bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathway Network Analysis of Complex Diseases Based on Multiple Biological Networks
Authors: Zheng Fang , Wei Le , Zhao Liang , Ni FuChuan
Published: July 2018

Biological pathways play important roles in the development of complex diseases, such as cancers, which are multifactorial complex diseases that are usually caused by multiple disorders gene mutations or pathway. It has become one of the most important issues to analyze pathways combining multiple types of high-throughput data, such as genomics and proteomics, to understand the mechanisms of complex diseases. In this paper, we propose a method for constructing the pathway network of gene phenotype and find out disease pathogenesis pathways through the analysis of the constructed network. The specific process of constructing the network includes, firstly, similarity calculation between genes expressing data combined with phenotypic mutual information and GO ontology information, secondly, calculating the correlation between pathways based on the similarity between differential genes and constructing the pathway network, and, finally, mining critical pathways to identify diseases. Experimental results on Breast Cancer Dataset using this method show that our method is better. In addition, testing on an alternative dataset proved that the key pathways we found were more accurate and reliable as biological markers of disease. These results show that our proposed method is effective.
Effect of Lycosome-Formulated Phosphatidylcholine on Parameters of Biological Oxidation after Single Intake of Moderate Amount of Alcohol
Authors: Petyaev Ivan M. , Chernyshova Marina P. , Pristensky Dmitry V. , Chalyk Natalia E. , Klochkov Victor A. , Kyle Nigel H. , Bashmakov Yuriy K.
Published: July 2018

Ingestion of a single dose of alcohol, ranging from the intake of a moderate amount alcohol to binge drinking, is the most frequent form of alcohol consumption with poorly understood medical consequences and obscure prophylactics. The study was aimed to determine whether lycosome formulated phosphatidylcholine (PC-Lyc) containing two highly bioavailable antioxidants (PC and lycopene) ingested shortly before the alcohol-containing beverage may alleviate the biochemical markers of liver damage and parameters of biological oxidation associated with the intake of a moderate amount of alcohol. Healthy middle-aged volunteers were requested to consume a moderate amount of alcohol – 0.5 ml/kg or 1.0 ml/kg shortly after ingestion of a capsule containing 450 mg of regular phosphatidylcholine (PC, n=10), PC-Lyc (n=10), or placebo pill (PP, n=10). Serum levels of ethanol (EtOH), acetaldehyde (AA), liver-specific enzymes, total antioxidant capacity of serum (TAC), oxidized LDL (LDL-Px), and malonic dialdehyde (MDA) were measured at 1, 2.5, and 5 hours after dosing with alcohol. Ingestion of PC regardless of the formulation used had no effect on serum EtOH concentration dynamics. However, volunteers supplemented with PC-Lyc showed a better clearance of AA in serum as compared to other groups. There was a reduction in serum TAC values by 18.5% and 16.1% in both placebo groups ingesting 0.5 and 1.0 ml/kg of alcohol, respectively, at the end of observational period. This decline was preventable by supplementation of volunteers with PC and especially with PC-Lyc. Moreover, PC-Lyc promoted a reduction of serum MDA and reversed an increase in serum LDL-Px. In addition, ingestion of alcohol at 1.0 ml/kg dose caused a transient increase in serum alanine-aminotransferase activity which was abolished by both formulations of PC. Therefore, combinatory lycosomal formulation of PC and lycopene may prevent some metabolic abnormalities associated with single intake of moderate amount of alcohol. This trial is registered with ACTRN12617001335381.
Gradenigo’s Syndrome and Labyrinthitis: Conservative versus Surgical Treatment
Authors: Al-juboori Ahmad , Al Hail Amira Nasser
Published: July 2018

Background. Extracranial intratemporal complications of chronic suppurative otitis media (CSOM) are extremely rare. Gradenigo’s syndrome is defined as a clinical triad of otitis media, severe pain originating from the trigeminal nerve, and ipsilateral sixth cranial nerve palsy. Case Report. A 61-year-old man presented with chronic left ear discharge, left-sided headache, diplopia associated with vertigo, tinnitus, and hearing impairment. MRI with contrast showed asymmetrical signal changes in the bilateral petrous bone with reduced enhancement on the left with high suspicion of petrositis; in the context of chronic tympanomastoiditis, there was a 10 × 4 mm enhancing lesion in the left internal auditory meatus involving the 7th-8th nerve complex. The patient was treated conservatively with local and systemic antimicrobial agents, he had satisfactory response and improvement regarding symptoms of ear discharge, vertigo, and diplopia, but there is no remarkable response regarding hearing loss and tinnitus. Conclusion. Although there is little evidence to support the use of conservative treatment in the treatment of Gradenigo’s syndrome resulting from chronic ear disease, we here demonstrate successful conservative treatment of Gradenigo’s syndrome.
Difference in Response to a Motor Imagery Task: A Comparison between Individuals with and without Painful Temporomandibular Disorders
Authors: Uritani Daisuke , Nishida Tomoko , Sakaguchi Nanami , Kawakami Tetsuji , Jones Lester E. , Kirita Tadaaki
Published: July 2018

The aim of the study was to investigate the difference in response to a motor imagery task between individuals with and without painful temporomandibular disorders (TMDs). The participants were 24 adults with and without TMD (TMD and control group, resp.). A set of photographic images of the profile view of a person’s head and neck and a hand and a foot were presented in a random order. The set consisted of six different orientations with rotations of each image at 0, 60, 120, 180, 240, and 300 degrees and included left and right representations. The participants were required to view the image and make a decision as to whether it was a left or a right side presented, that is, mental rotation (MR) task. Data were collected on 48 tasks (including left and right) at each orientation for each body part. Reaction times (RTs) for correct answers and accuracy in making the left or right judgements were recorded. The RT was slower in the TMD group than in the control group. The RT for the profile image was slower than those for the hand and foot images. For images that were 180 degrees, the RT was slower and the accuracy was lower than those for five of the other image orientations. The judgements made about the 180-degree rotated image were more inaccurate compared to images of all other orientations among all types of stimuli.
Treatment Outcome of Severe Acute Malnutrition and Its Determinants among Pediatric Patients in West Ethiopia
Authors: Mena Muluken Berhanu , Dedefo Mohammed Gebre , Billoro Bruke Berhanu
Published: July 2018

Background. Malnutrition is a silent killer that is underreported, underaddressed, and as a result underprioritized. It is reported that severe acute malnutrition is the commonest reason for pediatrics hospital admission in many poor countries; 25 to 30% of children with severe malnutrition die during hospital admissions. Objective. To determine treatment outcome of severe acute malnutrition and identify its determinants among pediatric patients in pediatrics ward of Nekemte Referral Hospital. Methods. A retrospective hospital-based cross-sectional study was done from November 2015 to April 2017. Data had been collected by using checklist for recording information from patient card and register book. Association between independent variables and depend variable was assessed using bivariate and stepwise multivariable logistic regression, respectively. Level of statistical significance was declared at p value < 0.05. Results. Out of 205 admitted children with severe acute malnutrition, 137 (66.8%) cases were cured from SAM, 9 (4.4%) cases were died because of SAM, and (16.6%) cases were defaulter from SAM management, and 25 (12.2%) cases were transferred out. Multivariable logistic regression showed that children admitted with both edema and wasting AOR = 8.30, 95% CI (1.72, 40.09) P=0.008, children without hypothermia AOR = 2.91, 95%CI (1.10, 7.69) P=0.031, children who stay 8-14 days AOR = 3.86, 95%CI (1.01, 14.75) P=0.048, children without pneumonia AOR = 7.82, 95%CI (2.74, 222.29) P=0.001, children without anemia AOR = 3.22, 95%CI (1.04, 9.97) P=0.042, and children without HIV AOR = 9.21, 95% CI (2.20, 38.54) P=0.002 were more likely to be cured from severe acute malnutrition. Conclusion. Treatment outcome of severe acute malnutrition in this study is good. It shows that around three-fourths of the children were cured. Factors such as admission criteria, hypothermia, length of stay, pneumonia, anemia, and presence of HIV were associated with treatment response.
The Immunodetection of Non-Falciparum Malaria in Ancient Egyptian Bones (Giza Necropolis)
Authors: AL-Khafif Ghada Darwish , El-Banna Rokia , Khattab Nancy , Gad Rashed Tamer , Dahesh Salwa
Published: July 2018

The detection of falciparum malaria in ancient Egyptian remains had been performed by many authors using several methodologies including the use of rapid diagnostic tests. Through the immunochromatographic analysis of bony specimens from Giza skeletal collection dated to Old Kingdom, we provide first evidence of non-falciparum malaria in Ancient Egypt. The histidine-rich protein-2 (HRP2) specific toPlasmodium falciparumwas absent in 100% of examined samples, while aldolase, common to the four types of plasmodial pathogens causing human malaria, was detected in 56% of individuals with no significant difference between the two tested social groups: high officials (HO) and workers (W). It is suggested that the main risk factor was the presence of residences near natural and artificial waterways, which allowed prolonged contact between the vector and human host.
Panax notoginseng Saponins Regulate Macrophage Polarization under Hyperglycemic Condition via NF-κB Signaling Pathway
Authors: Zhao Yan , Zheng Jianlei , Yu Yongmei , Wang Lihong
Published: July 2018

Panax notoginseng saponins (PNS), the principal constituents derived from Panax notoginseng, have been extensively used for treating cardiocerebral vascular diseases in China and other Asian countries. The main effects of PNS were anti-inflammatory properties, inhibition of platelet aggregation, improvement of blood flow and insulin resistance, and so on. This study was carried out to explore the effects of PNS on macrophage polarization under hyperglycemic conditions. Human acute monocyte leukemia cell line THP-1 cells were induced into macrophages with Phorbol ester (PMA). Macrophages were then divided into five groups as follows: control (5.5mMol/l glucose), hyperglycemia group (15mMol/l glucose), hyperglycemia plus low-dose PNS (20ug/ml), hyperglycemia plus moderate-dose PNS (40ug/ml), and hyperglycemia plus high-dose PNS (60ug/ml). After 48-hour cell culture, the percentages of M1- and M2-polarized macrophages were measured by flow cytometry analysis. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to evaluate the Ym1 and arginase 1 expression in macrophages. Protein expression of arginase 1, NF-κB p50, p65, and inhibitor of κB (IκB) alpha phosphorylation in macrophages was identified with Western blotting. PNS, especially the high-dose PNS, remarkably increased M2 phenotype ratio in macrophages cultured with hyperglycemia, and the mRNA expression of Ym1 and arginase 1 in macrophages was also upregulated. Meanwhile, PNS remarkably increased the protein expression of arginase 1 and decreased IκB-alpha phosphorylation and subunits of NF-κB p50 and p65 from macrophages in culture medium with hyperglycemia. Taken together, our work demonstrated that PNS promote macrophages to transform M2 phenotype under hyperglycemic conditions through downregulating NF-κB signaling pathway.
Supply Chain Decision-Making Based on Warehouse Receipt Pledge and Risk Consideration under Twice Ordering Mode
Authors: Wang Liang , Xu Tingjia , Zhu Shi
Published: July 2018

This paper studies supply chain decisions making between the retailer, supplier, and bank based on warehouse receipt pledge and risk consideration under twice ordering mode. The decentralized supply chain and centralized supply chain are divided by whether the supplier provides repurchase guarantees and whether the retailer offers revenue sharing. We develop a Stackelberg game model to analyze the influential mechanism among various actors and use the method of downside risk control to discuss the bank’s expected loss and the optimal loan pledge ratio. We carry out a simulation analysis, and the result is shown as follows: (i) either for decentralized or centralized supply chain, the retailer’s optimal order quantity and the optimal proportion that the number of goods pledged by the retailer’s twice ordering accounts for the number of first-ordering goods are all unique; (ii) the bank’s loan pledge ratio is a monotonically increasing function of disposal value of the unit remaining commodity; (iii) for centralized supply chain, the bank’s loan pledge ratio is the monotonically increasing function of repurchase ratio and wholesale price provided by the supplier, respectively; (iv) in the decentralized supply chain, the supplier’s return mainly comes from the wholesale revenue and is positively related to the wholesale volume and wholesale price; in the centralized supply chain, the supplier’s return is mainly from the retailer’s revenue sharing.
Efficient and Reliable Cluster-Based Data Transmission for Vehicular Ad Hoc Networks
Authors: Ji Xiang , Yu Huiqun , Fan Guisheng , Sun Huaiying , Chen Liqiong
Published: July 2018

Vehicular ad hoc network (VANET) is an emerging technology for the future intelligent transportation systems (ITSs). The current researches are intensely focusing on the problems of routing protocol reliability and scalability across the urban VANETs. Vehicle clustering is testified to be a promising approach to improve routing reliability and scalability by grouping vehicles together to serve as the foundation for ITS applications. However, some prominent characteristics, like high mobility and uneven spatial distribution of vehicles, may affect the clustering performance. Therefore, how to establish and maintain stable clusters has become a challenging problem in VANETs. This paper proposes a link reliability-based clustering algorithm (LRCA) to provide efficient and reliable data transmission in VANETs. Before clustering, a novel link lifetime-based (LLT-based) neighbor sampling strategy is put forward to filter out the redundant unstable neighbors. The proposed clustering scheme mainly composes of three parts: cluster head selection, cluster formation, and cluster maintenance. Furthermore, we propose a routing protocol of LRCA to serve the infotainment applications in VANET. To make routing decisions appropriate, we nominate special nodes at intersections to evaluate the network condition by assigning weights to the road segments. Routes with the lowest weights are then selected as the optimal data forwarding paths. We evaluate clustering stability and routing performance of the proposed approach by comparing with some existing schemes. The extensive simulation results show that our approach outperforms in both cluster stability and data transmission.
MELK Inhibition in Diffuse Intrinsic Pontine Glioma
Authors: Meel Michaël H. , de Gooijer Mark C. , Guillén Navarro Miriam , Waranecki Piotr , Breur Marjolein , Buil Levi C.M. , Wedekind Laurine E. , Twisk Jos W.R. , Koster Jan , Hashizume Rintaro , Raabe Eric H. , Montero Carcaboso Angel , Bugiani Marianna , van Tellingen Olaf , van Vuurden Dannis G. , Kaspers Gertjan J.L. , Hulleman Esther
Published: July 2018

Purpose: Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brain tumor, for which no effective therapeutic options currently exist. We here determined the potential of inhibition of the maternal embryonic leucine zipper kinase (MELK) for the treatment of DIPG.

Experimental Design: We evaluated the antitumor efficacy of the small-molecule MELK inhibitor OTSSP167 in vitro in patient-derived DIPG cultures, and identified the mechanism of action of MELK inhibition in DIPG by RNA sequencing of treated cells. In addition, we determined the blood–brain barrier (BBB) penetration of OTSSP167 and evaluated its translational potential by treating mice bearing patient-derived DIPG xenografts.

Results: This study shows that MELK is highly expressed in DIPG cells, both in patient samples and in relevant in vitro and in vivo models, and that treatment with OTSSP167 strongly decreases proliferation of patient-derived DIPG cultures. Inhibition of MELK in DIPG cells functions through reducing inhibitory phosphorylation of PPARγ, resulting in an increase in nuclear translocation and consequent transcriptional activity. Brain pharmacokinetic analyses show that OTSSP167 is a strong substrate for both MDR1 and BCRP, limiting its BBB penetration. Nonetheless, treatment of Mdr1a/b;Bcrp1 knockout mice carrying patient-derived DIPG xenografts with OTSSP167 decreased tumor growth, induced remissions, and resulted in improved survival.

Conclusions: We show a strong preclinical effect of the kinase inhibitor OTSSP167 in the treatment of DIPG and identify the MELK–PPARγ signaling axis as a putative therapeutic target in this disease. Clin Cancer Res; 24(22); 5645–57. ©2018 AACR.
Circulating Cell-Free miR-375 as Surrogate Marker of Tumor Burden in Merkel Cell Carcinoma
Authors: Fan Kaiji , Ritter Cathrin , Nghiem Paul , Blom Astrid , Verhaegen Monique E. , Dlugosz Andrzej , Ødum Niels , Woetmann Anders , Tothill Richard W. , Hicks Rodney J. , Sand Michael , Schrama David , Schadendorf Dirk , Ugurel Selma , Becker Jürgen C.
Published: July 2018

Purpose:

Merkel cell carcinoma (MCC) is an aggressive skin cancer with neuroendocrine differentiation. There is an unmet need for MCC-specific blood-based surrogate biomarkers of tumor burden; circulating cell-free miRNA may serve this purpose.

Experimental Design:

Expression of miR-375 was quantified in 24 MCC and 23 non-MCC cell lines, 67 MCC and 58 non-MCC tumor tissues, sera of 2 preclinical MCC models, and sera of 109 patients with MCC and 30 healthy controls by nCounter human-v2-miRNA expression or miR-375–specific real-time PCR assays. The patients’ sera consisted of two retrospective (discovery and training) and two prospective (validation) cohorts.

Results:

miR-375 expression was high in MCC cell lines and tissues compared with non-MCCs. It was readily detected in MCC-conditioned medium and sera of preclinical models bearing MCC xenografts. miR-375 levels were higher in sera from tumor-bearing patients with MCC than in tumor-free patients or healthy controls (P < 0.0005). Moreover, miR-375 serum levels correlated with tumor stage in tumor-bearing (P = 0.037) but not in tumor-free (P = 0.372) patients with MCC. miR-375 serum level showed high diagnostic accuracy to discriminate tumor-bearing and tumor-free patients with MCC as demonstrated by ROC curve analysis in the retrospective cohorts (AUC = 0.954 and 0.800) as well as in the prospective cohorts (AUC = 0.929 and 0.959). miR-375 serum level reflected dynamic changes in tumor burden of patients with MCC during therapeutic interventions.

Conclusions:

Circulating cell-free miR-375 proved as a surrogate marker for tumor burden in MCC without restriction to polyomavirus positivity; it thus appears to be useful for therapy monitoring and the follow-up of patients with MCC.
Genomic cfDNA Analysis of Aqueous Humor in Retinoblastoma Predicts Eye Salvage: The Surrogate Tumor Biopsy for Retinoblastoma
Authors: Berry Jesse L. , Xu Liya , Kooi Irsan , Murphree A. Linn , Prabakar Rishvanth K. , Reid Mark , Stachelek Kevin , Le Bao Han A. , Welter Lisa , Reiser Bibiana J. , Chévez-Barrios Patricia , Jubran Rima , Lee Thomas C. , Kim Jonathan W. , Kuhn Peter , Cobrinik David , Hicks James
Published: July 2018

Tumor-derived cell-free DNA (cfDNA) has biomarker potential; therefore, this study aimed to identify cfDNA in the aqueous humor (AH) of retinoblastoma eyes and correlate somatic chromosomal copy-number alterations (SCNA) with clinical outcomes, specifically eye salvage. AH was extracted via paracentesis during intravitreal injection of chemotherapy or enucleation. Shallow whole-genome sequencing was performed using isolated cfDNA to assess for highly recurrent SCNAs in retinoblastoma including gain of 1q, 2p, 6p, loss of 13q, 16q, and focal MYCN amplification. Sixty-three clinical specimens of AH from 29 eyes of 26 patients were evaluated; 13 eyes were enucleated and 16 were salvaged (e.g., saved). The presence of detectable SCNAs was 92% in enucleated eyes versus 38% in salvaged eyes (P = 0.006). Gain of chromosome 6p was the most common SCNA found in 77% of enucleated eyes, compared with 25% of salvaged eyes (P = 0.0092), and associated with a 10-fold increased odds of enucleation (OR, 10; 95% CI, 1.8–55.6). The median amplitude of 6p gain was 1.47 in enucleated versus 1.07 in salvaged eyes (P = 0.001). The presence of AH SCNAs was correlated retrospectively with eye salvage. The probability of ocular salvage was higher in eyes without detectable SCNAs in the AH (P = 0.0028), specifically 6p gain. This is the first study to correlate clinical outcomes with SCNAs in the AH from retinoblastoma eyes, as such these findings indicate that 6p gain in the aqueous humor is a potential prognostic biomarker for poor clinical response to therapy.

Implications: The correlation of clinical outcomes and SCNAs in the AH identified in the current study requires prospective studies to validate these finding before SCNAs, like 6p gain, can be used to predict clinical outcomes at diagnosis. Mol Cancer Res; 16(11); 1701–12. ©2018 AACR.
Having a Drink with Tchaikovsky: The Crossmodal Influence of Background Music on the Taste of Beverages
Authors: Hauck Pia , Hecht Heiko
Published: July 2018

Previous research has shown that auditory cues can influence the flavor of food and drink. For instance, wine tastes better when preferred music is played. We have investigated whether a music background can modify judgments of the specific flavor pattern of a beverage, as opposed to mere preference. This was indeed the case. We explored the nature of this crosstalk between auditory and gustatory perception, and hypothesized that the ‘flavor’ of the background music carries over to the perceived flavor (i.e., descriptive and evaluative aspects) of beverages. First, we collected ratings of the subjective flavor of different music pieces. Then we used a between-subjects design to cross the music backgrounds with taste evaluations of several beverages. Participants tasted four different samples of beverages under two contrasting audio conditions and rated their taste experiences. The emotional flavor of the music had the hypothesized effects on the flavor of the beverages. We also hypothesized that such an effect would be stronger for music novices than for music experts, and weaker for aqueous solutions than for wines. However, neither music expertise nor liquid type produced additional effects. We discuss implications of this audio-gustatory interaction.
Family Instability in Childhood and Criminal Offending During the Transition Into Adulthood
Authors: Bosick Stacey J. , Fomby Paula
Published: July 2018

The structure and stability of families have long stood as key predictors of juvenile delinquency. Boys from “broken homes” experience a higher prevalence of juvenile delinquency than those from intact families. Unresolved is whether the consequences of frequently disrupted family contexts endure to shape criminal trajectories into adulthood. Long-term influence may also be indirect. Life-course criminologists credit family formation during the transition to adulthood, and particularly marriage, for redirecting men’s criminal trajectories, but children who experience repeated changes in family structure are more likely to experience precarious starts to their own eventual family formation. Using data from the Panel Study of Income Dynamics and its two child-centered supplemental studies ( N = 1,127), we find that the experience of repeated family structure change is associated with higher rates of arrest and incarceration during early adulthood for White men but not for Black men. However, divergent patterns of own family formation among men in early adulthood do not mediate this association.
Application of Chemometrics Approaches to Analysis of Mid-Infrared Spectra of Ibuprofen Diluted in Supercritical Carbon Dioxide
Authors: Oparin Roman D. , Kiselev Michael G.
Published: July 2018

This work represents a comprehensive analysis of mid-infrared (mid-IR) spectra of ibuprofen diluted in supercritical CO2 (in the temperature range of 40–90 ℃ and at the CO2 density corresponding to 1.3 of its critical value). The study employed mathematical approaches based on data matrix analysis such as two-dimensional cross-correlation analysis (2D-COS) and principal component analysis (PCA). Two-dimensional cross-correlation analysis allowed us to reveal correlations between the spectral contributions constituting the analytical spectral band and assigned to certain ibuprofen conformers, as well as the significance of these correlations. It has been shown that the considerable increase in the total intensity of the analytical spectral band, proportional to the equilibrium ibuprofen concentration in the supercritical CO2 phase, is accompanied by certain redistribution of intensities of the spectral components related to the corresponding conformers. The PCA allowed us to determine the changes of intensities of individual spectral contributions for each thermodynamic point in the considered temperature range. It has been shown that these two complementary methods provide more precise information that may be used as the initial data in the classical analysis of spectral data based on spectral curve deconvolution into individual spectral contributions.
Estimation of the prevalence of cholesteryl ester storage disorder in a cohort of patients with clinical features of familial hypercholesterolaemia
Authors: Ashfield-Watt Pauline , Haralambos Kate , Edwards Rhiannon , Townsend Delyth , Gingell Rob , Wa Li Kah , Humphries Steve E , McDowell Ian
Published: July 2018

Background and aim

Familial hypercholesterolaemia is caused by variants in the low-density lipoprotein cholesterol metabolic pathway involving LDLR, APOB and PCSK9 genes. A national genetic testing service in Wales, UK has observed that no familial hypercholesterolaemia variant is found in almost 80% patients with the familial hypercholesterolaemia phenotype. It has recently been suggested that some adult patients with a familial hypercholesterolaemia phenotype may have cholesteryl ester storage disease which can also present as a mixed hyperlipidaemia. The commonest genetic cause of cholesteryl ester storage disease is an exon 8 splice junction variant in the LIPA gene (rs116928232, c.894G>A; E8SJM) previously found to have an allele frequency of 0.0011 (1 in 450 individuals) in a large European population. This study investigated the prevalence of the E8SJM in patients with a familial hypercholesterolaemia phenotype in Wales, UK.

Method

A total of 1203 patients with a clinical suspicion of familial hypercholesterolaemia but no familial hypercholesterolaemia variant were invited to participate. Of these, 668 patients provided informed written consent. Stored DNA samples from 663 patients were genotyped for the E8SJM variant.

Results

Three heterozygotes were identified (allele frequency 0.0023). Whole gene sequencing of the LIPA gene was undertaken in these three individuals, but no other variants were found. Therefore, there were no cholesteryl ester storage disease patients (homozygote or compound heterozygote) identified in this cohort.

Conclusion

The allele frequency 0.0023 (1 in 221 individuals) for the E8SJM variant was more prevalent in this cohort than in a European population study; however, no cholesteryl ester storage disease homozygotes were identified. We found no evidence to support routine testing for cholesteryl ester storage disease in adult patients with a familial hypercholesterolaemia phenotype.
Book Review: Peter Sutoris, Visions of Development: Films Division of India and the Imagination of Progress, 1948–1975
Authors: Roy Tirthankar
Published: July 2018

Peter Sutoris, Visions of Development: Films Division of India and the Imagination of Progress, 1948–1975, London: Hurst and Company, 2016, 318 pp.
Factors involved in the assessment of paediatric traffic injuries and deaths
Authors: O’Donovan Siobhan , van den Huevel Corinna , Baldock Matthew , Byard Roger W
Published: July 2018

Motor-vehicle collisions are the leading cause of unintentional injury and death in children in many parts of the world, including Europe, North America and Australia. The number of fatal collisions has decreased considerably in countries where safety measures such as child restraints, seat belts and air bags have been introduced, providing protection for children within vehicles, although it is recognised that there have been concomitant improvements in emergency responses and techniques, and in hospital treatments. Helmets and changes in external vehicle designs have been implemented to protect paediatric pedestrians and cyclists. However, despite the development of safety guidelines and technologies, injuries still occur. This paper provides an overview of the role of motor-vehicle collisions in paediatric morbidity and mortality to analyse the nature and aetiology of common fatal and non-fatal injuries in children that may present for forensic assessment as passengers, pedestrians or cyclists.
Fitting Nonlinear Mixed-effects Models With Alternative Residual Covariance Structures
Authors: Blozis Shelley A. , Harring Jeffrey R.
Published: July 2018

Nonlinear mixed-effects models are models in which one or more coefficients of the growth model enter in a nonlinear manner, such as appearing in the exponent of the growth function. In their applications, the within-individual residuals are often assumed to be independent with constant variance across time, an assumption that implies that the assumed growth function fully accounts for the dependencies and patterns of variation in the data. Studies have shown that a poorly specified within-individual residual covariance structure of a linear mixed-effects model can impact the estimated covariance matrix of the random effects at the second-level, model fit and statistical inference. The consequences for nonlinear mixed-effects models are not, however, clearly understood. This is due in part to the differences in the estimation needs of the two types of models. Using empirical data examples, this work illustrates the impact of fitting alternative residual covariance structures in nonlinear mixed-effects models that do not entirely parallel the results from studies of strictly linear mixed-effects models and call for the need of researchers to consider alternative structures when fitting nonlinear mixed-effects models.
Race matters: Addressing racism as a health issue
Authors: Garrison Camille B , McKinney-Whitson Veneshia , Johnston Bryan , Munroe Ashley
Published: July 2018

The World Health Organization proclaimed in 1948 that “health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.” In many underserved communities, the individual and social well-being of patients of color is threatened. The United States is currently experiencing an exacerbation of racial tensions, and as health-care providers, we are dealing with the effects of racism on a daily basis. To effectively address patients’ needs, it is imperative that physicians and behavioral health providers acknowledge the racial and socioeconomic challenges that patients face and recognize how these factors transcend to the physical and psychological medical conditions that patients experience. This article highlights an ongoing program that espouses the importance of addressing racism as a health issue and will reveal individual experiences and challenges in addressing it within urban underserved residency program settings. Various viewpoints on racism as a health issue will be offered and will be further clarified by the authors. Collaborators on this project are two underrepresented minority residency program faculty, a resident who is passionate about social justice and who is ethnically different from the majority of his patients, and lastly an international resident of color who has experienced racism directly and indirectly during residency training.
Strain and Satisfaction in Caregivers of Veterans With Type 2 Diabetes
Authors: Wakefield Bonnie J. , Vaughan-Sarrazin Mary
Published: July 2018

Purpose

The purpose of this study was to identify predictors of informal caregiver strain and satisfaction associated with caring for veterans with type 2 diabetes (T2DM).

Methods

This study is a secondary analysis of data from 2 prior studies of caregiving in the Veterans Health Administration. The original studies used a telephone survey to examine veteran and caregiver (CG) characteristics associated with caregivers’ responses to caregiving. The data reported here include 202 veterans with T2DM and 202 caregivers. Linear regression models were generated alternatively using forward and backward selection of veteran and caregiver characteristics.

Results

Higher caregiver strain was associated with the CG providing activities of daily living assistance, CG receiving less help from friends and relatives and use of unpaid help, CG use of coping strategies, and CG depression scores. Predictors of CG satisfaction included better relationship quality with the veteran and receipt of social support.

Conclusions

The important role of family and friends in supporting patients with T2DM is widely accepted. Clinicians may engage the caregiver when there is inadequate self-care by the patient. However, less attention has been focused on the effect of caregiving on the caregiver. Greater attention needs to be focused on in-depth exploration of family needs to design and test effective interventions to meet these needs.
Brokerage and Closure in Corporate Control: Shifting Sources of Power for a Fractured Corporate Board Network
Authors: Benton Richard A.
Published: July 2018

Structural sources of power have shifted dramatically in corporate America. Recently, the fracturing of the corporate interlock network threatens corporate managers’ capacity to act as a unified group in support of their shared interests, potentially destroying managerialism and elevating shareholder power. Paradoxically, however, the fracturing of the corporate elite has not led to a widespread retreat of managerialism. Corporate managers have replaced their collective structural resources, embedded in their board interlock network, with organizational structural resources located within their firms. By adopting lone-insider board structures where the CEO is the only employee on the board of directors, CEOs establish brokerage positions within their focal firms, allowing them to preserve their autonomy even as the broader network withers. Firms nested in cohesive communities were the first to adopt lone-insider boards, supplementing and eventually replacing closure with brokerage as a structural resource. These alternative structural resources operated to preserve managerialism during different times. Network closure traditionally helped to preserve managerialism against shareholder pressure, but this effect disappeared as the network fragmented in the mid-2000s. In its absence, managers increasingly relied on organizational brokerage positions to maintain their autonomy. Consequently, managerialism remains surprisingly robust in the era of a fractured corporate board interlock network because top managers have become more focused on establishing positions of power within their own firms.
Left ventricular dysfunction after two hours of polarizing or depolarizing cardioplegic arrest in a porcine model
Authors: Aass Terje , Stangeland Lodve , Moen Christian Arvei , Solholm Atle , Dahle Geir Olav , Chambers David J. , Urban Malte , Nesheim Knut , Haaverstad Rune , Matre Knut , Grong Ketil
Published: July 2018

Introduction:

This experimental study compares myocardial function after prolonged arrest by St. Thomas’ Hospital polarizing cardioplegic solution (esmolol, adenosine, Mg2+) with depolarizing (hyperkalaemic) St. Thomas’ Hospital No 2, both administered as cold oxygenated blood cardioplegia.

Methods:

Twenty anaesthetized pigs on tepid (34°C) cardiopulmonary bypass (CPB) were randomised to cardioplegic arrest for 120 min with antegrade, repeated, cold, oxygenated, polarizing (STH-POL) or depolarizing (STH-2) blood cardioplegia every 20 min. Cardiac function was evaluated at Baseline and 60, 150 and 240 min after weaning from CPB, using a pressure-conductance catheter and epicardial echocardiography. Regional tissue blood flow, cleaved caspase-3 activity and levels of malondialdehyde were evaluated in myocardial tissue samples.

Results:

Preload recruitable stroke work (PRSW) was increased after polarizing compared to depolarizing cardioplegia 150 min after declamping (73.0±3.2 vs. 64.3±2.4 mmHg, p=0.047). Myocardial tissue blood flow rate was high in both groups compared to the Baseline levels and decreased significantly in the STH-POL group only, from 60 min to 150 min after declamping (p<0.005). Blood flow was significantly reduced in the STH-POL compared to the STH-2 group 240 min after declamping (p<0.05). Left ventricular mechanical efficiency, the ratio between total pressure-volume area and blood flow rate, gradually decreased after STH-2 cardioplegia and was significantly reduced compared to STH-POL cardioplegia after 150 and 240 min (p<0.05 for both).

Conclusion:

Myocardial protection for two hours of polarizing cardioplegic arrest with STH-POL in oxygenated blood is non-inferior compared to STH-2 blood cardioplegia. STH-POL cardioplegia alleviates the mismatch between myocardial function and perfusion after weaning from CPB
Melodic intonation therapy in post-stroke nonfluent aphasia: a randomized pilot trial
Authors: Haro-Martínez Ana M , Lubrini Genny , Madero-Jarabo Rosario , Díez-Tejedor Exuperio , Fuentes Blanca
Published: July 2018

Objective:

To collect data to estimate the sample size of a definitive randomized controlled trial to evaluate the effects of Melodic Intonation Therapy in post-stroke nonfluent aphasia.

Design:

A randomized, crossover, interventional pilot trial.

Setting:

Departments of Neurology and Rehabilitation from a university general hospital.

Participants:

Stroke survivors with post-stroke nonfluent aphasia.

Interventions:

Patients randomized to group 1 had treatment with Melodic Intonation Therapy first (12 sessions over six weeks) followed by no treatment; the patients in group 2 started active treatment between three and six months after their inclusion in the study, serving as waiting list controls for the first phase.

Main measures:

The Communicative Activity Log (CAL) questionnaire and the Boston Diagnostic Aphasia Examination (BDAE) were evaluated at baseline, and at six and 12 weeks.

Results:

Twenty patients were included. Four of the patients allocated to group 2 crossed over to group 1, receiving the treatment at first. Intention-to-treat analysis: after adjustment for baseline scores, the mean difference in the CAL evaluation from baseline in the treated group was 8.5 points (95% confidence interval (CI), 0.11–17.0; P = .043), with no significant change in any of the BDAE sections. Per-protocol analysis showed similar results with a clear treatment effect ( P = .043) on the CAL.

Conclusion:

Melodic Intonation Therapy might have a positive effect on the communication skills of stroke survivors with nonfluent aphasia as measured by the CAL questionnaire. A full-scale trial with at least 27 patients per group is necessary to confirm these results.
In-vitro blood–brain barrier modeling: A review of modern and fast-advancing technologies
Authors: Sivandzade Farzane , Cucullo Luca
Published: July 2018

The development of realistic in vitro blood–brain barrier (BBB) models that recapitulate the physiological parameters and molecular aspect of the neurovascular unit (NVU) is of fundamental importance not only in CNS drug discovery but also in translational research. Successful modeling of the NVU would provide an invaluable tool to aid in dissecting out the pathological factors, mechanism of action (and corresponding targets) prodromal to the onset of CNS disorders. The field of BBB in vitro modeling has seen many radical changes in the last few years with the introduction on novel technologies and methods to improve over existing models and develop new ones. Therefore, the goal of this review is to provide the readers with updated technical and operational details concerning current BBB platforms with special focus on stem cell technology used to establish a functional BBB model in vitro. Furthermore, we provide a detailed update on rapidly advancing 3D printing technologies used for engineering BBB models which use is now fast expanding among researchers.
Pravastatin polarizes the phenotype of macrophages toward M2 and elevates serum cholesterol levels in apolipoprotein E knockout mice
Authors: Zhang Xiaoling , Xiao Shengjun , Li Quanzhong
Published: July 2018

Objective

Statins are clinically used for protection against cardiovascular disease with lipid-lowering and anti-inflammatory properties. These properties tip the balance of macrophage polarization, which is an essential process in the development and progression of atherosclerosis. This study aimed to investigate the effect of pravastatin on atherosclerosis of the aorta in apolipoprotein E knockout (apoE-KO) mice without high lipid feeding.

Methods

Six 8-week-old apoE-KO male mice were randomly divided into two groups: a control group and a pravastatin (40 mg·kg−1·day−1)-treated group. At 35 weeks, the mice were sacrificed and the size of plaques on the aorta was assessed by Oil Red O staining. M1 and M2 macrophages were identified by inducible nitric oxide synthase and arginase-I, respectively, using immunohistochemistry.

Results

Pravastatin increased the size of atherosclerotic plaques in apoE-KO mice without high lipid feeding. The ratio of M1/M2 macrophages increased in atherosclerotic plaques, which might slow the process of atherosclerosis, while blood cholesterol levels were elevated.

Conclusion

Our study suggests that pravastatin polarizes the phenotype of macrophages toward M2 in atherosclerotic lesions, despite an increase in serum cholesterol levels in ApoE-KO mice.
Working Memory-Driven Attention in Real-World Search
Authors: Jung Shinyoung , Yoon Yosun , Han Suk Won
Published: July 2018

People’s attention is well attracted to stimuli matching their working memory. This memory-driven attentional capture has been demonstrated in simplified and controlled laboratory settings. The present study investigated whether working memory contents capture attention in a setting that closely resembles real-world environment. In the experiment, participants performed a task of searching for a target object in real-world indoor scenes, while maintaining a visual object in working memory. To create a setting similar to real-world environment, images taken from IKEA®’s online catalogue were used. The results showed that participants’ attention was biased toward a working memory-matching object, interfering with the target search. This was so even when participants did not expect that a memory-matching stimulus would appear in the search array. These results suggest that working memory can bias attention in complex, natural environment and this memory-driven attentional capture in real-world setting takes place in an automatic manner.
Optimization of small wind turbine blades using improved blade element momentum theory
Authors: Tahir Ahmed , Elgabaili Mohamed , Rajab Zakariya , Buaossa Nagi , Khalil Ashraf , Mohamed Faisal
Published: July 2018

Typically, it is desired to operate the wind turbine at the maximum power point. However, in small wind turbines which have a storage system integrated with them, harvesting as much energy as possible is more crucial. This may be achieved by reducing the cut-in speed while maximizing the mechanical power. These two goals may be achieved by optimizing the turbine blades. In this article, the turbine blades are optimized using improved blade element momentum theory including Viterna-Corrigan stall model with the objective to yield low cut-in speed and high power level. Using the blade element momentum analysis, the power coefficient curves as functions of tip-speed ratio at various range of wind speeds are obtained for the optimized turbine. Using MATLAB/Simulink tool, a wind energy system, which consists of a wind turbine, permanent magnet synchronous generator and a resistive load, is simulated. The curves obtained from the blade element momentum analysis are used to emulate the wind turbine. The results obtained from the simulation are compared to experimental results. It is noticed that the wind turbine may be optimized to harvest more energy.
Do managers forecast asymmetric cost behaviour?
Authors: Bradbury Michael E , Scott Tom
Published: July 2018

This article examines cost behaviour in a municipal (local government) setting and finds evidence of cost stickiness. We also find that costs are super-sticky as they increase even when revenues decrease. Municipals in New Zealand are required to produce forecasts, which allow us to investigate whether asymmetric cost behaviour is incorporated into forecasts. Forecast cost behaviour is found to be statistically indistinguishable from actual behaviour. In our tests, we control for asset intensity, employee intensity, expected demand, operating slack and past cost structure. The finding that the asymmetric relation between costs and revenues is incorporated into managerial forecasts suggests that cost stickiness is understood by managers rather than being merely a mechanistic outcome of cost structure.

JEL Classification: M41, D24, H72
Successful Practices and Training Initiatives to Reduce Bus Accidents and Incidents at Transit Agencies: Abridged Version of TCRP Synthesis 126
Authors: Godfrey Jodi , Staes Lisa , Flynn Jenifer , Yegidis Roberta
Published: July 2018

The purpose of this study is to document successful practices and training initiatives that have been effective in reducing transit accidents and incidents. Recognizing that safety does not occur in a vacuum, this study also focuses on other system approaches that have been implemented to address safety hazards. These approaches include various technology applications, infrastructure modifications, and other programs and initiatives, such as driver incentive programs and close call/near miss reporting. The research team conducted a literature review; performed a survey of selected transit agencies; and identified and conducted detailed case studies of 11 public transit agencies, selected from the survey respondents based on their responses to the survey. Effective safety management is comprehensive and multifocused in nature. At the case study agencies, safety management methods are often undertaken concurrently or within a period that does not provide agencies the ability to establish, with certainty, that one method or strategy contributed more to improved safety versus another. Successful programs examined in the case studies have been effective because of multifaceted, coordinated efforts to address transit safety. Strategies such as increased or modified operator training, technology applications, infrastructure modifications, and safety campaigns and promotions were often implemented simultaneously. Thus, judging the relative success of one strategy in reducing transit incidents when multiple strategies were implemented concurrently was difficult. Case study participants agreed that the progress toward a mature safety management system (SMS) framework within their agencies would contribute to an overall reduction in transit safety risks.