Search results for: sensory substitution

Authors: Mary Deyo, Zmara Harrison

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This study reports the outcomes of an 8-week experiential learning program for 6 adults with Intellectual and Developmental Disabilities (IDD) at a day habilitation program. The intervention foci for this program include executive function, language learning in the domains of expressive, receptive, and pragmatic language, and quality of life. The interprofessional collaboration aimed at supporting adults with IDD to reach person-centered, functional goals across skill domains is critical. This study is a significant addition to the speech-language pathology literature in that it examines a therapy method that potentially meets this need while targeting domains within the speech-language pathology scope of practice. Communication therapy was provided during highly valued and meaningful hands-on learning experiences, referred to as the Garden Club, which incorporated all aspects of planting and caring for a garden as well as related journaling, sensory, cooking, art, and technology-based activities. Direct care staff and an undergraduate research assistant were trained by SLP to be impactful language guides during their interactions with participants in the Garden Club. SLP also provided direct therapy and modeling during Garden Club. Research methods used in this study included a mixed methods analysis of a literature review, a quasi-experimental implementation of communication therapy in the context of experiential learning activities, Quality of Life participant surveys, quantitative pre- post- data collection and linear mixed model analysis, qualitative data collection with qualitative content analysis and coding for themes. Outcomes indicated overall positive changes in expressive vocabulary, following multi-step directions, sequencing, problem-solving, planning, skills for building and maintaining meaningful social relationships, and participant perception of the Garden Project’s impact on their own quality of life. Implementation of this project also highlighted supports and barriers that must be taken into consideration when planning similar projects. Overall findings support the use of experiential learning projects in day habilitation programs for adults with IDD, as well as additional research to deepen understanding of best practices, supports, and barriers for implementation of experiential learning with this population. This research provides an important contribution to research in the fields of speech-language pathology and other professions serving adults with IDD by describing an interprofessional experiential learning program with positive outcomes for executive function, language learning, and quality of life.

Keywords: experiential learning, adults, intellectual and developmental disabilities, expressive language, receptive language, pragmatic language, executive function, communication therapy, day habilitation, interprofessionalism, quality of life

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Authors: Elena Ionescu, Elena Iacob, Marie-Louise Ionescu, Carmen Elena Tebrencu, Oana Teodora Ciuperca

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Echinacea species (Asteraceae) has received a global attention because it is widely used for treatment of cold, flu and upper respiratory tract infections. Echinacea species contain a great variety of chemical components that contribute to their activity. The most important components responsible for the biological activity are those with high molecular-weight such as polysaccharides, polyacetylenes, highly unsaturated alkamides and caffeic acid derivatives. The principal factors that may influence the chemical composition of Echinacea include the species and the part of plant used (aerial parts or roots ). In recent years the market for Echinacea has grown rapidly and also the cases of adultery/replacement especially for Echinacea root. The identification of presence or absence of same biomarkers provide information for safe use of Echinacea species in food supplements industry. The aim of the study was the preliminary evaluation and fingerprinting by UV-VISIBLE spectroscopy of biomarkers in terms of content in phenolic derivatives of some Echinacea species (E. purpurea, E. angustifolia and E. pallida) for identification and authentication of the species. The steps of the study were: (1) samples (extracts) preparation from Echinacea species (non-hydrolyzed and hydrolyzed ethanol extracts); (2) samples preparation of reference substances (polyphenol acids: caftaric acid, caffeic acid, chlorogenic acid, ferulic acid; flavonoids: rutoside, hyperoside, isoquercitrin and their aglycones: quercitri, quercetol, luteolin, kaempferol and apigenin); (3) identification of specific absorption at wavelengths between 700-200 nm; (4) identify the phenolic compounds from Echinacea species based on spectral characteristics and the specific absorption; each class of compounds corresponds to a maximum absorption in the UV spectrum. The phytochemical compounds were identified at specific wavelengths between 700-200 nm. The absorption intensities were measured. The obtained results proved that ethanolic extract showed absorption peaks attributed to: phenolic compounds (free phenolic acids and phenolic acids derivatives) registrated between 220-280 nm, unsymmetrical chemical structure compounds (caffeic acid, chlorogenic acid, ferulic acid) with maximum absorption peak and absorption "shoulder" that may be due to substitution of hydroxyl or methoxy group, flavonoid compounds (in free form or glycosides) between 330-360 nm, due to the double bond in position 2,3 and carbonyl group in position 4 flavonols. UV spectra showed two major peaks of absorption (quercetin glycoside, rutin, etc.). The results obtained by UV-VIS spectroscopy has revealed the presence of phenolic derivatives such as cicoric acid (240 nm), caftaric acid (329 nm), caffeic acid (240 nm), rutoside (205 nm), quercetin (255 nm), luteolin (235 nm) in all three species of Echinacea. The echinacoside is absent. This profile mentioned above and the absence of phenolic compound echinacoside leads to the conclusion that species harvested as Echinacea angustifolia and Echinacea pallida are Echinacea purpurea also; It can be said that preliminary fingerprinting of Echinacea species through correspondence with the phenolic derivatives profile can be achieved by UV-VIS spectroscopic investigation, which is an adequate technique for preliminary identification and authentication of Echinacea in medicinal herbs.

Keywords: Echinacea species, Fingerprinting, Phenolic compounds, UV-VIS spectroscopy

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Authors: Malkhaz Jokhadze, Vakhtang Mshvildadze, Levan Makaradze, Ekaterine Mosidze, Salome Barbaqadze, Mariam Murtazashvili, Dali Berashvili, Koba sivsivadze, Lasha Bakuridze, Aliosha Bakuridze

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Essential oils are one of the most important groups of biologically active substances present in plants. Due to the chemical diversity of components, essential oils and their preparations have a wide spectrum of pharmacological action. They have bactericidal, antiviral, fungicidal, antiprotozoal, anti-inflammatory, spasmolytic, sedative and other activities. They are expectorant, spasmolytic, sedative, hypotensive, secretion enhancing, antioxidant remedies. Based on preliminary pharmacological studies, we have developed a formulation called “Phytobiotic” containing essential oils, a feed additive for poultry as an alternative to antibiotics. Phytobiotic is a water-soluble powder containing a composition of essential oils of thyme, clary, monarda and auxiliary substances: dry extract of liquorice and inhalation lactose. On this stage of research, the goal was to study the chemical composition of provided phytobiotic, identify the main substances and determine their quantity, investigate the biological activity of phytobiotic through in vitro and in vivo studies. Using gas chromatography-mass spectrometry, 38 components were identified in phytobiotic, representing acyclic-, monocyclic-, bicyclic-, and sesquiterpenes. Together with identification of main active substances, their quantitative content was determined, including acyclic terpene alcohol β-linalool, acyclic terpene ketone linalyl acetate, monocyclic terpenes: D-limonene and γ-terpinene, monocyclic aromatic terpene thymol. Provided phytobiotic has pronounced and at the same time broad spectrum of antibacterial activity. In the cell model, phytobiotic showed weak antioxidant activity, and it was stronger in the ORAC (chemical model) tests. Meanwhile anti-inflammatory activity was also observed. When fowls were supplied feed enriched with phytobiotic, it was observed that gained weight of the chickens in the experimental group exceeded the same data for the control group during the entire period of the experiment. The survival rate of broilers in the experimental group during the growth period was 98% compared to -94% in the control group. As a result of conducted researches probable four different mechanisms which are important for the action of phytobiotics were identified: sensory, metabolic, antioxidant and antibacterial action. General toxic, possible local irritant and allergenic effects of phytobiotic were also investigated. Performed assays proved that formulation is safe.

Keywords: clary, essential oils, monarda, poultry, phytobiotics, thyme

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Authors: Rossana Roila, Raffaella Branciari, Lorenzo Cardinali, David Ranucci

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The wild boar (Sus scrofa) population has strongly increased across Europe in the last decades, also causing severe fauna management issues. In central Italy, wild boar is the main hunted wild game species, with approximately 40,000 animals killed per year only in the Umbria region. The meat of the game is characterized by high-quality nutritional value as well as peculiar taste and aroma, largely appreciated by consumers. This type of meat and products thereof can meet the current consumers’ demand for higher quality foodstuff, not only from a nutritional and sensory point of view but also in relation to environmental sustainability, the non-use of chemicals, and animal welfare. The game meat production chain is characterized by some gaps from a hygienic point of view: the harvest process is usually conducted in a wild environment where animals can be more easily contaminated during hunting and subsequent practices. The definition and implementation of a certified and controlled supply chain could ensure quality, traceability and safety for the final consumer and therefore promote game meat products. According to European legislation in some animal species, such as bovine, the use of weak acid solutions for carcass decontamination is envisaged in order to ensure the maintenance of optimal hygienic characteristics. A preliminary study was carried out to evaluate the applicability of similar strategies to control the hygienic level of wild boar carcasses. The carcasses, harvested according to the selective method and processed into the game-handling establishment, were treated by nebulization with two different solutions: a 2% food-grade lactic acid solution and aromatic vinegar. Swab samples were performed before treatment and in different moments after-treatment of the carcasses surfaces and subsequently tested for Total Aerobic Mesophilic Load, Total Aerobic Psychrophilic Load, Enterobacteriaceae, Staphylococcus spp. and lactic acid bacteria. The results obtained for the targeted microbial populations showed a positive effect of the application of the lactic acid solution on all the populations investigated, while aromatic vinegar showed a lower effect on bacterial growth. This study could lay the foundations for the optimization of the use of a lactic acid solution to treat wild boar carcasses aiming to guarantee good hygienic level and safety of meat.

Keywords: game meat, food safety, process hygiene criteria, microbial population, microbial growth, food control

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Authors: Masoume Pourmohamadreza-Tajrishi, Parviz Azadfallah

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Autism spectrum disorders (ASD) involve myriad aberrant perceptual, cognitive, linguistic, and social behaviors. The term spectrum emphasizes that the disabilities associated with ASD fall on a continuum from relatively mild to severe. People with ASD may display stereotyped behaviors such as twirling, spinning objects, flapping the hands, and rocking. The individuals with ASD exhibit communication problems due to repetitive/restricted behaviors. Children with ASD who lack the motivation to learn, who do not enjoy physical challenges, or whose sensory perception results in confusing or unpleasant feedback from movement may not become sufficiently motivated to practice motor activities. As a result, they may show both a delay in developing certain motor skills. Additionally, attention is an important component of learning. As far as children with ASD have problems in joint attention, many education-based programs are needed to consider some aspects of attention and motor activities development for students with ASD. These programs focus on the basic movement skills that are crucial for the future development of the more complex skills needed in games, dance, sports, gymnastics, active play, and recreational physical activities. The purpose of the present research was to determine the effectiveness of therapeutic exercise on motor skills and attention of male students with ASD. This was an experimental study with a control group. The population consisted of 8-10 year-old male students with ASD and 30 subjects were selected randomly from an available center suitable for the children with ASD. They were evaluated by the Basic Motor Ability Test (BMAT) and Persian version of computerized Stroop color-word test and randomly assigned to an experimental and control group (15 students in per group). The experimental group participated in 16 therapeutic exercise sessions and received therapeutic exercise program (twice a week; each lasting for 45 minutes) designed based on the Spark motor program while the control group did not. All subjects were evaluated by BMAT and Stroop color-word test after the last session again. The collected data were analyzed by using multivariate analysis of covariance (MANCOVA). The results of MANCOVA showed that experimental and control groups had a significant difference in motor skills and at least one of the components of attention (correct responses, incorrect responses, no responses, the reaction time of congruent words and reaction time of incongruent words in the Stroop test). The findings showed that the therapeutic exercise had a significant effect on motor skills and all components of attention in students with ASD. We can conclude that the therapeutic exercise led to promote the motor skills and attention of students with ASD, so it is necessary to design or plan such programs for ASD students to prevent their communication or academic problems.

Keywords: Attention, autism spectrum disorder, motor skills, therapeutic exercise

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Authors: Aikaterini Tavoulari, Mike Richardson

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Objective: This abstract presents a multisensory participatory design project, inspired by a deafblind PhD student's ambition to climb Mount Everest. The project aims to explore accessible routes for filmmaking and video content creation, catering to the needs of individuals with hearing and sight loss. By engaging participants from the Southwest area of England, recruited through multiple networks, the project seeks to gather qualitative data and insights to inform the development of inclusive media practices. Design: It will be a community-based participatory research design. The workshop will feature various stations that stimulate different senses, such as scent, touch, sight, hearing as well as movement. Participants will have the opportunity to engage with these multisensory experiences, providing valuable feedback on their effectiveness and potential for enhancing accessibility in filmmaking and video content. Methods: Brief semi-structured interviews will be conducted to collect qualitative data, allowing participants to share their perspectives, challenges, and suggestions for improvement. The participatory design approach emphasizes the importance of involving the target audience in the creative process. By actively engaging individuals with hearing and sight loss, the project aims to ensure that their needs and preferences are central to the development of accessible filmmaking techniques and video content. This collaborative effort seeks to bridge the gap between content creators and diverse audiences, fostering a more inclusive media landscape. Results: The findings from this study will contribute to the growing body of research on accessible filmmaking and video content creation. Via inductive thematic analysis of the qualitative data collected through interviews and observations, the researchers aim to identify key themes, challenges, and opportunities for creating engaging and inclusive media experiences for deafblind audiences. The insights will inform the development of best practices and guidelines for accessible filmmaking, empowering content creators to produce more inclusive and immersive video content. Conclusion: The abstract targets the hybrid International Conference for Disability and Diversity in Canada (January 2025), as this platform provides an excellent opportunity to share the outcomes of the project with a global audience of researchers, practitioners, and advocates working towards inclusivity and accessibility in various disability domains. By presenting this research at the conference in person, the authors aim to contribute to the ongoing discourse on disability and diversity, highlighting the importance of multisensory experiences and participatory design in creating accessible media content for the deafblind community and the community with sensory impairments more broadly.

Keywords: vision impairment, hearing impairment, deafblindness, accessibility, filmmaking

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Authors: Li Shuping, Shu Huaping, Yi Chaofan, Tao Jiang

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Equestrian practice is often considered having a unique effect on improving symptoms in children with autism. This study evaluated and measured the changes in daily behavior, morphological, physical function, and fitness indexes of two group children with autism by means of 12 weeks of equestrian and basketball exercises. 19 clinically diagnosed children with moderate/mild autism were randomly divided into equestrian group (9 children, age=10.11±1.90y) and basketball group (10 children, age=10.70±2.16y). Both the equestrian and basketball groups practiced twice a week for 45 to 60 minutes each time. Three scales, the Autism Behavior Checklist (ABC), the Childhood Autism Rating Scale (CARS) and the Clancy Autism Behavior Scale (CABS) were used to assess their human behavior and psychology. Four morphological, seven physical function and fitness indicators were measured to evaluate the effects of the two exercises on the children’s body. The evaluations were taken by every four weeks ( pre-exercise, the 4th week, the 8th week and 12th week (post exercise). The result showed that the total scores of ABC, CARS and CABS, the dimension scores of ABC on the somatic motor, language and life self-care obtained after exercise were significantly lower than those obtained before 12 week exercises in both groups. The ABC feeling dimension scores of equestrian group and ABC communication dimension score of basketball group were significantly lower,and The upper arm circumference, sitting forward flexion, 40 second sit-up, 15s lateral jump, vital capacity, and single foot standing of both groups were significantly higher than that of before exercise.. The BMI of equestrian group was significantly reduced. The handgrip strength of basketball group was significantly increased. In conclusion, both types of exercises could improve daily behavior, morphological, physical function, and fitness indexes of the children with autism. However, the behavioral psychological scores, body morphology and function indicators and time points were different in the middle and back of the two interventions.But the indicators and the timing of the improvement were different. To the group of equestrian, the improvement of the flexibility occurred at week 4, the improvement of the sensory perception, control and use their own body, and promote the development of core strength endurance, coordination and cardiopulmonary function occurred at week 8，and the improvement of core strength endurance, coordination and cardiopulmonary function occurred at week 12. To the group of basketball, the improvement of the hand strength, balance, flexibility and cardiopulmonary function occurred at week 4, the improvement of the self-care ability and language expression ability, and core strength endurance and coordination occurred at week 8, the improvement of the control and use of their own body and social interaction ability occurred at week 12. In comparison of the exercise effects, the equestrian exercise improved the physical control and application ability appeared earlier than that of basketball group. Basketball exercise improved the language expression ability, self-care ability, balance ability and cardiopulmonary function of autistic children appeared earlier than that of equestrian group.

Keywords: intervention, children with autism, equestrain, basketball

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Authors: Wen-Yang Hu, Ranli Lu, Mark Maienschein-Cline, Danping Hu, Larisa Nonn, Toshi Shioda, Gail S. Prins

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Background: Genetic mutations are highly associated with increased prostate cancer risk. In addition to whole genome sequencing, somatic mutations can be identified by aligning transcriptome sequences to the human genome. Here we analyzed bulk RNAseq and single cell RNAseq data of human prostate cancer cells and their matched non-cancer cells in benign regions from 4 individual patients. Methods: Sequencing raw reads were aligned to the reference genome hg38 using STAR. Variants were annotated using Annovar with respect to overlap gene annotation information, effect on gene and protein sequence, and SIFT annotation of nonsynonymous variant effect. We determined cancer-specific novel alleles by comparing variant calls in cancer cells to matched benign cells from the same individual by selecting unique alleles that were only detected in the cancer samples. Results: In bulk RNAseq data from 3 patients, the most common variants were the noncoding mutations at UTR3/UTR5, and the major variant types were single-nucleotide polymorphisms (SNP) including frameshift mutations. C>T transversion is the most frequently presented substitution of SNP. A total of 222 genes carrying unique exonic or UTR variants were revealed in cancer cells across 3 patients but not in benign cells. Among them, transcriptome levels of 7 genes (CITED2, YOD1, MCM4, HNRNPA2B1, KIF20B, DPYSL2, NR4A1) were significantly up or down regulated in cancer stem cells. Out of the 222 commonly mutated genes in cancer, 19 have nonsynonymous variants and 11 are damaged genes with variants including SIFT, frameshifts, stop gain/loss, and insertions/deletions (indels). Two damaged genes, activating transcription factor 6 (ATF6) and histone demethylase KDM3A are of particular interest; the former is a survival factor for certain cancer cells while the later positively activates androgen receptor target genes in prostate cancer. Further, single cell RNAseq data of cancer cells and their matched non-cancer benign cells from both primary 2D and 3D tumoroid cultures were analyzed. Similar to the bulk RNAseq data, single cell RNAseq in cancer demonstrated that the exonic mutations are less common than noncoding variants, with SNPs including frameshift mutations the most frequently presented types in cancer. Compared to cancer stem cell enriched-3D tumoroids, 2D cancer cells carried 3-times higher variants, 8-times more coding mutations and 10-times more nonsynonymous SNP. Finally, in both 2D primary and 3D tumoroid cultures, cancer stem cells exhibited fewer coding mutations and noncoding SNP or insertions/deletions than non-stem cancer cells. Summary: Our study demonstrates the usefulness of bulk and single cell RNAseaq data in identifying somatic mutations in prostate cancer, providing an alternative method in screening candidate genes for prostate cancer diagnosis and potential therapeutic targets. Cancer stem cells carry fewer somatic mutations than non-stem cancer cells due to their inherited immortal stand DNA from parental stem cells that explains their long-lived characteristics.

Keywords: prostate cancer, stem cell, genomic mutation, RNAseq

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Authors: Abhit Kumar

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The world is full of master slave Telemanipulator where the doctor’s masters the console and the surgical arm perform the operations, i.e. these robots are passive robots, what the world needs to focus is that in use of these passive robots we are acquiring doctors for operating these console hence the utilization of the concept of robotics is still not fully utilized ,hence the focus should be on active robots, Auto Surgical-Emissive Hand use the similar concept of active robotics where this anthropomorphic hand focuses on the autonomous surgical, emissive and scanning operation, enabled with the vision of 3 way emission of Laser Beam/-5°C < ICY Steam < 5°C/ TIC embedded in palm of the anthropomorphic hand and structured in a form of 3 way disc. Fingers of AS-EH (Auto Surgical-Emissive Hand) as called, will have tactile, force, pressure sensor rooted to it so that the mechanical mechanism of force, pressure and physical presence on the external subject can be maintained, conversely our main focus is on the concept of “emission” the question arises how all the 3 non related methods will work together that to merged in a single programmed hand, all the 3 methods will be utilized according to the need of the external subject, the laser if considered will be emitted via a pin sized outlet, this radiation is channelized via a thin channel which further connect to the palm of the surgical hand internally leading to the pin sized outlet, here the laser is used to emit radiation enough to cut open the skin for removal of metal scrap or any other foreign material while the patient is in under anesthesia, keeping the complexity of the operation very low, at the same time the TIC fitted with accurate temperature compensator will be providing us the real time feed of the surgery in the form of heat image, this gives us the chance to analyze the level, also ATC will help us to determine the elevated body temperature while the operation is being proceeded, the thermal imaging camera in rooted internally in the AS-EH while also being connected to the real time software externally to provide us live feedback. The ICY steam will provide the cooling effect before and after the operation, however for more utilization of this concept we can understand the working of simple procedure in which If a finger remain in icy water for a long time it freezes the blood flow stops and the portion become numb and isolated hence even if you try to pinch it will not provide any sensation as the nerve impulse did not coordinated with the brain hence sensory receptor did not got active which means no sense of touch was observed utilizing the same concept we can use the icy stem to be emitted via a pin sized hole on the area of concern ,temperature below 273K which will frost the area after which operation can be done, this steam can also be use to desensitized the pain while the operation in under process. The mathematical calculation, algorithm, programming of working and movement of this hand will be installed in the system prior to the procedure, since this AS-EH is a programmable hand it comes with the limitation hence this AS-EH robot will perform surgical process of low complexity only.

Keywords: active robots, algorithm, emission, icy steam, TIC, laser

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Authors: E. Obreque-Slier, P. Osorio-Umaña, G. Vidal-Acevedo, A. Peña-Neira, M. Medel-Marabolí

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Sensory and nutraceutical characteristics of a wine are determined by different chemical compounds, such as organic acids, sugars, alcohols, polysaccharides, aromas, and polyphenols. The polyphenols correspond to secondary metabolites that are associated with the prevention of several pathologies, and those are responsible for color, aroma, bitterness, and astringency in wines. These compounds come from grapes and wood during aging in barrels, which correspond to the format of wood most widely used in wine production. However, the barrels is a high-cost input with a limited useful life (3-4 years). For this reason, some oenological products have been developed in order to renew the barrels and increase their useful life in some years. These formats are being used slowly because limited information exists about the effect on the wine chemical characteristics. The objective of the study was to evaluate the effect of different laubarrel renewal systems (staves and zigzag) on the polyphenolic characteristics of a Carménère wine (Vitis vinifera), an emblematic cultivar of Chile. For this, a completely randomized experimental design with 5 treatments and three replicates per treatment was used. The treatments were: new barrels (T0), used barrels during 4 years (T1), scraped used barrels (T2), used barrels with staves (T3) and used barrels with zigzag (T4). The study was performed for 12 months, and different spectrophotometric parameters (phenols, anthocyanins, and total tannins) and HPLC-DAD (low molecular weight phenols) were evaluated. The wood inputs were donated by Toneleria Nacional and corresponded to products from the same production batch. The total phenols content increased significantly after 40 days, while the total tannin concentration decreased gradually during the study. The anthocyanin concentration increased after 120 days of the assay in all treatments. Comparatively, it was observed that the wine of T2 presented the lowest values of these polyphenols, while the T0 and T4 presented the highest total phenol contents. Also, T1 presented the highest values of total tannins in relation to the rest of the treatments in some samples. The low molecular weight phenolic compounds identified by HPLC-DAD were 7 flavonoids (epigallocatechin, catechin, procyanidin gallate, epicatechin, quercetin, rutin and myricetin) and 14 non-flavonoids (gallic, protocatechuic, hydroxybenzoic, trans-cutaric, vanillinic, caffeic, syringic, p-coumaric and ellagic acids; tyrosol, vanillin, syringaldehyde, trans-resveratrol and cis-resveratrol). Tyrosol was the most abundant compound, whereas ellagic acid was the lowest in the samples. Comparatively, it was observed that the wines of T2 showed the lowest concentrations of flavonoid and non-flavonoid phenols during the study. In contrast, wines of T1, T3, and T4 presented the highest contents of non-flavonoid polyphenols. In summary, the use of barrel renovators (zig zag and staves) is an interesting alternative which would emulate the contribution of polyphenols from the barrels to the wine.

Keywords: barrels, oak wood aging, polyphenols, red wine

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Authors: A. Abdouni, C. Thieulin, M. Djaghloul, R. Vargiolu, H. Zahouani

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A decline in the main sensory modalities (vision, hearing, taste, and smell) is well reported to occur with advancing age, it is expected a similar change to occur with touch sensation and perception. In this study, we have focused on the touch sensations highlighting ageing and gender influences with in vivo systems. The touch process can be divided into two main phases: The first phase is the first contact between the finger and the object, during this contact, an adhesive force has been created which is the needed force to permit an initial movement of the finger. In the second phase, the finger mechanical properties with their surface topography play an important role in the obtained sensation. In order to understand the age and gender effects on the touch sense, we develop different ideas and systems for each phase. To better characterize the contact, the mechanical properties and the surface topography of human finger, in vivo studies on the pulp of 40 subjects (20 of each gender) of four age groups of 26±3, 35+-3, 45+-2 and 58±6 have been performed. To understand the first touch phase a classical indentation system has been adapted to measure the finger contact properties. The normal force load, the indentation speed, the contact time, the penetration depth and the indenter geometry have been optimized. The penetration depth of a glass indenter is recorded as a function of the applied normal force. Main assessed parameter is the adhesive force F_ad. For the second phase, first, an innovative approach is proposed to characterize the dynamic finger mechanical properties. A contactless indentation test inspired from the techniques used in ophthalmology has been used. The test principle is to blow an air blast to the finger and measure the caused deformation by a linear laser. The advantage of this test is the real observation of the skin free return without any outside influence. Main obtained parameters are the wave propagation speed and the Young's modulus E. Second, negative silicon replicas of subject’s fingerprint have been analyzed by a probe laser defocusing. A laser diode transmits a light beam on the surface to be measured, and the reflected signal is returned to a set of four photodiodes. This technology allows reconstructing three-dimensional images. In order to study the age and gender effects on the roughness properties, a multi-scale characterization of roughness has been realized by applying continuous wavelet transform. After determining the decomposition of the surface, the method consists of quantifying the arithmetic mean of surface topographic at each scale SMA. Significant differences of the main parameters are shown with ageing and gender. The comparison between men and women groups reveals that the adhesive force is higher for women. The results of mechanical properties show a Young’s modulus higher for women and also increasing with age. The roughness analysis shows a significant difference in function of age and gender.

Keywords: ageing, finger, gender, touch

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Authors: Abdulwhab Alotaibi, Abdullah Alzahrani, Ziyad Bokhari, Abdulelah Alghamdi

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First described in 1975 by Dr. Miller, Medical dressings are uncommon but possible cause of hand digital ischemia due the tourniquet-like effect. The incident of this complication has been reported across wide range of age-groups, yet it seems like that the pediatric population are specifically vulnerable. Multiple dressing types were reported to have caused ischemic injury, such as elastic wrap, tubular gauze, and self-adherent dressings. We present a case of medical dressing induced digital ischemia in patient with Congenital insensitivity to pain and anhidrosis (CIPA), which further challenge the discovery of the condition. An 8-year-old girl known case of CIPA. Brought by her mother to the ER after nail bed injury, which she managed by application of elastic wrap that was left for 24 hours. When the mother found out she immediately removed the elastic band, and noticed the fingertip was black and cold with tense bullae. The color then changed later when she arrived to the ER to dark purple with bluish discoloration on the tip. On examination there was well demarcated tense bullae on the distal right fifth finger. Neurovascular intact, pulse oximetry on distal digit 100%, capillary refill time was delayed. She was seen under Plastic surgery and conservative management recommended, and patient was discharged with safety netting. Two days later the patient came as follow-up visit at which her condition demonstrated significant improvement, the bullae has since ruptured leaving behind sloughed skin, capillary refill and pulse oximetry were both within normal limits, sensory function couldn’t be assessed but her motor function and ROM were normal, topical bacitracin and bandage dressings were applied for the eroded skin. Patient was scheduled for a follow-up in 2 weeks. Preventatively it’s advisable to avoid the commonly implicated dressings such as elastic, tubular gauze or self-adherent wraps in hand or digital injuries when possible, but in cases where the use of these dressings is of necessity the appropriate precautions must be taken, Dr. Makarewich proposed the following 5 measures to help minimize the incidence of the injury: 1-Unwrapping 12 inches of the dressing before rolling the injured finger. 2-Wrapping from distal to proximal with minimal tension to avoid vascular embarrassment. 3-The use of 5-25 inch to overlap the entire wrap. 4-Maintaining light pressure over the wrap to allow adherence of the dressing. 5-Minimization of the number of layers used to wrap the affected digit. Also assessing the capillary refill after the application can help in determining the patency of the supplying blood vessels. It’s also important to selectively determine if the patient is a candidate for conservative management, as tailored approach can help in maximizing the positive outcomes for our patients.

Keywords: congenital insensitivity to pain, digital ischemia, medical dressing, conservative management

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Authors: Dong Yue, Hua Chen

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The study region Xihu Harbor in Xiangshan County, Ningbo City is located in the central coast of Zhejiang Province. Concerning the wave dispating issue, Ningbo government firstly introduced Spartina alterniflora in 1980s. In the 1990s, S. alterniflora spread so rapidly thus a ‘grassland’ in the sea has been created nowadays. It has become the most important invasive plant of China’s coastal tidal flats. Although S. alterniflora had some ecological and economic functions, it has also brought series of hazards. It has ecological hazards on many aspects, including biomass and biodiversity, hydrodynamic force and sedimentation process, nutrient cycling of tidal flat, succession sequence of soil and plants and so on. On engineering, it courses problems of poor drainage and channel blocking. On economy, the hazard mainly reflected in the threat on aquaculture industry. The purpose of this study is to explore an ecological, feasible and economical way to manage Spartina alterniflora and use the land formed by it, taking Xihu Harbor in Xiangshan County as a case. Comparison method, mathematical modeling, qualitative and quantitative analysis are utilized to proceed the study. Main outcomes are as follows. By comparing a series of S. alterniflora managing methods which include the combination of mechanical cutting and hydraulic reclamation, waterlogging, herbicide and biological substitution from three standpoints – ecology, engineering and economy. It is inferred that the combination of mechanical cutting and hydraulic reclamation is among the top rank of S. alternifora managing methods. The combination of mechanical cutting and hydraulic reclamation means using large-scale mechanical equipment like large screw seagoing dredger to excavate the S. alterniflora with root and mud together. Then the mix of mud and grass was blown off nearby coastal tidal zone transported by pipelines, which can cushion the silt of tidal zone to form a land. However, as man-made land by coast, the reclamation area’s ecological sensitivity is quite high and will face high possibility of flood threat. Therefore, the reclamation area has many reasonability requirements, including ones on location, specific scope, water surface rate, direction of main watercourse, site of water-gate, the ratio of ecological land to urban construction land. These requirements all became important basis when the planning was being made. The water system planning, green space system planning, road structure and land use all need to accommodate the ecological requests. Besides, the profits from the formed land is the managing project’s source of funding, so how to utilize land efficiently is another considered point in the planning. It is concluded that by aiming at managing a large area of S. alterniflora, the combination of mechanical cutting and hydraulic reclamation is an ecological, feasible and economical method. The planning of reclamation area should fully respect the natural environment and possible disasters. Then the planning which makes land use efficient, reasonable, ecological will promote the development of the area’s city construction.

Keywords: ecological management, ecological planning method, reclamation area, Spartina alternifora, Xihu harbor

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Authors: Ana Paula Soares, Alexandrina Lages, Helena Oliveira, Francisco-Javier Gutiérrez-Domínguez, Marisa Lousada

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From an early age, exposure to a spoken language allows us to implicitly capture the structure underlying the succession of the speech sounds in that language and to segment it into meaningful units (words). Statistical learning (SL), i.e., the ability to pick up patterns in the sensory environment even without intention or consciousness of doing it, is thus assumed to play a central role in the acquisition of the rule-governed aspects of language and possibly to lie behind the language difficulties exhibited by children with development language disorder (DLD). The research conducted so far has, however, led to inconsistent results, which might stem from the behavioral tasks used to test SL. In a classic SL experiment, participants are first exposed to a continuous stream (e.g., syllables) in which, unbeknownst to the participants, stimuli are grouped into triplets that always appear together in the stream (e.g., ‘tokibu’, ‘tipolu’), with no pauses between each other (e.g., ‘tokibutipolugopilatokibu’) and without any information regarding the task or the stimuli. Following exposure, SL is assessed by asking participants to discriminate between triplets previously presented (‘tokibu’) from new sequences never presented together during exposure (‘kipopi’), i.e., to perform a two-alternative-forced-choice (2-AFC) task. Despite the widespread use of the 2-AFC to test SL, it has come under increasing criticism as it is an offline post-learning task that only assesses the result of the learning that had occurred during the previous exposure phase and that might be affected by other factors beyond the computation of regularities embedded in the input, typically the likelihood two syllables occurring together, a statistic known as transitional probability (TP). One solution to overcome these limitations is to assess SL as exposure to the stream unfolds using online techniques such as event-related potentials (ERP) that is highly sensitive to the time-course of the learning in the brain. Here we collected ERPs to examine the neurofunctional correlates of SL in preschool children with DLD, and chronological-age typical language development (TLD) controls who were exposed to an auditory stream in which eight three-syllable nonsense words, four of which presenting high-TPs and the other four low-TPs, to further analyze whether the ability of DLD and TLD children to extract-word-like units from the steam was modulated by words’ predictability. Moreover, to ascertain if the previous knowledge of the to-be-learned-regularities affected the neural responses to high- and low-TP words, children performed the auditory SL task, firstly, under implicit, and, subsequently, under explicit conditions. Although behavioral evidence of SL was not obtained in either group, the neural responses elicited during the exposure phases of the SL tasks differentiated children with DLD from children with TLD. Specifically, the results indicated that only children from the TDL group showed neural evidence of SL, particularly in the SL task performed under explicit conditions, firstly, for the low-TP, and, subsequently, for the high-TP ‘words’. Taken together, these findings support the view that children with DLD showed deficits in the extraction of the regularities embedded in the auditory input which might underlie the language difficulties.

Keywords: development language disorder, statistical learning, transitional probabilities, word segmentation

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Authors: Cassandra Branham, Danielle Farrar

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As writing instructors and writing center administrators at a large research university with a significant population of English language learners (ELLs), we are interested in how peer feedback pedagogy can be effectively translated for writing center purposes, as well as how various modes of peer feedback can enrich the learning experiences of L1 and L2 writers in these spaces. Although peer feedback is widely used in classrooms and centers, instructor, student, and researcher opinions vary in respect to its effectiveness. We argue that peer feedback - traditional and digital, synchronous and asynchronous - is an indispensable element for both classrooms and centers and emphasize that it should occur with both L1 and L2 students to further develop an array of reading and writing skills. We also believe that further understanding of the best practices of peer feedback in such cross-cultural spaces, like the classroom and center, can optimize the benefits of peer feedback. After a critical review of the literature, we implemented an embedded tutoring program in our university’s writing center in collaboration with its First-Year Composition (FYC) program and Language Institute. The embedded tutoring program matches a graduate writing consultant with L1 and L2 writers enrolled in controlled-matriculation composition courses where ELLs make up at least 50% of each class. Furthermore, this program is informed by what we argue to be some best practices of peer feedback for both classroom and center purposes, including expectation-based training through rubrics, modeling effective feedback, hybridizing traditional and digital modes of feedback, recognizing the significance the body in composition (what we call writer embodiment), and maximizing digital technologies to exploit extended cognition. After conducting surveys and follow-up interviews with students, instructors, and writing consultants in the embedded tutoring program, we found that not only did students see an increased value in peer feedback, but also instructors saw an improvement in both writing style and critical thinking skills. Our L2 participants noted improvements in language acquisition while our L1 students recognized a broadening of their worldviews. We believe that both L1 and L2 students developed self-efficacy and agency in their identities as writers because they gained confidence in their abilities to offer feedback, as well as in the legitimacy of feedback they received from peers. We also argue that these best practices situate novice writers as experts, as writers become a valued and integral part of the revision process with their own and their peers’ papers. Finally, the use of iPads in embedded tutoring recovered the importance of the body and its senses in writing; the highly sensory feedback from these multi-modal sessions that offer audio and visual input underscores the significant role both the body and mind play in compositional practices. After beginning with a brief review of the literature that sparked this research, this paper will discuss the embedded tutoring program in detail, report on the results of the pilot program, and will conclude with a discussion of the pedagogical implications that arise from this research for both classroom and center.

Keywords: English language learners, peer feedback, writing center, writing classroom

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Authors: N. Cihan KayaçEtin, Stijn Verdoodt, Alexis Versele

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The construction industry is accounted for one-third of all waste generated in the European Union (EU) countries. The Circular Economy Action Plan of the EU aims to tackle this issue and aspires to enhance the sustainability of the construction industry by adopting more circular principles and bio-based material use. The Interreg Circular Bio-Based Construction Industry (CBCI) project was conceived to research how this adoption can be facilitated. For this purpose, an approach is developed that integrates technical, legal and social aspects and provides business models for circular designing and building with bio-based materials. In the scope of the project, the research outputs are to be displayed in a real-life setting by constructing a demo terraced single-family house, the living lab (LL) located in Ghent (Belgium). The realization of the LL is conducted in a step-wise approach that includes iterative processes for design, description, criteria definition and multi-criteria assessment of building components. The essence of the research lies within the exploratory approach to the state-of-art building envelope and technical systems options for achieving an optimum combination for a circular and bio-based construction. For this purpose, nine preliminary designs (PD) for building envelope are generated, which consist of three basic construction methods: masonry, lightweight steel construction and wood framing construction supplemented with bio-based construction methods like cross-laminated timber (CLT) and massive wood framing. A comparative analysis on the PDs was conducted by utilizing several complementary tools to assess the circularity. This paper focuses on the life cycle assessment (LCA) approach for evaluating the environmental impact of the LL Ghent. The adoption of an LCA methodology was considered critical for providing a comprehensive set of environmental indicators. The PDs were developed at the component level, in particular for the (i) inclined roof, (ii-iii) front and side façade, (iv) internal walls and (v-vi) floors. The assessment was conducted on two levels; component and building level. The options for each component were compared at the first iteration and then, the PDs as an assembly of components were further analyzed. The LCA was based on a functional unit of one square meter of each component and CEN indicators were utilized for impact assessment for a reference study period of 60 years. A total of 54 building components that are composed of 31 distinct materials were evaluated in the study. The results indicate that wood framing construction supplemented with bio-based construction methods performs environmentally better than the masonry or steel-construction options. An analysis on the correlation between the total weight of components and environmental impact was also conducted. It was seen that masonry structures display a high environmental impact and weight, steel structures display low weight but relatively high environmental impact and wooden framing construction display low weight and environmental impact. The study provided valuable outputs in two levels: (i) several improvement options at component level with substitution of materials with critical weight and/or impact per unit, (ii) feedback on environmental performance for the decision-making process during the design phase of a circular single family house.

Keywords: circular and bio-based materials, comparative analysis, life cycle assessment (LCA), living lab

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Authors: Anna Carolina De Paula Sermarini, Rodrigo Flora Calili

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Energy Efficiency (EE) needs investments, new technologies, greater awareness and management on the side of citizens and organizations, and more planning. However, this issue is usually remembered and discussed only in moments of energy crises, and opportunities are missed to take better advantage of the potential of EE in the various sectors of the economy. In addition, there is little concern about the subject among the less favored classes, especially in low-income communities. Accordingly, this article presents suggestions for public policies that aim to increase EE for low-income housing and communities based on international and national experiences. After reviewing the literature, eight policies were listed, and to evaluate them; a multicriteria decision model was developed using the AHP (Analytical Hierarchy Process) and TOPSIS (Technique for Order of Preference by Similarity to Ideal Solution) methods, combined with fuzzy logic. Nine experts analyzed the policies according to 9 criteria: economic impact, social impact, environmental impact, previous experience, the difficulty of implementation, possibility/ease of monitoring and evaluating the policies, expected impact, political risks, and public governance and sustainability of the sector. The results found in order of preference are (i) Incentive program for equipment replacement; (ii) Community awareness program; (iii) EE Program with a greater focus on low income; (iv) Staggered and compulsory certification of social interest buildings; (v) Programs for the expansion of smart metering, energy monitoring and digitalization; (vi) Financing program for construction and retrofitting of houses with the emphasis on EE; (vii) Income tax deduction for investment in EE projects in low-income households made by companies; (viii) White certificates of energy for low-income. First, the policy of equipment substitution has been employed in Brazil and the world and has proven effective in promoting EE. For implementation, efforts are needed from the federal and state governments, which can encourage companies to reduce prices, and provide some type of aid for the purchase of such equipment. In second place is the community awareness program, promoting socio-educational actions on EE concepts and with energy conservation tips. This policy is simple to implement and has already been used by many distribution utilities in Brazil. It can be carried out through bids defined by the government in specific areas, being executed by third sector companies with public and private resources. Third on the list is the proposal to continue the Energy Efficiency Program (which obliges electric energy companies to allocate resources for research in the area) by suggesting the return of the mandatory investment of 60% of the resources in projects for low income. It is also relatively simple to implement, requiring efforts by the federal government to make it mandatory, and on the part of the distributors, compliance is needed. The success of the suggestions depends on changes in the established rules and efforts from the interested parties. For future work, we suggest the development of pilot projects in low-income communities in Brazil and the application of other multicriteria decision support methods to compare the results obtained in this study.

Keywords: energy efficiency, low-income community, public policy, multicriteria decision making

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Authors: Chethana V. Casiker, Jagadishakumara B., Sunil G. M., Chaithra K., M. Soubadra Devy

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A majority of the world’s food crops depends on insects for pollination, among which bees are the most dominant taxon. Bees pollinate vegetables, fruits and oilseeds which are rich in essential micronutrients. Besides being a prerequisite for a nutritionally secure diet, agrarian economies such as India depend heavily on pollination for good yield and quality of the product. As cities all over the world expand rapidly, large tracts of green spaces are being built up. This, along with high usage of agricultural chemicals has reduced floral diversity and shrunk bee habitats. Indeed, pollinator decline is being reported from various parts of the world. Further, the FAO has reported a huge increase in the area of land under cultivation of pollinator-dependent crops. In the light of increasing demand for pollination and disappearing natural habitats, it is critical to understand whether and how urban spaces can support pollinators. To this end, this study investigates the influence of landscape and local habitat quality on bee community dynamics. To capture the dynamics of expanding cityscapes, the study employs a space for time substitution, wherein a transect along the gradient of urbanization substitutes a timeframe of increasing urbanization. This will help understand how pollinators would respond to changes induced by increasing intensity of urbanization in the future. Bengaluru, one of the fastest growing cities of Southern India, is an excellent site to study impacts associated with urbanization. With sites moving away from the Bengaluru’s centre and towards its peripheries, this study captures the changes in bee species diversity and richness along a gradient of urbanization. Bees were sampled under different land use types as well as in different types of vegetation, including plantations, croplands, fallow land, parks, lake embankments, and private gardens. The relationship between bee community metrics and key drivers such as a percentage of built-up area, land use practices, and floral resources was examined. Additionally, data collected using questionnaire interviews were used to understand people’s perceptions towards and level of dependence on pollinators. Our results showed that urban areas are capable of supporting bees. In fact, a greater diversity of bees was recorded in urban sites compared to adjoining rural areas. This suggests that bees are able to seek out patchy resources and survive in small fragments of habitat. Bee abundance and species richness correlated positively with floral abundance and richness, indicating the role of vegetation in providing forage and nesting sites which are crucial to their survival. Bee numbers were seen to decrease with increase in built-up area demonstrating that impervious surfaces could act as deterrents. Findings from this study challenge the popular notion of cities being biodiversity-bare spaces. There is indeed scope for conserving bees in urban landscapes, provided that there are city-scale planning and local initiative. Bee conservation can go hand in hand with efforts such as urban gardening and terrace farming that could help cities urbanize sustainably.

Keywords: bee, landscape ecology, urbanization, urban pollination

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Authors: Atefeh Omidkhah, Mohammadreza Bemanian

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The issue of way-finding earmarks a wide range of literature in architecture and despite the 50 year background of way-finding studies, it still lacks a comprehensive theory for indoor settings. Way-finding has a notable role in emergency evacuation as well. People in the panic situation of a fire emergency need to find the safe egress route correctly and in as minimum time as possible. In this regard the parameters of an appropriate way-finding are mentioned in the evacuation related researches albeit scattered. This study reviews the fire safety related literature to extract a way-finding related framework for architectural purposes of the design of a safe evacuation route. In this regard a research trend review in addition with applied methodological approaches review is conducted. Then by analyzing eight original researches related to way-finding parameters in fire evacuation, main parameters that affect way-finding in emergency situation of a fire incident are extracted and a framework was developed based on them. Results show that the issues related to exit route and emergency evacuation can be chased in task oriented studies of way-finding. This research trend aims to access a high-level framework and in the best condition a theory that has an explanatory capability to define differences in way-finding in indoor/outdoor settings, complex/simple buildings and different building types or transitional spaces. The methodological advances demonstrate the evacuation way-finding researches in line with three approaches that the latter one is the most up-to-date and precise method to research this subject: real actors and hypothetical stimuli as in evacuation experiments, hypothetical actors and stimuli as in agent-based simulations and real actors and semi-real stimuli as in virtual reality environment by adding multi-sensory simulation. Findings on data-mining of 8 sample of original researches in way-finding in evacuation indicate that emergency way-finding design of a building should consider two level of space cognition problems in the time of emergency and performance consequences of them in the built environment. So four major classes of problems in way-finding which are visual information deficiency, confusing layout configuration, improper navigating signage and demographic issues had been defined and discussed as the main parameters that should be provided with solutions in design and interior of a building. In the design phase of complex buildings, which face more reported problem in way-finding, it is important to consider the interior components regarding to the building type of occupancy and behavior of its occupants and determine components that tend to become landmarks and set the architectural features of egress route in line with the directions that they navigate people. Research on topological cognition of environmental and its effect on way-finding task in emergency evacuation is proposed for future.

Keywords: architectural design, egress route, way-finding, fire safety, evacuation

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Authors: Flavia Oliveira de A. M. Cruz, Edison Tostes Faria, Paula Elaine D. Reis

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When the breast is submitted to radiation therapy (RT), the most common effects are pain, skin changes, mobility restrictions, local sensory alteration, and fatigue. These effects, if not managed properly, may reduce the quality of life of cancer patients and may lead to the treatment discontinuation. Therefore, promoting knowledge and guidelines for symptom management remain a high priority for patients and a challenge for health professionals, due to the need to handle side effects in a population with a life-threatening disease. Printed materials are important strategies for supporting educative activities since they help the individual to assimilate and understand the amount of information transmitted. Nurses' behavior can be systematized through the use of an educative manual, which may be effective in promoting information regarding the treatment, self-care and how to control the effects of RT at home. In view of the importance of guaranteeing the validity of the material before its use, the objective of this research was to validate the content and appearance of an educative manual for breast cancer patients undergoing RT. The Theory of Psychometrics was used for the validation process in this descriptive methodological research. A minimum agreement rate (AR) of 80% was considered to guarantee the validity of the material. The data were collected from October to December 2017, by means of two assessments tools, constructed in the form of a Likert scale, with five levels of understanding. These instruments addressed different aspects of the evaluation, in view of two different groups of participants; 17 experts in the theme area of the educative manual, and 12 women that received RT previously to treat breast cancer. The manual was titled 'Orientation Manual: radiation therapy in breast', and was focused on breast cancer patients attended at the Department of Oncology of the Brasília University Hospital (UNACON/HUB). The research project was submitted to the Research Ethics Committee at the School of Health Sciences of the University of Brasília (CAAE: 24592213.1.0000.0030). Only two items of the assessment tool for the experts, one related to the manual's ability to promote behavioral and attitude changes and the other related to the extent of its use for other health services, obtained AR < 80% and were reformulated based on the participants' suggestions and in the literature. All other items were considered appropriate and/or complete appropriate in the three blocks proposed for the experts: objectives - 89%, structure and form - 93%, and relevance - 93%; and good and/or very good in the five blocks of analysis proposed for patients: objectives - 100%, organization - 100%, writing style - 100%, appearance - 100%, and motivation. The appearance and content validation of the educative manual proposed were attended to. The educative manual was considered relevant and pertinent and may contribute to the understanding of the therapeutic process by breast cancer patients during RT, as well as support clinical practice through the nursing consultation.

Keywords: oncology nursing, nursing care, validation studies, educational technology

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Authors: Akanksha Bhatnagar, Sandhya Kortegare, Felice Elefant

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Context: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive cognitive decline and memory loss. The cause of AD is not fully understood, but it is thought to be caused by a combination of genetic, environmental, and lifestyle factors. One of the hallmarks of AD is the loss of neurons in the hippocampus, a brain region that is important for memory and learning. This loss of neurons is thought to be caused by a decrease in histone acetylation, which is a process that regulates gene expression. Research Aim: The research aim of the study was to develop mall molecule compounds that can enhance the activity of Tip60, a histone acetyltransferase that is important for memory and learning. Methodology/Analysis: The researchers used in silico structural modeling and a pharmacophore-based virtual screening approach to design and synthesize small molecule compounds strongly predicted to target and enhance Tip60’s HAT activity. The compounds were then tested in vitro and in vivo to assess their ability to enhance Tip60 activity and rescue cognitive deficits in AD models. Findings: The researchers found that several of the compounds were able to enhance Tip60 activity and rescue cognitive deficits in AD models. The compounds were also developed to cross the blood-brain barrier, which is an important factor for the development of potential AD therapeutics. Theoretical Importance: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Data Collection: The study collected data from a variety of sources, including in vitro assays and animal models. The in vitro assays assessed the ability of compounds to enhance Tip60 activity using histone acetyltransferase (HAT) enzyme assays and chromatin immunoprecipitation assays. Animal models were used to assess the ability of the compounds to rescue cognitive deficits in AD models using a variety of behavioral tests, including locomotor ability, sensory learning, and recognition tasks. The human clinical trials will be used to assess the safety and efficacy of the compounds in humans. Questions: The question addressed by this study was whether Tip60 HAT activators could be developed as therapeutic agents for AD. Conclusions: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Further research is needed to confirm the safety and efficacy of these compounds in humans.

Keywords: Alzheimer's disease, cognition, neuroepigenetics, drug discovery

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Authors: Amina Sa'id Muhammad, Asmau Ishaq Alhassan, Beba Raymond, Fatima Bello

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Severe acute malnutrition (SAM) remains a major killer of children under five years of age. Nigeria has the second highest burden of stunted children in the world, with a national prevalence rate of 32 percent of children under five. An estimated 2 million children in Nigeria suffer from severe acute malnutrition (SAM), and 3.9% of children in northwest Nigeria suffer from SAM, which is significantly higher than the national average of 2.1%. Community-Based Management of Acute Malnutrition (CMAM) has proven to be an effective intervention in the treatment of SAM in children using Ready-to-Use Therapeutic Food (RUTF). Ready-to-use therapeutic food (RUTF) is a key component for the treatment of Severe Acute Malnutrition. It contains all the energy and nutrients required for rapid catch-up growth and used particularly in the treatment of children over 6 months of age with SAM without medical complications. However, almost all RUTFs are currently imported to Nigeria from other countries. Shortages of RUTF due to logistics (shipping costs, delays, donor fatigue etc) and funding issues present a threat to the achievement of the 2030 World Health Assembly (WHA) targets for reducing malnutrition in addition to 2030 SDGs 2 (Zero Hunger), 3 (Good Health and Wellbeing), 12 (Responsible Consumption and Production), and 17 (Partnerships for the Goals), thus undermining its effectiveness in combating malnutrition On the other hand, the availability of human and material resources that will aid local production of RUTF presents an opportunity to fill in the gap in regular RUTF supply. About one thousand Nigerian children die of malnutrition-related causes every day, reaching a total of 361,000 each year. Owing to the high burden of malnutrition in Nigeria, the local production of RUTF is a logical step, that will ensure increased availability, acceptability, access, and efficiency in supply, and at lower costs. Objective(s): The objectives of this study were therefore, to formulate RUTF from locally available resources and to determine its energy and nutrients composition, incommensurate with the standard/commercial RUTF. Methods: Three samples of RUTF were formulated using locally available resources (soya beans, wheat, rice, baobab, brown-sugar, date palm and soya oil); which were subjected to various analysis to determine their energy/proximate composition, vitamin and mineral contents and organoleptic properties were also determined using sensory evaluation. Results: The energy values of the three samples of locally produced RUTF were found to be in conformity with WHO recommendation of ≥ 500 kcal per 100g. The energy values of the three RUTF samples produced in the current study were found to be 563.08, 503.67 and 528.98 kcal respectively. Sample A, B and C had protein content of 13.56% 16.71% and 14.62% respectively, which were higher than that of commercial RUTF (10.9%). Conclusions/recommendations: The locally formulated RUTF samples had energy value of more than 500 kcal per 100g; with an appreciable amount of macro and micro nutrients. The appearance, taste, flavor and general acceptability of the formulated RUTF samples were also commendable.

Keywords: energy, malnutrition, nutrients, RUTF

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Authors: Stephen Bahooshy

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Co-producing services with the people that access them is considered best practice in the United Kingdom, with the Care Act 2014 arguing that people who access services and their carers should be involved in the design, commissioning and delivery of services. Co-production is a way of working with the community, breaking down barriers of access and providing meaningful opportunity for people to engage. Unfortunately, owing to a number of reported factors such as time constraints, practitioner experience and departmental budget restraints, this process is not always followed. In 2019, in a south London borough, d/Deaf people who access services were engaged in the design, commissioning and delivery of an information and advice service that would support their community to access local government services. To do this, sensory impairment social workers and commissioners collaborated to host a series of engagement events with the d/Deaf community. Interpreters were used to enable communication between the commissioners and d/Deaf participants. Initially, the community’s opinions, ideas and requirements were noted. This was then summarized and fed back to the community to ensure accuracy. Subsequently, a service specification was developed which included performance metrics, inclusive of qualitative and quantitative indicators, such as ‘I statements’, whereby participants respond on an adapted Likert scale how much they agree or disagree with a particular statement in relation to their experience of the service. The service specification was reviewed by a smaller group of d/Deaf residents and social workers, to ensure that it met the community’s requirements. The service was then tendered using the local authority’s e-tender process. Bids were evaluated and scored in two parts; part one was by commissioners and social workers and part two was a presentation by prospective providers to an evaluation panel formed of four d/Deaf residents. The internal evaluation panel formed 75% of the overall score, whilst the d/Deaf resident evaluation panel formed 25% of the overall tender score. Co-producing the evaluation panel with social workers and the d/Deaf community meant that commissioners were able to meet the requirements of this community by developing evaluation questions and tools that were easily understood and use by this community. For example, the wording of questions were reviewed and the scoring mechanism consisted of three faces to reflect the d/Deaf residents’ scores instead of traditional numbering. These faces were a happy face, a neutral face and a sad face. By making simple changes to the commissioning and tender evaluation process, d/Deaf people were able to have meaningful involvement in the design and commissioning process for a service that would benefit their community. Co-produced performance metrics means that it is incumbent on the successful provider to continue to engage with people accessing the service and ensure that the feedback is utilized. d/Deaf residents were grateful to have been involved in this process as this was not an opportunity that they had previously been afforded. In recognition of their time, each d/Deaf resident evaluator received a £40 gift voucher, bringing the total cost of this co-production to £160.

Keywords: co-production, community engagement, deaf and hearing impaired, service design

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Authors: Kayla Belanger, Pascale Vigneron, Guy Schlatter, Bernard Devauchelle, Christophe Egles

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A severe injury to a peripheral nerve leads to its degeneration and the loss of sensory and motor function. To this day, there still lacks a more effective alternative to the autograft which has long been considered the gold standard for nerve repair. In order to overcome the numerous drawbacks of the autograft, tissue engineered biomaterials may be effective alternatives. Silk fibroin is a favorable biomaterial due to its many advantageous properties such as its biocompatibility, its biodegradability, and its robust mechanical properties. In this study, bio-mimicking multi-channeled nerve guidance conduits made of aligned nanofibers achieved by electrospinning were functionalized with signaling biomolecules and were tested in vitro and in vivo for nerve regeneration support. Silk fibroin (SF) extracted directly from silkworm cocoons was put in solution at a concentration of 10wt%. Poly(ethylene oxide) (PEO) was added to the resulting SF solution to increase solution viscosity and the following three electrospinning solutions were made: (1) SF/PEO solution, (2) SF/PEO solution with nerve growth factor and ciliary neurotrophic factor, and (3) SF/PEO solution with nerve growth factor and neurotrophin-3. Each of these solutions was electrospun into a multi-layer architecture to obtain mechanically optimized aligned nanofibrous mats. For in vitro studies, aligned fibers were treated to induce β-sheet formation and thoroughly rinsed to eliminate presence of PEO. Each material was tested using rat embryo neuron cultures to evaluate neurite extension and the interaction with bio-functionalized or non-functionalized aligned fibers. For in vivo studies, the mats were rolled into 5mm long multi-, micro-channeled conduits then treated and thoroughly rinsed. The conduits were each subsequently implanted between a severed rat sciatic nerve. The effectiveness of nerve repair over a period of 8 months was extensively evaluated by cross-referencing electrophysiological, histological, and movement analysis results to comprehensively evaluate the progression of nerve repair. In vitro results show a more favorable interaction between growing neurons and bio-functionalized silk fibers compared to pure silk fibers. Neurites can also be seen having extended unidirectionally along the alignment of the nanofibers which confirms a guidance factor for the electrospun material. The in vivo study has produced positive results for the regeneration of the sciatic nerve over the length of the study, showing contrasts between the bio-functionalized material and the non-functionalized material along with comparisons to the experimental control. Nerve regeneration has been evaluated not only by histological analysis, but also by electrophysiological assessment and motion analysis of two separate natural movements. By studying these three components in parallel, the most comprehensive evaluation of nerve repair for the conduit designs can be made which can, therefore, more accurately depict their overall effectiveness. This work was supported by La Région Picardie and FEDER.

Keywords: electrospinning, nerve guidance conduit, peripheral nerve regeneration, silk fibroin

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Authors: Rachana Tank, Donald. M. Lyall, Kristin Flegal, Joey Ward, Jonathan Cavanagh

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Alzheimer’s research UK estimates by 2050, 2 million individuals will be living with Late Onset Alzheimer’s disease (LOAD). However, individuals experience considerable cognitive deficits and brain pathology over decades before reaching clinically diagnosable LOAD and studies have utilised gene candidate studies such as genome wide association studies (GWAS) and polygenic risk (PGR) scores to identify high risk individuals and potential pathways. This investigation aims to determine whether high genetic risk of LOAD is associated with worse brain MRI and cognitive performance in healthy older adults within the UK Biobank cohort. Previous studies investigating associations of PGR for LOAD and measures of MRI or cognitive functioning have focused on specific aspects of hippocampal structure, in relatively small sample sizes and with poor ‘controlling’ for confounders such as smoking. Both the sample size of this study and the discovery GWAS sample are bigger than previous studies to our knowledge. Genetic interaction between loci showing largest effects in GWAS have not been extensively studied and it is known that APOE e4 poses the largest genetic risk of LOAD with potential gene-gene and gene-environment interactions of e4, for this reason we  also analyse genetic interactions of PGR with the APOE e4 genotype. High genetic loading based on a polygenic risk score of 21 SNPs for LOAD is associated with worse brain MRI and cognitive outcomes in healthy individuals within the UK Biobank cohort. Summary statistics from Kunkle et al., GWAS meta-analyses (case: n=30,344, control: n=52,427) will be used to create polygenic risk scores based on 21 SNPs and analyses will be carried out in N=37,000 participants in the UK Biobank. This will be the largest study to date investigating PGR of LOAD in relation to MRI. MRI outcome measures include WM tracts, structural volumes. Cognitive function measures include reaction time, pairs matching, trail making, digit symbol substitution and prospective memory. Interaction of the APOE e4 alleles and PGR will be analysed by including APOE status as an interaction term coded as either 0, 1 or 2 e4 alleles. Models will be adjusted partially for adjusted for age, BMI, sex, genotyping chip, smoking, depression and social deprivation. Preliminary results suggest PGR score for LOAD is associated with decreased hippocampal volumes including hippocampal body (standardised beta = -0.04, P = 0.022) and tail (standardised beta = -0.037, P = 0.030), but not with hippocampal head. There were also associations of genetic risk with decreased cognitive performance including fluid intelligence (standardised beta = -0.08, P<0.01) and reaction time (standardised beta = 2.04, P<0.01). No genetic interactions were found between APOE e4 dose and PGR score for MRI or cognitive measures. The generalisability of these results is limited by selection bias within the UK Biobank as participants are less likely to be obese, smoke, be socioeconomically deprived and have fewer self-reported health conditions when compared to the general population. Lack of a unified approach or standardised method for calculating genetic risk scores may also be a limitation of these analyses. Further discussion and results are pending.

Keywords: Alzheimer's dementia, cognition, polygenic risk, MRI

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Authors: A. M. Plante, F. O’Halloran, A. L. McCarthy

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By 2050 it is projected that 2 billion of the global population will be more than 60 years old. Older adults have unique dietary requirements and aging is associated with physiological changes that affect appetite, sensory perception, metabolism, and digestion. Therefore, it is essential that foods recommended and designed for older adults promote healthy aging. To assess cheese as a functional food for the elderly, a range of commercial cheese products were selected and compared for their antioxidant properties. Cheese from various milk sources (bovine, goats, sheep) with different textures and fat content, including cheddar, feta, goats, brie, roquefort, halloumi, wensleydale and gouda, were initially digested with two different simulated in vitro gastrointestinal digestion (SGID) models. One SGID model represented a validated in vitro adult digestion system and the second model, an elderly SGID, was designed to consider the physiological changes associated with aging. The antioxidant potential of all cheese digestates was investigated using in vitro chemical-based antioxidant assays, (2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP) and total phenolic content (TPC)). All adult model digestates had high antioxidant activity across both DPPH ( > 70%) and FRAP ( > 700 µM Fe²⁺/kg.fw) assays. Following in vitro digestion using the elderly SGID model, full-fat red cheddar, low-fat white cheddar, roquefort, halloumi, wensleydale, and gouda digestates had significantly lower (p ≤ 0.05) DPPH radical scavenging properties compared to the adult model digestates. Full-fat white cheddar had higher DPPH radical scavenging activity following elderly SGID digestion compared to the adult model digestate, but the difference was not significant. All other cheese digestates from the elderly model were comparable to the digestates from the adult model in terms of radical scavenging activity. The FRAP of all elderly digestates were significantly lower (p ≤ 0.05) compared to the adult digestates. Goats cheese was significantly higher (p ≤ 0.05) in FRAP (718 µM Fe²/kg.fw) compared to all other digestates in the elderly model. TPC levels in the soft cheeses (feta, goats) and low-fat cheeses (red cheddar, white cheddar) were significantly lower (p ≤ 0.05) in the elderly digestates compared to the adult digestates. There was no significant difference in TPC levels, between the elderly and adult model for full-fat cheddar (red, white), roquefort, wensleydale, gouda, and brie digestates. Halloumi cheese was the only cheese that was significantly higher in TPC levels following elderly digestion compared to adult digestates. Low fat red cheddar had significantly higher (p ≤ 0.05) TPC levels compared to all other digestates for both adult and elderly digestive systems. Findings from this study demonstrate that aging has an impact on the bioactivity of cheese, as antioxidant activity and TPC levels were lower, following in vitro elderly digestion compared to the adult model. For older adults, soft cheese, particularly goats cheese, was associated with high radical scavenging and reducing power, while roquefort cheese had low antioxidant activity. Also, elderly digestates of halloumi and low-fat red cheddar were associated with high TPC levels. Cheese has potential as a functional food for the elderly, however, bioactivity can vary depending on the cheese matrix. Funding for this research was provided by the RISAM Scholarship Scheme, Cork Institute of Technology, Ireland.

Keywords: antioxidants, cheese, in-vitro digestion, older adults

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Authors: Jelena Filipovic, Marija Bodroza-Solarov, Milenko Kosutic, Nebojsa Novkovic, Vladimir Filipovic, Vesna Vucurovic

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Spelt wheat is suitable raw material for extruded products such as pasta, special types of bread and other products of altered nutritional characteristics compared to conventional wheat products. During the process of extrusion, spelt is exposed to high temperature and high pressure, during which raw material is also mechanically treated by shear forces. Spelt wheat is growing without the use of pesticides in harsh ecological conditions and in marginal areas of cultivation. So it can be used for organic and health safe food. Pasta is the most popular foodstuff; its consumption has been observed to rise. Pasta quality depends mainly on the properties of flour raw materials, especially protein content and its quality but starch properties are of a lesser importance. Pasta is characterized by significant amounts of complex carbohydrates, low sodium, total fat fiber, minerals, and essential fatty acids and its nutritional value can be improved with additional functional component. Over the past few decades, wheat pasta has been successfully formulated using different ingredients in pasta to cater health-conscious consumers who prefer having a product rich in protein, healthy lipids and other health benefits. Flaxseed flour is used in the production of bakery and pasta products that have properties of functional foods. However, it should be taken into account that food products retain the technological and sensory quality despite the added flax seed. Flaxseed contains important substances in its composition such as vitamins and minerals elements, and it is also an excellent source of fiber and one of the best sources of ω-3 fatty acids and lignin. In this paper, the quality and identification of spelt extruded product with the addition of flax seed, which is positively contributing to the nutritive and technology changes of the product, is investigated. ω-3 fatty acids are polyunsaturated essential fatty acids, and they must be taken with food to satisfy the recommended daily intake. Flaxseed flour is added in the quantity of 10/100 g of sample and 20/100 g of sample on farina. It is shown that the presence of ω-3 fatty acids in pasta can be clearly distinguished from other fatty acids by gas chromatography with mass spectrometry. Addition of flax seed flour influence chemical content of pasta. The addition of flax seed flour in spelt pasta in the quantities of 20g/100 g significantly increases the share of ω-3 fatty acids, which results in improved ratio of ω-6/ω-3 1:2.4 and completely satisfies minimum daily needs of ω-3 essential fatty acids (3.8 g/100 g) recommended by FDA. Flex flour influenced the pasta quality by increasing of hardness (2377.8 ± 13.3; 2874.5 ± 7.4; 3076.3 ± 5.9) and work of shear (102.6 ± 11.4; 150.8 ± 11.3; 165.0 ± 18.9) and increasing of adhesiveness (11.8 ± 20.6; 9.,98 ± 0.12; 7.1 ± 12.5) of the final product. Presented data point at good indicators of technological quality of spelt pasta with flax seed and that GC-MS analysis can be used in the quality control for flax seed identification. Acknowledgment: The research was financed by the Ministry of Education and Science of the Republic of Serbia (Project No. III 46005).

Keywords: GC-MS analysis, ω-3 fatty acids, flex seed, spelt wheat, daily needs

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Authors: Atefeh Omidkhah Kharashtomi, Rasoul Hedayat Nejad, Saeed Bakhtiyari

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Circulation paths and indoor connection network of the building play an important role both in the daily operation of the building and during evacuation in emergency situations. The degree of legibility of the paths for navigation inside the building has a deep connection with the perceptive and cognitive system of human, and the way the surrounding environment is being perceived. Human perception of the space is based on the sensory systems in a three-dimensional environment, and non-linearly, so it is necessary to avoid reducing its representations in architectural design as a two-dimensional and linear issue. Today, the advances in the field of virtual reality (VR) technology have led to various applications, and architecture and building science can benefit greatly from these capabilities. Especially in cases where the design solution requires a detailed and complete understanding of the human perception of the environment and the behavioral response, special attention to VR technologies could be a priority. Way-finding in the indoor circulation network is a proper example for such application. Success in way-finding could be achieved if human perception of the route and the behavioral reaction have been considered in advance and reflected in the architectural design. This paper discusses the VR technology applications for the way-finding improvements in indoor engineering of the building. In a systematic review, with a database consisting of numerous studies, firstly, four categories for VR applications for circulation way-finding have been identified: 1) data collection of key parameters, 2) comparison of the effect of each parameter in virtual environment versus real world (in order to improve the design), 3) comparing experiment results in the application of different VR devices/ methods with each other or with the results of building simulation, and 4) training and planning. Since the costs of technical equipment and knowledge required to use VR tools lead to the limitation of its use for all design projects, priority buildings for the use of VR during design are introduced based on case-studies analysis. The results indicate that VR technology provides opportunities for designers to solve complex buildings design challenges in an effective and efficient manner. Then environmental parameters and the architecture of the circulation routes (indicators such as route configuration, topology, signs, structural and non-structural components, etc.) and the characteristics of each (metrics such as dimensions, proportions, color, transparency, texture, etc.) are classified for the VR way-finding experiments. Then, according to human behavior and reaction in the movement-related issues, the necessity of scenario-based and experiment design for using VR technology to improve the design and receive feedback from the test participants has been described. The parameters related to the scenario design are presented in a flowchart in the form of test design, data determination and interpretation, recording results, analysis, errors, validation and reporting. Also, the experiment environment design is discussed for equipment selection according to the scenario, parameters under study as well as creating the sense of illusion in the terms of place illusion, plausibility and illusion of body ownership.

Keywords: virtual reality (VR), way-finding, indoor, circulation, design

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Authors: Bernice Jeanne Lottering, Yi-Wen Lin

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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.

Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception

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Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

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Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

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