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Technological advancement in smart cities can have adverse effects on the environment. Timely monitoring of smart cities to preserve environmental sustainability is a thrust area of research. It can be done by using change detection with multi-temporal satellite data. The success of these methods solely depends on the calibre of the backend image segmentation and Land-use Land-cover classification technique. The limitation of using cutting-edge classification algorithms is the availability of a proper dataset and identification of the edge structure of different LULC classes. In contrast, a segmentation algorithm cannot detect LULC classes automatically. In this research, we eliminated these shortcomings by considering a hybrid approach. We proposed a multi-class Support Vector Machine (SVM) and ISODATA-embedded large-scale change detection method. This method can automatically segment, detect, and perform LULC change analysis. We have considered the multi-sensor dataset of Barasat, West Bengal, India, obtained from the WorldView satellite sensor for the experimental study. The proposed method is validated concerning three different cutting-edge methods. [ABSTRACT FROM AUTHOR]

This article explores the relationship between a specific gene polymorphism (CDHR3) and pediatric asthma and its treatment response. The study used a dataset of 1100 children and young adults with a clinical diagnosis of pediatric asthma and analyzed associations between the CDHR3 genotype and prescriptions for asthma medication over a 13-year period. The results showed that individuals with the GA genotype had a more severe phenotype and a higher prevalence of hospitalizations and asthma exacerbations compared to those with the wild-type genotype. However, individuals with the AA genotype had a less severe phenotype and a lower prevalence of certain asthma medications. The study suggests that further research is needed to understand the mechanisms of CDHR3 and its effects on asthma. [Extracted from the article]

The masses and radii of non-rotating and rotating configurations of pure hadronic stars mixed with self-interacting fermionic asymmetric dark matter are calculated within the two-fluid formalism of stellar structure equations in general relativity. The Equation of State (EoS) of nuclear matter is obtained from the density dependent M3Y effective nucleon-nucleon interaction. We consider the dark matter particle mass of 1 GeV. The EoS of self-interacting dark matter is taken from two-body repulsive interactions of the scale of strong interactions. We explore the conditions of equal and different rotational frequencies of nuclear matter and dark matter and find that the maximum mass of differentially rotating stars with self-interacting dark matter to be $${\sim }1.94 \;\mathrm{M}_\odot $$ with radius $${\sim }10.4$$ km. [ABSTRACT FROM AUTHOR]

Background: Asthma is a common problem in children and, if inadequately controlled, may seriously diminish their quality of life. Inhaled short-acting beta2 agonists such as salbutamol are usually prescribed as 'reliever' medication to help control day-to-day symptoms such as wheeze. As with many medications currently prescribed for younger children (defined as those aged 2 years 6 months to 6 years 11 months), there has been no pre-licensing age-specific pharmacological testing; consequently, the doses currently prescribed (200-1000 μg) may be ineffective or likely to induce unnecessary side effects. We plan to use the interrupter technique to measure airway resistance in this age group, allowing us for the first time to correlate inhaled salbutamol dose with changes in clinical response. We will measure urinary salbutamol levels 30 min after dosing as an estimate of salbutamol doses in the lungs, and also look for genetic polymorphisms linked to poor responses to inhaled salbutamol. Methods: This is a phase IV, randomised, controlled, observer-blinded, single-centre trial with four parallel groups (based on a sparse sampling approach) and a primary endpoint of the immediate bronchodilator response to salbutamol so that we can determine the most appropriate dose for an individual younger child. Simple randomisation will be used with a 1:1:1:1 allocation. Discussion: The proposed research will exploit simple, non-invasive and inexpensive tests that can mostly be performed in an outpatient setting in order to help develop the evidence for the correct dose of salbutamol in younger children with recurrent wheeze who have been prescribed salbutamol by their doctor. [ABSTRACT FROM AUTHOR]

Background To compare the role of topically applied serum therapy with preservative-free artificial tear (AT) drops in patients with moderate to severe dry eye in Hansen's disease along with change in tear protein profile. Methods 144 consecutive patients were randomly divided into three groups. After a baseline examination of clinical parameters, each of the patients received designated modality of topical therapy six times a day for 6 weeks. Post-treatment documentation of clinical parameters was done at 6 weeks, and then at 12 weeks after discontinuation of topical therapy. Analysis of three tear proteins using gel electrophoresis (sodium dodecyl sulfate polyacrylamide gel electrophoresis) was done at baseline, at the first and second post-treatment visits. Results In the cord blood serum (CBS) group, except for McMonnies score and staining score, all other clinical parameters showed continued improvement in the first and second post-treatment analyses. In the autologous serum (ALS) group, all the clinical parameters except Schirmer's I showed significant improvement in the first post-treatment analysis .This was sustained at a significant level in the second analysis except for tear film break-up time (TBUT) and conjunctival impression cytology grading. In the AT group, all the parameters improved at a non-significant level except for TBUT in the first analysis. In the next analysis, apart from McMonnies score and TBUT, other clinical parameters did not improve. In the ALS and CBS groups, tear lysozyme, lactoferrin levels improved in both posttreatment measurements (statistically insignificant).Total tear protein continued to increase at statistically significant levels in the first and second post-treatment analyses in the CBS group and at a statistically insignificant level in the ALS group. In the AT group, the three tear proteins continued to decrease in both the analyses. Conclusions In moderate to severe dry eye in Hansen's disease, serum therapy in comparison with AT drops, improves clinical parameters and causes betterment in tear protein profile. [ABSTRACT FROM AUTHOR]

This paper proposed a fuzzy-based switching technique that aims at detection and filtering of impulse noises from digital images. Two types of noise models are used to obtain the noisy images. In this two-step process, the noise-free pixels are remained unchanged. The proposed detection algorithm uses 5 $$\times $$ 5 window, based on all neighboring pixels on the center of the window of a noisy pixel. Two weighted median filters are devised, and a particular one is applied selectively to the noisy pixel based on the characteristics of the neighboring pixels within the window. Instead of a single threshold, two threshold values are used in the proposed fuzzy membership function to partition the noise level, and accordingly, a filtering method is applied to restore the corrupted pixel. Experimental results show that the proposed technique outperforms the existing impulse denoising methods in terms of peak signal-to-noise ratio and visual effects, with a comparable time complexity with the existing methods. [ABSTRACT FROM AUTHOR]

Determining the attributes that influence the success of e-commerce is difficult due to a limited conceptual basis necessary for success measures. Keeney (1999) proposed twenty-five objectives separated into two sets-fundamental objectives (the important goals of customers) and means objectives (important goals to be achieved by e-businesses) for successful e-transactions. Based on Keeney's research, Torkzadeh and Dhillon (2002) developed two instruments that together measure the factors that influence e-commerce success. This research uses these instruments to empirically investigate the Internet shopping behavior of college students (undergraduate and graduate). The research determines the adequacy of multivariate linear relationships between the variables of the two instruments through canonical correlation and redundancy analyses. The research formalizes and tests a series of research hypotheses on Internet shopping behaviors. The article also summarizes the research results with important conclusions and future research directions. [ABSTRACT FROM AUTHOR]

Abstract: Although chest physiotherapy is central to the management of cystic fibrosis many report problems with adherence. Research in other long-term conditions suggests that non-adherence may be exacerbated as the child grows older and self-care responsibilities are transferred to the young person. We explored the nature and variation in roles of family members, how responsibility was transferred from the parent/family to the child, and what factors aided or hindered this process. We conducted in-depth interviews with 32 children with a diagnosis of cystic fibrosis aged 7–17 years, and with 31 parents attending cystic fibrosis clinics in two Scottish regions. Family responsibilities were primarily focused on mothers. The level and nature of involvement varied along a continuum that separated into six parental and five child roles and changed over time. However, this movement was frequently reversed during periods of illness or mistrust. The day to day experience of such a transfer was not straightforward, linear or unproblematic for any of the family members. Three factors were identified as assisting the transfer of responsibility: parents’ perceptions of the benefits of transferring responsibility, children''s perceptions of the benefits, and the available physical, social and psychological resources to support such a transfer. The principles and lessons from “concordance” (a therapeutic alliance based on a negotiation between equals and which may lead to agreement on management or agreement to differ) may provide a foundation for newly developing relationships between parents and their children emerging into adulthood. Further research is required to develop more specifically the content and structure of required support, its effectiveness in achieving more concordant relationships, and the resulting impact on adherence, perceived health and well-being from the perspective of the young person and parent. [Copyright &y& Elsevier]

Abstract: CB2 cannabinoid receptors exist in immune cells including macrophages. Affinity-purified antibodies against the CB2 receptor identified a 45 kDa protein in rat brain, human tonsil and rat and mouse microglia, but not mouse N18TG2 neuroblastoma cells. Intracerebroventricular lipopolysaccharide (LPS) increased immunoreactive CB2 receptors in brain membranes detected by Western blot. LPS increased immunodetectable CB2 receptors in cultured RAW 264.7 macrophages, and this was partially attenuated by cyclohexamide or the protein kinase A and C inhibitors H8 and bis-indolylmaleimide. Forskolin or dibutyryl cyclic AMP increased CB2 receptor immunoreactivity, suggesting the involvement of the cyclic AMP–protein kinase A–Cyclic AMP response element pathway in the regulation of CB2 receptor levels. [Copyright &y& Elsevier]

Effects of cannabinoid compounds on neurons are predominantly mediated by the CB1 cannabinoid receptor. Onset of signaling cascades in response to cannabimimetic drugs is triggered by the interaction of the cannabinoid receptor with Gi/o proteins. Much work has been done to delineate the cannabinoid agonist-induced downstream signaling events; however, it remains to define the molecular basis of cannabinoid receptor-G protein interactions that stimulate these signaling pathways. In this review, we discuss several signal transduction pathways, focusing on studies that demonstrate the efficacy of CB1 receptor agonists through G protein mediated pathways. [Copyright &y& Elsevier]

Examines the association of cannabinoid (CB) receptor with G protein. Role of G proteins in signal transduction; Inhibition of the adenulate cyclase; Reduction of the pertussis toxin in the CB receptor.

Examines the regulation of Gi by the CB1 cannabinoid receptor C-terminal juxtamembrane region. Structural analysis determined by peptide analysis; Activation of Bi by peptide CB1; Determination of functionally critical amino acids of CB1 peptide; Evaluation of the CB1 receptor juxtamembrane C-terminal conformation using peptide fragments.

The article focuses on a meta-analysis of nebulized antibiotics used in the treatment of cystic fibrosis. The controversy surrounding the nebulized anti-pseudomonal antibiotic therapy for cystic fibrosis is discussed, as well as the characteristics of the randomized controlled trials listed for the meta-analysis. The meta-analysis found no major side-effects with nebulized anti-pseudomonal antibiotic therapy, although a trend towards an increase in resistance to Pseudomonas aeruginosa in sputum was noted.

Presents an algorithm for constructing and training a class of higher-order perceptrons for classification problems. Linear programming model for classification; The sequential masking (SM) algorithm and some properties; Computational results of the implementation of SM; Classifying sonar targets; Conclusion of the study.

Provides information on a method for pattern classification that uses linear programming formulations. Generation on neural network computer; Discussion on parallel computation.

Investigates the presence of a high-affinity G protein-coupled prostaglandin (PGE)-2 binding site on the type II pneumocyte apical membrane of the term guinea pig fetus. Modulation of high-affinity GTPase activity; Protein-dependent components of Na+ transport through conductive pathways.

Provides information on a study exploring the hypothesis that G protein-coupled prostaglandin (PG) E2 receptor controls perinatal lung alveolar Na+ transport. Methodology and materials used to conduct the study; Results of the study.

A letter to the editor is presented in response to a study about the Best Add-on Therapy Giving Effective Responses (BADGER) trial, which showed the likelihood of step-up therapy with long-acting beta agonists (LABA) to provide the best response to controlling asthma compared with either inhaled corticosteroids (ICS) or leukotriene-receptor antagonists (LTRA).

In the present work, we explore the Rossby mode perturbations in case of neutron stars as sources of continuous gravitational waves. The intensity and time evolution of the emitted gravitational waves in terms of the amplitude of the strain tensor are estimated in the slow rotation approximation using β -equilibrated neutron star matter obtained from density dependent M3Y effective interaction. For a wide range of neutron star masses, the fiducial gravitational and various viscous time scales, the critical frequencies and the time evolutions of the frequencies are calculated. Unlike other non-radial perturbations, amplitude of Rossby mode perturbation increases due to the emission of gravitational waves which carry angular momentum of the star to infinity. Hence, existence of such perturbation in a star implies a positive rate of change in the angular momentum transfer. It, therefore, implies that for a particular neutron star, the intensity of gravitational wave emission increases with time until the angular frequency reduces down to a critical value below which the star stops emitting radiation. • R-mode perturbation in neutron star as source of Gravitational Waves (GWs) explored. • R-mode perturbation amplitude increases due to the emission of GWs. • Emitted GWs carry angular momentum of the star to infinity. • Intensity & time evolution of GWs in terms of strain tensor amplitude estimated. • Estimated amplitude is compared with LIGO -Virgo results. [ABSTRACT FROM AUTHOR]

In this research, we proposed a new PAN-sharpening algorithm by using edge-directed Gaussian Radial Basis Function (RBF) and Principal Component Analysis (PCA). Up-scaling is a procedure to upgrade the spectral data of a Low Resolution (LR) Multi Spectral (MS) imagery. Non-linear up-scaling methods generate fewer artefacts in the interpolated image as they are edge-adaptive in nature. Adaptive interpolation techniques consider different features of an image during up-scaling. These techniques are proven efficient compared with non-adaptive methods. However, they may generate distorted output in fine-textured areas and can have lower luminance information. We consider the Laplacian of Gaussian (LoG) or Marr-Hildreth edge detection operator to preserve missing structure and luminance information. It generates smooth edges by minimizing artefacts in the interpolated image. We have considered multi-source and multi-sensor datasets obtained from LISS-IV, CATROSAT-I, and Quickbird to perform all experiments. We have carried out a broad quantitative and subjective assessment and comparison of the proposed algorithm with the standard and cutting-edge methods. [ABSTRACT FROM AUTHOR]

Indian Railway Catering and Tourism Corporation (IRCTC) is among the busiest railways reservation systems since the Indian Railways (IR) is the vital and economical mode of transportation in India. Hence, rating of the trains seems to be critical aspect for selecting an appropriate train for travelling. In this study, we have considered 7 vital attributes of 500 popular trains and rate their performance based on 7 important related attributes. For this purpose, we have employed 2 different approaches to analyse of the train attributes, which eventually contribute to the overall performance of the trains. Here, we have developed a rule based rough set decision support system to analyse the criticality of the train attributes while rating the train performance. Furthermore, we have also used 3 Machine Learning (ML) model estimators: Extra Trees Classifier (ETC), Support Vector Machine Classifier (SVMC) and Multinomial Naive Bayes Classifier (MNBC) and perform their comparative analysis with respect to 7 performance metrics while predicting the overall train rating based. [ABSTRACT FROM AUTHOR]

Children with asthma and eczema who carry filaggrin (FLG) loss-of-function mutations are more likely to use antibiotics throughout childhood and early adulthood. The dysfunctional skin barrier caused by FLG mutations may contribute to increased bacterial entry, leading to a higher risk of bacterial infections and subsequent antibiotic use. This study, conducted in Scotland, analyzed data from 1,001 participants with asthma and found that those with FLG mutations had a greater incidence of antibiotic prescriptions, particularly for topical antibiotics. The findings suggest that personalized medicine approaches and education on bacterial infections may benefit this vulnerable population, while also emphasizing the importance of responsible antibiotic use to prevent antibiotic resistance. [Extracted from the article]

In this work, we study the r-mode instability windows and the gravitational wave signatures of neutron stars in the slow rotation approximation using the equation of state obtained from the density-dependent M3Y effective interaction. We consider the neutron star matter to be β-equilibrated neutron-proton-electron matter at the core with a rigid crust. The fiducial gravitational and viscous timescales, the critical frequencies, the time evolutions of the frequencies, and the rates of frequency change are calculated for a range of neutron star masses. We show that the young and hot rotating neutron stars lie in the r-mode instability region. We also emphasize that if the dominant dissipative mechanism of the r mode is the shear viscosity along the boundary layer of the crust-core interface, then the neutron stars with low L value lie in the r-mode instability region and hence emit gravitational radiation. [ABSTRACT FROM AUTHOR]

A healthy 22-year-old male presented to Institutional Cornea Clinic with an intracorneal mass overlying the pupil with lobulated edges having many tiny greyish white dots. The patient had a history of trauma while swimming in a pond with subsequent removal of intracorneal foreign body in the left eye approximately a year prior to presentation. Anterior segment optical coherence tomography (OCT) confirmed that an intracorneal mass sparing deep stroma and Descemet's membrane. A deep anterior lamellar keratoplasty (DALK) was performed in left eye and the mass was sent for histology examination. Histology evaluation was suggestive of rhinosporidiosis. The patient achieved 20/60 BCVA with -1.25 × 120° 1 year postoperatively without any evidence of recurrence at the graft-host interface. This unique presentation (as an 'intracorneal mass') of ocular rhinosporidiosis emphasizes that clinicians from our region of the world must consider rhinosporidiosis in the differential diagnosis especially with a history of penetrating injury while swimming in pond or river water. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor regarding an article by Furness and Atkinson on recruiting for clinical academic medicine and mentions Abbasi's pillars of academic medicine.

Focuses on the study which found that cannabinoid anandamide and a metabolically stable analog, methanandamide, produced dose-dependent vasorelaxation in rabbit aortic rings in an endothelium-dependent manner. Implications of pretreatment of aortic rings with pertussis toxin; Components exhibited by methanandamide-induced vasorelaxation in the rabbit aorta.

In this paper, we introduce a method of portfolio formation through vertical and horizontal clustering. The clustering algorithm incorporates sufficiently diversified number of stocks in the portfolio with exposure limits on each stock. On obtaining the near Pareto optimal portfolios by using the proposed variable-length Non-dominated Sorting based Genetic Algorithm (NSGA-II), quarter-wise weights of each portfolio's constituent stocks are determined through the proposed single objective Genetic Algorithm (GA) based Markowitz model. This enables dynamic realignment of the portfolios and can incorporate the macroeconomic environment of the time. The performance of the portfolios is then compared with a benchmark portfolio. Our results show that returns from each of our portfolios, dynamically realigned each quarter, have been able to beat the benchmark index return over our study's time period. The performance of the clustering algorithm is validated with 4 well-known clustering algorithms. • Vertical and Horizontal Clustering using Multi-Objective Optimization algorithm. • Designing clustering algorithm to have a sufficiently diversified number of stocks. • Determining Quarter-wise Weights of the Constituent Stocks for each Portfolio. • Comparing each Portfolio Returns with Nifty Returns as the benchmark. • Implemented robust cross over and mutation methods in variable length NSGA-II. [ABSTRACT FROM AUTHOR]

Image steganography is a mechanism that imperceptibly conceals information in a cover image while also enabling the concealed details to be reliably retrieved from that image. The three important criteria for calculating the effect and impact of any steganographic method are high embedding ability, better visual quality and privacy and security. In this paper, a double layered pencil shaped shell matrix based image steganography methodology with high security is proposed and with this extra layer an extra 2 bits can be hidden within every single pixel pair of the pencil shaped shell matrix. Dependent on the shell matrix made of pencil-shaped shells, every private digit is fitted in each cover pixel pair. Various experimental outcomes imply that the proposed methodology has achieved a higher capacity of 3.0 bpp with average 43.25 dB of PSNR and it outperforms other existing shell matrix based image steganographic schemes. Furthermore, the results of RS analysis, JPEG compression analysis, Q-index analysis, normalized absolute error (NAE) analysis etc. are clearly proves the robustness and security of the proposed methodology. Numerous sectors of various private and government organizations, including intellectual property rights, education, intelligent bureau, defence, etc. can be benefited immensely from this scheme. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents methods for training pattern (prototype) selection, class-specific feature selection and classification for automated learning. For training pattern selection, we propose a method of sampling that extracts a small number of representative training patterns (prototypes) from the dataset. The idea is to extract a set of prototype training patterns that represents each class region in a classification problem. In class-specific feature selection, we try to find a separate feature set for each class such that it is the best one to separate that class from the other classes. We then build a separate classifier for that class based on its own feature set. The paper also presents a new hypersphere classification algorithm. Hypersphere nets are similar to radial basis function (RBF) nets and belong to the group of kernel function nets. Polynomial time complexity of the methods is proven. Polynomial time complexity of learning algorithms is important to the field of neural networks. Computational results are provided for a number of well-known datasets. None of the parameters of the algorithm were fine tuned for any of the problems solved and this supports the idea of automation of learning methods. Automation of learning is crucial to wider deployment of learning technologies. [Copyright &y& Elsevier]

Hypokalemic periodic paralysis (HOPP) is a rare disease associated with attacks of muscle weakness and hypokalemia. In the present study, immunoprecipitation/Western blotting has shown that a HOPP patient was deficient in sarcolemmal KATP channels. Real-time RT-PCR has revealed that HOPP has decreased mRNA levels of Kir6.2, a pore-forming KATP channel subunit, without affecting the expression of other KATP channel-forming proteins. Based on these findings, we conclude that HOPP could be associated with impaired expression of Kir6.2 which leads to deficiency in skeletal muscle KATP channels, which may explain the symptoms and clinical signs of this disease. [ABSTRACT FROM AUTHOR]

Leukotrienes play a central pathophysiological role in both paediatric and adult asthma. However, 35% to 78% of asthmatics do not respond to leukotriene inhibitors. In this study we tested the role of the LTA4H regulatory variant rs2660845 and age of asthma onset in response to montelukast in ethnically diverse populations. We identified and genotyped 3,594 asthma patients treated with montelukast (2,514 late-onset and 1,080 early-onset) from seven cohorts (UKBiobank, GoSHARE, BREATHE, Tayside RCT, PAGES, GALA II and SAGE). Individuals under montelukast treatment experiencing at least one exacerbation in a 12-month period were compared against individuals with no exacerbation, using logistic regression for each cohort and meta-analysis. While no significant association was found with European late-onset subjects, a meta-analysis of 523 early-onset individuals from European ancestry demonstrated the odds of experiencing asthma exacerbations by carriers of at least one G allele, despite montelukast treatment, were increased (odds-ratio = 2.92, 95%confidence interval (CI): 1.04–8.18, I2 = 62%, p = 0.0412) compared to those in the AA group. When meta-analysing with other ethnic groups, no significant increased risk of asthma exacerbations was found (OR = 1.60, 95% CI: 0.61–4.19, I2 = 85%, p = 0.342). Our study demonstrates that genetic variation in LTA4H, together with timing of asthma onset, may contribute to variability in montelukast response. European individuals with early-onset (≤18y) carrying at least one copy of rs2660845 have increased odd of exacerbation under montelukast treatment, presumably due to the up-regulation of LTA4H activity. These findings support a precision medicine approach for the treatment of asthma with montelukast. [ABSTRACT FROM AUTHOR]

Background: The polymorphism Arg16 in β2‐adrenergic receptor (ADRB2) gene has been associated with an increased risk of exacerbations in asthmatic children treated with long‐acting β2‐agonists (LABA). However, it remains unclear whether this increased risk is mainly attributed to this single variant or the combined effect of the haplotypes of polymorphisms at codons 16 and 27. Objective: We assessed whether the haplotype analysis could explain the association between the polymorphisms at codons 16 (Arg16Gly) and 27 (Gln27Glu) in ADRB2 and risk of asthma exacerbations in patients treated with inhaled corticosteroids (ICS) plus LABA. Methods: The study was undertaken using data from 10 independent studies (n = 5903) participating in the multi‐ethnic Pharmacogenomics in Childhood Asthma (PiCA) consortium. Asthma exacerbations were defined as asthma‐related use of oral corticosteroids or hospitalizations/emergency department visits in the past 6 or 12 months prior to the study visit/enrolment. The association between the haplotypes and the risk of asthma exacerbations was performed per study using haplo.stats package adjusted for age and sex. Results were meta‐analysed using the inverse variance weighting method assuming random‐effects. Results: In subjects treated with ICS and LABA (n = 832, age: 3–21 years), Arg16/Gln27 versus Gly16/Glu27 (OR: 1.40, 95% CI: 1.05–1.87, I2 = 0.0%) and Arg16/Gln27 versus Gly16/Gln27 (OR: 1.43, 95% CI: 1.05–1.94, I2 = 0.0%), but not Gly16/Gln27 versus Gly16/Glu27 (OR: 0.99, 95% CI: 0.71–1.39, I2 = 0.0%), were significantly associated with an increased risk of asthma exacerbations. The sensitivity analyses indicated no significant association between the ADRB2 haplotypes and asthma exacerbations in the other treatment categories, namely as‐required short‐acting β2‐agonists (n = 973), ICS monotherapy (n = 2623), ICS plus leukotriene receptor antagonists (LTRA; n = 338), or ICS plus LABA plus LTRA (n = 686). Conclusion and clinical relevance: The ADRB2 Arg16 haplotype, presumably mainly driven by the Arg16, increased the risk of asthma exacerbations in patients treated with ICS plus LABA. This finding could be beneficial in ADRB2 genotype‐guided treatment which might improve clinical outcomes in asthmatic patients. [ABSTRACT FROM AUTHOR]

Keywords: asthma; atopic dermatitis; pharmacogenomics; pharmacology; rhinitis EN asthma atopic dermatitis pharmacogenomics pharmacology rhinitis 1089 1092 4 08/03/21 20210801 NES 210801 Key Messages We explored associations between genotype and prescriptions for allergic conditions in the BREATHE cohort. Asthma, atopic dermatitis, pharmacogenomics, pharmacology, rhinitis Of the 927 participants included in the study, 493 (53.2%) reported having eczema, 397 (42.8%) reported having rhinitis, 230 (24.8%) reported having rhinitis and eczema, and 267 (28.8%) reported having neither eczema nor rhinitis. We decided to perform rhinitis-related analysis in the entire sample due to discrepant reporting in the data and add a sensitivity analysis, analysing only children and young adults that reported having rhinitis (see Supplementary Material for more details on the methodology). [Extracted from the article]

Background: Some children with asthma experience exacerbations despite long‐acting beta2‐agonist (LABA) treatment. While this variability is partly caused by genetic variation, no genome‐wide study until now has investigated which genetic factors associated with risk of exacerbations despite LABA use in children with asthma. We aimed to assess whether genetic variation was associated with exacerbations in children treated with LABA from a global consortium. Methods: A meta‐analysis of genome‐wide association studies (meta‐GWAS) was performed in 1,425 children and young adults with asthma (age 6‐21 years) with reported regular use of LABA from six studies within the PiCA consortium using a random effects model. The primary outcome of each study was defined as any exacerbation within the past 6 or 12 months, including at least one of the following: 1) hospital admissions for asthma, 2) a course of oral corticosteroids or 3) emergency room visits because of asthma. Results: Genome‐wide association results for a total of 82 996 common single nucleotide polymorphisms (SNPs, MAF ≥1%) with high imputation quality were meta‐analysed. Eight independent variants were suggestively (P‐value threshold ≤5 × 10−6) associated with exacerbations despite LABA use. Conclusion: No strong effects of single nucleotide polymorphisms (SNPs) on exacerbations during LABA use were identified. We identified two loci (TBX3 and EPHA7) that were previously implicated in the response to short‐acting beta2‐agonists (SABA). These loci merit further investigation in response to LABA and SABA use. [ABSTRACT FROM AUTHOR]

Differentially expressed genes in the discovery were examined to determine whether they also showed changes in peripheral blood mononuclear cells (PBMCs) obtained from ICS non-responders (n = 3) and ICS responders (n = 3) from the SLOVENIA study,4 defined based on the presence or absence of asthma exacerbations despite ICS therapy. Asthma treatment, childhood asthma, exacerbations, genetic polymorphism, pharmacogenomics Keywords: asthma treatment; childhood asthma; exacerbations; genetic polymorphism; pharmacogenomics EN asthma treatment childhood asthma exacerbations genetic polymorphism pharmacogenomics 1238 1243 6 04/14/21 20210401 NES 210401 To the Editor, An increasing number of therapies are available to treat asthma, but inhaled corticosteroids (ICS) are still the most commonly prescribed and effective controller asthma medication.1 Both environmental and genetic factors are involved in ICS response. Details about each study are described at the Supporting Information and elsewhere.4 Individuals with asthma exacerbations despite ICS treatment were considered as ICS non-responders and those without asthma exacerbations as ICS responders. [Extracted from the article]

Measuring the proportion of and reasons for asthma-related school absence in England Keywords: asthma; children; exacerbations; school absences; triggers EN asthma children exacerbations school absences triggers 752 755 4 06/04/20 20200601 NES 200601 To the Editor, Asthma affects 300 million people across all age groups and ethnicities and is the most common chronic condition affecting children.[[1]] In the UK, the healthcare costs associated with asthma are estimated at £1.1 billion; however, this amount typically excludes some societal costs (eg the absence from work to care for children).[3] The total number of school days missed in England in the 2017/18 academic year was 59.1 million of which 54.7% were due to illness[4] although the reasons for those illness-related absences are unknown. To our knowledge, this is the first study to look at school data in England on the proportion of asthma-related school absenteeism and the precipitating factors which led to the exacerbation. This project demonstrates the potential for Studybugs to collect community-wide data on school absence, to identify triggers and potentially to deliver tailored interventions that could improve children's health and reduce illness-related school absence. [Extracted from the article]

Background: Chronic ethanol (EtOH) exposure has been found to inhibit adult hippocampal neurogenesis in multiple models of alcohol addiction. However, acute EtOH inhibition of adult neurogenesis is not well studied. Although many abused drugs have been found to inhibit adult neurogenesis, few have studied cannabinoids or cannabinoids with EtOH, although human use of both together is becoming more common. We used an acute binge alcohol drinking model in combination with select cannabinoid receptor agonists and antagonists to investigate the actions of each alone and together on hippocampal neurogenesis. Methods: Adult male Wistar rats were treated with an acute binge dose of EtOH (5 g/kg, i.g.), cannabinoid 1 receptor (CB1R) or cannabinoid 2 receptor (CB2R) agonists, as well as selective cannabinoid (CB) antagonists, alone or combined. Hippocampal doublecortin (DCX), Ki67, and activated cleaved caspase‐3 (CC3) immunohistochemistry were used to assess neurogenesis, neuroprogenitor proliferation, and cell death, respectively. Results: We found that treatment with EtOH or the CB1R agonist, arachidonoyl‐2′‐chloroethylamide (ACEA), and the combination significantly reduced DCX‐positive neurons (DCX + IR) in dentate gyrus (DG) and increased CC3. Further, using an inhibitor of endocannabinoid metabolism, for example, JZL195, we also found reduced DCX + IR neurogenesis. Treatment with 2 different CB1R antagonists (AM251 or SR141716) reversed both CB1R agonist and EtOH inhibition of adult neurogenesis. CB2R agonist HU‐308 treatment did not produce any significant change in DCX + IR. Interestingly, neither EtOH nor CB1R agonist produced any alteration in cell proliferation in DG as measured by Ki67 + cell population, but CC3‐positive cell numbers increased following EtOH or ACEA treatment suggesting an increase in cell death. Conclusions: Together, these findings suggest that acute CB1R cannabinoid receptor activation and binge EtOH treatment reduce neurogenesis through mechanisms involving CB1R. [ABSTRACT FROM AUTHOR]

In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is considered a chronic disease that specifically targets the brain and causes HIV-1-associated neurocognitive disorders (HAND). Endocannabinoids (eCBs) elicit neuroprotective and anti-inflammatory actions in several central nervous system (CNS) disease models, but their effects in HAND remain unknown. HIV-1 does not infect neurons, but produces viral toxins, such as transactivator of transcription (Tat), that disrupt neuronal calcium equilibrium and give rise to synaptodendritic injuries and cell death, the former being highly correlated with HAND. Consequently, we tested whether the eCBs N -arachidonoylethanolamine (anandamide/AEA) and 2-arachidonoyl-glycerol (2-AG) offer neuroprotective actions in a neuronal culture model. Specifically, we examined the neuroprotective actions of these eCBs on Tat excitotoxicity in primary cultures of prefrontal cortex neurons (PFC), and whether cannabinoid receptors mediate this neuroprotection. Tat-induced excitotoxicity was reflected by increased intracellular calcium levels, synaptodendritic damage, neuronal excitability, and neuronal death. Further, upregulation of cannabinoid 1 receptor (CB 1 R) protein levels was noted in the presence of HIV-1 Tat. The direct application of AEA and 2-AG reduced excitotoxic levels of intracellular calcium and promoted neuronal survival following Tat exposure, which was prevented by the CB 1 R antagonist rimonabant, but not by the CB 2 R antagonist AM630. Overall, our findings indicate that eCBs protect PFC neurons from Tat excitotoxicity in vitro via a CB 1 R-related mechanism. Thus, the eCB system possesses promising targets for treatment of neurodegenerative disorders associated with HIV-1 infection. [ABSTRACT FROM AUTHOR]

Background The use of antibiotic therapy early in life might influence the risk of developing asthma. Studies assessing the influence of early life antibiotic use on the risk of asthma exacerbations are limited, and the results are inconsistent. Therefore, the aim of this study was to assess the association between use of antibiotic during the first 3 years of life and the risk of developing childhood asthma and the occurrence of asthma exacerbations. Methods Data from four large childhood cohorts were used; two population-based cohorts to study the risk of developing asthma: Generation R (n=7393, The Netherlands) and SEATON (n=891, Scotland, UK), and two asthma cohorts to assess the risk of asthma exacerbations: PACMAN (n=668, The Netherlands) and BREATHE (n=806, Scotland, UK). Odds ratios ( ORs) were derived from logistic regression analysis within each database followed by pooling the results using a fixed- or random-effect model. Results Antibiotic use in early life was associated with an increased risk of asthma in a meta-analysis of the Generation R and SEATON data ( OR: 2.18, 95% CI: 1.04-4.60; I2: 76.3%). There was no association between antibiotic use in early life and risk of asthma exacerbations later in life in a meta-analysis of the PACMAN and BREATHE data ( OR: 0.93, 95% CI: 0.65-1.32; I2: 0.0%). Conclusion Children treated with antibiotic in the first 3 years of life are more likely to develop asthma, but there is no evidence that the exposure to antibiotic is associated with increased risk of asthma exacerbations. [ABSTRACT FROM AUTHOR]

(1) Background. The endocannabinoid (eCB) system, which regulates physiological and cognitive processes, presents a promising therapeutic target for treating HIV-associated neurocognitive disorders (HAND). Here we examine whether upregulating eCB tone has potential protective effects against HIV-1 Tat (a key HIV transactivator of transcription) protein-induced alterations in synaptic activity. (2) Methods. Whole-cell patch-clamp recordings were performed to assess inhibitory GABAergic neurotransmission in prefrontal cortex slices of Tat transgenic male and female mice, in the presence and absence of the fatty acid amide hydrolase (FAAH) enzyme inhibitor PF3845. Western blot and mass spectrometry analyses assessed alterations of cannabinoid receptor and enzyme protein expression as well as endogenous ligands, respectively, to determine the impact of Tat exposure on the eCB system. (3) Results. GABAergic activity was significantly altered upon Tat exposure based on sex, whereas the effectiveness of PF3845 to suppress GABAergic activity in Tat transgenic mice was not altered by Tat or sex and involved CB1R-related mechanisms that depended on calcium signaling. Additionally, our data indicated sex-dependent changes for AEA and related non-eCB lipids based on Tat induction. (4) Conclusion. Results highlight sex- and/or Tat-dependent alterations of GABAergic activity and eCB signaling in the prefrontal cortex of Tat transgenic mice and further increase our understanding about the role of FAAH inhibition in neuroHIV. [ABSTRACT FROM AUTHOR]

Increased matrix metalloproteinase (MMP) activity contributes to glial scar formation that inhibits the repair path after spinal cord injury (SCI). We examined whether treatment with N -​(2-​chloroethyl)-​5Z,​8Z,​11Z,​14Z-​eicosatetraenamide (ACEA), a selective synthetic cannabinoid receptor (CB1R) agonist, inhibits MMP and improves functional and histological recovery in a mouse spinal cord compression injury model. Injured mice randomly received either intraperitoneal ACEA (3 mg/kg/day) or vehicle for up to 3 weeks. Behavioral, histological and biochemical assays were performed. Rotarod assessment and the Basso Mouse Scale score showed an improved performance following ACEA treatment concomitant with a decrease in compression lesion volume. MMP-9 and MMP-2 activity was measured at 1, 7 and 14 days post-SCI. SCI markedly increased MMP-9, but had negligible effect on MMP-2 activity. ACEA-treatment decreased MMP-9 activity by 80%, 49%, and 56%, respectively ( P < 0.05) and had a smaller effect on MMP-2 activity. The CB1R antagonist SR141716, but not the CB2R antagonist SR144528, blocked ACEA-mediated decrease in MMP-9 activity confirming the role of the CB1R in the process. Collectively these data demonstrate that post-injury CB1R agonism can improve SCI outcome and also indicate marked attenuation of MMP-9 proteolytic enzyme activity as a biochemical mechanism. [ABSTRACT FROM AUTHOR]

Background Our understanding of factors which affect adherence to health sustaining self-care behaviours in adolescents with food allergy is limited. This study used the Health Belief Model to explore the relationship between food allergic adolescents' health beliefs, demographic, structural and social psychological factors with adherence to self-care behaviours, including allergen avoidance and carrying emergency medication. Methods A cross-sectional study of 188 13- to 19- olds identified from hospital prescribed auto-injectable epinephrine for food allergy. Data were collected on demographics, structural factors, social psychological factors, health beliefs and current adherence behaviour using a postal questionnaire. Results Full adherence was reported by 16% of participants. Multivariate analysis indicated that adherence was more likely to be reported if the adolescents belonged to a support group ( OR = 2.54, (1.04, 6.20) 95% CI), had an anaphylaxis management plan ( OR = 3.22, (1.18, 8.81) 95% CI), perceived their food allergy to be more severe ( OR = 1.24, (1.01, 1.52) 95% CI) and perceived fewer barriers to disease management ( OR = 0.87, (0.79, 0.96) 95% CI). Conclusions Membership of a patient support group and having an anaphylaxis management plan were associated with good adherence to self-care behaviours in adolescents with food allergy. Our results suggest that interventions to improve provision and utilisation of management plans, address adolescents' perceptions of the severity of anaphylaxis and reduce barriers to disease management may facilitate good adherence behaviours than focussing on knowledge-based interventions. [ABSTRACT FROM AUTHOR]

Objectives To identify explanations for adherence to self-care behaviours amongst adolescents with food allergy-induced anaphylaxis using two social cognition models: the health belief model ( HBM) and the common sense self-regulation model ( CS- SRM). Design Cross-sectional self-completion questionnaire study to gain initial evidence of the two models' feasibility/effectiveness in explaining adherence in an adolescent food-allergic population. Methods Participants aged 13-19 years with a diagnosis of severe food allergy and a prescription of an adrenaline auto-injector were recruited from hospital outpatients. Adherence to self-care behaviours was measured in addition to constructs from the HBM and CS- SRM. Results One hundred and eighty-eight food-allergic adolescents completed the questionnaire. The HBM, specifically the constructs perceived severity and barriers, accounted for 21% of the explained variance in adherence behaviours. CS- SRM constructs, illness identity, timeline cyclical beliefs and emotional representations explained 25% of the variance. Conclusions Both models performed similarly in explaining adherence to self-care behaviours in adolescents with food allergy. Interventions designed to elicit personal barriers to adherence and to address perceptions of severity and the unpredictable nature of symptoms may be more effective in improving adherence to self-care behaviours than current interventions. Statement of contribution What is already known on this subject? Patients' poor management of food allergy induced anaphylaxis is commonly attributed to lack of knowledge and ability in using the adrenaline auto-injector. Adherence to recommended preventive self-care behaviours, like allergen avoidance and carrying emergency medication, are rarely assessed. Social Cognition Models ( SCMs) have been successfully applied to a number of adherence-related studies in disease conditions such as asthma and diabetes, but have not yet been applied to food allergy induced anaphylaxis. What does this study add? This is the first large-scale quantitative study of adherence behaviours in adolescents with food allergy., This is the first study to apply theoretical models to explain adherence in the adolescent food allergic population., This is the first application of both models to food allergy, and the first to compare the two models' measurement instruments. [ABSTRACT FROM AUTHOR]

• A Qutrit Genetic Algorithm is proposed for thresholding of hyperspectral images. • A new quantum mutation procedure is implemented to bring diversity in the offsprings. • Interactive Information method and BS-NET-Conv Network reduce the number of bands. • Modified Otsu Criterion and Masi entropy are used as fitness functions. • A quantum disaster operation prevents the population to get stuck into local optima. Hyperspectral images contain rich spectral information about the captured area. Exploiting the vast and redundant information, makes segmentation a difficult task. In this paper, a Qutrit Genetic Algorithm is proposed which exploits qutrit based chromosomes for optimization. Ternary quantum logic based selection and crossover operators are introduced in this paper. A new qutrit based mutation operator is also introduced to bring diversity in the off-springs. In the preprocessing stage two methods, called Interactive Information method and Band Selection Convolutional Neural Network are used for band selection. The modified Otsu Criterion and Masi entropy are employed as the fitness functions to obtain optimum thresholds. A quantum based disaster operation is applied to prevent the quantum population from getting stuck in local optima. The proposed algorithm is applied on the Salinas Dataset, the Pavia Centre Dataset and the Indian Pines dataset for experimental purpose. It is compared with classical Genetic Algorithm, Particle Swarm Optimization, Ant Colony Optimization, Gray Wolf Optimizer, Harris Hawk Optimization, Qubit Genetic Algorithm and Qubit Particle Swarm Optimization to establish its effectiveness. The peak signal-to-noise ratio and S ø rensen-Dice Similarity Index are applied to the thresholded images to determine the segmentation accuracy. The segmented images obtained from the proposed method are also compared with those obtained by two supervised methods, viz., U-Net and Hybrid Spectral Convolutional Neural Network. In addition to this, a statistical superiority test, called the one-way ANOVA test, is also conducted to judge the efficacy of the proposed algorithm. Finally, the proposed algorithm is also tested on various real life images to establish its diversity and efficiency. [ABSTRACT FROM AUTHOR]

G protein-coupled receptor kinases (GRKs) phosphorylate the activated form of G protein-coupled receptors leading to receptor desensitization and downregulation. We have recently shown that the chemokine receptor, CXCR2, couples to GRK6 to regulate cellular responses including chemotaxis, angiogenesis, and wound healing. In this study, we investigate the role of GRK6 in tumorigenesis using murine models of human lung cancer. Mice deficient in GRK6 (GRK6-/-) exhibited a significant increase in Lewis lung cancer growth and metastasis relative to control littermates (GRK6+/+). GRK6 deletion had no effect on the expression of proangiogenic chemokine or vascular endothelial growth factor, but upregulated matrix metalloproteinase (MMP)-2 and MMP-9 release, tumor-infiltrating PMNs, and microvessel density. Because β-arrestin-2-deficient (βarr2-/-) mice exhibited increased Lewis lung cancer growth and metastasis similar to that of GRK6-/-, we developed a double GRK6-/-/βarr2-/- mouse model. Surprisingly, GRK6-/-/βarr2-/- mice exhibited faster tumor growth relative to GRK6-/- or βarr2-/- mice. Treatment of the mice with anti-CXCR2 Ab inhibited tumor growth in both GRK6-/- and GRK6-/-/βarr2-/- animals. Altogether, the results indicate that CXCR2 couples to GRK6 to regulate angiogenesis, tumor progression, and metastasis. Deletion of GRK6 increases the activity of the host CXCR2, resulting in greater PMN infiltration and MMP release in the tumor microenvironment, thereby promoting angiogenesis and metastasis. Because GRK6-/-/βarr2-/- showed greater tumor growth relative to GRK6-/- or βarr2-/- mice, the data further suggest that CXCR2 couples to different mechanisms to mediate tumor progression and metastasis. [ABSTRACT FROM AUTHOR]

The Arg16 ß2 receptor genotype confers increased susceptibility to exacerbations in asthmatic children taking regular LABA (long-acting ß2 agonists). We therefore evaluated using montelukast as an alternative to salmeterol as tailored second-line asthma controller therapy in children expressing this susceptible genotype. A total of 62 persistent asthmatic children with the homozygous Arg16 genotype were randomized to receive salmeterol (50 µg, b.i.d.) or montelukast (5 or 10 mg, once daily) as an add-on to inhaled fluticasone for 1 year. School absences (the primary outcome) were reduced with montelukast compared with salmeterol {difference in score= -0.40 [95% CI (confidence interval), -0.22 to -0.58]; P=0.005}. Salbutamol use was also reduced with montelukast compared with salmeterol [difference in score= -0.47 (95% CI, -0.16 to -0.79); P<0.0001]. Greater improvements occurred in both symptom and quality of life scores with montelukast against salmeterol, whereas there was no difference in FEV1 (forced expiratory volume in 1 s). In conclusion, montelukast may be suitable as tailored second-line controller therapy instead of salmeterol in asthmatic children expressing the susceptible Arg16 genotype, a move towards a personalized medicine approach to management. [ABSTRACT FROM AUTHOR]

Abstract: The endocannabinoid system comprises the G-protein coupled CB1 cannabinoid receptor (CB1R) and CB2 cannabinoid receptor (CB2R), their endogenous ligands (endocannabinoids), and the enzymes responsible for their synthesis and catabolism. Recent works have revealed several important interactions between the endocannabinoid system and cancer. Moreover, it is now well established that synthetic small molecule cannabinoid receptor agonist acting on either CB1R or CB2R or both exerts anti-cancer effects on a variety of tumor cells. Recent results from many laboratories reported that the expression of CB1R and CB2R in prostate cancer, breast cancer, and many other cancer cells is higher than that in corresponding non-malignant tissues. The mechanisms by which cannabinoids acting on CB1R or CB2R exert their effects on cancer cells are quite diverse and complex. Further, several studies demonstrated that some of the anti-proliferative and apoptotic effects of cannabinoids are mediated by receptor-independent mechanisms. In this minireview we provide an overview of the major findings on the effects of endogenous and/or synthetic cannabinoids on breast and prostate cancers. We also provide insight into receptor independent mechanisms of the anti-cancer effects of cannabinoids under in vitro and in vivo conditions. [Copyright &y& Elsevier]

BackgroundAlthough an increased concentration of degraded elastin products in patients with chronic obstructive pulmonary disease (COPD) has been reported for many years, its clinical validity and utility remain uncertain due to technical difficulties, small study groups and the unknown relationship between exacerbation and elastin degradation. The objectives of this study were to determine the validity of urinary and blood total desmosine/isodesmosine in patients with COPD and asthma and to evaluate their relationship to exacerbation status and lung function.MethodsUrinary and blood desmosine levels were measured using validated isotopic dilution liquid chromatography–tandem mass spectrometry methods.Results390 study participants were recruited from the following groups: healthy volunteers, stable asthma, stable and ‘during an exacerbation’ COPD. Compared with healthy non-smokers, we found increased urinary or blood desmosine levels in patients with COPD, but no differences in patients with asthma or healthy smokers. The elevation of urinary desmosine levels was associated with the exacerbation status in patients with COPD. Approximately 40% of patients with stable and ‘during an exacerbation’ COPD showed elevated blood desmosine levels. Blood desmosine levels were strongly associated with age and were negatively correlated with lung diffusing capacity for carbon monoxide.ConclusionThe results suggest that urinary desmosine levels are raised by exacerbations of COPD whereas blood desmosine levels are elevated in a subgroup of patients with stable COPD and reduced lung diffusing capacity. The authors speculate that a raised blood desmosine level may identify patients with increased elastin degradation suitable for targeted therapy. Future prospective studies are required to investigate this hypothesis. [ABSTRACT FROM AUTHOR]