Search results for: Green’s Function

Authors: Natasa Ilic, Alisa Gruden-Movsesijan, Maja Kosanovic, Sofija Glamoclija, Marina Bekic, Ljiljana Sofronic-Milosavljevic, Sergej Tomic

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As a very promising candidate for modulation of immune response in the sense of biasing the inflammatory towards an anti-inflammatory type of response, Trichinella spiralis infection was shown to successfully alleviate the severity of experimental autoimmune encephalomyelitis, the animal model of human disease multiple sclerosis. This effect is achieved via its excretory-secretory muscle larvae (ES L1) products which affect the maturation status and function of dendritic cells (DCs) by inducing the tolerogenic status of DCs, which leads to the mitigation of the Th1 type of response and the activation of a regulatory type of immune response both in vitro and in vivo. ES L1 alone or via treated DCs successfully mitigated EAE in the same manner as the infection itself. On the other hand, it has been shown that T. spiralis infection slows down the tumour growth and significantly reduces the tumour size in the model of mouse melanoma, while ES L1 possesses a pro-apoptotic and anti-survival effect on melanoma cells in vitro. Hence, although the mechanisms still need to be revealed, T. spiralis infection and its ES L1 products have a bit of controversial potential to modulate both inflammatory diseases and malignancies. The recent discovery of T. spiralis extracellular vesicles (TsEVs) suggested that the induction of complex regulation of the immune response requires simultaneous delivery of different signals in nano-sized packages. This study aimed to explore whether TsEVs bare the similar potential as ES L1 to influence the status of DCs in initiation, progression and regulation of immune response, but also to investigate the effect of both ES L1 and TsEVs on myeloid derived suppressor cells (MDSC) which present the regular tumour tissue environment. TsEVs were enriched from the conditioned medium of T. spiralis muscle larvae by differential centrifugation and used for the treatment of human monocyte-derived DCs and MDSC. On DCs, TsEVs induced low expression of HLA DR and CD40, moderate CD83 and CD86, and increased expression of ILT3 and CCR7 on treated DCs, i.e., they induced tolerogenic DCs. Such DCs possess the capacity to polarize T cell immune response towards regulatory type, with an increased proportion of IL-10 and TGF-β producing cells, similarly to ES L1. These findings indicated that the ability of TsEVs to induce tolerogenic DCs favoring anti-inflammatory responses may be helpful in coping with diseases that involve Th1/Th17-, but also Th2-mediated inflammation. In MDSC in vitro model, although both ES L1 and TsEVs had the same impact on MDSC phenotype i.e., they acted suppressive, ES L1 treated MDSC, unlike TsEVs treated ones, induced T cell response characterized by the increased RoRγT and IFN-γ, while the proportion of regulatory cells was decreased followed by the decrease in IL-10 and TGF-β positive cells proportion within this population. These findings indicate the interesting ability of ES L1 to modulate T cells response via MDSC towards pro-inflamatory type, suggesting that, unlike TsEVs which consistently demonstrate the suppresive effect on inflammatory response, it could be used also for the development of new approaches aimed for the treatment of malignant diseases. Acknowledgment: This work was funded by the Promis project – Nano-MDCS-Thera, Science Fund, Republic of Serbia.

Keywords: dendritic cells, myeloid derived suppressor cells, immunomodulation, Trichinella spiralis

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Authors: Gabrielle Robertson, Matthew Downs, Joseph Dagher

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Iron deposition in the brain has been linked with a host of neurological disorders such as Alzheimer’s, Parkinson’s, and Multiple Sclerosis. While some treatment options exist, there are no objective measurement tools that allow for the monitoring of iron levels in the brain in vivo. An emerging Magnetic Resonance Imaging (MRI) method has been recently proposed to deduce iron concentration through quantitative measurement of magnetic susceptibility. This is a multi-step process that involves repeated modeling of physical processes via approximate numerical solutions. For example, the last two steps of this Quantitative Susceptibility Mapping (QSM) method involve I) mapping magnetic field into magnetic susceptibility and II) mapping magnetic susceptibility into iron concentration. Process I involves solving an ill-posed inverse problem by using regularization via injection of prior belief. The end result from Process II highly depends on the model used to describe the molecular content of each voxel (type of iron, water fraction, etc.) Due to these factors, the accuracy and repeatability of QSM have been an active area of research in the MRI and medical imaging community. This work aims to estimate iron concentration in the brain via a single step. A synthetic numerical model of the human head was created by automatically and manually segmenting the human head on a high-resolution grid (640x640x640, 0.4mm³) yielding detailed structures such as microvasculature and subcortical regions as well as bone, soft tissue, Cerebral Spinal Fluid, sinuses, arteries, and eyes. Each segmented region was then assigned tissue properties such as relaxation rates, proton density, electromagnetic tissue properties and iron concentration. These tissue property values were randomly selected from a Probability Distribution Function derived from a thorough literature review. In addition to having unique tissue property values, different synthetic head realizations also possess unique structural geometry created by morphing the boundary regions of different areas within normal physical constraints. This model of the human brain is then used to create synthetic MRI measurements. This is repeated thousands of times, for different head shapes, volume, tissue properties and noise realizations. Collectively, this constitutes a training-set that is similar to in vivo data, but larger than datasets available from clinical measurements. This 3D convolutional U-Net neural network architecture was used to train data-driven Deep Learning models to solve for iron concentrations from raw MRI measurements. The performance was then tested on both synthetic data not used in training as well as real in vivo data. Results showed that the model trained on synthetic MRI measurements is able to directly learn iron concentrations in areas of interest more effectively than other existing QSM reconstruction methods. For comparison, models trained on random geometric shapes (as proposed in the Deep QSM method) are less effective than models trained on realistic synthetic head models. Such an accurate method for the quantitative measurement of iron deposits in the brain would be of important value in clinical studies aiming to understand the role of iron in neurological disease.

Keywords: magnetic resonance imaging, MRI, iron deposition, machine learning, quantitative susceptibility mapping

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Authors: Shagufta Jabeen, Faez J. Firdaus Abdullah, Zunita Zakaria, Nurulfiza M. Isa, Yung C. Tan, Wai Y. Yee, Abdul R. Omar

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Pasteurella multocida (PM) is an important veterinary opportunistic pathogen particularly associated with septicemic pasteurellosis, pneumonic pasteurellosis and hemorrhagic septicemia in cattle and buffaloes. P. multocida serotype A has been reported to cause fatal pneumonia and septicemia. Pasteurella multocida subspecies multocida of serotype A Malaysian isolate PMTB2.1 was first isolated from buffaloes died of septicemia. In this study, the genome of P. multocida strain PMTB2.1 was sequenced using third-generation sequencing technology, PacBio RS2 system and analyzed bioinformatically via de novo analysis followed by in-depth analysis based on comparative genomics. Bioinformatics analysis based on de novo assembly of PacBio raw reads generated 3 contigs followed by gap filling of aligned contigs with PCR sequencing, generated a single contiguous circular chromosome with a genomic size of 2,315,138 bp and a GC content of approximately 40.32% (Accession number CP007205). The PMTB2.1 genome comprised of 2,176 protein-coding sequences, 6 rRNA operons and 56 tRNA and 4 ncRNAs sequences. The comparative genome sequence analysis of PMTB2.1 with nine complete genomes which include Actinobacillus pleuropneumoniae, Haemophilus parasuis, Escherichia coli and five P. multocida complete genome sequences including, PM70, PM36950, PMHN06, PM3480, PMHB01 and PMTB2.1 was carried out based on OrthoMCL analysis and Venn diagram. The analysis showed that 282 CDs (13%) are unique to PMTB2.1and 1,125 CDs with orthologs in all. This reflects overall close relationship of these bacteria and supports the classification in the Gamma subdivision of the Proteobacteria. In addition, genomic distance analysis among all nine genomes indicated that PMTB2.1 is closely related with other five Pasteurella species with genomic distance less than 0.13. Synteny analysis shows subtle differences in genetic structures among different P.multocida indicating the dynamics of frequent gene transfer events among different P. multocida strains. However, PM3480 and PM70 exhibited exceptionally large structural variation since they were swine and chicken isolates. Furthermore, genomic structure of PMTB2.1 is more resembling that of PM36950 with a genomic size difference of approximately 34,380 kb (smaller than PM36950) and strain-specific Integrative and Conjugative Elements (ICE) which was found only in PM36950 is absent in PMTB2.1. Meanwhile, two intact prophages sequences of approximately 62 kb were found to be present only in PMTB2.1. One of phage is similar to transposable phage SfMu. The phylogenomic tree was constructed and rooted with E. coli, A. pleuropneumoniae and H. parasuis based on OrthoMCL analysis. The genomes of P. multocida strain PMTB2.1 were clustered with bovine isolates of P. multocida strain PM36950 and PMHB01 and were separated from avian isolate PM70 and swine isolates PM3480 and PMHN06 and are distant from Actinobacillus and Haemophilus. Previous studies based on Single Nucleotide Polymorphism (SNPs) and Multilocus Sequence Typing (MLST) unable to show a clear phylogenetic relatedness between Pasteurella multocida and the different host. In conclusion, this study has provided insight on the genomic structure of PMTB2.1 in terms of potential genes that can function as virulence factors for future study in elucidating the mechanisms behind the ability of the bacteria in causing diseases in susceptible animals.

Keywords: comparative genomics, DNA sequencing, phage, phylogenomics

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Authors: Jatziri Y. Moreno-Martinez, Arturo Galvan, Xavier Chavez Cardenas, Hiram Arroyo

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Several methods have been utilized to study the prediction of cracking of concrete structural under loading. The finite element analysis is an alternative that shows good results. The aim of this work was the numerical study of the width crack in reinforced concrete beams with dapped ends, these are frequently found in bridge girders and precast concrete construction. Properly restricting cracking is an important aspect of the design in dapped ends, it has been observed that the cracks that exceed the allowable widths are unacceptable in an aggressive environment for reinforcing steel. For simulating the crack width, the discrete crack approach was considered by means of a Cohesive Zone (CZM) Model using a function to represent the crack opening. Two cases of dapped-end were constructed and tested in the laboratory of Structures and Materials of Engineering Institute of UNAM. The first case considers a reinforcement based on hangers as well as on vertical and horizontal ring, the second case considers 50% of the vertical stirrups in the dapped end to the main part of the beam were replaced by an equivalent area (vertically projected) of diagonal bars under. The loading protocol consisted on applying symmetrical loading to reach the service load. The models were performed using the software package ANSYS v. 16.2. The concrete structure was modeled using three-dimensional solid elements SOLID65 capable of cracking in tension and crushing in compression. Drucker-Prager yield surface was used to include the plastic deformations. The reinforcement was introduced with smeared approach. Interface delamination was modeled by traditional fracture mechanics methods such as the nodal release technique adopting softening relationships between tractions and the separations, which in turn introduce a critical fracture energy that is also the energy required to break apart the interface surfaces. This technique is called CZM. The interface surfaces of the materials are represented by a contact elements Surface-to-Surface (CONTA173) with bonded (initial contact). The Mode I dominated bilinear CZM model assumes that the separation of the material interface is dominated by the displacement jump normal to the interface. Furthermore, the opening crack was taken into consideration according to the maximum normal contact stress, the contact gap at the completion of debonding, and the maximum equivalent tangential contact stress. The contact elements were placed in the crack re-entrant corner. To validate the proposed approach, the results obtained with the previous procedure are compared with experimental test. A good correlation between the experimental and numerical Load-Displacement curves was presented, the numerical models also allowed to obtain the load-crack width curves. In these two cases, the proposed model confirms the capability of predicting the maximum crack width, with an error of ± 30 %. Finally, the orientation of the crack is a fundamental for the prediction of crack width. The results regarding the crack width can be considered as good from the practical point view. Load-Displacement curve of the test and the location of the crack were able to obtain favorable results.

Keywords: cohesive zone model, dapped-end beams, discrete crack approach, finite element analysis

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Authors: Sanaz Alizadeh, Yves Comeau, Arshath Abdul Rahim, Sunhasis Ghoshal

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The application of silver nanoparticles (AgNPs) in personal care products, various household and industrial products has resulted in an inevitable environmental exposure of such engineered nanoparticles (ENPs). Ag ENPs, released via household and industrial wastes, reach water resource recovery facilities (WRRFs), yet the fate and transport of ENPs in WRRFs and their potential risk in the biological wastewater processes are poorly understood. Accordingly, our main objective was to elucidate the impact of long-term continuous exposure to AgNPs on biological activity of aerobic wastewater biofilm. The fate, transport and toxicity of 10 μg.L-1and 100 μg.L-1 PVP-stabilized AgNPs (50 nm) were evaluated in an attached growth biological treatment process, using lab-scale moving bed bioreactors (MBBRs). Two MBBR systems for organic matter removal were fed with a synthetic influent and operated at a hydraulic retention time (HRT) of 180 min and 60% volumetric filling ratio of Anox-K5 carriers with specific surface area of 800 m2/m3. Both reactors were operated for 85 days after reaching steady state conditions to develop a mature biofilm. The impact of AgNPs on the biological performance of the MBBRs was characterized over a period of 64 days in terms of the filtered biodegradable COD (SCOD) removal efficiency, the biofilm viability and key enzymatic activities (α-glucosidase and protease). The AgNPs were quantitatively characterized using single-particle inductively coupled plasma mass spectroscopy (spICP-MS), determining simultaneously the particle size distribution, particle concentration and dissolved silver content in influent, bioreactor and effluent samples. The generation of reactive oxygen species and the oxidative stress were assessed as the proposed toxicity mechanism of AgNPs. Results indicated that a low concentration of AgNPs (10 μg.L-1) did not significantly affect the SCOD removal efficiency whereas a significant reduction in treatment efficiency (37%) was observed at 100 μg.L-1AgNPs. Neither the viability nor the enzymatic activities of biofilm were affected at 10 μg.L-1AgNPs but a higher concentration of AgNPs induced cell membrane integrity damage resulting in 31% loss of viability and reduced α-glucosidase and protease enzymatic activities by 31% and 29%, respectively, over the 64-day exposure period. The elevated intercellular ROS in biofilm at a higher AgNPs concentration over time was consistent with a reduced biological biofilm performance, confirming the occurrence of a nanoparticle-induced oxidative stress in the heterotrophic biofilm. The spICP-MS analysis demonstrated a decrease in the nanoparticles concentration over the first 25 days, indicating a significant partitioning of AgNPs into the biofilm matrix in both reactors. The concentration of nanoparticles increased in effluent of both reactors after 25 days, however, indicating a decreased retention capacity of AgNPs in biofilm. The observed significant detachment of biofilm also contributed to a higher release of nanoparticles due to cell-wall destabilizing properties of AgNPs as an antimicrobial agent. The removal efficiency of PVP-AgNPs and the biofilm biological responses were a function of nanoparticle concentration and exposure time. This study contributes to a better understanding of the fate and behavior of AgNPs in biological wastewater processes, providing key information that can be used to predict the environmental risks of ENPs in aquatic ecosystems.

Keywords: biofilm, silver nanoparticle, single particle ICP-MS, toxicity, wastewater

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Authors: Shereen Ismail Fawaz, Shin-Ichi Izumi, Nouran Mohamed Salah, Heba G. Saber, Ibrahim Mohamed Roushdi

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Background: Multiple sclerosis (MS) is a chronic, inflammatory, mainly demyelinating disease of the central nervous system, more common in young adults. Cerebellar involvement is one of the most disabling lesions in MS and is usually a sign of disease progression. It plays a major role in the planning, initiation, and organization of movement via its influence on the motor cortex and corticospinal outputs. Therefore, it contributes to controlling movement, motor adaptation, and motor learning, in addition to its vast connections with other major pathways controlling balance, such as the cerebellopropriospinal pathways and cerebellovestibular pathways. Hence, trying to stimulate the cerebellum by facilitatory protocols will add to our motor control and balance function. Non-invasive brain stimulation, both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), has recently emerged as effective neuromodulators to influence motor and nonmotor functions of the brain. Anodal tDCS has been shown to improve motor skill learning and motor performance beyond the training period. Similarly, rTMS, when used at high frequency (>5 Hz), has a facilitatory effect on the motor cortex. Objective: Our aim was to determine the effect of high-frequency rTMS over the cerebellum in improving balance and functional ambulation of multiple sclerosis patients with Ataxia. Patients and methods: This was a randomized single-blinded placebo-controlled prospective trial on 40 patients. The active group (N=20) received real rTMS sessions, and the control group (N=20) received Sham rTMS using a placebo program designed for this treatment. Both groups received 12 sessions of high-frequency rTMS over the cerebellum, followed by an intensive exercise training program. Sessions were given three times per week for four weeks. The active group protocol had a frequency of 10 Hz rTMS over the cerebellar vermis, work period 5S, number of trains 25, and intertrain interval 25s. The total number of pulses was 1250 pulses per session. The control group received Sham rTMS using a placebo program designed for this treatment. Both groups of patients received an intensive exercise program, which included generalized strengthening exercises, endurance and aerobic training, trunk abdominal exercises, generalized balance training exercises, and task-oriented training such as Boxing. As a primary outcome measure the Modified ICARS was used. Static Posturography was done with: Patients were tested both with open and closed eyes. Secondary outcome measures included the expanded Disability Status Scale (EDSS) and 8 Meter walk test (8MWT). Results: The active group showed significant improvements in all the functional scales, modified ICARS, EDSS, and 8-meter walk test, in addition to significant differences in static Posturography with open eyes, while the control group did not show such differences. Conclusion: Cerebellar high-frequency rTMS could be effective in the functional improvement of balance in MS patients with ataxia.

Keywords: brain neuromodulation, high frequency rTMS, cerebellar stimulation, multiple sclerosis, balance rehabilitation

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Authors: Alberto Fina, Samuele Colonna, Maria del Mar Bernal, Orietta Monticelli, Mauro Tortello, Renato Gonnelli, Julio Gomez, Chiara Novara, Guido Saracco

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Thermally conductive polymer nanocomposites are of high interest for several applications including low-temperature heat recovery, heat exchangers in a corrosive environment and heat management in electronics and flexible electronics. In this paper, the preparation of thermally conductive nanocomposites exploiting graphene-related materials is addressed, along with their thermal characterization. In particular, correlations between 1- chemical and physical features of the nanoflakes and 2- processing conditions with the heat conduction properties of nanocomposites is studied. Polymers are heat insulators; therefore, the inclusion of conductive particles is the typical solution to obtain a sufficient thermal conductivity. In addition to traditional microparticles such as graphite and ceramics, several nanoparticles have been proposed, including carbon nanotubes and graphene, for the use in polymer nanocomposites. Indeed, thermal conductivities for both carbon nanotubes and graphenes were reported in the wide range of about 1500 to 6000 W/mK, despite such property may decrease dramatically as a function of the size, number of layers, the density of topological defects, re-hybridization defects as well as on the presence of impurities. Different synthetic techniques have been developed, including mechanical cleavage of graphite, epitaxial growth on SiC, chemical vapor deposition, and liquid phase exfoliation. However, the industrial scale-up of graphene, defined as an individual, single-atom-thick sheet of hexagonally arranged sp2-bonded carbons still remains very challenging. For large scale bulk applications in polymer nanocomposites, some graphene-related materials such as multilayer graphenes (MLG), reduced graphene oxide (rGO) or graphite nanoplatelets (GNP) are currently the most interesting graphene-based materials. In this paper, different types of graphene-related materials were characterized for their chemical/physical as well as for thermal properties of individual flakes. Two selected rGOs were annealed at 1700°C in vacuum for 1 h to reduce defectiveness of the carbon structure. Thermal conductivity increase of individual GNP with annealing was assessed via scanning thermal microscopy. Graphene nano papers were prepared from both conventional RGO and annealed RGO flakes. Characterization of the nanopapers evidenced a five-fold increase in the thermal diffusivity on the nano paper plane for annealed nanoflakes, compared to pristine ones, demonstrating the importance of structural defectiveness reduction to maximize the heat dissipation performance. Both pristine and annealed RGO were used to prepare polymer nanocomposites, by melt reactive extrusion. Thermal conductivity showed two- to three-fold increase in the thermal conductivity of the nanocomposite was observed for high temperature treated RGO compared to untreated RGO, evidencing the importance of using low defectivity nanoflakes. Furthermore, the study of different processing paremeters (time, temperature, shear rate) during the preparation of poly (butylene terephthalate) nanocomposites evidenced a clear correlation with the dispersion and fragmentation of the GNP nanoflakes; which in turn affected the thermal conductivity performance. Thermal conductivity of about 1.7 W/mK, i.e. one order of magnitude higher than for pristine polymer, was obtained with 10%wt of annealed GNPs, which is in line with state of the art nanocomposites prepared by more complex and less upscalable in situ polymerization processes.

Keywords: graphene, graphene-related materials, scanning thermal microscopy, thermally conductive polymer nanocomposites

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Authors: Ajit Rai, Hamza Deroui, Blandine Vacher, Khwansiri Ninpan, Arthur Aumont, Francesco Vitillo, Robert Plana

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Large-scale critical industrial scheduling problems are based on Resource-Constrained Project Scheduling Problems (RCPSP), that necessitate integration with other optimization problems (e.g., vehicle routing, supply chain, or unique industrial ones), thus requiring practical solutions (i.e., modular, computationally efficient with feasible solutions). To the best of our knowledge, the current industrial state of the art is not addressing this holistic problem. We propose an original modular solution that answers the issues exhibited by the delivery of complex projects. With three interlinked entities (project, task, resources) having their constraints, it uses a greedy heuristic with a dynamic cost function for each task with a situational assessment at each time step. It handles large-scale data and can be easily integrated with other optimization problems, already existing industrial tools and unique constraints as required by the use case. The solution has been tested and validated by domain experts on three use cases: outage management in Nuclear Power Plants (NPPs), planning of future NPP maintenance operation, and application in the defense industry on supply chain and factory relocation. In the first use case, the solution, in addition to the resources’ availability and tasks’ logical relationships, also integrates several project-specific constraints for outage management, like, handling of resource incompatibility, updating of tasks priorities, pausing tasks in a specific circumstance, and adjusting dynamic unit of resources. With more than 20,000 tasks and multiple constraints, the solution provides a feasible schedule within 10-15 minutes on a standard computer device. This time-effective simulation corresponds with the nature of the problem and requirements of several scenarios (30-40 simulations) before finalizing the schedules. The second use case is a factory relocation project where production lines must be moved to a new site while ensuring the continuity of their production. This generates the challenge of merging job shop scheduling and the RCPSP with location constraints. Our solution allows the automation of the production tasks while considering the rate expectation. The simulation algorithm manages the use and movement of resources and products to respect a given relocation scenario. The last use case establishes a future maintenance operation in an NPP. The project contains complex and hard constraints, like on Finish-Start precedence relationship (i.e., successor tasks have to start immediately after predecessors while respecting all constraints), shareable coactivity for managing workspaces, and requirements of a specific state of "cyclic" resources (they can have multiple states possible with only one at a time) to perform tasks (can require unique combinations of several cyclic resources). Our solution satisfies the requirement of minimization of the state changes of cyclic resources coupled with the makespan minimization. It offers a solution of 80 cyclic resources with 50 incompatibilities between levels in less than a minute. Conclusively, we propose a fast and feasible modular approach to various industrial scheduling problems that were validated by domain experts and compatible with existing industrial tools. This approach can be further enhanced by the use of machine learning techniques on historically repeated tasks to gain further insights for delay risk mitigation measures.

Keywords: deterministic scheduling, optimization coupling, modular scheduling, RCPSP

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Authors: Marit D. Murry, Amy K. Marks

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The transition to college is a critical period that affords abundant opportunities for growth in conjunction with novel challenges for emerging adults. During this time, emerging adults are garnering experiences and acquiring hosts of new information that they are required to synthesize and use to inform life-shaping decisions. This stage is characterized by instability and exploration, which necessitates a diverse set of coping skills to successfully navigate and positively adapt to their evolving environment. However, important sociocultural factors result in differences that occur developmentally for minority emerging adults (i.e., emerging adults with an identity that has been or is marginalized). While the transition to college holds vast potential, not all are afforded the same chances, and many individuals enter into this stage at varying degrees of readiness. Understanding the nuance and diversity of student preparedness for college and contextualizing these factors will better equip systems to support incoming students. Emerging adulthood for ethnic, racial minority students presents itself as an opportunity for growth and resiliency in the face of systemic adversity. Ethnic, racial identity (ERI) is defined as an identity that develops as a function of one’s ethnic-racial group membership. Research continues to demonstrate ERI as a resilience factor that promotes positive adjustment in young adulthood. Adaptive coping responses (e.g., engaging in help-seeking behavior, drawing on personal and community resources) have been identified as possible mechanisms through which ERI buffers youth against stressful life events, including discrimination. Additionally, trait mindfulness has been identified as a significant predictor of general psychological health, and mindfulness practice has been shown to be a self-regulatory strategy that promotes healthy stress responses and adaptive coping strategy selection. The current study employed a person-centered approach to explore emerging patterns across ethnic identity development and psychological well-being criterion variables among college freshmen. Data from 283 incoming college freshmen at Northeastern University were analyzed. The Brief COPE Acceptance and Emotional Support scales, the Five Factor Mindfulness Questionnaire, and MIEM Exploration and Affirmation measures were used to inform the cluster profiles. The TwoStep auto-clustering algorithm revealed an optimal three-cluster solution (BIC = 848.49), which classified 92.6% (n = 262) of participants in the sample into one of the three clusters. The clusters were characterized as ‘Mixed Adjustment’, ‘Lowest Adjustment’, and ‘Moderate Adjustment.’ Cluster composition varied significantly by ethnicity X² (2, N = 262) = 7.74 (p = .021) and gender X² (2, N = 259) = 10.40 (p = .034). The ‘Lowest Adjustment’ cluster contained the highest proportion of students of color, 41% (n = 32), and male-identifying students, 44.2% (n = 34). Follow-up analyses showed higher ERI exploration in ‘Moderate Adjustment’ cluster members, also reported higher levels of psychological distress, with significantly elevated depression scores (p = .011), psychological diagnoses of depression (p = .013), anxiety (p = .005) and psychiatric disorders (p = .025). Supporting prior research, students engaging with identity exploration processes often endure more psychological distress. These results indicate that students undergoing identity development may require more socialization and different services beyond normal strategies.

Keywords: adjustment, coping, college, emerging adulthood, ethnic-racial identity, psychological well-being, resilience

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Authors: Fossarello Maurizio, Mattana Giorgio, Tatti Filippo.

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The most widely performed surgical procedure in Open-Angle Glaucoma (OAG) is trabeculectomy. Although this filtering procedure is extremely effective, surgical failure and postoperative complications are reported. Due to the its invasive nature and possible complications, trabeculectomy is usually reserved, in practice, for patients who are refractory to medical and laser therapy. Recently, a number of micro-invasive surgical techniques (MIGS: Micro-Invasive Glaucoma Surgery), have been introduced in clinical practice. They meet the criteria of micro-incisional approach, minimal tissue damage, short surgical time, reliable IOP reduction, extremely high safety profile and rapid post-operative recovery. Xen45 Gel Implant (Allergan, Dublin, Ireland) is one of the MIGS alternatives, and consists in a porcine gelatin tube designed to create an aqueous flow from the anterior chamber to the subconjunctival space, bypassing the resistance of the trabecular meshwork. In this study we report the results of this technique as a favorable option in the treatment of OAG for its benefits in term of efficacy and safety, either alone or in combination with cataract surgery. This is a retrospective, single-center study conducted in consecutive OAG patients, who underwent Xen45 Gel Stent implantation alone or in combination with phacoemulsification, from October 2018 to June 2019. The primary endpoint of the study was to evaluate the reduction of both IOP and number of antiglaucoma medications at 12 months. The secondary endpoint was to correlate filtering bleb morphology evaluated by means of anterior segment OCT with efficacy in IOP lowering and eventual further procedures requirement. Data were recorded on Microsoft Excel and study analysis was performed using Microsoft Excel and SPSS (IBM). Mean values with standard deviations were calculated for IOPs and number of antiglaucoma medications at all points. Kolmogorov-Smirnov test showed that IOP followed a normal distribution at all time, therefore the paired Student’s T test was used to compare baseline and postoperative mean IOP. Correlation between postoperative Day 1 IOP and Month 12 IOP was evaluated using Pearson coefficient. Thirty-six eyes of 36 patients were evaluated. As compared to baseline, mean IOP and the mean number of antiglaucoma medications significantly decreased from 27,33 ± 7,67 mmHg to 16,3 ± 2,89 mmHg (38,8% reduction) and from 2,64 ± 1,39 to 0,42 ± 0,8 (84% reduction), respectively, at 12 months after surgery (both p < 0,001). According to bleb morphology, eyes were divided in uniform group (n=8, 22,2%), subconjunctival separation group (n=5, 13,9%), microcystic multiform group (n=9, 25%) and multiple internal layer group (n=14, 38,9%). Comparing to baseline, there was no significative difference in IOP between the 4 groups at month 12 follow-up visit. Adverse events included bleb function decrease (n=14, 38,9%), hypotony (n=8, 22,2%) and choroidal detachment (n=2, 5,6%). All eyes presenting bleb flattening underwent needling and MMC injection. The higher percentage of patients that required secondary needling was in the uniform group (75%), with a significant difference between the groups (p=0,03). Xen45 gel stent, either alone or in combination with phacoemulsification, provided a significant lowering in both IOP and medical antiglaucoma treatment and an elevated safety profile.

Keywords: anterior segment OCT, bleb morphology, micro-invasive glaucoma surgery, open angle glaucoma, Xen45 gel implant

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Authors: M. Shahab Uddin, Pennung Warnitchai

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Currently more than half of the world’s populations are living in cities, and the number and sizes of cities are growing faster than ever. Cities rely on the effective functioning of complex and interdependent critical infrastructures networks to provide public services, enhance the quality of life, and save the community from hazards and disasters. In contrast, complex connectivity and interdependency among the urban critical infrastructures bring management challenges and make the urban system prone to the domino effect. Unplanned rapid growth, increased connectivity, and interdependency among the infrastructures, resource scarcity, and many other socio-political factors are affecting the typical state of an urban system and making it susceptible to numerous sorts of diversion. In addition to internal vulnerabilities, urban systems are consistently facing external threats from natural and manmade hazards. Cities are not just complex, interdependent system, but also makeup hubs of the economy, politics, culture, education, etc. For survival and sustainability, complex urban systems in the current world need to manage their vulnerabilities and hazardous incidents more wisely and more interactively. Coordinated management in such systems makes for huge potential when it comes to absorbing negative effects in case some of its components were to function improperly. On the other hand, ineffective management during a similar situation of overall disorder from hazards devastation may make the system more fragile and push the system to an ultimate collapse. Following the quantum, the current research hypothesizes that a hazardous event starts its journey as an emergency, and the system’s internal vulnerability and response capacity determine its destination. Connectivity and interdependency among the urban critical infrastructures during this stage may transform its vulnerabilities into dynamic damaging force. An emergency may turn into a disaster in the absence of effective management; similarly, mismanagement or lack of management may lead the situation towards a catastrophe. Situation awareness and factual decision-making is the key to win a battle. The current research proposed a contextual decision support system for an urban critical infrastructure system while integrating three different models: 1) Damage cascade model which demonstrates damage propagation among the infrastructures through their connectivity and interdependency, 2) Restoration model, a dynamic restoration process of individual infrastructure, which is based on facility damage state and overall disruptions in surrounding support environment, and 3) Optimization model that ensures optimized utilization and distribution of available resources in and among the facilities. All three models are tightly connected, mutually interdependent, and together can assess the situation and forecast the dynamic outputs of every input. Moreover, this integrated model will hold disaster managers and decision makers responsible when it comes to checking all the alternative decision before any implementation, and support to produce maximum possible outputs from the available limited inputs. This proposed model will not only support to reduce the extent of damage cascade but will ensure priority restoration and optimize resource utilization through adaptive and collaborative management. Complex systems predictably fail but in unpredictable ways. System understanding, situation awareness, and factual decisions may significantly help urban system to survive and sustain.

Keywords: disaster prevention, decision support system, emergency response, urban critical infrastructure system

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Authors: Kartik Gupta, Virendra Kumar, Sanjeev Sinha, N. Jagannathan

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Introduction: A significant number of patients having human immunodeficiency virus (HIV) infection show a neurocognitive decline (NCD) ranging from minor cognitive impairment to severe dementia. The possible causes of NCD in HIV-infected patients include brain injury by HIV before cART, neurotoxic viral proteins and metabolic abnormalities. In the present study, we compared the level of NCD in asymptomatic HIV-infected patients with changes in brain metabolites measured by using magnetic resonance spectroscopy (MRS). Methods: 43 HIV-positive patients (30 males and 13 females) coming to ART center of the hospital and HIV-seronegative healthy subjects were recruited for the study. All the participants completed MRI and MRS examination, detailed clinical assessments and a battery of neuropsychological tests. All the MR investigations were carried out at 3.0T MRI scanner (Ingenia/Achieva, Philips, Netherlands). MRI examination protocol included the acquisition of T2-weighted imaging in axial, coronal and sagittal planes, T1-weighted, FLAIR, and DWI images in the axial plane. Patients who showed any apparent lesion on MRI were excluded from the study. T2-weighted images in three orthogonal planes were used to localize the voxel in left frontal lobe white matter (FWM) and left basal ganglia (BG) for single voxel MRS. Single voxel MRS spectra were acquired with a point resolved spectroscopy (PRESS) localization pulse sequence at an echo time (TE) of 35 ms and a repetition time (TR) of 2000 ms with 64 or 128 scans. Automated preprocessing and determination of absolute concentrations of metabolites were estimated using LCModel by water scaling method and the Cramer-Rao lower bounds for all metabolites analyzed in the study were below 15\%. Levels of total N-acetyl aspartate (tNAA), total choline (tCho), glutamate + glutamine (Glx), total creatine (tCr), were measured. Cognition was tested using a battery of tests validated for Indian population. The cognitive domains tested were the memory, attention-information processing, abstraction-executive, simple and complex perceptual motor skills. Z-scores normalized according to age, sex and education standard were used to calculate dysfunction in these individual domains. The NCD was defined as dysfunction with Z-score ≤ 2 in at least two domains. One-way ANOVA was used to compare the difference in brain metabolites between the patients and healthy subjects. Results: NCD was found in 23 (53%) patients. There was no significant difference in age, CD4 count and viral load between the two groups. Maximum impairment was found in the domains of memory and simple motor skills i.e., 19/43 (44%). The prevalence of deficit in attention-information processing, complex perceptual motor skills and abstraction-executive function was 37%, 35%, 33% respectively. Subjects with NCD had a higher level of Glutamate in the Frontal region (8.03 ± 2.30 v/s. 10.26 ± 5.24, p-value 0.001). Conclusion: Among newly diagnosed, ART-naïve retroviral disease patients from India, cognitive decline was found in 53\% patients using tests validated for this population. Those with neurocognitive decline had a significantly higher level of Glutamate in the left frontal region. There was no significant difference in age, CD4 count and viral load at initiation of ART between the two groups.

Keywords: HIV, neurocognitive decline, neurometabolites, magnetic resonance spectroscopy

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Authors: Kim Ji-Hyun, Jeon Hye-Seon, Kwon Oh-Yun, Park Eun-Young, Hwang Ui-Jae, Gwak Gyeong-Tae, Yoon Hyeo-Bin

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Stress urinary incontinence (SUI), a common women health problem, is an involuntary leakage of urine while sneezing, coughing, or physical exertion caused by insufficient strength of the pelvic floor and sphincter muscles. SUI also leads to decrease in quality of life and limits sexual activities. SUI is related to the increased bladder neck angle, bladder neck movement, funneling index, urethral width, and decreased urethral length. Various pelvic floor muscle electrical stimulation (ES) interventions have been applied to improve the symptoms of the people with SUI. ES activates afferent fibers of pudendal nerve and smoothly induces contractions of the pelvic floor muscles such as striated periurethral muscles and striated pelvic floor muscles. ES via intravaginal electrodes are the most frequently used types of the pelvic floor muscle ES for the female SUI. However, inserted electrode is uncomfortable and it increases the risks of infection. The purpose of this preliminary study was to determine if the 8-week transcutaneous pelvic floor ES would be effective to improve the symptoms and satisfaction of the females with SUI. Easy-K, specially designed ES equipment for the people with SUI, was used in this study. The oval shape stimulator can be placed on a toilet seat, and the surface has invaded electrode fit to contact with the entire vulva area while users are sitting on the stimulator. Five women with SUI were included in this experiment. Prior to the participation, subjects were instructed about procedures and precautions in using the ES. They have used the stimulator once a day for 20 minutes for each session at home. Outcome data was collected 3 times at the baseline, 4 weeks and 8 weeks after the intervention. Intravaginal sonography was used to measure the bladder neck angle, bladder neck movement, funneling index, thickness of an anterior rhabdosphincter and a posterior rhabdosphincter, urethral length, and urethral width. Leavator ani muscle (LAM) contraction strength was assessed by manual palpation according to the oxford scoring system. In addition, incontinence quality of life (IQOL) and female sexual function index (FSFI) questionnaires were used to obtain addition subjective information. Friedman test, a nonparametric statistical test, was used to determine the effectiveness of the ES. The Wilcoxon test was used for the post-hoc analysis and the significance level was set at .05. The bladder neck angle, funneling index and urethral width were significantly decreased after 8-weeks of intervention (p<.05). LAM contraction score, urethral length and anterior and posterior rhabdosphicter thickness were statistically increased by the intervention (p<.05). However, no significant change was found in the bladder neck movement. Although total score of the IQOL did not improve, the score of the ‘avoidance’ subscale of IQOL had significant improved (p<.05). FSFI had statistical difference in FSFI total score and ‘desire’ subscale (p<.05). In conclusion, 8-week use of a transcutaneous ES on peri-vulva area improved dynamic mechanical structures of the pelvic floor musculature as well as IQOL and conjugal relationship.

Keywords: electrical stimulation, Pelvic floor muscle, sonography, stress urinary incontinence, women health

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Authors: Patricia Shirley Almeida Prado, Liz Brito, Selma Paixão Argollo, Gracie Moreira, Leticia Matos Sobrinho

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Diffuse idiopathic skeletal hyperostosis (DISH) is a degenerative bone disease also known as Forestier´s disease and ankylosing hyperostosis of the spine is characterized by a tendency toward ossification of half the anterior longitudinal spinal ligament without intervertebral disc disease. DISH is not considered to be osteoarthritis, although the two conditions commonly occur together. Diagnostic criteria include fusion of at least four vertebrae by bony bridges arising from the anterolateral aspect of the vertebral bodies. These vertebral bodies have a 'dripping candle wax' appearance, also can be seen periosteal new bone formation on the anterior surface of the vertebral bodies and there is no ankylosis at zygoapophyseal facet joint. Clinically, patients with DISH tend to be asymptomatic some patients mention moderate pain and stiffness in upper back. This disease is more common in man, uncommon in patients younger than 50 years and rare in patients under 40 years old. In modern populations, DISH is found in association with obesity, (type II) diabetes; abnormal vitamin A metabolism and also associated with higher levels of serum uric acid. There is also some association between the increase of risk of stroke or other cerebrovascular disease. The DISH condition can be confused with Heterotopic Ossification, what is the bone formation in the soft tissues as the result of trauma, wounding, surgery, burnings, prolonged immobility and some central nervous system disorder. All these conditions have been described extensively as myositis ossificans which can be confused with the fibrodysplasia (myositis) ossificans progressive. As in the DISH symptomatology it can be asymptomatic or extensive enough to impair joint function. A third confusion osteoarthritis disease that can bring confusion are the enthesopathies that occur in the entire skeleton being common on the ischial tuberosities, iliac crests, patellae, and calcaneus. Ankylosis of the sacroiliac joint by bony bridges may also be found. CASE 1: this case is skeletal remains presenting skull, some vertebrae and scapulae. This case remains unidentified and due to lack of bone remains. Sex, age and ancestry profile was compromised, however the DISH pathognomonic findings and diagnostic helps to estimate sex and age characteristics. Moreover to presenting DISH these skeletal remains also showed some bone alterations and non-metrics as fusion of the first vertebrae with occipital bone, maxillae and palatine torus and scapular foramen on the right scapulae. CASE 2: this skeleton remains shows an extensive bone heterotopic ossification on the great trochanter area of left femur, right fibula showed a healed fracture in its body however in its inteosseous crest there is an extensive bone growth, also in the Ilium at the region of inferior gluteal line can be observed some pronounced bone growth and the skull presented a pronounced mandibular, maxillary and palatine torus. Despite all these pronounced heterotopic ossification the whole skeleton presents moderate bone overgrowth that is not linked with aging, since the skeleton belongs to a young unidentified individual. The appropriate osteopathological diagnosis support the human identification process through medical reports and also assist with epidemiological data that can strengthen vulnerable anthropological estimates.

Keywords: bone disease, DISH, human identification, human remains

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Authors: Alexandre Faure, Yoko Mizokami, éRic Dinet

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These recent years, the potential of light in assisting visually impaired people in their indoor mobility has been demonstrated by different studies. Implementing smart lighting systems for selective visual enhancement, especially designed for low-vision people, is an approach that breaks with the existing visual aids. The appearance of the surface of an object is significantly influenced by the lighting conditions and the constituent materials of the objects. Appearance of objects may appear to be different from expectation. Therefore, lighting conditions lead to an important part of accurate material recognition. The main objective of this work was to investigate the effect of the spatial distribution of light on object identification in the context of low vision. The purpose was to determine whether and what specific lighting approaches should be preferred for visually impaired people. A psychophysical experiment was designed to study the ability of individuals to identify the smallest cube of a pair under different lighting diffusion conditions. Participants were divided into two distinct groups: a reference group of observers with normal or corrected-to-normal visual acuity and a test group, in which observers were required to wear visual impairment simulation glasses. All participants were presented with pairs of cubes in a "miniature room" and were instructed to estimate the relative size of the two cubes. The miniature room replicates real-life settings, adorned with decorations and separated from external light sources by black curtains. The correlated color temperature was set to 6000 K, and the horizontal illuminance at the object level at approximately 240 lux. The objects presented for comparison consisted of 11 white cubes and 11 black cubes of different sizes manufactured with a 3D printer. Participants were seated 60 cm away from the objects. Two different levels of light diffuseness were implemented. After receiving instructions, participants were asked to judge whether the two presented cubes were the same size or if one was smaller. They provided one of five possible answers: "Left one is smaller," "Left one is smaller but unsure," "Same size," "Right one is smaller," or "Right one is smaller but unsure.". The method of constant stimuli was used, presenting stimulus pairs in a random order to prevent learning and expectation biases. Each pair consisted of a comparison stimulus and a reference cube. A psychometric function was constructed to link stimulus value with the frequency of correct detection, aiming to determine the 50% correct detection threshold. Collected data were analyzed through graphs illustrating participants' responses to stimuli, with accuracy increasing as the size difference between cubes grew. Statistical analyses, including 2-way ANOVA tests, showed that light diffuseness had no significant impact on the difference threshold, whereas object color had a significant influence in low vision scenarios. The first results and trends derived from this pilot experiment clearly and strongly suggest that future investigations could explore extreme diffusion conditions to comprehensively assess the impact of diffusion on object identification. For example, the first findings related to light diffuseness may be attributed to the range of manipulation, emphasizing the need to explore how other lighting-related factors interact with diffuseness.

Keywords: Lighting, Low Vision, Visual Aid, Object Identification, Psychophysical Experiment

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Authors: Antonis Skouloudis, Konstantinos Evangelinos, Walter Leal-Filho, Panagiotis Vouros, Ioannis Nikolaou

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Organizational resilience capacity to extreme weather events (EWEs) has sparked a growth in scholarly attention over the past decade as an essential aspect in business continuity management, with supporting evidence for this claim to suggest that it retains a key role in successful responses to adverse situations, crises and shocks. Small and medium-sized enterprises (SMEs) are more vulnerable to face floods compared to their larger counterparts, so they are disproportionately affected by such extreme weather events. The limited resources at their disposal, the lack of time and skills all conduce to inadequate preparedness to challenges posed by floods. SMEs tend to plan in the short-term, reacting to circumstances as they arise and focussing on their very survival. Likewise, they share less formalised structures and codified policies while they are most usually owner-managed, resulting in a command-and-control management culture. Such characteristics result in them having limited opportunities to recover from flooding and quickly turnaround their operation from a loss making to a profit making one. Scholars frame the capacity of business entities to be resilient upon an EWE disturbance (such as flash floods) as the rate of recovery and restoration of organizational performance to pre-disturbance conditions, the amount of disturbance (i.e. threshold level) a business can absorb before losing structural and/or functional components that will alter or cease operation, as well as the extent to which the organization maintains its function (i.e. impact resistance) before performance levels are driven to zero. Nevertheless, while it seems to be accepted as an essential trait of firms effectively transcending uncertain conditions, research deconstructing the enabling conditions and/or inhibitory factors of SMEs resilience capacity to natural hazards is still sparse, fragmentary and mostly fuelled by anecdotal evidence or normative assumptions. Focusing on the individual level of analysis, i.e. the individual enterprise and its endeavours to succeed, the emergent picture from this relatively new research strand delineates the specification of variables, conceptual relationships or dynamic boundaries of resilience capacity components in an attempt to provide prescriptions for policy-making as well as business management. This study will present the development of a flood resilience capacity index (FRCI) and its application to Greek SMEs. The proposed composite indicator pertains to cognitive, behavioral/managerial and contextual factors that influence an enterprise’s ability to shape effective responses to meet flood challenges. Through the proposed indicator-based approach, an analytical framework is set forth that will help standardize such assessments with the overarching aim of reducing the vulnerability of SMEs to flooding. This will be achieved by identifying major internal and external attributes explaining resilience capacity which is particularly important given the limited resources these enterprises have and that they tend to be primary sources of vulnerabilities in supply chain networks, generating Single Points of Failure (SPOF).

Keywords: Floods, Small & Medium-Sized enterprises, organizational resilience capacity, index development

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Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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Authors: Nikolas Aasheim, Laura Sakalauskaitė, Julie Dubois, Malina Ploug Larsen, Paul Michael Petersen, Marcus S. Carstensen, Marcus S. Carstensen, Mai Nguyen, Line Katrine Harder Clemmensen, Kamilla Miskowiak, Klaus Martiny

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Background: Major depressive disorder (MDD) is a debilitating condition that affects more than 300 million people worldwide and profoundly impacts well-being and health. Current treatments are based on a trial-and-error approach, and reliable biomarkers are needed for more informed and personalized treatment solutions. One potential biomarker is aberrant gamma-frequency (30-80 Hz) brainwaves, hypothesized to originate from deficiencies in the excitatory-inhibitory interaction between the pyramidal cells and interneurons. An imbalance within this interaction is described as a crucial pathological mechanism in various neuropsychiatric conditions, including MDD, and the modulation of this pathological interaction has been investigated as a potential target. A specific type of steady-state visually evoked potential (SSVEP) in the gamma frequency band, referred to as gamma entrainment using sensory stimuli (GENUS), particularly around the 40Hz spectrum, entrains large scale, fast-spiking PV+ interneurons, facilitating coordinated activity in key brain regions, reduced neuronal and synaptic loss, and enhanced synaptic stability and plasticity. GENUS has shown promise in improving sleep, offering neuroprotective effects in Alzheimer's disease (AD), and reducing pathological markers like Amyloid Beta and TAU proteins, as seen in animal models. In this study, we explore the antidepressant, cognitive, and electrophysiological effects of a novel, non-invasive brain stimulation (NIBS) approach utilizing a 40 Hz invisible spectral flicker to induce gamma activity in patients diagnosed with Major Depressive Disorder (MDD). This non-invasive targeted stimulation of lower gamma band activity (40 Hz) is designed to modulate neural circuits associated with mood and cognitive functions, providing a potential new therapeutic avenue for MDD. Methods and Design: 60 patients with a current diagnosis of a major depressive episode will be enrolled in a randomized, double-blinded, placebo-controlled trial. The active treatment group will receive 40 Hz invisible spectral flickering light stimulation while the control group will receive continuous light matched in colour temperature and brightness. Patients in both groups will get an hour of daily light treatment in their own homes and will attend four follow-up visits to assess depression severity measured by Hamilton Depression Rating Scale (HAM-D₆), several aspects of sleep, cognitive function, quality of life. Additionally, exploratory EEG is conducted to assess spectral changes throughout the protocol. The primary endpoint is the mean change from baseline to week 6 in depression severity (HAM-D₆ subset) between the groups. Current state of affairs/timeline: The FELIX study was initiated in the beginning of 2022, planning to reach stage of publication in December 2025. 21 participants have been enrolled in the protocol thus far, expecting to be finished with trials and recruitment by the end of 2024.

Keywords: major depressive disorder, gamma, neurostimulation, EEG

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Authors: Maari Sugawara

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This research critically engages with the erotic and political entanglements of male clientele of Dominatrices who identify as submissives (hereafter referred to as submissives) within Hong Kong's BDSM scene. Employing masochism as an analytical framework, it interrogates the intersections of capitalism, heteropatriarchy, postcolonialism, and commodified desire. BDSM (Bondage and Discipline, Dominance and Submission, Sadism and Masochism) encompasses practices that explore power, control, and subordination through both physical and psychological role-play, predicated on consent, negotiation, and boundary delineation. This makes BDSM a fertile site for examining how dominance and submission are mobilized, challenged, and reiterated. This study focuses on the dynamics between thirty male submissives and three professional Dominatrices active in Hong Kong since 2019. The predominance of male interviewees reflects the demographic reality that most clients engaging with professional Dominatrices are male. These submissives—men who willfully relinquish control—offer a critical lens for exploring how BDSM, as both practice and market, mirrors and destabilizes dominant power structures. BDSM relationships occasionally replicate the hierarchical logics of heterosexual marriage, particularly in the expectation that submissives engage exclusively with a single Dominatrix, reflecting a dynamic of devotion and fidelity akin to traditional marital structures. However, these relationships also function as counter-normative spaces where care and control are reconfigured, enabling the negotiation of alternative power configurations. By centering BDSM work rather than broader kink practices, this study foregrounds the commodification of intimacy as a key site where suppressed desires, economic forces, and political tensions converge. The submissives in this study are predominantly affluent, cisgender men, underscoring the socio-economic asymmetries in the BDSM market. Furthermore, the research examines how Hong Kong’s political turbulence—particularly the 2019 Yellow Umbrella Movement and the COVID-19 pandemic—has reverberated through the BDSM scene, reshaping the contours of desire, trust, and power in these intimate transactions. The increasing tensions with mainland China, alongside the erosion of public trust in state institutions, form a critical backdrop to this evolving landscape. Grounded in gender and sexuality theories, this research interrogates how the desires of male submissives are constructed within and resist heteronormative frameworks. BDSM practices, far from existing outside capitalist and colonial logics, often act as both a mirror and critique of these systems, revealing complex ways in which power is commodified, enacted, and contested. In their pursuit of emotional care and alternative forms of control, male submissives navigate a paradoxical terrain where their masochistic desires both subvert and perpetuate the socio-political status quo. By examining the intersections of desire, commodification, and the shifting socio-political landscape, this research provides a nuanced understanding of how BDSM functions as a site of negotiation for those navigating the turbulent crosscurrents of capitalist and colonial legacies. Ultimately, it uncovers the complex interplay between erotic practices and the structures of power and identity in a city undergoing profound transformation.

Keywords: masochism, Hong Kong, identity, BDSM, dominatrix, masculinity, gender studies

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Authors: Andreas Rudisch, Ralf Lampert, Andreas Kolbitsch

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It is a well-known fact among the engineering community that earthquakes with comparatively low magnitudes can cause serious damage to nonstructural components (NSCs) of buildings, even when the supporting structure performs relatively well. Past research works focused mainly on NSCs of nuclear power plants and industrial plants. Particular attention should also be given to architectural façade elements of old masonry buildings (e.g. ornamental figures, balustrades, vases), which are very vulnerable under seismic excitation. Large numbers of these historical nonstructural components (HiNSCs) can be found in highly frequented historical city centers and in the event of failure, they pose a significant danger to persons. In order to estimate the vulnerability of acceleration sensitive HiNSCs, the peak horizontal floor acceleration (PHFA) is used. The PHFA depends on the dynamic characteristics of the building, the ground excitation, and induced nonlinearities. Consequently, the PHFA can not be generalized as a simple function of height. In the present research work, an extensive case study was conducted to investigate the influence of induced nonlinearity on the PHFA for old masonry buildings. Probabilistic nonlinear FE time-history analyses considering three different hazard levels were performed. A set of eighteen synthetically generated ground motions was used as input to the structure models. An elastoplastic macro-model (multiPlas) for nonlinear homogenized continuum FE-calculation was calibrated to multiple scales and applied, taking specific failure mechanisms of masonry into account. The macro-model was calibrated according to the results of specific laboratory and cyclic in situ shear tests. The nonlinear macro-model is based on the concept of multi-surface rate-independent plasticity. Material damage or crack formation are detected by reducing the initial strength after failure due to shear or tensile stress. As a result, shear forces can only be transmitted to a limited extent by friction when the cracking begins. The tensile strength is reduced to zero. The first goal of the calibration was the consistency of the load-displacement curves between experiment and simulation. The calibrated macro-model matches well with regard to the initial stiffness and the maximum horizontal load. Another goal was the correct reproduction of the observed crack image and the plastic strain activities. Again the macro-model proved to work well in this case and shows very good correlation. The results of the case study show that there is significant scatter in the absolute distribution of the PHFA between the applied ground excitations. An absolute distribution along the normalized building height was determined in the framework of probability theory. It can be observed that the extent of nonlinear behavior varies for the three hazard levels. Due to the detailed scope of the present research work, a robust comparison with code-recommendations and simplified PHFA distributions are possible. The chosen methodology offers a chance to determine the distribution of PHFA along the building height of old masonry structures. This permits a proper hazard assessment of HiNSCs under seismic loads.

Keywords: nonlinear macro-model, nonstructural components, time-history analysis, unreinforced masonry

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Authors: Bassem M. Darwish, Robert H. Ablove

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Introduction: Total knee arthroscopy (TKA) is a commonly performed procedure in patients with end-stage osteoarthritis and inaccuracy of component alignment in TKA has been shown to have many adverse post-operative outcomes such as accelerated implant wear, reduced functional outcomes, and shorter overall implant survival. Robotic surgical systems have been introduced to try and improve joint alignment and functional outcomes in knee arthroscopy, one recent iteration is the ROSA knee system, released to the market in 2019. The objective of this scoping review is to map the available evidence, identify the current types of evidence, and identify knowledge gaps to guide future studies on patient outcomes following ROSA-assisted total knee arthroplasties. Methods: An electronic search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. Search terms included ROSA, knee arthroscopy, osteoarthritis, robotic, and malalignment. Types of study participants included patients with osteoarthritis, ages 18 and older, male or female, who received manual TKA (mTKA) or ROSA-assisted TKA (rTKA), and human patients or cadavers. Published, peer-reviewed controlled trials, observational studies, and case series were included. Case reports were not included in article review. Resulting articles were first screened based on title and abstract. Articles meeting inclusion criteria based on title and abstract review then underwent full-text review by the same reviewer. Results: This scoping review identified 11 total studies, 3 prospective observational studies, and 8 retrospective observational studies - a total of 970 rTKA patients and 1745 mTKA patients. There were no case series or randomized controlled trials comparing rTKA and mTKA. Patient-centered outcomes showed promise for rTKA, where it frequently showed significantly favorable functional outcomes, measured via KOOS-JR, VAS, KSS, OKS, FJS, and PROMIS scores, at various times postoperatively. However, there was much discrepancy about which score yielded significance at which postoperative follow-up. Complication rates, reoperation rates, and LOS were very similar between mTKA and rTKA groups. Studies also showed rTKA had more accurate joint alignment within the 0 ± 3o corridor and had significantly higher rates of achieving postoperative joint angles similar to the preoperative plan. Finally, there was major agreement that rTKA cases take significantly longer time at the start, however, there is a rapid learning curve. Once past the learning curve, rTKA cases are performed in a similar time to mTKA and reduced physician stress and strain. Conclusion: The ROSA knee system represents a promising option for the management of osteoarthritis via total knee arthroscopy. The studies reviewed in this paper favor the patient-centered function outcomes, joint alignments, and physician health implications of the ROSA knee system to conventional total knee arthroscopy. Further study is warranted, however, to better understand recovery periods, longer-term functional outcomes, operative fatigue, and reduction in radiation exposure.

Keywords: arthroplasty, knee, robotics, malalignment

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Authors: Hamda Ajmal, Karen Young, Ruth Melia, John Bogue, Mary O'Sullivan, Jim Duggan, Hannah Wood

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The Covid-19 pandemic led to a range of public health mitigation strategies in order to suppress the SARS-CoV-2 virus. The drastic changes in everyday life due to lockdowns had the potential for a significant negative impact on public mental health, and a key public health goal is to now assess the evidence from available Irish datasets to provide useful insights on this issue. Text-50808 is an online text-based mental health support service, established in Ireland in 2020, and can provide a measure of revealed distress and mental health concerns across the population. The aim of this study is to explore statistical associations between public mental health in Ireland and the Covid-19 pandemic. Uniquely, this study combines two measures of emotional wellbeing in Ireland: (1) weekly text volume at Text-50808, and (2) emotional wellbeing indicators reported by respondents of the Amárach public opinion survey, carried out on behalf of the Department of Health, Ireland. For this analysis, a multivariate graphical exploratory data analysis (EDA) was performed on the Text-50808 dataset dated from 15th June 2020 to 30th June 2021. This was followed by time-series analysis of key mental health indicators including: (1) the percentage of daily/weekly texts at Text-50808 that mention Covid-19 related issues; (2) the weekly percentage of people experiencing anxiety, boredom, enjoyment, happiness, worry, fear and stress in Amárach survey; and Covid-19 related factors: (3) daily new Covid-19 case numbers; (4) daily stringency index capturing the effect of government non-pharmaceutical interventions (NPIs) in Ireland. The cross-correlation function was applied to measure the relationship between the different time series. EDA of the Text-50808 dataset reveals significant peaks in the volume of texts on days prior to level 3 lockdown and level 5 lockdown in October 2020, and full level 5 lockdown in December 2020. A significantly high positive correlation was observed between the percentage of texts at Text-50808 that reported Covid-19 related issues and the percentage of respondents experiencing anxiety, worry and boredom (at a lag of 1 week) in Amárach survey data. There is a significant negative correlation between percentage of texts with Covid-19 related issues and percentage of respondents experiencing happiness in Amárach survey. Daily percentage of texts at Text-50808 that reported Covid-19 related issues to have a weak positive correlation with daily new Covid-19 cases in Ireland at a lag of 10 days and with daily stringency index of NPIs in Ireland at a lag of 2 days. The sudden peaks in text volume at Text-50808 immediately prior to new restrictions in Ireland indicate an association between a rise in mental health concerns following the announcement of new restrictions. There is also a high correlation between emotional wellbeing variables in the Amárach dataset and the number of weekly texts at Text-50808, and this confirms that Text-50808 reflects overall public sentiment. This analysis confirms the benefits of the texting service as a community surveillance tool for mental health in the population. This initial EDA will be extended to use multivariate modeling to predict the effect of additional Covid-19 related factors on public mental health in Ireland.

Keywords: COVID-19 pandemic, data analysis, digital health, mental health, public health, digital health

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Authors: Shikha Rani, Neeta Sehgal, Vipin Kumar Verma, Om Prakash

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Introduction: Fish is an important protein source for humans and has great economic value. Fish cultures are affected due to various anthropogenic activities that lead to bacterial and viral infections. Aeromonas hydrophila is a fish pathogenic bacterium that causes several aquaculture outbreaks throughout the world and leads to huge mortalities. In this study, plants of no commercial value were used to investigate their immunostimulatory, antioxidant, anti-inflammatory, anti-bacterial, and disease resistance potential in fish against Aeromonas hydrophila, through fish feed fortification. Methods: The plant was dried at room temperature in the shade, dissolved in methanol, and analysed for biological compounds through GC-MS/MS. DPPH, FRAP, Phenolic, and flavonoids were estimated following standardized protocols. In silico molecular docking was also performed to validate its broad-spectrum activities based on binding affinity with specific proteins. Fish were divided into four groups (n=6; total 30 in a group): Group 1, non-challenged fish (fed on a non-supplemented diet); Group 2, fish challenged with bacteria (fed on a non-supplemented diet); Group 3 and 4, fish challenged with bacteria (A. hydrophila) and fed on plant supplemented feed at 2.5% and 5%. Blood was collected from the fish on 0, 7th, 14th, 21st, and 28th days. Serum was separated for glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase assay (ALP), lysozyme activity assay, superoxide dismutase assay (SOD), lipid peroxidation assay (LPO) and molecular parameters (including cytokine levels) were estimated through ELISA. The phagocytic activity of macrophages from the spleen and head kidney, along with quantitative analysis of immune-related genes, were analysed in different tissue samples. The digestive enzymes (Pepsin, Trypsin, and Chymotrypsin) were also measured to evaluate the effect of plant-supplemented feed on freshwater fish. Results and Discussion: GC-MS/MS analysis of a methanolic extract of plant validated the presence of key compounds having antioxidant, anti-inflammatory, anti-bacterial, anti-inflammatory, and immunomodulatory activities along with disease resistance properties. From biochemical investigations like ABTS, DPPH, and FRAP, the amount of total flavonoids, phenols, and promising binding affinities towards different proteins in molecular docking analysis helped us to realize the potential of this plant that can be used for investigation in the supplemented feed of fish. Measurement liver function tests, ALPs, oxidation-antioxidant enzyme concentrations, and immunoglobulin concentrations in the experimental groups (3 and 4) showed significant improvement as compared to the positive control group. The histopathological evaluation of the liver, spleen, and head kidney supports the biochemical findings. The isolated macrophages from the group fed on supplemented feed showed a higher percentage of phagocytosis and a phagocytic index, indicating an enhanced cell-mediated immune response. Significant improvements in digestive enzymes were also observed in fish fed on supplemented feed, even after weekly challenges with bacteria. Hence, the plant-fortified feed can be recommended as a regular feed to enhance fish immunity and disease resistance against the Aeromonas hydrophila infection after confirmation from the field trial.

Keywords: immunostimulation, antipathogen, plant fortified feed, macrophages, GC-MS/MS, in silico molecular docking

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Authors: Majid Alenezi, Abdelbare Algamode, Amy Hayes, Gavin Lawrence, Nichola Callow

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The purpose of this study was to translate and culturally adapt the Vividness of Movement Imagery Questionnaire-2 (VMIQ-2) from English to produce a new Arabic version (VMIQ-2A), and to evaluate the reliability and validity of the translated questionnaire. The questionnaire assesses how vividly and clearly individuals are able to imagine themselves performing everyday actions. Its purpose is to measure individuals’ ability to conduct movement imagery, which can be defined as “the cognitive rehearsal of a task in the absence of overt physical movement.” Movement imagery has been introduced in physiotherapy as a promising intervention technique, especially when physical exercise is not possible (e.g. pain, immobilisation.) Considerable evidence indicates movement imagery interventions improve physical function, but to maximize efficacy it is important to know the imagery abilities of the individuals being treated. Given the increase in the global sharing of knowledge it is desirable to use standard measures of imagery ability across language and cultures, thus motivating this project. The translation procedure followed guidelines from the Translation and Cultural Adaptation group of the International Society for Pharmacoeconomics and Outcomes Research and involved the following phases: Preparation; the original VMIQ-2 was adapted slightly to provide additional information and simplified grammar. Forward translation; three native speakers resident in Saudi Arabia translated the original VMIQ-2 from English to Arabic, following instruction to preserve meaning (not literal translation), and cultural relevance. Reconciliation; the project manager (first author), the primary translator and a physiotherapist reviewed the three independent translations to produce a reconciled first Arabic draft of VMIQ-2A. Backward translation; a fourth translator (native Arabic speaker fluent in English) translated literally the reconciled first Arabic draft to English. The project manager and two study authors compared the English back translation to the original VMIQ-2 and produced the second Arabic draft. Cognitive debriefing; to assess participants’ understanding of the second Arabic draft, 7 native Arabic speakers resident in the UK completed the questionnaire, and rated the clearness of the questions, specified difficult words or passages, and wrote in their own words their understanding of key terms. Following review of this feedback, a final Arabic version was created. 142 native Arabic speakers completed the questionnaire in community meeting places or at home; a subset of 44 participants completed the questionnaire a second time 1 week later. Results showed the translated questionnaire to be valid and reliable. Correlation coefficients indicated good test-retest reliability. Cronbach’s a indicated high internal consistency. Construct validity was tested in two ways. Imagery ability scores have been found to be invariant across gender; this result was replicated within the current study, assessed by independent-samples t-test. Additionally, experienced sports participants have higher imagery ability than those less experienced; this result was also replicated within the current study, assessed by analysis of variance, supporting construct validity. Results provide preliminary evidence that the VMIQ-2A is reliable and valid to be used with a general population who are native Arabic speakers. Future research will include validation of the VMIQ-2A in a larger sample, and testing validity in specific patient populations.

Keywords: motor imagery, physiotherapy, translation and validation, imagery ability

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Authors: Dmitriy Berillo, Areej K. A. Al-Jwaid, Jonathan L. Caplin, Andrew Cundy, Irina Savina

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Chlorophenols (CPs) are used as a precursor in the production of higher CPs and dyestuffs, and as a preservative. Contamination by CPs of the ground water is located in the range from 0.15-100mg/L. The EU has set maximum concentration limits for pesticides and their degradation products of 0.1μg/L and 0.5μg/L, respectively. People working in industries which produce textiles, leather products, domestic preservatives, and petrochemicals are most heavily exposed to CPs. The International Agency for Research on Cancers categorized CPs as potential human carcinogens. Existing multistep water purification processes for CPs such as hydrogenation, ion exchange, liquid-liquid extraction, adsorption by activated carbon, forward and inverse osmosis, electrolysis, sonochemistry, UV irradiation, and chemical oxidation are not always cost effective and can cause the formation of even more toxic or mutagenic derivatives. Bioremediation of CPs derivatives utilizing microorganisms results in 60 to 100% decontamination efficiency and the process is more environmentally-friendly compared with existing physico-chemical methods. Microorganisms immobilized onto a substrate show many advantages over free bacteria systems, such as higher biomass density, higher metabolic activity, and resistance to toxic chemicals. They also enable continuous operation, avoiding the requirement for biomass-liquid separation. The immobilized bacteria can be reused several times, which opens the opportunity for developing cost-effective processes for wastewater treatment. In this study, we develop a bioremediation system for CPs based on macroporous materials, which can be efficiently used for wastewater treatment. Conditions for the preparation of the macroporous material from specific bacterial strains (Pseudomonas mendocina and Rhodococus koreensis) were optimized. The concentration of bacterial cells was kept constant; the difference was only the type of cross-linking agents used e.g. glutaraldehyde, novel polymers, which were utilized at concentrations of 0.5 to 1.5%. SEM images and rheology analysis of the material indicated a monolithic macroporous structure. Phenol was chosen as a model system to optimize the function of the cryogel material and to estimate its enzymatic activity, since it is relatively less toxic and harmful compared to CPs. Several types of macroporous systems comprising live bacteria were prepared. The viability of the cross-linked bacteria was checked using Live/Dead BacLight kit and Laser Scanning Confocal Microscopy, which revealed the presence of viable bacteria with the novel cross-linkers, whereas the control material cross-linked with glutaraldehyde(GA), contained mostly dead cells. The bioreactors based on bacteria were used for phenol degradation in batch mode at an initial concentration of 50mg/L, pH 7.5 and a temperature of 30°C. Bacterial strains cross-linked with GA showed insignificant ability to degrade phenol and for one week only, but a combination of cross-linking agents illustrated higher stability, viability and the possibility to be reused for at least five weeks. Furthermore, conditions for CPs degradation will be optimized, and the chlorophenol degradation rates will be compared to those for phenol. This is a cutting-edge bioremediation approach, which allows the purification of waste water from sustainable compounds without a separation step to remove free planktonic bacteria. Acknowledgments: Dr. Berillo D. A. is very grateful to Individual Fellowship Marie Curie Program for funding of the research.

Keywords: bioremediation, cross-linking agents, cross-linked microbial cell, chlorophenol degradation

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Authors: Zdravko Trivic, Kelvin E. Y. Low, Darko Radovic, Raymond Lucas

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Our understanding and experience of the built environment are primarily shaped by multi‐sensory, emotional and symbolic modes of exchange with spaces. Associated sensory and cognitive declines that come with ageing substantially affect the overall quality of life of the elderly citizens and the ways they perceive and use urban environment. Reduced mobility and increased risk of falls, problems with spatial orientation and communication, lower confidence and independence levels, decreased willingness to go out and social withdrawal are some of the major consequences of sensory declines that challenge almost all segments of the seniors’ everyday living. However, contemporary urban environments are often either sensory overwhelming or depleting, resulting in physical, mental and emotional stress. Moreover, the design and planning of housing neighbourhoods hardly go beyond the passive 'do-no-harm' and universal design principles, and the limited provision of often non-integrated eldercare and inter-generational facilities. This paper explores and discusses the largely neglected relationships between the 'hard' and 'soft' aspects of housing neighbourhoods and urban experience, focusing on seniors’ perception and multi-sensory experience as vehicles for design and planning of high-density housing neighbourhoods that are inclusive and empathetic yet build senior residents’ physical and mental abilities at different stages of ageing. The paper outlines methods and key findings from research conducted in two high-density housing neighbourhoods in Singapore with aims to capture and evaluate multi-sensorial qualities of two neighbourhoods from the perspective of senior residents. Research methods employed included: on-site sensory recordings of 'objective' quantitative sensory data (air temperature and humidity, sound level and luminance) using multi-function environment meter, spatial mapping of patterns of elderly users’ transient and stationary activity, socio-sensory perception surveys and sensorial journeys with local residents using eye-tracking glasses, and supplemented by walk-along or post-walk interviews. The paper develops a multi-sensory framework to synthetize, cross-reference, and visualise the activity and spatio-sensory rhythms and patterns and distill key issues pertinent to ageing-friendly and health-supportive neighbourhood design. Key findings show senior residents’ concerns with walkability, safety, and wayfinding, overall aesthetic qualities, cleanliness, smell, noise, and crowdedness in their neighbourhoods, as well as the lack of design support for all-day use in the context of Singaporean tropical climate and for inter-generational social interaction. The (ongoing) analysis of eye-tracking data reveals the spatial elements of senior residents’ look at and interact with the most frequently, with the visual range often directed towards the ground. With capacities to meaningfully combine quantitative and qualitative, measured and experienced sensory data, multi-sensory framework shows to be fruitful for distilling key design opportunities based on often ignored aspects of subjective and often taken-for-granted interactions with the familiar outdoor environment. It offers an alternative way of leveraging the potentials of housing neighbourhoods to take a more active role in enabling healthful living at all stages of ageing.

Keywords: ageing-friendly neighbourhoods, eye-tracking, high-density environment, multi-sensory approach, perception

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Authors: Gousilin Leandra Rocha Da Silva, Stéfani T. A. Dantas, Bruna F. Rossi, Erika R. Bonsaglia, Ivana G. Castilho, Terue Sadatsune, Ary Fernandes Júnior, Vera l. M. Rall

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Kidney failure causes decreased diuresis and accumulation of nitrogenous substances in the body. To increase patient survival, hemodialysis is used as a partial substitute for renal function. However, contamination of the water used in this treatment, causing bacteremia in patients, is a worldwide concern. The Burkholderia cepacia complex (Bcc), a group of bacteria with more than 20 species, is frequently isolated from hemodialysis water samples and comprises opportunistic bacteria, affecting immunosuppressed patients, due to its wide variety of virulence factors, in addition to innate resistance to several antimicrobial agents, contributing to the permanence in the hospital environment and to the pathogenesis in the host. The objective of the present work was to characterize molecularly and phenotypically Bcc isolates collected from the water and dialysate of the Hemodialysis Unit and from the blood of patients at a Public Hospital in Botucatu, São Paulo, Brazil, between 2019 and 2021. We used 33 Bcc isolates, previously obtained from blood cultures from patients with bacteremia undergoing hemodialysis treatment (2019-2021) and 24 isolates obtained from water and dialysate samples in a Hemodialysis Unit (same period). The recA gene was sequenced to identify the specific species among the Bcc group. All isolates were tested for the presence of some genes that encode virulence factors such as cblA, esmR, zmpA and zmpB. Considering the epidemiology of the outbreak, the Bcc isolates were molecularly characterized by Multi Locus Sequence Type (MLST) and by pulsed-field gel electrophoresis (PFGE). The verification and quantification of biofilm in a polystyrene microplate were performed by submitting the isolates to different incubation temperatures (20°C, average water temperature and 35°C, optimal temperature for group growth). The antibiogram was performed with disc diffusion tests on agar, using discs impregnated with cefepime (30µg), ceftazidime (30µg), ciprofloxacin (5µg), gentamicin (10µg), imipenem (10µg), amikacin 30µg), sulfametazol/trimethoprim (23.75/1.25µg) and ampicillin/sulbactam (10/10µg). The presence of ZmpB was identified in all isolates, while ZmpA was observed in 96.5% of the isolates, while none of them presented the cblA and esmR genes. The antibiogram of the 33 human isolates indicated that all were resistant to gentamicin, colistin, ampicillin/sulbactam and imipenem. 16 (48.5%) isolates were resistant to amikacin and lower rates of resistance were observed for meropenem, ceftazidime, cefepime, ciprofloxacin and piperacycline/tazobactam (6.1%). All isolates were sensitive to sulfametazol/trimethoprim, levofloxacin and tigecycline. As for the water isolates, resistance was observed only to gentamicin (34.8%) and imipenem (17.4%). According to PFGE results, all isolates obtained from humans and water belonged to the same pulsotype (1), which was identified by recA sequencing as B. cepacia¸, belonging to sequence type ST-767. By observing a single pulse type over three years, one can observe the persistence of this isolate in the pipeline, contaminating patients undergoing hemodialysis, despite the routine disinfection of water with peracetic acid. This persistence is probably due to the production of biofilm, which protects bacteria from disinfectants and, making this scenario more critical, several isolates proved to be multidrug-resistant (resistance to at least three groups of antimicrobials), turning the patient care even more difficult.

Keywords: hemodialysis, burkholderia cepacia, PFGE, MLST, multi drug resistance

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Authors: Clorinda Hogan, Shaun Abbott, Mark Halaki, Marcela Torres Catiglioni, Goshi Yamauchi, Lachlan Mitchell, James Salter, Michael Romann, Stephen Cobley

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Introduction: Common annual age-group competition structures unintentionally introduce participation inequalities, performance (dis)advantages and selection biases due to the effect of maturational variation between youth swimmers. On this basis, there are implications for improving performance evaluation strategies. Therefore the aim was to: (1) To determine maturity timing distributions in female youth swimming; (2) quantify the relationship between maturation status and 100-m FC performance; (3) apply Maturational-based Corrective Adjustment Procedures (Mat-CAPs) for removal of maturational status performance influences. Methods: (1) Cross-sectional analysis of 663 female (10-15 years) swimmers who underwent assessment of anthropometrics (mass, height and sitting height) and estimations of maturity timing and offset. (2) 100-m front-crawl performance (seconds) was assessed at Australian regional, state, and national-level competitions between 2016-2020. To determine the relationship between maturation status and 100-m front-crawl performance, MO was plotted against 100-m FC performance time. The expected maturity status - performance relationship for females aged 10-15 years of age was obtained through a quadratic function (y = ax2 + bx + c) from unstandardized coefficients. The regression equation was subsequently used for Mat-CAPs. (3) Participants aged 10-13 years were categorised into maturity-offset categories. Maturity offset distributions for Raw (‘All’, ‘Top 50%’ & ‘Top 25%’) and Correctively Adjusted swim times were examined. Chi-square, Cramer’s V and ORs determined the occurrence of maturation biases for each age group and selection level. Results—: (1) Maturity timing distributions illustrated overrepresentation of ‘normative’ maturing swimmers (11.82 ± 0.40 years), with a descriptive shift toward the early maturing relative to the normative population. (2) A curvilinear relationship between maturity-offset and swim performance was identified (R2 = 0.53, P < 0.001) and subsequently utilised for Mat-CAPs. (3) Raw maturity offset categories identified partial maturation status skewing towards biologically older swimmers at 10/11 and 12 years, with effect magnitudes increasing in the ‘Top 50%’ and ‘25%’ of performance times. Following Mat-CAPs application, maturity offset biases were removed in similar age groups and selection levels. When adjusting performance times for maturity offset, Mat-CAPs was successful in mitigating against maturational biases until approximately 1-year post Peak Height Velocity. The overrepresentation of ‘normative’ maturing female swimmers contrasted with the substantial overrepresentation of ‘early’ maturing male swimmers found previously in 100-m front-crawl. These findings suggest early maturational timing is not advantageous in females, but findings associated with Aim 2, highlight how advanced maturational status remained beneficial to performance. Observed differences between female and male maturational biases may relate to the differential impact of physiological development during pubertal years. Females experience greater increases of fat mass and potentially differing changes in body shape which can negatively affect swim performance. Conclusions: Transient maturation status-based participation and performance advantages were apparent within a large sample of Australian female youth 100-m FC swimmers. By removing maturity status performance biases within female youth swimming, Mat-CAPs could help improve participation experiences and the accuracy of identifying genuinely skilled female youth swimmers.

Keywords: athlete development, long-term sport participation, performance evaluation, talent identification, youth competition

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Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

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Polymeric nanoparticles-based drug delivery systems and therapeutics have a great potential in the treatment of a numerous diseases, due to they are characterizing the flexible properties which is giving possibility to modify their structures with a complex definition over their structures, compositions and properties. Important characteristics of the polymeric nanoparticles (PNPs) used as drug carriers are high particle’s stability, high carrier capacity, feasibility of encapsulation of both hydrophilic and hydrophobic drugs, and feasibility of variable routes of administration, including oral application and inhalation; NPs are especially effective for intracellular drug delivery since they penetrate into the cells’ interior though endocytosis. A variety of PNPs based drug delivery systems including charged and neutral, degradable and non-degradable polymers of both natural and synthetic origin have been developed. Among these huge varieties the biodegradable PNPs which can be cleared from the body after the fulfillment of their function could be considered as one of the most promising. For intracellular uptake it is highly desirable to have positively charged PNPs since they can penetrate deep into cell membranes. For long-lasting circulation of PNPs in the body it is important they have so called “stealth coatings” to protect them from the attack of immune system of the organism. One of the effective ways to render the PNPs “invisible” for immune system is their PEGylation which represent the process of pretreatment of polyethylene glycol (PEG) on the surface of PNPs. The present work deals with constructing PNPs from amino acid based biodegradable polymers – regular poly(ester amide) (PEA) composed of sebacic acid, leucine and 1,6-hexandiol (labeled as 8L6), cationic PEA composed of sebacic acid, arginine and 1,6-hexandiol (labeled as 8R6), and comb-like co-PEA composed of sebacic acid, malic acid, leucine and 1,6-hexandiol (labeled as PEG-PEA). The PNPs were fabricated using the polymer deposition/solvent displacement (nanoprecipitation) method. The regular PEA 8L6 form stable negatively charged (zeta-potential within 2-12 mV) PNPs of desired size (within 150-200 nm) in the presence of various surfactants (Tween 20, Tween 80, Brij 010, etc.). Blending the PEAs 8L6 and 8R6 gave the 130-140 nm sized positively charged PNPs having zeta-potential within +20 ÷ +28 mV depending 8L6/8R6 ratio. The PEGylating PEA PEG-PEA was synthesized by interaction of epoxy-co-PEA [8L6]0,5-[tES-L6]0,5 with mPEG-amine-2000 The stable and positively charged PNPs were fabricated using pure PEG-PEA as a surfactant. A firm anchoring of the PEG-PEA with 8L6/8R6 based PNPs (owing to a high afinity of the backbones of all three PEAs) provided good stabilization of the NPs. In vitro biocompatibility study of the new PNPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed they are biocompatible. Considering high stability and cell compatibility of the elaborated PNPs one can conclude that they are promising for subsequent therapeutic applications. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 “New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications”.

Keywords: biodegradable poly(ester amide)s, cationic poly(ester amide), pegylating poly(ester amide), nanoparticles

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Authors: Yung-Chih Kuo, Che-Yu Lin, Jay-Shake Li, Yung-I Lou

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Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with cardiolipin (CL) to downregulate the phosphorylation of mitogen-activated protein kinases for Alzheimer’s disease (AD) management. AD belongs to neurodegenerative disorder with a gradual loss of memory, yielding irreversible dementia. CL-conjugated LIP loaded with CRM (CRM-CL/LIP) and that with NGF (NGF-CL/LIP) were applied to AD models of SK-N-MC cells and Wistar rats with an insult of β-amyloid peptide (Aβ). Lipids comprising 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (Avanti Polar Lipids, Alabaster, AL), 1',3'-bis[1,2- dimyristoyl-sn-glycero-3-phospho]-sn-glycerol (CL; Avanti Polar Lipids), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (Avanti Polar Lipids), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (Avanti Polar Lipids) and CRM (Sigma–Aldrich, St. Louis, MO) were dissolved in chloroform (J. T. Baker, Phillipsburg, NJ) and condensed using a rotary evaporator (Panchum, Kaohsiung, Taiwan). Human β-NGF (Alomone Lab, Jerusalem, Israel) was added in the aqueous phase. Wheat germ agglutinin (WGA; Medicago AB, Uppsala, Sweden) was grafted on LIP loaded with CRM for (WGA-CRM-LIP) and CL-conjugated LIP loaded with CRM (WGA-CRM-CL/LIP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (Sigma–Aldrich) and N-hydroxysuccinimide (Alfa Aesar, Ward Hill, MA). The protein samples of SK-N-MC cells (American Type Tissue Collection, Rockville, MD) were used for sodium dodecyl sulfate (Sigma–Aldrich) polyacrylamide gel (Sigma–Aldrich) electrophoresis. In animal study, the LIP formulations were administered by intravenous injection via a tail vein of male Wistar rats (250–280 g, 8 weeks, BioLasco, Taipei, Taiwan), which were housed in the Animal Laboratory of National Chung Cheng University in accordance with the institutional guidelines and the guidelines of Animal Protection Committee under the Council of Agriculture of the Republic of China. We found that CRM-CL/LIP could inhibit the expressions of phosphorylated p38 (p-p38), p-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 (p-Ser202) to retard the neuronal apoptosis. Free CRM and released CRM from CRM-LIP and CRM-CL/LIP were not in a straightforward manner to effectively inhibit the expression of p-p38 and p-JNK in the cytoplasm. In addition, NGF-CL/LIP enhanced the quantities of p-neurotrophic tyrosine kinase receptor type 1 (p-TrkA) and p-extracellular-signal-regulated kinase 5 (p-ERK5), preventing the Aβ-induced degeneration of neurons. The membrane fusion of NGF-LIP activated the ERK5 pathway and the targeting capacity of NGF-CL/LIP enhanced the possibility of released NGF to affect the TrkA level. Moreover, WGA-CRM-LIP improved the permeation of CRM across the blood–brain barrier (BBB) and significantly reduced the Aβ plaque deposition and malondialdehyde level and increased the percentage of normal neurons and cholinergic function in the hippocampus of AD rats. This was mainly because the encapsulated CRM was protected by LIP against a rapid degradation in the blood. Furthermore, WGA on LIP could target N-acetylglucosamine on endothelia and increased the quantity of CRM transported across the BBB. In addition, WGA-CRM-CL/LIP could be effective in suppressing the synthesis of acetylcholinesterase and reduced the decomposition of acetylcholine for better neurotransmission. Based on the in vitro and in vivo evidences, WGA-CRM-CL/LIP can rescue neurons from apoptosis in the brain and can be a promising drug delivery system for clinical AD therapy.

Keywords: Alzheimer’s disease, β-amyloid, liposome, mitogen-activated protein kinase

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