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With over 2 million people in the UK suffering from chronic wounds, understanding the biochemistry and pharmacology that underpins these wounds and wound healing is of high importance. Chronic wounds are characterised by high levels of matrix metalloproteinases (MMPs), which are necessary for the modification of healthy tissue in the healing process. Overexposure of MMPs, however, adversely affects healing of the wound by causing further destruction of the surrounding extracellular matrix. In this work, we propose a mathematical model that focuses on the interaction of MMPs with dermal cells using a system of partial differential equations. Using biologically realistic parameter values, this model gives rise to travelling waves corresponding to a front of healthy cells invading a wound. From the arising travelling wave analysis, we observe that deregulated apoptosis results in the emergence of chronic wounds, characterised by elevated MMP concentrations. We also observe hysteresis effects when both the apoptotic rate and MMP production rate are varied, providing further insight into the management (and potential reversal) of chronic wounds.

BackgroundNicotine intake by cigarettes is linked to the maintenance and development of anxiety disorders and impairs adaptive discrimination of threat and safety in humans. Yet, it is unclear if nicotine exerts a causal pharmacological effect on the affective and neural mechanisms that underlie aversive learning.MethodsWe conducted a pre-registered, pseudo-randomly and double-blinded pharmacological fMRI study to investigate the effect of acute nicotine on Fear Acquisition and Extinction in non-smokers (n=88). Participants were pseudo-randomly and double-blinded assigned to one of three experimental groups:1. nicotine administration before Fear Acquisition, 2. nicotine administration before Extinction training or 3. placebo control group.ResultsOur results show that nicotine administration led to decreased discrimination between threat and safety in subjective fear. Nicotine furthermore decreased differential (threat vs. safety) activation in the hippocampus, which was functionally coupled with Nucleus Accumbens and amygdala, compared to placebo controls. Additionally, nicotine led to overactivation of the ventral tegmental area.ConclusionsThis study provides mechanistic evidence for impaired discrimination between threat and safety by the acute intake of Nicotine in non-smoking individuals. Nicotine intake directly impairs neural substrate of adaptive aversive learning and might therefore constitute a profound risk factor for the development of pathological anxiety.This study was preregistered at the German Clinical Trials Register (Deutsches Register Klinischer Studien (DRKS);https://drks.de/search/en/trial/DRKS00025233; DRKS-ID: DRKS00025233).

The article examines the features of Soviet-Iranian and further Russian-Iranian relations, starting with the Islamic revolution in Iran in 1979 to the present. The paper reveals the main stages and events in bilateral relations with particular emphasis on bilateral cooperation on the issue of Syria and the consideration of Iran’s interests in this country, including economic ones. The author attempts to determine the grade of the achieved bilateral relations established at soviet times as confrontational, although in the very last years of the existence of the Soviet Union they began to improve. The tendency to improve and intensify relations continued after the collapse of the USSR. However, Russian-Iranian relations at the present stage, on the whole, cannot be characterized as allied. Although in the case of Syria, one can indeed observe their alliance, nevertheless, in general, relations between Russia and Iran keep far from being deep enough, and in a number of cases in recent decades there has been rivalry or even conflict between the two countries, as, for example, in the issuance of Russia’s refusal to supply Iran with air S-300 defense systems. Nevertheless, given the external pressure on both countries, along with the growing attention to traditional values, there is a certain likelihood of expanding and deepening Russian-Iranian relations to the level of allies.

We analyse a multiphase, moving boundary model that describes solid tumour growth. We consider the evolution of a motile, viscous cell phase and an inviscid extracellular liquid phase. The model comprises two partial differential equations that govern the cell volume fraction and the cell velocity, together with a moving boundary condition for the tumour edge. Numerical simulations of the model indicate that patterned solutions can be obtained, which correspond to multiple regions of high cell density separated by regions of low cell density. In other parameter regimes, solutions of the model can develop into a forward- or backward-moving travelling wave, corresponding to tumour growth or extinction, respectively. A travelling-wave analysis allows us to find the corresponding wave speed, as well as criteria for the growth or extinction of the tumour. Furthermore, a stability analysis of these travelling-wave solutions provides us with criteria for the occurrence of patterned solutions. Finally, we discuss how the initial cell distribution, as well as parameters related to cellular motion and cell-liquid drag, control the qualitative features of patterned solutions.

Background: The high prevalence of insomnia in children and its adverse consequences on children and their family indicate that investigation about treatment of insomnia is necessary. Objectives: This research was conducted to compare the effectiveness of cognitive-behavioral therapy program for insomnia, named the KiSS program (Kinder mit Schafstörungen Programm) and reflexotherapy on insomnia in children. Methods: The method of the present research was quasi-experimental in which a pretest, posttest and follow-up design was used in two experimental and two control groups. In order to perform this study among children of 8 to 10 years with insomnia referring to Medical & Psychology Clinic of Shokoufeh in, Tehran, Iran, within July to October 2021, 80 children were selected through the convenience sampling method based on inclusion and exclusion criteria and were assigned randomly into two experimental and two control groups. The Personal Information Questionnaire, Sleep Disturbance Scale for Children (SDSC), Child Symptoms Inventory-4 (CSI-4) were used to collect data. In the experimental groups, the KiSS program and reflexotherapy were performed. In the control groups, the interventions of watching cartoon in group and watching cartoon individually were performed. The data were analyzed with SPSS 22 using descriptive statistical indicators including mean and standard deviation as well as inferential statistics indicators, including mixed-design analysis of variance (ANOVA) method. Results: The results of data analysis showed that the KiSS program reduced mean scores of insomnia in the posttest stage significantly compared to the first control group and the changes in the follow-up stage remained stable. The mean scores of insomnia in reflexotherapy group also decreased significantly in the posttest stage than second control group. However, the effectiveness of the reflexotherapy intervention is temporary, and after two-months follow-up, the insomnia reappear in children. Conclusions: Both the KiSS program and reflexotherapy can be used as uncomplicated and safe nondrug intervention to improve insomnia in children of 8-10 years. Nevertheless, the KiSS program showed more promising results.

It is unclear whether deviations in brain and behavioral development, which may underpin elevated substance use during adolescence, are predispositions for or consequences of substance use initiation. Here, we examine behavioral and neuroimaging indices at early and mid-adolescence in drug-naive youths to identify possible predisposing factors for substance use initiation and its possible consequences.Among 304 drug-naive adolescents at baseline (age 14 years) from the IMAGEN dataset, 83 stayed drug-naive, 133 used alcohol on 1 to 9 occasions, 42 on 10 to 19 occasions, 27 on 20 to 39 occasions, and 19 on40 occasions at follow-up (age 16 years). Baseline measures included brain activation during the Monetary Incentive Delay task. Data at both baseline and follow-up included measures of trait impulsivity and delay discounting.From baseline to follow-up, impulsivity decreased in the 0 and 1- to 9-occasions groups (p .004), did not change in the 10- to 19-occasions and 20- to 29-occasions groups (p.294), and uncharacteristically increased in the40-occasions group (p = .046). Furthermore, blunted medial orbitofrontal cortex activation during reward outcome at baseline significantly predicted higher alcohol use frequency at follow-up, above and beyond behavioral and clinical variables (p = .008).These results suggest that the transition from no use to frequent drinking in early to mid-adolescence may disrupt normative developmental changes in behavioral control. In addition, blunted activity of the medial orbitofrontal cortex during reward outcome may underscore a predisposition toward the development of more severe alcohol use in adolescents. This distinction is clinically important, as it informs early intervention efforts in preventing the onset of substance use disorder in adolescents.

Objective Irritable mood, a common and impairing symptom in psychopathology, has been proposed to underlie the developmental link between oppositional problems in youth and depression in adulthood. We examined the neural correlates of adolescent irritability in IMAGEN, a sample of 2,024 14-year-old adolescents from 5 European countries. Method The Development and Well-Being Assessment (DAWBA) was used to assess attention-deficit/hyperactivity disorder, major depressive disorder, oppositional defiant disorder, and generalized anxiety disorder. Three items from the DAWBA, selected as close matches to the Affective Reactivity Index, were used to assess irritability. Structural magnetic resonance imaging was examined using whole-brain voxel-based morphometry analysis, and functional magnetic resonance imaging was examined during a stop signal task of inhibitory control. Imaging data were included in structural equation models to examine the direct and indirect associations between irritable mood and comorbid DSM diagnoses. Results Whole-brain voxelwise analysis showed that adolescent irritable mood was associated with less gray matter volume and less neural activation underlying inhibitory control in frontal and temporal cortical areas (cluster-correction at p Conclusion This study identifies adolescent irritability as an independent construct and points to a neurobiological correlate to irritability that is an important contributing feature to many psychopathological disorders.

Apossible mechanism of methylphenidate (MPH) action upon reproductive system, in particular on the fertility rate of male mice, is discussed.

Introduction: Recently it has been shown that Astragalus fasciculifolius may be an effective remedy in the treatment of diabetes and wound healing. Current study was designed to examine the effects of topical administration of A. fasciculifolius (common name: sarcocolla) cream on treatment of wounds in streptozotocin-induced diabetic rats. Methods: A circle deep wound having 15-mm diameter was created on the back of 32 streptozotocin-induced diabetic rats. Thirty-two wounds were evaluated in four groups of animals (n = 8). The animals in first and second groups were treated using distilled water and petrolatum for 20 days, respectively. The third and fourth groups were treated using sarcocolla cream 5% and 10% for 20 days, respectively. The evaluation was performed in all groups on days 1, 3, 5, 7, 10, 14, 17 and 20. Results: The sarcocolla cream 5% and sarcocolla cream 10% exerted significant healing effects on diabetic rat wounds (PConclusion: Sarcocolla (topical) therapy is possibly a useful approach for wound healing in diabetic rats. More investigations are needed to elucidate the possible protective mechanisms and safety.

BackgroundStandardized neuropsychological testing serves to quantify cognitive impairment in multiple sclerosis (MS) patients. However, the exact mechanism underlying the translation of cognitive dysfunction into difficulties in everyday tasks has remained unclear. To answer this question, we tested if MS patients with intact vs. impaired information processing speed measured by the Symbol Digit Modalities Test (SDMT) differ in their visual search behavior during ecologically valid tasks reflecting everyday activities.MethodsForty-three patients with relapsing-remitting MS enrolled in an eye-tracking experiment consisting of a visual search task with naturalistic images. Patients were grouped into “impaired” and “unimpaired” according to their SDMT performance. Reaction time, accuracy and eye-tracking parameters were measured.ResultsThe groups did not differ regarding age, gender, and visual acuity. Patients with impaired SDMT (cut-off SDMT-z-score < −1.5) performance needed more time to find and fixate the target (q = 0.006). They spent less time fixating the target (q = 0.042). Impaired patients had slower reaction times and were less accurate (both q = 0.0495) even after controlling for patients' upper extremity function. Exploratory analysis revealed that unimpaired patients had higher accuracy than impaired patients particularly when the announced target was in unexpected location (p = 0.037). Correlational analysis suggested that SDMT performance is inversely linked to the time to first fixation of the target only if the announced target was in its expected location (r = −0.498, p = 0.003 vs. r = −0.212, p = 0.229).ConclusionDysfunctional visual search behavior may be one of the mechanisms translating cognitive deficits into difficulties in everyday tasks in MS patients. Our results suggest that cognitively impaired patients search their visual environment less efficiently and this is particularly evident when top-down processes have to be employed.

We derive a multiphase, moving boundary model to represent the development of tissue in vitro in a porous tissue engineering scaffold. We consider a cell, extra-cellular liquid and a rigid scaffold phase, and adopt Darcy’s law to relate the velocity of the cell and liquid phases to their respective pressures. Cell-cell and cell-scaffold interactions which can drive cellular motion are accounted for by utilising relevant constitutive assumptions for the pressure in the cell phase. We reduce the model to a nonlinear reaction-diffusion equation for the cell phase, coupled to a moving boundary condition for the tissue edge, the diffusivity being dependent on the cell and scaffold volume fractions, cell and liquid viscosities, and parameters that relate to cellular motion. Numerical simulations reveal that the reduced model admits three regimes for the evolution of the tissue edge at large-time: linear, logarithmic and stationary. Employing travelling wave and asymptotic analysis, we characterise these regimes in terms of parameters related to cellular production and motion. The results of our investigation allow us to suggest optimal values for the governing parameters, so as to stimulate tissue growth in an engineering scaffold.

We derive a multiphase, moving boundary model to represent the development of tissue in vitro in a porous tissue engineering scaffold. We consider a cell, extra-cellular liquid and a rigid scaffold phase, and adopt Darcy’s law to relate the velocity of the cell and liquid phases to their respective pressures. Cell–cell and cell–scaffold interactions which can drive cellular motion are accounted for by utilising relevant constitutive assumptions for the pressure in the cell phase. We reduce the model to a nonlinear reaction–diffusion equation for the cell phase, coupled to a moving boundary condition for the tissue edge, the diffusivity being dependent on the cell and scaffold volume fractions, cell and liquid viscosities and parameters that relate to cellular motion. Numerical simulations reveal that the reduced model admits three regimes for the evolution of the tissue edge at large time: linear, logarithmic and stationary. Employing travelling-wave and asymptotic analysis, we characterise these regimes in terms of parameters related to cellular production and motion. The results of our investigation allow us to suggest optimal values for the governing parameters, so as to stimulate tissue growth in an engineering scaffold.

Background: Multiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness. Methods: We conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. Results: 146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care. Conclusion: Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection. Trial Registration: ClinicalTrials.gov number, NCT04416399 Funding: Oxford NIHR Biomedical Research Centre and AstraZeneca Declaration of Interests: Dr. Ramakrishnan reports grants and non-financial support from Oxford Respiratory NIHR BRC, during the conduct of the study; non-financial support from AstraZeneca, personal fees from Australian Government Research Training Program, outside the submitted work; . Dr. Nicolau has nothing to disclose. Mrs Langford has nothing to disclose. Mr. Mahdi has nothing to disclose. Mrs Helen Jeffers reports personal fees from AstraZeneca, outside the submitted work; . Miss Mwasuku has nothing to disclose. Mrs Krassowska has nothing to disclose. Dr Fox has nothing to disclose. Dr Binnian has nothing to disclose. Dr Glover has nothing to disclose. Dr Bright has nothing to disclose. Dr. Butler reports grants from National Institute for Health Research (NIHR), Roche Molecular Diagnostics, Janssen Pharmaceuticals, and various public funding bodies for research related to diagnostics and infections. He has revcied personal fees from Pfizer INC, Roche Diagnostics, and Janssen Pharmaceuticals, outside the submitted work. Dr. Cane has nothing to disclose. Mr. Halner has nothing to disclose. Dr. Matthews has nothing to disclose. Dr. Donnelly reports grants from AstraZeneca, from Boehringer-Ingelheim, outside the submitted work; . Dr. Simpson has nothing to disclose. Dr Baker has nothing to disclose. Dr. Fadai has nothing to disclose. Dr. Peterson reports personal fees from AstraZeneca, outside the submitted work; . Mr. Bengtsson reports personal fees from AstraZeneca, outside the submitted work; Dr. Barnes reports grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Teva, personal fees from Covis, during the conduct of the study; Dr. Russell reports grants from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi UK, personal fees from Glaxo-SmithKline, during the conduct of the study; . Dr. Bafadhel reports grants from AstraZeneca, personal fees from AstraZeneca, Chiesi, GSK, other from Albus Health, ProAxsis, outside the submitted work; . Ethics Approval Statement: The trial was sponsored by the University of Oxford, and was approved by the Fulham London Research Ethics Committee (20/HRA/2531) and the National Health Research Authority.The ethical approval number is 20/HRA/2531.

The objective of the present study was to investigate the effects of dietary supplementation with zinc oxide (ZnO) and chitosan–zinc nanoparticles (chitosan–ZnO NPs) on biochemical, immunological, and antioxidant biomarkers in blood of juvenile belugas (Huso huso). The beluga juveniles with initial weight of 287 ± 46 g were fed with eight experimental diets containing 0 g kg−1 ZnO (the control diet); 10, 20, and 40 mg kg−1 ZnO; and 10, 20, and 40 mg kg−1 chitosan–ZnO NPs and 36 mg kg−1 chitosan. After 28 days of culture, the fish were fed with ZnO and chitosan–ZnO NP–supplemented diets showed a more significant increase in total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activity (p 0.05) in malondialdehyde (MDA) and glucose level in all treatment groups. The results showed that with increasing levels of ZnO and chitosan–ZnO NPs, alternative complement activity (ACH50), and total immunoglobulin, total protein, albumin, and lysozyme had a significant increase in fish fed with ZnO and chitosan–ZnO NP–supplemented diets compared to the control group (p 0.05), while the levels of LDH enzyme activity, urea, and creatinine decreased by increasing both ZnO and chitosan–ZnO NP levels. These results demonstrated that dietary chitosan–ZnO NPs could improve the health status, immune function, and antioxidant capacity of the cultured beluga juvenile.

The article examines the question of the women religious mentorship in modern Iran. It is shown that Iranian theologians differed in their opinion whether a woman can be a religious mentor (marja): many of them supported it, others agreed to it only if she should mentor other women, and many others, including Ayatollah Khomeini, opposed it. Brief biographies of two most prominent female marjas are given: those of Nesrat Amin and Zahra Sefati. Both of them received a permission to interpret Islamic texts from distinguished Iranian ayatollahs. With theirinitiative and eagernessfor knowledge, they managed to succeed in Shiite theology and their works were highly regarded by Iranian ayatollahs. It is evident that their activities were closely linked to important events that happened in Iranian society during their lifetime: the Constitutional Revolution, anti-religious Shah regime, Islamic Revolution. Currently due to increase in the education and social activity among women, a need arose to officially allow women to become marja. Today, in Iran there works the Women Council on Islamic Law, what allows to expand the role of women in development of Islamic Law

Background Studying the neural consequences of tobacco smoking during adolescence, including those associated with early light use, may help expose the mechanisms that underlie the transition from initial use to nicotine dependence in adulthood. However, only a few studies in adolescents exist, and they include small samples. In addition, the neural mechanism, if one exists, that links nicotinic receptor genes to smoking behavior in adolescents is still unknown. Methods Structural and diffusion tensor magnetic resonance imaging data were acquired from a large sample of 14-year-old adolescents who completed an extensive battery of neuropsychological, clinical, personality, and drug-use assessments. Additional assessments were conducted at 16 years of age. Results Exposure to smoking in adolescents, even at low doses, is linked to volume changes in the ventromedial prefrontal cortex and to altered neuronal connectivity in the corpus callosum. The longitudinal analyses strongly suggest that these effects are not preexisting conditions in those who progress to smoking. There was a genetic contribution wherein the volume reduction effects were magnified in smokers who were carriers of the high-risk genotype of the alpha 5 nicotinic receptor subunit gene, rs16969968. Conclusions These findings give insight into a mechanism involving genes, brain structure, and connectivity underlying why some adolescents find nicotine especially addictive.

Epidemic models have previously been employed to better understand the spread of internet content, such as individual viral videos. Motivated by geographical differences between viewing populations, as well as by multiple viral videos which are linked or related in some way, we propose a multi-group susceptible–exposed–infected–recovered–susceptible (SEIRS) delay differential equation epidemic model for the popularity evolution of viral videos. The model accounts for the multi-group environment via (in general, heterogeneous) networks of single-group SEIRS equations. Existence and stability conditions for disease-free and endemic equilibrium states are obtained, while numerical simulations demonstrate the emergence of non-symmetric endemic equilibrium states across the network — in the case of heterogeneous parameters. In order to demonstrate the effectiveness of our modeling approach, we compare solutions to our model with data obtained from coupled YouTube videos. Our results demonstrate that the inclusion of coupling between such videos allows for better agreement with data than considering each video in isolation. Such results suggest that the multi-group epidemic modeling approach including time delays and coupling between videos is a useful tool for understanding the dynamics of viral videos which are connected in some manner. While the proposed network SEIRS differential delay equation epidemic model was applied to viral video data, it may be applicable to a wide variety of internet content and, more generally, may be used to model information propagation within and between communities under the assumption of time delays in information propagation.

Macroscale deformations in a roasting coffee bean are important mechanisms in determining flavour development, moisture loss, and consistency of the bean. In this paper, we model the stresses and strains in the cellulose structure of a roasting coffee bean via temperature-dependent poroviscoelastic constitutive equations. This model accounts for the deformations that are created and controlled by the moisture content, temperature, and gas pressure inside of the roasting coffee bean. The model combines previously derived multiphase heat and mass transfer models for roasting coffee beans with these poroviscoelastic equations, to determine when and where macroscale deformations of the cellular matrix are likely to occur. By exploiting reasonable asymptotic reductions of the poroviscoelastic equations, we find that a large surge of stress is produced in the interior of a coffee bean. We determine that this build-up of stress is due to the viscoelastic interior of the bean being contained by a rigid elastic exterior and unable to expand. Our theoretical results suggest directions for possible improvement in standard industrial coffee roasting techniques, which may allow the macroscale deformations of the cellular matrix to be controlled and thereby improve properties such as flavour, moisture loss, and consistency of the final product.

This study provides an overview of sustainable reusable load-bearing constructions as a contribution to the debate over whether building construction provides the building industry with the best and most environmentally friendly qualities. By contrasting their building-specific features, it demonstrates the benefits and drawbacks of particular structural elements and envelope solutions and ecological aspects using various system boundaries of life-cycle assessment (LCA). Following a careful consideration of ecological factors and sustainable circular economy criteria, a structural component that is sustainably optimized is defined. This component should be chosen based on external conditions. By selecting environmentally friendly building materials and proper connecting procedures that enable separability, resource-efficient and sustainable buildings can be achieved. Both the selection of load-bearing elements and the necessary insulating material have a significant impact on the ecological performance and reusability options of the components. The elements of homogeneity, separability, and pollutant-freeness play a significant influence in the reuse process, namely in terms of details and construction type in general, as well as the ways of reusing and recycling them. Sustainable solutions for load-bearing building components can be created by simultaneously investigating environmentally friendly building materials and the structure of the components. This paper illustrates how the natural resources can be used both optimally and sustainably. It presents a conceptual framework for scenario development of the LCA of load-bearing structures, their effect on the design and decision-making process. There is a potential of increasing total resource efficiency at the building level with a suitable combination of the material components employed at the component level. Because of this, the overall energy efficiency and its consequent ecological impacts are the main topics of this study.

Summary Background Multiple early reports of patients admitted to hospital with COVID-19 showed that patients with chronic respiratory disease were significantly under-represented in these cohorts. We hypothesised that the widespread use of inhaled glucocorticoids among these patients was responsible for this finding, and tested if inhaled glucocorticoids would be an effective treatment for early COVID-19. Methods We performed an open-label, parallel-group, phase 2, randomised controlled trial (Steroids in COVID-19; STOIC) of inhaled budesonide, compared with usual care, in adults within 7 days of the onset of mild COVID-19 symptoms. The trial was done in the community in Oxfordshire, UK. Participants were randomly assigned to inhaled budsonide or usual care stratified for age (≤40 years or >40 years), sex (male or female), and number of comorbidities (≤1 and ≥2). Randomisation was done using random sequence generation in block randomisation in a 1:1 ratio. Budesonide dry powder was delivered using a turbohaler at a dose of 400 μg per actuation. Participants were asked to take two inhalations twice a day until symptom resolution. The primary endpoint was COVID-19-related urgent care visit, including emergency department assessment or hospitalisation, analysed for both the per-protocol and intention-to-treat (ITT) populations. The secondary outcomes were self-reported clinical recovery (symptom resolution), viral symptoms measured using the Common Cold Questionnare (CCQ) and the InFLUenza Patient Reported Outcome Questionnaire (FLUPro), body temperature, blood oxygen saturations, and SARS-CoV-2 viral load. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. This trial is registered with ClinicalTrials.gov, NCT04416399. Findings From July 16 to Dec 9, 2020, 167 participants were recruited and assessed for eligibility. 21 did not meet eligibility criteria and were excluded. 146 participants were randomly assigned—73 to usual care and 73 to budesonide. For the per-protocol population (n=139), the primary outcome occurred in ten (14%) of 70 participants in the usual care group and one (1%) of 69 participants in the budesonide group (difference in proportions 0·131, 95% CI 0·043 to 0·218; p=0·004). For the ITT population, the primary outcome occurred in 11 (15%) participants in the usual care group and two (3%) participants in the budesonide group (difference in proportions 0·123, 95% CI 0·033 to 0·213; p=0·009). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was eight. Clinical recovery was 1 day shorter in the budesonide group compared with the usual care group (median 7 days [95% CI 6 to 9] in the budesonide group vs 8 days [7 to 11] in the usual care group; log-rank test p=0·007). The mean proportion of days with a fever in the first 14 days was lower in the budesonide group (2%, SD 6) than the usual care group (8%, SD 18; Wilcoxon test p=0·051) and the proportion of participants with at least 1 day of fever was lower in the budesonide group when compared with the usual care group. As-needed antipyretic medication was required for fewer proportion of days in the budesonide group compared with the usual care group (27% [IQR 0–50] vs 50% [15–71]; p=0·025) Fewer participants randomly assigned to budesonide had persistent symptoms at days 14 and 28 compared with participants receiving usual care (difference in proportions 0·204, 95% CI 0·075 to 0·334; p=0·003). The mean total score change in the CCQ and FLUPro over 14 days was significantly better in the budesonide group compared with the usual care group (CCQ mean difference −0·12, 95% CI −0·21 to −0·02 [p=0·016]; FLUPro mean difference −0·10, 95% CI −0·21 to −0·00 [p=0·044]). Blood oxygen saturations and SARS-CoV-2 load, measured by cycle threshold, were not different between the groups. Budesonide was safe, with only five (7%) participants reporting self-limiting adverse events. Interpretation Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery after early COVID-19. Funding National Institute for Health Research Biomedical Research Centre and AstraZeneca.

Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions.

Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions.

Riots originating during, or in the aftermath of, sports events can incur significant costs in damages, as well as large-scale panic and injuries. A mathematical description of sports riots is therefore sought to better understand their propagation and limit these physical and financial damages. In this work, we present an agent-based modelling (ABM) framework that describes the qualitative features of populations engaging in riotous behaviour. Agents, pertaining to either a ‘rioter’ or a ‘bystander’ sub-population, move on an underlying lattice and can either be recruited or defect from their respective sub-population. In particular, we allow these individual-level recruitment and defection processes to vary with local population density. This agent-based modelling framework provides the unifying link between multi-population stochastic models and density-dependent reaction processes. Furthermore, the continuum description of this ABM framework is shown to be a system of nonlinear reaction–diffusion equations and faithfully agrees with the average ABM behaviour from individual simulations. Finally, we determine the unique correspondence between the underlying individual-level recruitment and defection mechanisms with their population-level counterparts, providing a link between local-scale effects and macroscale rioting phenomena.

BackgroundMultiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness.MethodsWe conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment.Results146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care.ConclusionEarly administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection.(Funded by Oxford NIHR Biomedical Research Centre and AstraZeneca;ClinicalTrials.govnumber,NCT04416399)Research in contextEvidence before this studyThe majority of interventions studied for the COVID-19 pandemic are focused on hospitalised patients. Widely available and broadly relevant interventions for mild COVID-19 are urgently needed.Added value of this studyIn this open label randomised controlled trial, inhaled budesonide, when given to adults with early COVID-19 illness, reduces the likelihood of requiring urgent care, emergency department consultation or hospitalisation. There was also a quicker resolution of fever, a known poor prognostic marker in COVID-19 and a faster self-reported and questionnaire reported symptom resolution. There were fewer participants with persistent COVID-19 symptoms at 14 and 28 days after budesonide therapy compared to usual care.Implications of all the available evidenceThe STOIC trial potentially provides the first easily accessible effective intervention in early COVID-19. By assessing health care resource utilisation, the study provides an exciting option to help with the worldwide pressure on health care systems due to the COVID-19 pandemic. Data from this study also suggests a potentially effective treatment to prevent the long term morbidity from persistent COVID-19 symptoms.

The existence and uniqueness of the infectious steady-state, as well as a description of the global sensitivity analysis via eFAST.

We present a solid theoretical foundation for interpreting the origin of Allee effects by providing the missing link in understanding how local individual-based mechanisms translate to global population dynamics. Allee effects were originally proposed to describe population dynamics that cannot be explained by exponential and logistic growth models. However, standard methods often calibrate Allee effect models to match observed global population dynamics without providing any mechanistic insight. By introducing a stochastic individual-based model, with proliferation, death, and motility rates that depend on local density, we present a modelling framework that translates particular global Allee effects to specific individual-based mechanisms. Using data from ecology and cell biology, we unpack individual-level mechanisms implicit in an Allee effect model and provide simulation tools for others to repeat this analysis.

In the last years several projects of medium and high-rise timber-based multi-story buildings have been proposed and developed. In most of the cases timber-concrete composite (TCC) floors play a significant role for the design of the structural slabs due to acoustic performance, fire protection and structural issues. Within several research projects and with the aim to optimize the structural and ecological characteristics of building components the Department of Structural Design and Timber Engineering (ITI) at the Vienna University of Technology (TU Wien) developed timber-steel hybrid beams that can be used independently or combined with concrete floors, proposing for this last case prefabricated and semi-prefabricated timber-steel-concrete ribbed elements that make the most of all this potential.In order to recognize the potential for future market implementation and to demonstrate the competiveness of the developed hybrid ribbed floor slabs, the economic feasibility and the ecological impact, structural elements were analyzed in several case studies. The environmental assessment shows the ecological advantages of the developed concepts and underlines the potential for further developments. This paper contains an introduction on the state-of-the-art floor solutions for timber-based multistory buildings, the fundamental ideas and design concepts behind the timber-steel and timber-steel-concrete proposals as well as a short review of the tests carried until now and results obtained.

While the processes underlying the roasting of a single coffee bean have been the focus of a number of recent studies, the more industrially relevant problem of roasting an array of coffee beans has not been well studied from a modeling standpoint. Starting with a microscale model for the heat and mass transfer processes within a single bean during roasting, we apply homogenization theory to upscale this model to an effective macroscale model for the roasting of an array of coffee beans. We then numerically simulate this effective model for two caricatures of roasting configurations which are of great importance to industrial scale coffee bean roasting: namely, drum roasters (where the beans are placed in a rotating drum) and fluidized bed roasters (where hot air is blown through the beans). The derivation of the homogenization problem has been carried out in a three-dimensional rectangular geometry. Simulations are presented both for simplified one-dimensional arrays of three-dimensional beans (as these are easier to visualize), as well as cross sections of full three-dimensional arrays of beans (for the sake of verification). We also verify our simulation results against experimental data from the literature. Among the findings is that increasing the air-to-bean volume fraction ratio decreases the drying time for the array of beans in a linear manner. We also find that, in the case of a fluidized bed, an increase in the hot air inflow velocity will decrease the drying time in a nonlinear manner, with diminishing returns observed beyond some point for large enough air inflow velocities.

Within several research projects and with the aim to optimize structural performance, energy efficiency and ecological characteristics of structural building components the Department of Structural Design and Timber Engineering (ITI) at the Vienna University of Technology (TU Wien) developed several wood-based composite systems, which combine timber products with other conventional building materials and components. As a representative example for these developments, this paper illustrates the results of the joint research project “Wood-based concrete: building construction with composite elements of wood-concrete compounds and timber (WooCon)”. The objective of the research project “WooCon” is to develop a multi-layer wall system composed of wood lightweight concrete (WLC), connected timber sections, textile reinforcement as well as glass layers on the exterior to gain and use advantages of each used material - lightweight, structural, thermal storage and insulation, ecological and economic benefits - to name the most important ones. In order to assess the structural physical properties of wood-based composite wall elements, in a first step measurements of the thermal properties with respect to thermal-insulating properties and thermal storage capacity are carried out. In following step, the results obtained are used further to simulate the thermodynamic and hygrothermal building behavior. The aim of the simulations is to investigate the effect of the wood-based composite wall elements to the annual heating demand as well as to the operative room temperature of a typical south-orientated living space.

Objective: White matter microstructure alterations have recently been associated with depressive episodes during adolescence, but it is unknown whether they predate depression. The authors investigated whether subthreshold depression in adolescence is associated with white matter microstructure variations and whether they relate to depression outcome. Method: Adolescents with subthreshold depression (N=96) and healthy control subjects (N=336) drawn from a community-based cohort were compared using diffusion tensor imaging and whole brain tract-based spatial statistics (TBSS) at age 14 to assess white matter microstructure. They were followed up at age 16 to assess depression. Probabilistic tractography was used to reconstruct white matter streamlines spreading from the regions identified in the TBSS analysis and along bundles implicated in emotion regulation, the uncinate fasciculus and the cingulum. The authors searched for mediating effects of white matter microstructure on the relationship between baseline subthreshold depression and depression at follow-up, and then explored the specificity of the findings. Results: Lower fractional anisotropy (FA) and higher radial diffusivity were found in the anterior corpus callosum in the adolescents with subthreshold depression. Tractography analysis showed that they also had lower FA in the right cingulum streamlines, along with lower FA and higher mean diffusivity in tracts connecting the corpus callosum to the anterior cingulate cortex. The relation between subthreshold depression at baseline and depression at follow-up was mediated by FA values in the latter tracts, and lower FA values in those tracts distinctively predicted higher individual risk for depression. Conclusions: Early FA variations in tracts projecting from the corpus callosum to the anterior cingulate cortex may denote a higher risk of transition to depression in adolescents.

Background and objectives Through the use of an experimental design with a baseline and post intervention, the aim of this study was to investigate the effectiveness of a psychological intervention in increasing public health and communication skills for caregivers. Methods This randomized controlled trial was designed in Razi Hospital in Tehran, Iran. A sample size of 90 participants was evenly divided into intervention and control groups. The intervention group was given routine treatments and also participated in planned educational sessions. The planned educational program was implemented in 10 group sessions over a period of 5 weeks. Each session lasted 45–60 min. The outcome measures were: (1) improvement in the caregiver's general health as measured by the changes in their General Health Questionnaire (GHQ) scores taken at baseline and post intervention and (2) changes in the caregiver's communication skills, measured by the communication skills questionnaire taken at baseline and after 3 months. Results An independent samples t-test revealed that there was a significant difference between the two groups in the mean scores of communication skill at baseline (P Conclusion Results of our study confirm that providing education on effective communication skills can be an effective, cost-efficient, and convenient strategy to reduce the psychological complications for caregivers and improve the care of patients living with schizophrenia.

By bringing to bear previously unstudied Soviet archival documents and conducting firsthand interviews with former diplomats, the article traces the ways in which the Soviet Union sought out opportunities to reinvigorate deteriorated Soviet‒Iranian ties through cultural organizations and events in Iran during the decades following World War II. A variety of Soviet cultural representatives—from wrestlers to classical musicians to scholars of Iranian literature—were marshaled for this effort, which bore unexpected fruit considering the modest expectations of the Soviet leadership, ideological differences between the two countries, and increasingly dominant US cultural projection. The connections between cultural ties and state goals, Iranian perceptions of Russia, and the Soviet/Russian sympathies of some members of the shah’s government are among sub-themes examined.

This article traces the careers and fates of several Iranian female communists who were not professional intelligence agents but engaged in clandestine activities. They are presented primarily through their own writings – memoirs and letters – and documents preserved in Russian archives. Socialist ideas resonated strongly in early 20th century Iran, and the women examined here were driven by a zeal to improve the hard lot faced by many of their fellow Iranians. They hailed from diverse family backgrounds: Mariam Firuz’s roots lay in the aristocracy; Zuleykhah Asadi came from the working class; and Akhtar Kiānuri’s family had been prominent in the clergy. Their husbands or fathers were also communists and spent time in jail. All of the women traveled to the Soviet Union to study, drawn to the Communist University for Laborers of the East in Moscow, known by its acronym of KUTV and called a “Red Mecca” by some Iranian students. Upon returning to Iran, these women were forced to work underground as the communist party was banned in the country for much of the 20th century, with members and sympathizers harassed, arrested and accused of espionage. These women’s accounts were produced for different readers: some feel romanticized at times, while others are brutally honest. Their fates were also very different. The wave of revolution both raised individuals to new heights and tossed them to the shore as it churned onward. While Mariam Firuz became a living legend, Akhtar and others faded into obscurity, and Zuleykha and countless others were never known.

Background and objective About one percent of the world's population are affected by Schizophrenia. It is assumed that antipsychotic drugs cause sexual dysfunction, but the main mechanism of it, is not specified. Few researches that have addressed this issue showed that there is a relationship between neuroleptics and sexual dysfunction. A number of studies found that bupropion could improve the sexual dysfunction. So the purpose of this study is to investigate the effect of bupropion on sexual function of the patients with Schizophrenia. Methods This randomized clinical trial was performed on 40 schizophrenic patients admitted to Kamrani psychiatry clinic in Tehran during 2015–2016. Participants were randomly divided into two experimental and control groups. The experiment group was taken bupropion tablets 150 mg/day and the control group were given placebo for one-month. The sexual performance of participants was studied before and after the intervention by the sexual functioning questionnaire (SFQ). Obtained data were analyzed using the SPSS software with student t-test and chi-square tests. Results 40 patients older than 18 year old participated in the study. Before treatment the two groups did not have significant difference based on a general score of SFQ questionnaire, but There was a significant difference between two groups after the intervention. Experiment group (bupropion) showed significant improvement in sexual function. Using bupropion in the experiment group led to significant change in the score of sexual desire, erection and orgasm, but it had no effect on sexual arousal and ejaculation. The associations of ejaculation and orgasm were significance. Using the bupropion changed the erection and orgasm in the two groups of control and experimental. Conclusion This study shows that 150 mg/day dose have considerable effect on sexual dysfunction of patients that are under treatment with anti-psychotic drugs. Also, this drug does not have any special side effects.

Recent modelling of coffee bean roasting suggests that in the early stages of roasting, within each coffee bean, there are two emergent regions: a dried outer region and a saturated interior region. The two regions are separated by a transition layer (or, drying front). In this paper, we consider the asymptotic analysis of a recent multiphase model in order to gain a better understanding of its salient features. The model consists of a PDE system governing the thermal, moisture, and gas pressure profiles throughout the interior of the bean. By obtaining asymptotic expansions for these quantities in relevant limits of the physical parameters, we are able to determine the qualitative behaviour of the outer and interior regions, as well as the dynamics of the drying front. Although a number of simplifications and scalings are used, we take care not to discard aspects of the model which are fundamental to the roasting process. Indeed, we find that for all of the asymptotic limits considered, our approximate solutions faithfully reproduce the qualitative features evident from numerical simulations of the full model. From these asymptotic results, we have a better qualitative understanding of the drying front (which is hard to resolve precisely in numerical simulations), and hence, of the various mechanisms at play including heating, evaporation, and pressure changes. This qualitative understanding of solutions to the multiphase model is essential when creating more involved models that incorporate chemical reactions and solid mechanics effects.

We study the spectrum of a new class of nonlocal eigenvalue problems (NLEPs) that characterize the linear stability properties of localized spike solutions to the singularly perturbed two-component Gierer-Meinhardt (GM) reaction-diffusion (RD) system with a fixed time-delay \begin{document}$T$\end{document} in only the nonlinear autocatalytic activator kinetics. Our analysis of this model is motivated by the computational study of Seirin Lee et al. [Bull. Math. Bio., 72(8), (2010)] on the effect of gene expression time delays on spatial patterning for both the GM and some related RD models. For various limiting forms of the GM model, we show from a numerical study of the associated NLEP, together with an analytical scaling law analysis valid for large delay \begin{document}$T$\end{document} , that a time-delay in only the activator kinetics is stabilizing in the sense that there is a wider region of parameter space where the spike solution is linearly stable than when there is no time delay. This enhanced stability behavior with a delayed activator kinetics is in marked contrast to the de-stabilizing effect on spike solutions of having a time-delay in both the activator and inhibitor kinetics. Numerical results computed from the RD system with delayed activator kinetics are used to validate the theory for the 1-D case.

Background: Little published research have assessed factors predicting the uptake of HIV-testing services for people who inject drugs (PWID) in Iranian settings. The objectives of the present study were to determine factors associated with HIV testing uptake among PWID in Tehran.Methods: We surveyed 500 PWID in Tehran concerning demographic characteristics, drug-related and sexual risk behaviors, and HIV testing. HIV-related stigma variables were assessed using a scale consisted of 22 agree/disagree statements in three subscales including shame/blame/isolation, perceived discrimination, and equity. We used multivariate logistic regression to identify factors associated with HIV testing.Results: Participant ages ranged from 19 to 67 years. Multivariable model shows that factors independently associated with recent HIV testing included level of education (adjusted odds ratios [aOR] 1.12, 95% CI 1.44–4.42), living status (aOR 1.91, 95% confidence interval [CI] 1.35–2.71), income (aOR 1.64, 95% CI 1.1...

On 23 January 2017, renowned Georgian scholar of Iran, Doctor of Philology (Dr. Habilitatus), professor and author of over 200 scholarly publications in Russian, Georgian, Persian and other languag...

Various facade-glazing systems have long been in use and are generally considered state of the art. However, with these solutions, the glass serves no stiffening function. The objective of several ...

With the aim to optimize energy efficiency and ecological characteristics of structural building components, through several research projects, the Department of Structural Design and Timber Engine...