bluuebunny/crossref_metadata_2025 huggingface dataset:
Framework for developing labour-hour prediction models from project design features: case study in structural steel fabrication
Authors: Mohsenijam Arash , Lu Ming
Published: February 2019

Assigning labour-hours to a certain scope of work during design and estimating is still more of an art than a science. This research proposes a data-driven approach that uses multiple linear regression (MLR) and available historical data from building information models (BIM) to associate project labour-hours and project design features. The framework relies on an enhanced version of stepwise regression technique to select the most relevant predictive factors and generate a predictive model without compromising the achievable accuracy of regression. The framework also encompasses analytical methods for justifying MLR application, validating the resulting model, and establishing range estimates for point-value predictions. In collaboration with an industry partner, the framework application is exemplified by analyzing labour-hours and design features for structural steel fabrication, leading to the creation of a valid MLR model in the simplest form. Finally, pros and cons for the proposed framework and opportunities for future research are discussed.
Evolution of migrating transform faults in anisotropic oceanic crust: examples from Iceland
Authors: Karson Jeffrey A. , Brandsdóttir Bryndís , Einarsson Páll , Sæmundsson Kristján , Farrell James A. , Horst Andrew J.
Published: February 2019

Major transform fault zones link extensional segments of the North American – Eurasian plate boundary as it transects the Iceland Hotspot. Changes in plate boundary geometry, involving ridge jumps, rift propagation, and related transform fault zone migration, have occurred as the boundary has moved relative to the hotspot. Reconfiguration of transform fault zones occurred at about 6 Ma in northern Iceland and began about 3 Ma in southern Iceland. These systems show a range of different types of transform fault zones, ranging from diffuse, oblique rift zones to narrower, well-defined, transform faults oriented parallel to current plate motions. Crustal deformation structures correlate with the inferred duration and magnitude of strike-slip displacements. Collectively, the different expressions of transform zones may represent different stages of development in an evolutionary sequence that may be relevant for understanding the tectonic history of plate boundaries in Iceland as well as the structure of transform fault zones on more typical parts of the mid-ocean ridge system.
Strong–Weak Pruning for Brain Network Identification in Connectome-Wide Neuroimaging: Application to Amyotrophic Lateral Sclerosis Disease Stage Characterization
Authors: Serra Angela , Galdi Paola , Pesce Emanuele , Fratello Michele , Trojsi Francesca , Tedeschi Gioacchino , Tagliaferri Roberto , Esposito Fabrizio
Published: February 2019

Magnetic resonance imaging allows acquiring functional and structural connectivity data from which high-density whole-brain networks can be derived to carry out connectome-wide analyses in normal and clinical populations. Graph theory has been widely applied to investigate the modular structure of brain connections by using centrality measures to identify the “hub” of human connectomes, and community detection methods to delineate subnetworks associated with diverse cognitive and sensorimotor functions. These analyses typically rely on a preprocessing step (pruning) to reduce computational complexity and remove the weakest edges that are most likely affected by experimental noise. However, weak links may contain relevant information about brain connectivity, therefore, the identification of the optimal trade-off between retained and discarded edges is a subject of active research. We introduce a pruning algorithm to identify edges that carry the highest information content. The algorithm selects both strong edges (i.e. edges belonging to shortest paths) and weak edges that are topologically relevant in weakly connected subnetworks. The newly developed “strong–weak” pruning (SWP) algorithm was validated on simulated networks that mimic the structure of human brain networks. It was then applied for the analysis of a real dataset of subjects affected by amyotrophic lateral sclerosis (ALS), both at the early (ALS2) and late (ALS3) stage of the disease, and of healthy control subjects. SWP preprocessing allowed identifying statistically significant differences in the path length of networks between patients and healthy subjects. ALS patients showed a decrease of connectivity between frontal cortex to temporal cortex and parietal cortex and between temporal and occipital cortex. Moreover, degree of centrality measures revealed significantly different hub and centrality scores between patient subgroups. These findings suggest a widespread alteration of network topology in ALS associated with disease progression.
AUTOMATED GLAUCOMA DETECTION USING CENTER SLICE OF HIGHER ORDER STATISTICS
Authors: SHARMA RAHUL , SIRCAR PRADIP , PACHORI R. B. , BHANDARY SULATHA V. , ACHARYA U. RAJENDRA
Published: February 2019

Glaucoma is one of the leading causes of blindness. The raised intraocular pressure is one of the important modifiable risk factor causing glaucomatous optic nerve damage. Glaucomatous optic nerve damage is seen as increase in the cupping of the optic disc and loss of neuroretinal rim. An automated detection system using nonlinear higher order statistics (HOS) based method is used to capture the detailed information present in the fundus image efficiently. The center slice of bispectrum and bicepstrum are applied on fundus images. Various features are extracted from the diagonal of these central slices. In order to reduce the number of features the locality sensitive discriminant analysis (LSDA) data reduction technique method is implemented. The ranked LSDA features are fed to support vector machine (SVM) classifier with various kernels for automated glaucoma detection. The simulation is performed on two databases. The proposed algorithm has yielded classification accuracy of 98.8% and 95% using entire private and public databases, respectively. The proposed technique achieved the highest classification accuracy, hence, confirm the diagnosis of ophthalmologists and can be employed in the community health care centers and hospitals.
Characterizing the interaction modes of PAR4 receptor with agonist and antagonist by molecular simulation approach
Authors: Lu Nan , Meng Fancui , Yuan Jing , Liu Lei , Wang Yanshi , Li Lingjun , Zhao Tong , Xu Weiren , Tang Lida , Xu Youjun
Published: February 2019

Protease-activated receptor 4 (PAR4) is a promising target for antiplatelet therapy. In this study, homology modeling and molecular docking methods were used to investigate the binding modes of PAR4 agonists and antagonists. The outcomes show that agonists have good docking scores, and they also form more hydrogen bonds with PAR4 than antagonists. To reveal the different conformational changes caused by agonist and antagonist, molecular dynamic simulations were carried out on three selected PAR4 systems. Simulation results show that PAR4 activation involves breaking interactions of 3–7 lock switch (Try157 and Tyr322) and ionic lock switch (Arg188 and Asp173), and formation of transmission switch among Tyr161, Asn300 and Phe296. In addition, principal component analysis (PCA) indicates that the major change for agonist bound system takes place in the intracellular region while that for antagonist bound system is in the extracellular region. The binding free energy of BMS-986120 is much lower than AYPGKF, suggesting high affinity of antagonist. Moreover, the electronegative aspartic residues Asp230 and Asp235 at ECL2 are important for PAR4 binding to agonist. Clarifying the PAR4 structural characteristics may be helpful to understand the activation mechanism, giving insights into the molecular design and discovery of novel potential PAR4 antagonists in the future.
THE BIG FIVE PERSONALITY OF THE SME MANAGER AND THEIR COMPANY’S PERFORMANCE
Authors: ANTONCIC JASNA AUER , ANTONCIC BOSTJAN , GRUM DARJA KOBAL , RUZZIER MITJA
Published: February 2019

This study addresses a certain research issue: how do the Big Five personality traits of managers of small and medium-sized enterprises (SMEs) impact the business performance of companies? A representative random sample of managers of SMEs in Slovenia was used for data collection through survey research. Hypotheses and the model were tested using structural equation modeling. A valuable contribution is made in the form of a new model of Big Five personality induced SME growth, profitability and new value creation. Openness of managers can be predictive of growth and new value creation of their companies, with the new value creation impact especially expressed in female-managed companies. Conscientiousness may not be crucial for performance, except for new value creation in females where this relationship can be negative. Extraversion can predict the growth and profitability. Agreeableness can have negative effects on all performance elements. Neuroticism can be predictive of growth and profitability. Practitioners must be aware of the importance of managers’ Big Five personality traits for SME performance. Where possible, managers may like to develop their levels of openness, extraversion, non-agreeableness and neuroticism.
Multimodal use of the porphyrin TMPyP: From cancer therapy to antimicrobial applications
Authors: Garcia-Sampedro Andres , Tabero Andrea , Mahamed Ismahan , Acedo Pilar
Published: February 2019

The cationic porphyrin meso-tetra(4-[Formula: see text]-methylpyridyl)porphine (TMPyP) has a high yield of singlet oxygen generation upon light activation and a strong affinity for DNA. These advantageous properties have turned it into a promising photosensitizer for use in photodynamic therapy (PDT). In this review, we have summarized the current state-of-the-art applications of TMPyP for the treatment of cancer as well as its implementation in antimicrobial PDT. The most relevant studies reporting its pharmacokinetics, subcellular localization, mechanism of action, tissue biodistribution and dosimetry are discussed. Combination strategies using TMPyP-PDT together with other photosensitizers and chemotherapeutic agents to achieve synergistic anti-tumor effects and reduce resistance to therapy are also explored. Finally, we have addressed emerging applications of this porphyrin, including nanoparticle-mediated delivery, controlled drug release, biosensing and G-quadruplex stabilization for tumor growth inhibition. Altogether, this work highlights the great potential and versatility that TMPyP can offer in different fields of biomedicine such us cancer treatment or antimicrobial therapy.
The crustal structure of the Himalaya: A synthesis
Authors: Priestley Keith , Ho Tak , Mitra Supriyo
Published: February 2019

This chapter examines the along-arc variation in the crustal structure of the Himalayan Mountain Range. Using results from published seismological studies, plus large teleseismic body-wave and surface-wave datasets which we analyse, we illustrate the along-arc variation by comparing the crustal properties beneath four representative areas of the Himalayan Mountain Range: the Western Syntaxis, the Garhwal–Kumaon, the Eastern Nepal–Sikkim, and the Bhutan–Northeastern India regions. The Western Syntaxis and the Bhutan–Northeastern India regions have a complicated structure extending far out in front of the main Range, whereas the Central Himalaya appear to have a much simpler structure. The deformation is more distributed beneath the western and eastern ends of the Range, but in general, the crust gradually thickens from
c.
40 km on the southern side of the Foreland Basin to
c.
80 km beneath the Tethys Himalaya. While the gross crustal structure of much of the Himalaya is becoming better known, our understanding of the internal structure of the Himalaya is still sketchy. The detailed geometry of the Main Himalayan Thrust and the role of the secondary structures on the underthrusting Indian Plate are yet to be characterized satisfactorily.
Mucosal RNA and protein expression as the next frontier in IBS: abnormal function despite morphologically intact small intestinal mucosa
Authors: Rodiño-Janeiro Bruno Kotska , Pardo-Camacho Cristina , Santos Javier , Martínez Cristina
Published: February 2019

Irritable bowel syndrome (IBS) is one of the commonest gastrointestinal disorders. Although long-time considered a pure functional disorder, intense research in past years has rendered a very complex and varied array of observations indicating the presence of structural and molecular abnormalities underlying characteristic motor and sensitive changes and clinical manifestations. Analysis of gene and protein expression in the intestinal mucosa has shed light on the molecular mechanisms implicated in IBS physiopathology. This analysis uncovers constitutive and inductive genetic and epigenetic marks in the small and large intestine that highlight the role of epithelial barrier, immune activation, and mucosal processing of foods and toxins and several new molecular pathways in the origin of IBS. The incorporation of innovative high-throughput techniques into IBS research is beginning to provide new insights into highly structured and interconnected molecular mechanisms modulating gene and protein expression at tissue level. Integration and correlation of these molecular mechanisms with clinical and environmental data applying systems biology/medicine and data mining tools emerge as crucial steps that will allow us to get meaningful and more definitive comprehension of IBS-detailed development and show the real mechanisms and causality of the disease and the way to identify more specific diagnostic biomarkers and effective treatments.
Multimodal Action of Mas Activation for Systemic Cancer Cachexia Therapy
Authors: Rupert Joseph E. , Koniaris Leonidas G. , Zimmers Teresa A.
Published: February 2019

Cancer cachexia remains a largely intractable, deadly condition for patients with no approved, effective therapies. However, research progress over the past few decades demonstrates that cachexia is a disease with specific, targetable mechanisms. New work by Murphy and colleagues in this issue of Cancer Research suggests that activation of the alternative renin–angiotensin system with the nonpeptide Mas receptor agonist AVE 0991 holds promise for reducing muscle wasting in cancer. Their cell studies demonstrate on-target activity in skeletal muscle cells, whereas their mouse results suggest potentially more important systemic effects.

See related article by Murphy et al., p. 706
ATM Inhibition Sensitizes Tumors to High-Dose Irradiation
Authors: Hallahan Dennis
Published: February 2019

Mechanistic studies of high-dose irradiation are important to improve our understanding on how the efficacy of stereotactically delivered high-dose irradiation can be enhanced by therapeutics such as ataxia-telangiesctasia–mutated (ATM) inhibitors. In this issue of Cancer Research, Torok and colleagues found that a single 15 Gy radiation dose eliminated lung tumor growth in mice when ATM was deleted in cancer cells versus when deleted in endothelial cells. These data support the establishment of clinical trials testing ATM inhibitors in combination with highly conformal radiotherapy or high-dose rate brachytherapy.

See related article by Torok et al., p. 773
Is There Etiologic Heterogeneity between Subtypes of Childhood Acute Lymphoblastic Leukemia? A Review of Variation in Risk by Subtype
Authors: Williams Lindsay A. , Yang Jun J. , Hirsch Betsy A. , Marcotte Erin L. , Spector Logan G.
Published: February 2019

Although substantial advances in the identification of cytogenomic subtypes of childhood acute lymphoblastic leukemia (ALL) have been made in recent decades, epidemiologic research characterizing the etiologic heterogeneity of ALL by subtype has not kept pace. The purpose of this review is to summarize the current literature concerning subtype-specific epidemiologic risk factor associations with ALL subtype defined by immunophenotype (e.g., B-cell vs. T-cell) and cytogenomics (including gross chromosomal events characterized by recurring numerical and structural abnormalities, along with cryptic balanced rearrangements, and focal gene deletions). In case–control analyses investigating nongenetic risk factors, home paint exposure is associated with hyperdiploid, MLL-rearranged, and ETV6-RUNX1 subtypes, yet there are few differences in risk factor associations between T- and B-ALL. Although the association between maternal smoking and ALL overall has been null, maternal smoking is associated with an increasing number of gene deletions among cases. GWAS-identified variants in ARID5B have been the most extensively studied and are strongly associated with hyperdiploid B-ALL. GATA3 single nucleotide variant rs3824662 shows a strong association with Ph-like ALL (OR = 3.14). However, there have been relatively few population-based studies of adequate sample size to uncover risk factors that may define etiologic heterogeneity between and within the currently defined cytogenomic ALL subtypes.
Multiple Signal Pathways Involved in Crocetin-Induced Apoptosis in KYSE-150 Cells
Authors: Li Sheng , Qu Yuhua , Shen Xiu-Yin , Ouyang Ting , Fu Wen-Bin , Luo Tao , Wang Hua-Qiao
Published: February 2019

Background: Crocetin is a carotenoid extracted from the traditional Chinese medical herb saffron. Previous studies have demonstrated that crocetin possesses anticancer properties that are effective against various cancers. As an extension of our earlier study, the present study explored the underlying mechanisms in crocetin’s anticancer effect on KYSE-150 cells. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT), Mitogen-activated protein kinases (MAPK), and p53/p21 signal pathways play an important role in carcinogenesis, progression, and metastasis of carcinoma cells. Thus, we investigated crocetin’s effects on the PI3K/AKT, MAPK, and p53/p21 pathways in esophageal squamous carcinoma cell line KYSE-150 cells. Methods: KYSE-150 cells were treated with various concentrations of crocetin. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltertrazolium bromide assay, Annexin V/PI stain as well as Rh123 stain were used to evaluate the cell viability, apoptosis, and MMP. Western blot was used to detect the expression of PI3K, AKT, ERK1/2, p38, c-Jun NH-terminal kinase (JNK), P53, P21, Bcl-2, Bax, and cleaved caspase-3, which were associated with cell proliferation and apoptosis. Results: Our results showed that crocetin significantly inhibited the proliferation of KYSE-150 cells in a dose- and time-dependent manner. Crocetin also markedly induced cell apoptosis. Furthermore, we have found that crocetin not only inhibited the activation of PI3K/AKT, extracellular signal–regulated kinase-1/2 (ERK1/2), and p38 but also upregulated the p53/p21 level. These regulations ultimately triggered the mitochondrial-mediated apoptosis pathway with an eventual disruption of MMP, increased levels of Bax and cleaved caspase-3, and decreased levels of Bcl-2. Conclusions: These findings suggested that crocetin interfered with multiple signal pathways in KYSE-150 cells. Therefore, this study suggested that crocetin could potentially be used as a therapeutic candidate for the treatment of esophageal cancer.
From HPV Infection to Lesion Progression: The Role of HLA Alleles and Host Immunity
Authors: Paaso Anna , Jaakola Anna , Syrjänen  Stina , Louvanto Karolina 
Published: February 2019

Persistent high-risk human papillomavirus (HPV) infection has been associated with increased risk for cervical precancerous lesions and cancer. The host’s genetic variability is known to play a role in the development of cervical cancer. The human leukocyte antigen (HLA) genes are highly polymorphic and have shown to be important risk determinants of HPV infection persistence and disease progression. HLA class I and II cell surface molecules regulate the host’s immune system by presenting HPV-derived peptides to T-cells. The activation of T-cell response may vary depending on the HLA allele polymorphism. The engagement of the T-cell receptor with the HPV peptide-HLA complex to create an active costimulatory signal is essential for the activation of the T-cell response. Functional peptide presentation by both HLA class I and II molecules is needed to activate efficient helper and effector T-cell responses in HPV infection recognition and clearance. Some of these HLA risk alleles could also be used as preventive tools in the detection of HPV-induced cervical lesions and cancer. These HLA alleles, together with HPV vaccines, could potentially offer possible solutions for reducing HPV-induced cervical cancer as well as other HPV-related cancers.
Epigenetic Factors in Schizophrenia: Mechanisms and Experimental Approaches
Authors: Föcking Melanie , Doyle Benjamin , Munawar Nayla , Dillon Eugene T. , Cotter David , Cagney Gerard
Published: February 2019

Schizophrenia is a chronic mental disorder that is still poorly understood despite decades of study. Many factors have been found to contribute to the pathogenesis, including neurodevelopmental disturbance, genetic risk, and environmental insult, but no single root cause has emerged. While evidence from twin studies suggests a strong heritable component, few individual loci have been identified in genomewide screens, suggesting a role for epigenetic effects. Rather, large numbers of weakly acting loci may cumulatively increase disease risk, including several mapping to epigenetic pathways. In this review, we discuss mechanisms of epigenetic regulation and evidence for an epigenetic contribution to disease phenotype. We further describe the range of experimental tools currently available to study epigenetic effects associated with the disease.
Treating Untreatable Rectal Varices
Authors: Garrido Mónica , Gonçalves Belarmino , Ferreira Sofia , Rocha Marta , Salgado Marta , Pedroto Isabel
Published: February 2019

Background: Rectal varices are portosystemic collaterals that arise as a complication of portal hypertension. Despite their significant prevalence among cirrhotic patients, clinically important bleeding occurs only in a minority. Various treatment options are available, with endoscopic therapies being widely used, and both interventional radiology and surgery being considered for refractory bleeding rectal varices. Case: We report the case of a 61-year-old male with hepatic cirrhosis and bleedingrectal varices refractory to endoscopic therapy, successfully managed with a combination of transjugular intrahepatic portosystemic shunt (TIPS) and selective variceal embolization. Conclusions: Radiological techniques are effective options for refractory bleeding. Adding embolization to TIPS implantation could represent a valid adjunctive measure for haemostasis of recurrent rectal variceal bleeding.
Current Status of p16 Immunohistochemistry and HPV Testing in Fine Needle Aspiration Specimens of the Head and Neck
Authors: Jalaly Jalal B. , Hosseini Sayed Mohsen , Shafique Khurram , Baloch Zubair W.
Published: February 2019

Human papilloma virus (HPV)-related squamous cell carcinoma (SCC) is biologically unique and has a better prognosis than conventional SCC of the head and neck. p16 immunohistochemistry emerged as a valuable surrogate marker for HPV in oropharyngeal SCC. The criteria for a positive p16 result in tissue specimens are well established. However, there is no consensus regarding interpreting p16 staining in cell blocks and other cytology specimens. This review discusses the current evidence on p16 testing in cytology specimens and also highlights other methods for HPV testing, including DNA and RNA in situ hybridization, as well as other molecular HPV tests.
Measurement of Structural Parameters of the Lamina Cribrosa in Primary Open-Angle Glaucoma and Chronic Primary Angle-Closure Glaucoma by Optical Coherence Tomography and Its Correlations with Ocular Parameters
Authors: Hao Linlin , Xiao Hui , Gao Xue , Xu Xiaoyu , Liu Xing
Published: February 2019

Purpose: To measure lamina cribrosa thickness (LCT) and anterior lamina cribrosa surface depth (ALCSD) in primary open-angle glaucoma (POAG), chronic primary angle-closure glaucoma (CPACG), and control patients using spectral-domain optical coherence tomography (SD-OCT) and examine its association with relevant ocular parameters. Methods: In this cross-sectional study, 61 healthy volunteers (61 eyes), 65 POAG patients (65 eyes), and 55 CPACG patients (55 eyes) were recruited to obtain radial B-scans of the optic nerve head by way of enhanced depth imaging using Heidelberg SD-OCT. The obtained LCT and ALCSD were compared among the control, POAG, and CPACG groups. In addition, we evaluated the relationships of mean lamina cribrosa (LC) parameters with visual field (VF) mean deviation (MD), retinal nerve fiber layer (RNFL) thickness, intraocular pressure (IOP), and axial length. Results: The mean LCT of CPACG eyes was greater than that of POAG eyes (p = 0.003), but less than that of normal eyes (p < 0.001). The mean ALCSD of POAG and CPACG eyes was greater than that of normal control eyes (both p < 0.001). However, the mean ALCSD showed no significant difference between the POAG and CPACG groups (p = 0.073). Among all eyes, lower MD and thinner RNFL thickness were associated with a deeper and thinner LC (all p < 0.001). Conclusion: LCT is thinner in POAG compared to CPACG eyes. This is compatible with less deformation and compression of the LC in CPACG eyes, implying that the mechanisms of glaucomatous damage are different between POAG and CPACG eyes. Furthermore, VF MD and RNFL thickness were related to LCT and ALCSD in all patients.
Association of Menopausal Age with Unruptured Intracranial Aneurysm Morphology
Authors: Dharmadhikari Sushrut , Atchaneeyasakul Kunakorn , Ambekar Sudheer , Saini Vasu , Haussen Diogo C. , Yavagal Dileep
Published: February 2019

Background: The prevalence of unruptured intracranial aneurysms (UIAs) increases rapidly in aging women compared with younger women. The impact of menopausal age on UIAs and treatment outcomes with endovascular therapy has not been well studied. We hypothesized that premenopausal age may have a protective effect on presentation size and treatment outcomes. Objective: To evaluate the association of menopause with UIA size and outcome with endovascular therapy. Methods: Retrospective analysis of consecutive female patients with UIAs treated with endovascular therapy at our academic tertiary care center. UIA characteristics, complications, and outcomes were recorded and compared. Results: 117 patients were included: 23 patients in the premenopausal age (PRM) group and 94 in the postmenopausal age (POM) group. 93.6% of all aneurysms in the PRM group were in the internal carotid artery (ICA) segments (p < 0.05). Hence only ICA segment aneurysms were further studied. A total of 21 patients in the PRM group and 60 in the POM group were found to have ICA segment aneurysms. Baseline characteristics were similar between the 2 groups. The mean size of the aneurysms in the PRM group was 8.6 ± 3.9 versus 10.8 ± 5.6 mm in the POM group (p = 0.055). There was a trend to higher aneurysm neck size seen in the POM group (4.7 ± 2.5 vs. 3.7 ± 1.7 mm; p = 0.07). The number of aneurysm lobes was higher in the PRM group (1.23 ± 0.54 vs. 1.07 ± 0.31; p = 0.18). In multivariate analysis, the PRM group had a significantly higher number of UIA lobes. Complications and endovascular therapy outcomes were similar between the 2 groups. Conclusions: A trend to increased UIA maximal diameter and neck size was seen in the POM group compared to the PRM group. The PRM group had a significantly higher number of UIA lobes. Larger prospective trials are needed to confirm these findings.
Renal Impairment Is Associated with Intracerebral Hemorrhage after Mechanical Thrombectomy in Vertebrobasilar Stroke
Authors: Laible Mona , Jenetzky Ekkehart , Möhlenbruch Markus A. , Neuberger Ulf , Bendszus Martin , Ringleb Peter A. , Rizos Timolaos
Published: February 2019

Background and Purpose: Renal dysfunction (RD) is overall associated with unfavorable functional outcome and higher risk of mortality after acute ischemic stroke. Associations between RD and outcome in patients with acute vertebrobasilar stroke treated with thrombectomy have not been evaluated so far. Materials and Methods: Consecutive patients with vertebrobasilar stroke treated with mechanical thrombectomy between October 2010 and July 2017 at our center were analyzed. RD was defined as glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 at admission. Endpoints were (I) poor clinical outcome (modified Rankin Scale > 2) at 3 months, (II) 3-month mortality, and (III) intracerebral hemorrhage (ICH) after treatment. Results: Overall, 106 patients were included. Median age was 73.0 years (interquartile range 62.0–80.0), and RD was present in 20.8%. Multivariate analysis revealed that RD was associated with a higher risk for any ICH (OR 3.54; 95% CI 1.09–11.49; p = 0.035). Stroke severity at onset predicted poor clinical outcome (OR 1.08; 95% CI 1.03–1.14; p = 0.003). Neither low GFR nor any ICH, but stroke severity (OR 1.08; 95% CI 1.03–1.14; p = 0.002) and poor recanalization results (OR 11.38; 95% CI 2.01–64.41; p = 0.006) were associated with a higher risk for mortality. Conclusions: Patients with RD and acute vertebrobasilar stroke should be thoroughly monitored to prevent ICH after thrombectomy. Our results support performing mechanical thrombectomy in acute stroke patients with large vessel occlusions of the posterior circulation, irrespective of their renal function.
Efeitos adversos do uso de imunobiológicos no tratamento da psoríase
Authors: Fernandes Mariana Oliveira , Pereira Lucas Ferreira Gomes , Monteiro Letícia Vilela Portugal , Nascimento Henrique José do , Fonseca Walter Luiz Moraes Sampaio da
Published: February 2019

A psoríase é uma doença sistêmica e inflamatória que apresenta evolução de intensidades variadas, relaciona-se a um grande impacto físico e psicológico. Nos casos moderados a graves da enfermidade, o uso de imunobiológicos é a terapêutica de escolha uma vez que o tratamento tradicional não apresente resultados satisfatórios. No entanto, como o emprego destes medicamentos é relativamente recente nesta doença, devido aos efeitos colaterais ainda não totalmente esclarecidos e custo elevado, seu uso é recomendado por especialistas com cautela. Com o objetivo de estudar os efeitos adversos dos imunobiológicos (Etanercepte, Adalimumabe, Infliximabe, Efalizumabe e Ustekinumabe) foi realizada uma revisão integrativa da literatura, na qual foram selecionados, após a adequação aos critérios de inclusão e exclusão, 5 dos 66 artigos obtidos. Após a análise dos dados, concluiu-se que, ela deve ser usada com cautela e seguindo os protocolos nacionais e internacionais, devido a grande variedade de efeitos adversos encontrados.
Contemporary Discrepancies of Stenosis Assessment by Computed Tomography and Invasive Coronary Angiography
Authors: Song Young Bin , Arbab-Zadeh Armin , Matheson Matthew B. , Ostovaneh Mohammad R. , Vavere Andrea L. , Dewey Marc , Rochitte Carlos , Niinuma Hiroyuki , Laham Roger , Schuijf Joanne D. , Cox Christopher , Brinker Jeffrey , di Carli Marcelo , Lima João A.C. , Miller Julie M.
Published: February 2019

Background

Ongoing advancements of coronary computed tomographic angiography (CTA) continue to challenge the role of invasive coronary angiography (ICA) as the gold standard for the evaluation of coronary artery disease (CAD). We sought to investigate the diagnostic accuracy of 320-slice CTA for detecting obstructive CAD in reference to ICA and nuclear myocardial perfusion imaging using single-photon emission computed tomography.

Methods

For the CORE320 study (Coronary Artery Evaluation Using 320-Row Multidetector Computed Tomography Angiography and Myocardial Perfusion), 381 patients at 16 centers underwent CTA, nuclear myocardial perfusion imaging by single-photon emission computed tomography, and ICA for the evaluation of CAD. Imaging studies were analyzed in blinded core laboratories, and a stenosis of ≥50% by quantitative coronary angiography was considered obstructive, whereas a stress difference score of ≥1 indicated inducible myocardial ischemia. The area under the receiver operating characteristic curve was used to evaluate diagnostic accuracy.

Results

Of 381 patients, 229 (60%) had obstructive CAD by quantitative coronary angiography. Diagnostic accuracy of CTA on a per-patient analysis revealed an area under the receiver operating characteristic curve of 0.90 (95% CI, 0.87–0.93). Per-vessel and per-segment analysis revealed lower area under the receiver operating characteristic curve of 0.87 (0.84–0.90) and 0.81 (0.78–0.83), respectively. Median radiation dose was lower for CTA versus ICA: 3.16 (interquartile range, 2.82–3.59) versus 11.97 (interquartile range, 7.60–17.8) mSv (
P
<0.001). Accuracy for identifying patients with inducible myocardial ischemia by SPECT-MPI was similar for CTA and ICA (area under the receiver operating characteristic curve, 0.68 versus 0.71 by quantitative coronary angiography and 0.68 by visual angiographic assessment;
P
>0.05). Furthermore, accuracy for identifying patients who subsequently underwent clinically driven coronary revascularization also was similar for CTA (0.76 [0.71–0.81]) and ICA (0.78 [0.74–0.83];
P
=0.20).

Conclusions

Contemporary CTA accurately identifies patients with obstructive CAD by ICA at lower radiation exposure; however, agreement is lower in vessel- and segment-level analyses. Both CTA and ICA perform similarly for predicting clinically driven revascularization and for detecting myocardial ischemia by myocardial perfusion imaging using single-photon emission computed tomography, suggesting that limitations by both CTA and ICA contribute to variability of stenosis quantification.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00934037.
Sequential Monitoring of the Comparative Effectiveness and Safety of Dabigatran in Routine Care
Authors: Schneeweiss Sebastian , Gopalakrishnan Chandrasekar , Bartels Dorothee B. , Franklin Jessica M. , Zint Kristina , Kulldorff Martin , Huybrechts Krista F.
Published: February 2019

Background:

The increasing availability of electronic healthcare data enables ongoing monitoring of the effectiveness and safety of newly marketed medications. We sought to demonstrate a 5-year prospective monitoring system of dabigatran for stroke prevention that may expedite discovery and allow ongoing evidence development.

Methods and Results:

Between 2011 and 2015, we conducted 9 sequential analyses of dabigatran versus warfarin users in a sequential cohort design in 2 US claims databases. Analyses 4 through 9 were prespecified, and analyses 1 through 3 were added subsequently using the same methodology. New users of anticoagulants with nonvalvular atrial fibrillation were followed until a study outcome of hospitalization for stroke (hemorrhagic and ischemic) or hospitalization for major hemorrhage (intracranial and extracranial). Hazard ratios and 95% CIs were estimated after 1:1 propensity score matching. Sequential analyses 1 through 3 on stroke prevention using data through June 2012 were limited by few events leading to wide CIs. As data accumulated the effect estimate in analysis 4 visually stabilized at a 25% risk reduction with increasingly narrower CIs (−46% to +9% in December 2012 and −42% to −2% in September 2015). Improved data-adaptive confounding adjustment with high-dimensional propensity score reached a stable state already at analysis 3 and was slightly closer to the randomized clinical trial finding (−39%). The risk of major hemorrhage was 28% lower in dabigatran initiators (−35% to −20%) a finding that was stable throughout analyses 2 to 9.

Conclusions:

Prospectively monitoring the effectiveness and safety of dabigatran for stroke prevention allowed for early insights with increasing precision over time.
Maintenance of Gains, Morbidity, and Mortality at 1 Year Following Cardiac Rehabilitation in a Middle‐Income Country: A Wait‐List Control Crossover Trial
Authors: Chaves Gabriela S. S. , Lima de Melo Ghisi Gabriela , Britto Raquel R. , Grace Sherry L.
Published: February 2019

Background

Despite the epidemic of cardiovascular diseases in middle‐income countries, few trials are testing the benefits of cardiac rehabilitation (
CR
). This trial assessed (1) maintenance of functional capacity, risk factor control, knowledge, and heart‐health behaviors and (2) mortality and morbidity at 6 months following
CR
in a middle‐income country.

Methods and Results

Eligible Brazilian coronary patients were initially randomized (1:1:1 concealed) to 1 of 3 parallel arms (comprehensive
CR
[exercise plus education], exercise‐only
CR
, or wait‐list control). The
CR
programs were 6 months in duration, at which point follow‐up assessments were performed. Mortality and morbidity were ascertained from chart and patient or family report (blinded). Controls were then offered
CR
(crossover). Outcomes were again assessed 6 months later (blinded). ANCOVA was performed for each outcome at 12 months. Overall, 115 (88.5%) patients were randomized, and 62 (53.9%) were retained at 1 year. At 6 months, 23 (58.9%) of those 39 initially randomized to the wait‐list control elected to attend
CR
. Functional capacity, risk factors, knowledge, and heart‐health behaviors were maintained from 6 to 12 months in participants from both
CR
arms (all
P
>0.05). At 1 year, knowledge was significantly greater with comprehensive
CR
at either time point (
P
<0.001). There were 2 deaths. Hospitalizations (
P
=0.03), nonfatal myocardial infarctions (
P
=0.04), and percutaneous coronary interventions (
P
=0.03) were significantly fewer with
CR
than control at 6 months.

Conclusions

CR
participation is associated with lower morbidity, long‐term maintenance of functional capacity, risk factors, and heart‐health behaviors, as well as with greater cardiovascular knowledge compared with no
CR
.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02575976.
Guiding Neuroevolution with Structural Objectives
Authors: Ellefsen Kai Olav , Huizinga Joost , Torresen Jim
Published: February 2019

The structure and performance of neural networks are intimately connected, and by use of evolutionary algorithms, neural network structures optimally adapted to a given task can be explored. Guiding such neuroevolution with additional objectives related to network structure has been shown to improve performance in some cases, especially when modular neural networks are beneficial. However, apart from objectives aiming to make networks more modular, such structural objectives have not been widely explored. We propose two new structural objectives and test their ability to guide evolving neural networks on two problems which can benefit from decomposition into subtasks. The first structural objective guides evolution to align neural networks with a user-recommended decomposition pattern. Intuitively, this should be a powerful guiding target for problems where human users can easily identify a structure. The second structural objective guides evolution towards a population with a high diversity in decomposition patterns. This results in exploration of many different ways to decompose a problem, allowing evolution to find good decompositions faster. Tests on our target problems reveal that both methods perform well on a problem with a very clear and decomposable structure. However, on a problem where the optimal decomposition is less obvious, the structural diversity objective is found to outcompete other structural objectives—and this technique can even increase performance on problems without any decomposable structure at all.
Multiclass Alpha Integration of Scores from Multiple Classifiers
Authors: Safont Gonzalo , Salazar Addisson , Vergara Luis
Published: February 2019

Alpha integration methods have been used for integrating stochastic models and fusion in the context of detection (binary classification). Our work proposes separated score integration (SSI), a new method based on alpha integration to perform soft fusion of scores in multiclass classification problems, one of the most common problems in automatic classification. Theoretical derivation is presented to optimize the parameters of this method to achieve the least mean squared error (LMSE) or the minimum probability of error (MPE). The proposed alpha integration method was tested on several sets of simulated and real data. The first set of experiments used synthetic data to replicate a problem of automatic detection and classification of three types of ultrasonic pulses buried in noise (four-class classification). The second set of experiments analyzed two databases (one publicly available and one private) of real polysomnographic records from subjects with sleep disorders. These records were automatically staged in wake, rapid eye movement (REM) sleep, and non-REM sleep (three-class classification). Finally, the third set of experiments was performed on a publicly available database of single-channel real electroencephalographic data that included epileptic patients and healthy controls in five conditions (five-class classification). In all cases, alpha integration performed better than the considered single classifiers and classical fusion techniques.
Filtering Compensation for Delays and Prediction Errors during Sensorimotor Control
Authors: Crevecoeur F. , Gevers M.
Published: February 2019

Compensating for sensorimotor noise and for temporal delays has been identified as a major function of the nervous system. Although these aspects have often been described separately in the frameworks of optimal cue combination or motor prediction during movement planning, control-theoretic models suggest that these two operations are performed simultaneously, and mounting evidence supports that motor commands are based on sensory predictions rather than sensory states. In this letter, we study the benefit of state estimation for predictive sensorimotor control. More precisely, we combine explicit compensation for sensorimotor delays and optimal estimation derived in the context of Kalman filtering. We show, based on simulations of human-inspired eye and arm movements, that filtering sensory predictions improves the stability margin of the system against prediction errors due to low-dimensional predictions or to errors in the delay estimate. These simulations also highlight that prediction errors qualitatively account for a broad variety of movement disorders typically associated with cerebellar dysfunctions. We suggest that adaptive filtering in cerebellum, instead of often-assumed feedforward predictions, may achieve simple compensation for sensorimotor delays and support stable closed-loop control of movements.
Deconstructing Odorant Identity via Primacy in Dual Networks
Authors: Kepple Daniel R. , Giaffar Hamza , Rinberg Dmitry , Koulakov Alexei A.
Published: February 2019

In the olfactory system, odor percepts retain their identity despite substantial variations in concentration, timing, and background. We study a novel strategy for encoding intensity-invariant stimulus identity that is based on representing relative rather than absolute values of stimulus features. For example, in what is known as the primacy coding model, odorant identities are represented by the conditions that some odorant receptors are activated more strongly than others. Because, in this scheme, odorant identity depends only on the relative amplitudes of olfactory receptor responses, identity is invariant to changes in both intensity and monotonic nonlinear transformations of its neuronal responses. Here we show that sparse vectors representing odorant mixtures can be recovered in a compressed sensing framework via elastic net loss minimization. In the primacy model, this minimization is performed under the constraint that some receptors respond to a given odorant more strongly than others. Using duality transformation, we show that this constrained optimization problem can be solved by a neural network whose Lyapunov function represents the dual Lagrangian and whose neural responses represent the Lagrange coefficients of primacy and other constraints. The connectivity in such a dual network resembles known features of connectivity in olfactory circuits. We thus propose that networks in the piriform cortex implement dual computations to compute odorant identity with the sparse activities of individual neurons representing Lagrange coefficients. More generally, we propose that sparse neuronal firing rates may represent Lagrange multipliers, which we call the dual brain hypothesis. We show such a formulation is well suited to solve problems with multiple interacting relative constraints.
An Opaque Pun
Authors: Chen Ruixuan
Published: February 2019

Various interpretations of Kāśyapaparivarta § 68 have been attempted in the Yogācāra-Vijñānavāda tradition. This passage, which consists in a simile likening a magician devoured by his own creation to a monk involved in meditation practice, appears prima facie absurd, insofar as the similarity between the tenor and the vehicle is not readily apparent. This article mainly consists of two parts: The first part examines the received interpretations of the simile and reconstructs their interrelationship from a historical perspective. The second part explores the literary dimension of the simile and argues that its ostensible absurdity is rooted in a pun which is visible only in Middle Indo-Aryan and seems to serve no purpose. Coming to terms with the opaque and pointless pun, this essay is aimed at a new interpretation of Kāśyapaparivarta § 68 and, it is hoped, a deeper understanding of the literary playfulness inherent in the making of the Kāśyapaparivarta as a so-called early Mahāyāna sūtra against the backdrop of the Sanskritization of Buddhist sūtra literature.
Another alien bug in Europe: the first case of transcontinental introduction
of the Asiatic burrower bug Macroscytus subaeneus (Dallas, 1851) (Hemiptera: Heteroptera: Cydnidae) to the U.K. through maritime transport
Authors: LIS JERZY A. , WHITEHEAD PAUL F.
Published: February 2019

The Oriental burrower bug Macroscytus subaeneus (Dallas, 1851) (Hemiptera: Heteroptera: Cydnidae: Cydninae), presently known only from single localities in Flores (Indonesia), the Philippines and Thailand, is recorded from the United Kingdom (hereafter U.K.). A single female specimen was collected on the semi-rural edge of Bath city by a Starling (Sturnus vulgaris L.) and taken to its nest from which it was retrieved during 2015. The specimen is illustrated and its diagnostic characters are provided. We hypothesize that this specimen could have been imported with a shipping container from Thailand.
A new subspecies of Glabroculus elvira (Eversmann, 1854) (Lepidoptera, Lycaenidae) from the Dzhungarian Gobi desert, Mongolia
Authors: CHURKIN SERGEI V. , KOLESNICHENKO KIRILL A.
Published: February 2019

Glabroculus elvira suadela ssp. n. is described from the Dzhungarian Gobi desert. The species was not previously recorded in Mongolia. The new subspecies can be easily differentiated from other known conspecific taxa by the bright shiny upperside in males and contrasting upperside in females, with conspicuous whitish spots.
Explaining Extreme Events of 2017 from a Climate Perspective
Authors: Herring Stephanie C. , Christidis Nikolaos , Hoell Andrew , Hoerling Martin P. , Stott Peter A.
Published: February 2019

Editors note: For easy download the posted pdf of the Explaining Extreme Events of 2016 is a very low-resolution file. A high-resolution copy of the report is available by clicking here. Please be patient as it may take a few minutes for the high-resolution file to download.