 1,054 procedures on 974 patients, 52.7% were performed on females. Mean age was 54.2 ± 15.4 yr. At time of discharge, the LACE index was low (1-4) in 58.3% of patients, moderate (5-9) in 32.4%, and high (10-19) in 9.3%. Rates of readmission and mortality within 30 d were 7.0, 11.4, and 14.3% in the low-, moderate-, and high-risk groups, respectively. Moderate-risk (odds ratio [OR] 1.62, 95% CI 1.02-2.56, P = .04) and high-risk LACE indexes (OR 2.20, 95% CI 1.15-4.19, P = .02) were associated with greater odds of readmission or mortality, adjusting for all variables. Additionally, longer operations (OR 1.11, 95% CI 1.02-1.21, P = .02) had greater odds of readmission. Specificity of the high-risk score to predict 30-d readmission or mortality was 91.2%.

CONCLUSION

A moderate- or high-risk LACE index can be applied to neurosurgical populations to predict 30-d readmission and mortality. Longer operations are potential predictors of readmission or mortality.
Class I TCP Transcription Factors Target the Gibberellin Biosynthesis GeneGA20ox1and the Growth-Promoting GenesHBI1andPRE6during Thermomorphogenic Growth inArabidopsis
Authors: Ferrero Luc�a V , Viola Ivana L , Ariel Federico D , Gonzalez Daniel H
Published: July 2019

Plants respond to a rise in ambient temperature by increasing the growth of petioles and hypocotyls. In this work, we show that Arabidopsis thaliana class I TEOSINTE BRANCHED 1, CYCLOIDEA, PCF (TCP) transcription factors TCP14 and TCP15 are required for optimal petiole and hypocotyl elongation under high ambient temperature. These TCPs influence the levels of the DELLA protein RGA and the expression of growth-related genes, which are induced in response to an increase in temperature. However, the class I TCPs are not required for the induction of the auxin biosynthesis gene YUCCA8 or for auxin-dependent gene expression responses. TCP15 directly targets the gibberellin biosynthesis gene GA20ox1 and the growth regulatory genes HBI1 and PRE6. Several of the genes regulated by TCP15 are also targets of the growth regulator PIF4 and show an enrichment of PIF4- and TCP-binding motifs in their promoters. PIF4 binding to GA20ox1 and HBI1 is enhanced in the presence of the TCPs, indicating that TCP14 and TCP15 directly participate in the induction of genes involved in gibberellin biosynthesis and cell expansion by high temperature functionally interacting with PIF4. In addition, overexpression of HBI1 rescues the growth defects of tcp14 tcp15 double mutants, suggesting that this gene is a major outcome of regulation by both class I TCPs during thermomorphogenesis.
The Possibility of Unity
Authors: Noonan H W
Published: July 2019

In One Priest argues for the contradictoriness of Unity. The argument is that the unity of complex things is contradictory. It is contradictory that there are complex wholes composed of many parts. But there are. Thus, the explanation of unity has to be a contradictory entity, a gluon, which both is and is not an object. The book then develops and utilises a theory of gluons. The argument for the contradictoriness of Unity is crucial; without it there is no motivation for the theory of gluons. It fails. It does so because ‘because’ is a sentential connective. So what follows it must be a sentence, not a list. So Priest is wrong to say that in a complex whole there must be something, an entity, which binds the parts together.
P329G-CAR-J: a novel Jurkat-NFAT-based CAR-T reporter system recognizing the P329G Fc mutation
Authors: Darowski Diana , Jost Christian , Stubenrauch Kay , Wessels Uwe , Benz Jörg , Ehler Andreas , Freimoser-Grundschober Anne , Brünker Peter , Mössner Ekkehard , Umaña Pablo , Kobold Sebastian , Klein Christian
Published: July 2019

Monoclonal antibody-based therapeutics are an integral part of treatment of different human diseases, and the selection of suitable antibody candidates during the discovery phase is essential. Here, we describe a novel, cellular screening approach for the identification and characterization of therapeutic antibodies suitable for conversion into T cell bispecific antibodies using chimeric antigen receptor (CAR) transduced Jurkat-NFAT-luciferase reporter cells (CAR-J). For that purpose, we equipped a Jurkat-NFAT reporter cell line with a universal CAR, based on a monoclonal antibody recognizing the P329G mutation in the Fc-part of effector-silenced human IgG1-antibodies. In addition to scFv-based second generation CARs, Fab-based CARs employing the P329G-binder were generated. Using these anti-P329G-CAR-J cells together with the respective P329G-mutated IgG1-antibodies, we established a system, which facilitates the rapid testing of therapeutic antibody candidates in a flexible, high throughput setting during early stage discovery. We show that both, scFv- and Fab-based anti-P329G-CAR-J cells elicit a robust and dose-dependent luciferase signal if the respective antibody acts as an adaptor between tumor target and P329G-CAR-J cells. Importantly, we could demonstrate that functional characteristics of the antibody candidates, derived from the anti-P329G-CAR-J screening assay, are predictive for the functionality of these antibodies in the T cell bispecific antibody format.