Search results for: motor coordination

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: Carolyn Hatch, Laurent Simon

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Urban mobility and the transportation industry are undergoing a transformation, shifting from an auto production-consumption model that has dominated since the early 20th century towards new forms of personal and shared multi-modality [1]. This is shaped by key forces such as climate change, which has induced a shift in production and consumption patterns and efforts to decarbonize and improve transport services through, for instance, the integration of vehicle automation, electrification and mobility sharing [2]. Advanced innovation practices and platforms for experimentation and validation of new mobility products and services that are increasingly complex and multi-stakeholder-oriented are shaping this new world of mobility. Transportation hubs – such as airports - are emblematic of these disruptive forces playing out in the mobility industry. Airports are emerging as the core of innovation ecosystems on and around contemporary mobility issues, and increasingly recognized as complex public/private nodes operating in many societal dimensions [3,4]. These include urban development, sustainability transitions, digital experimentation, customer experience, infrastructure development and data exploitation (for instance, airports generate massive and often untapped data flows, with significant potential for use, commercialization and social benefit). Yet airport innovation practices have not been well documented in the innovation literature. This paper addresses this gap by proposing a model of airport innovation that aims to equip airport stakeholders to respond to these new and complex innovation needs in practice. The methodology involves: 1 – a literature review bringing together key research and theory on airport innovation management, open innovation and innovation ecosystems in order to evaluate airport practices through an innovation lens; 2 – an international benchmarking of leading airports and their innovation practices, including such examples as Aéroports de Paris, Schipol in Amsterdam, Changi in Singapore, and others; and 3 – semi-structured interviews with airport managers on key aspects of organizational practice, facilitated through a close partnership with the Airport Council International (ACI), a major stakeholder in this research project. Preliminary results find that the most successful airports are those that have shifted to a multi-stakeholder, platform ecosystem model of innovation. The recent entrance of new actors in airports (Google, Amazon, Accor, Vinci, Airbnb and others) have forced the opening of organizational boundaries to share and exchange knowledge with a broader set of ecosystem players. This has also led to new forms of governance and intermediation by airport actors to connect complex, highly distributed knowledge, along with new kinds of inter-organizational collaboration, co-creation and collective ideation processes. Leading airports in the case study have demonstrated a unique capacity to force traditionally siloed activities to “think together”, “explore together” and “act together”, to share data, contribute expertise and pioneer new governance approaches and collaborative practices. In so doing, they have successfully integrated these many disruptive change pathways and forced their implementation and coordination towards innovative mobility outcomes, with positive societal, environmental and economic impacts. This research has implications for: 1 - innovation theory, 2 - urban and transport policy, and 3 - organizational practice - within the mobility industry and across the economy.

Keywords: airport management, ecosystem, innovation, mobility, platform, transport hubs

Procedia PDF Downloads 181

Authors: Bryan Jenkins

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Introduction: The expansion of irrigation in the Canterbury region has led to the sustainability limits being reached for water availability and the cumulative effects of land use intensification. The institutional framework under New Zealand’s Resource Management Act was found to be an inadequate basis for managing water at sustainability limits. An alternative paradigm for water management was developed based on collaborative governance and nested adaptive systems. This led to the formulation and implementation of the Canterbury Water Management Strategy. Methods: The nested adaptive system approach was adopted. Sustainability issues were identified at multiple spatial and time scales and defined potential failure pathways for the water resource system. These included biophysical and socio-economic issues such as water availability, cumulative effects on water quality due to land use intensification, projected changes in climate, public health, institutional arrangements, economic outcomes and externalities, and, social effects of changing technology. This led to the derivation of sustainability strategies to address these failure pathways. The collaborative governance approach involved stakeholder participation and community engagement to decide on a regional strategy; regional and zone committees of community and rūnanga (Māori groups) members to develop implementation programmes for the strategy; and, farmer collectives for operational management. Findings: The strategy identified improvements in the efficiency of use of water already allocated was more effective in improving water availability than a reliance on increased storage alone. New forms of storage with less adverse impacts were introduced, such as managed aquifer recharge and off-river storage. Reductions of nutrients from land use intensification by improving management practices has been a priority. Solutions packages for addressing the degradation of vulnerable lakes and rivers have been prepared. Biodiversity enhancement projects have been initiated. Greater involvement of Māori has led to the incorporation of kaitiakitanga (resource stewardship) into implementation programmes. Emerging issues are the need for improved integration of surface water and groundwater interactions, increased use of modelling of water and financial outcomes to guide decision making, and, equity in allocation among existing users as well as between existing and future users. Conclusions: However, sustainability analysis indicates that the proposed levels of management interventions are not sufficient to achieve community targets for water management. There is a need for more proactive recovery and rehabilitation measures. Managing to environmental limits is not sufficient, rather managing adaptive cycles is needed. Better measurement and management of water use efficiency is required. Proposed implementation packages are not sufficient to deliver desired water quality outcomes. Greater attention to targets important to environmental and recreational interests is needed to maintain trust in the collaborative process. Implementation programmes don’t adequately address climate change adaptations and greenhouse gas mitigation. Affordability is a constraint on adaptive capacity of farmers and communities. More funding mechanisms are required to implement proactive measures. The legislative and institutional framework needs to be changed to incorporate water framework legislation, regional sustainability strategies and water infrastructure coordination.

Keywords: collaborative governance, irrigation management, nested adaptive systems, sustainable water management

Procedia PDF Downloads 158

Authors: Ali Ahmed Ali Al-Juboori, H. Zhu, D. Wexler, H. Li, C. Lu, J. McLeod, S. Pannila, J. Barnes

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A number of studies have focused on the formation mechanics of white etching layer and its origin in the railway operation. Until recently, the following hypotheses consider the precise mechanics of WELs formation: (i) WELs are the result of thermal process caused by wheel slip; (ii) WELs are mechanically induced by severe plastic deformation; (iii) WELs are caused by a combination of thermo-mechanical process. The mechanisms discussed above lead to occurrence of white etching layers on the area of wheel and rail contact. This is because the contact patch which is the active point of the wheel on the rail is exposed to highest shear stresses which result in localised severe plastic deformation; and highest rate of heat caused by wheel slipe during excessive traction or braking effort. However, if the WELs are not on the running band area, it would suggest that there is another cause of WELs formation. In railway system, particularly electrified railway, arcing phenomenon has been occurring more often and regularly on the rails. In electrified railway, the current is delivered to the train traction motor via contact wires and then returned to the station via the contact between the wheel and the rail. If the contact between the wheel and the rail is temporarily losing, due to dynamic vibration, entrapped dirt or water, lubricant effect or oxidation occurrences, high current can jump through the gap and results in arcing. The other resources of arcing also include the wheel passage the insulated joint and lightning on a train during bad weather. During the arcing, an extensive heat is generated and speared over a large area of top surface of rail. Thus, arcing is considered another heat source in the rail head (rather than wheel slipe) that results in microstructural changes and white etching layer formation. A head hardened (HH) rail steel, cut from a curved rail truck was used for the investigation. Samples were sectioned from a depth of 10 mm below the rail surface, where the material is considered to be still within the hardened layer but away from any microstructural changes on the top surface layer caused by train passage. These samples were subjected to electrical discharges by using Gas Tungsten Arc Welding (GTAW) machine. The arc current was controlled and moved along the samples surface in the direction of travel, as indicated by an arrow. Five different conditions were applied on the surface of the samples. Samples containing pre-existed WELs, taken from ex-service rail surface, were also considered in this study for comparison. Both simulated and ex-serviced WELs were characterised by advanced methods including SEM, TEM, TKD, EDS, XRD. Samples for TEM and TKFD were prepared by Focused Ion Beam (FIB) milling. The results showed that both simulated WELs by electrical arcing and ex-service WEL comprise similar microstructure. Brown etching layer was found with WELs and likely induced by a concurrent tempering process. This study provided a clear understanding of new formation mechanics of WELs which contributes to track maintenance procedure.

Keywords: white etching layer, arcing, brown etching layer, material characterisation

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Authors: Reham Khalaf-Nazzal, Imad Dweikat, Paula Gimenez, Iker Oyenarte, Alfonso Martinez-Cruz, Domonik Muller

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Metal cation transport mediator (CNNM) gene family comprises 4 isoforms that are expressed in various human tissues. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a DUF21 transmembrane domain, a ‘Bateman module’ and a C-terminal cNMP-binding domain. Mutations in CNNM2 cause familial dominant hypomagnesaemia. Growing evidence highlights the role of CNNM2 in neurodevelopment. Mutations in CNNM2 have been implicated in epilepsy, intellectual disability, schizophrenia, and others. In the present study, we aim to elucidate the function of CNNM2 in the developing brain. Thus, we present the genetic origin of symptoms in two family cohorts. In the first family, three siblings of a consanguineous Palestinian family in which parents are first cousins, and consanguinity ran over several generations, presented a varying degree of intellectual disability, cone-rod dystrophy, and autism spectrum disorder. Exome sequencing and segregation analysis revealed the presence of homozygous pathogenic mutation in the CNNM2 gene, the parents were heterozygous for that gene mutation. Magnesium blood levels were normal in the three children and their parents in several measurements. They had no symptoms of hypomagnesemia. The CNNM2 mutation in this family was found to locate in the CBS1 domain of the CNNM2 protein. The crystal structure of the mutated CNNM2 protein was not significantly different from the wild-type protein, and the binding of AMP or MgATP was not dramatically affected. This suggests that the CBS1 domain could be involved in pure neurodevelopmental functions independent of its magnesium-handling role, and this mutation could have affected a protein partner binding or other functions in this protein. In the second family, another autosomal dominant CNNM2 mutation was found to run in a large family with multiple individuals over three generations. All affected family members had hypomagnesemia and hypermagnesuria. Oral supplementation of magnesium did not increase the levels of magnesium in serum significantly. Some affected members of this family have defects in fine motor skills such as dyslexia and dyslalia. The detected mutation is located in the N-terminal part, which contains a signal peptide thought to be involved in the sorting and routing of the protein. In this project, we describe heterogenous clinical phenotypes related to CNNM2 mutations and protein functions. In the first family, and up to the authors’ knowledge, we report for the first time the involvement of CNNM2 in retinal photoreceptor development and function. In addition, we report the presence of a neurophenotype independent of magnesium status related to the CNNM2 protein mutation. Taking into account the different modes of inheritance and the different positions of the mutations within CNNM2 and its different structural and functional domains, it is likely that CNNM2 might be involved in a wide spectrum of neuropsychiatric comorbidities with considerable varying phenotypes.

Keywords: magnesium transport, autosomal recessive, autism, neurodevelopment, CBS domain

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Authors: Nikhilesh Singh, Shishir Gaur, Anitha K. Sharma

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Climate change and anthropogenic stress have severely affected ecosystems all over the globe. Indian rivers are under immense pressure, facing challenges like pollution, encroachment, extreme fluctuation in the flow regime, local ignorance and lack of coordination between stakeholders. To counter all these issues a holistic river rejuvenation plan is needed that tests, innovates and implements sustainable solutions in the river space for sustainable river management. Smart Laboratory for Clean Rivers (SLCR) an Indo-Danish collaboration project, provides a living lab setup that brings all the stakeholders (government agencies, academic and industrial partners and locals) together to engage, learn, co-creating and experiment for a clean and sustainable river that last for ages. Just like every mega project requires piloting, SLCR has opted for a small catchment of the Varuna River, located in the Middle Ganga Basin in India. Considering the integrated approach of river rejuvenation, SLCR embraces various techniques and upgrades for rejuvenation. Likely, maintaining flow in the channel in the lean period, Managed Aquifer Recharge (MAR) is a proven technology. In SLCR, Floa-TEM high-resolution lithological data is used in MAR models to have better decision-making for MAR structures nearby of the river to enhance the river aquifer exchanges. Furthermore, the concerns of quality in the river are a big issue. A city like Varanasi which is located in the last stretch of the river, generates almost 260 MLD of domestic waste in the catchment. The existing STP system is working at full efficiency. Instead of installing a new STP for the future, SLCR is upgrading those STPs with an IoT-based system that optimizes according to the nutrient load and energy consumption. SLCR also advocate nature-based solutions like a reed bed for the drains having less flow. In search of micropollutants, SLCR uses fingerprint analysis involves employing advanced techniques like chromatography and mass spectrometry to create unique chemical profiles. However, rejuvenation attempts cannot be possible without involving the entire catchment. A holistic water management plan that includes storm management, water harvesting structure to efficiently manage the flow of water in the catchment and installation of several buffer zones to restrict pollutants entering into the river. Similarly, carbon (emission and sequestration) is also an important parameter for the catchment. By adopting eco-friendly practices, a ripple effect positively influences the catchment's water dynamics and aids in the revival of river systems. SLCR has adopted 4 villages to make them carbon-neutral and water-positive. Moreover, for the 24×7 monitoring of the river and the catchment, robust IoT devices are going to be installed to observe, river and groundwater quality, groundwater level, river discharge and carbon emission in the catchment and ultimately provide fuel for the data analytics. In its completion, SLCR will provide a river restoration manual, which will strategise the detailed plan and way of implementation for stakeholders. Lastly, the entire process is planned in such a way that will be managed by local administrations and stakeholders equipped with capacity-building activity. This holistic approach makes SLCR unique in the field of river rejuvenation.

Keywords: sustainable management, holistic approach, living lab, integrated river management

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Authors: Koteswara Rao Pagolu, Raghava Rao Tamanam

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The present study was aimed to find out the prevalence of DD's in Visakhapatnam, one of the north coastal districts of Andhra Pradesh, India during a span of five years. A cross-sectional investigation was held at District early intervention center (DEIC), Visakhapatnam from 2016 to 2020. To identify the pattern and trend of different DD's including seasonal variations, a retrospective analysis of the health center's inpatient database for the past 5 years was done. Male and female children aged 2 months-18 years are included in the study with the prior permission of the concerned medical officer. The screening tool developed by the Ministry of health and family welfare, India, was used for the study. Among 26,423 cases, children with birth defects are 962, 2229 with deficiencies, 7516 with diseases, and 15716 with disabilities were admitted during the study period. From birth defects, congenital deafness occurred in large numbers with 22.66%, and neural tube defect observed in a small number of cases with 0.83% during the period. From the side of deficiencies, severe acute malnutrition has mostly occurred (66.80 %) and a small number of children were affected with goiter (1.70%). Among the diseases, dental carriers (67.97%) are mostly found and these cases were at peak during the years 2016 and 2019. From disabilities, children with vision impairment (20.55%) have mostly approached the center. Over the past 5 years, the admission rate of down's syndrome and congenital deafness cases showed a rising trend up to 2019 and then declined. Hearing impairment, motor delay, and learning disorder showed a steep rise and gradual decline trend, whereas severe anemia, vitamin-D deficiency, otitis media, reactive airway disease, and attention deficit hyperactivity disorder showed a declining trend. However, congenital heart diseases, dental caries, and vision impairment admission rates showed a zigzag pattern over the past 5 years. This center had inadequate diagnostic facilities related to genetic disease management. For advanced confirmation, the cases are referred to a district government hospital or private diagnostic laboratories in the city for genetic tests. Information regarding the overall burden and pattern of admissions in the health center is obtained by the review of DEIC records. Through this study, it is observed that the incidence of birth defects, as well as genetic disease burden, is high in the Visakhapatnam district. Hence there is a need for strengthening of management services for these diseases in this region.

Keywords: child health screening, developmental delays, district early intervention center, genetic disease management, infrastructural facility, Visakhapatnam district

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Authors: Emma Castiglioni, Nigel Scrutton, Derren Heyes, Alistair Fielding

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By using light as trigger, it is possible to study many biological processes, such as the activity of genes, proteins, and other molecules, with precise spatiotemporal control. Caged compounds, where biologically active molecules are generated from an inert precursor upon laser photolysis, offer the potential to initiate such biological reactions with high temporal resolution. As light acts as the trigger for cleaving the protecting group, the ‘caging’ technique provides a number of advantages as it can be intracellular, rapid and controlled in a quantitative manner. We are developing caging strategies to study the catalytic cycle of a number of enzyme systems, such as nitric oxide synthase and ethanolamine ammonia lyase. These include the use of caged substrates, caged electrons and the possibility of caging the enzyme itself. In addition, we are developing a novel freeze-quench instrument to study these reactions, which combines rapid mixing and flashing capabilities. Reaction intermediates will be trapped at low temperatures and will be analysed by using electron paramagnetic resonance (EPR) spectroscopy to identify the involvement of any radical species during catalysis. EPR techniques typically require relatively long measurement times and very often, low temperatures to fully characterise these short-lived species. Therefore, common rapid mixing techniques, such as stopped-flow or quench-flow are not directly suitable. However, the combination of rapid freeze-quench (RFQ) followed by EPR analysis provides the ideal approach to kinetically trap and spectroscopically characterise these transient radical species. In a typical RFQ experiment, two reagent solutions are delivered to the mixer via two syringes driven by a pneumatic actuator or stepper motor. The new mixed solution is then sprayed into a cryogenic liquid or surface, and the frozen sample is then collected and packed into an EPR tube for analysis. The earliest RFQ instrument consisted of a hydraulic ram unit as a drive unit with direct spraying of the sample into a cryogenic liquid (nitrogen, isopentane or petroleum). Improvements to the RFQ technique have arisen from the design of new mixers in order to reduce both the volume and the mixing time. In addition, the cryogenic isopentane bath has been coupled to a filtering system or replaced by spraying the solution onto a surface that is frozen via thermal conductivity with a cryogenic liquid. In our work, we are developing a novel RFQ instrument which combines the freeze-quench technology with flashing capabilities to enable the studies of both thermally-activated and light-activated biological reactions. This instrument also uses a new rotating plate design based on magnetic couplings and removes the need for mechanical motorised rotation, which can otherwise be problematic at cryogenic temperatures.

Keywords: caged compounds, freeze-quench apparatus, photolysis, radicals

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Authors: Sarah M. Schoellhammer, Stephen Gibb

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Bureaucracy, in particular, its core element, a formal and stable hierarchy of authority, is proving less and less appropriate under the conditions of today’s knowledge economy. Centralization and formalization were consistently found to hinder innovation, undermining cross-functional collaboration, personal responsibility, and flexibility. With its focus on systematical planning, controlling and monitoring the development of new or improved solutions for customers, even innovation management as a discipline is to a significant extent based on a mechanistic understanding of organizations. The most important drivers of innovation, human creativity, and initiative, however, can be more hindered than supported by central elements of classic innovation management, such as predefined innovation strategies, rigid stage gate processes, and decisions made in management gate meetings. Heterarchy, as an alternative network form of organization, is essentially characterized by its dynamic influence structures, whereby the biggest influence is allocated by the collective to the persons perceived the most competent in a certain issue. Theoretical arguments that the non-hierarchical concept better supports innovation than bureaucracy have been supported by empirical research. These prior studies either focus on the structure and general functioning of non-hierarchical organizations or on their innovativeness, that means innovation as an outcome. Complementing classic innovation management approaches, this work aims to shed light on how innovations are initiated and realized in heterarchies in order to identify alternative solutions practiced under conditions of the post-bureaucratic organization. Through an initial individual case study, which is part of a multiple-case project, the innovation practices of an innovative and highly heterarchical medium-sized company in the German fire engineering industry are investigated. In a pragmatic mixed methods approach media resonance, company documents, and workspace architecture are analyzed, in addition to qualitative interviews with the CEO and employees of the case company, as well as a quantitative survey aiming to characterize the company along five scaled dimensions of a heterarchy spectrum. The analysis reveals some similarities and striking differences to approaches suggested by classic innovation management. The studied heterarchy has no predefined innovation strategy guiding new product and service development. Instead, strategic direction is provided by the CEO, described as visionary and creative. Procedures for innovation are hardly formalized, with new product ideas being evaluated on the basis of gut feeling and flexible, rather general criteria. Employees still being hesitant to take responsibility and make decisions, hierarchical influence is still prominent. Described as open-minded and collaborative, culture and leadership were found largely congruent with definitions of innovation culture. Overall, innovation efforts at the case company tend to be coordinated more through cultural than through formal organizational mechanisms. To better enable innovation in mainstream organizations, responsible practitioners are recommended not to limit changes to reducing the central elements of the bureaucratic organization, formalization, and centralization. The freedoms this entails need to be sustained through cultural coordination mechanisms, with personal initiative and responsibility by employees as well as common innovation-supportive norms and values. These allow to integrate diverse competencies, opinions, and activities and, thus, to guide innovation efforts.

Keywords: bureaucracy, heterarchy, innovation management, values

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Authors: S. Raghibdoust, E. Kamari

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Research show that reduced functional hearing has a detrimental influence on the ability of an individual to establish proper phonological representations of words, since the phonological representations are claimed to mediate the conceptual processing of written words. Word processing efficiency is expected to decrease with a decrease in functional hearing. In other words, it is predicted that hearing individuals would be more capable of word processing than individuals with hearing loss, as their functional hearing works normally. Studies also demonstrate that the quality of the functional hearing affects reading comprehension via its effect on their word processing skills. In other words, better hearing facilitates the development of phonological knowledge, and can promote enhanced strategies for the recognition of written words, which in turn positively affect higher-order processes underlying reading comprehension. The aims of this study were to investigate and compare the effect of deafness on the participants’ abilities to process written words at the lexical and sentence levels through using two online and one offline reading comprehension tests. The performance of a group of 8 deaf male students (ages 8-12) was compared with that of a control group of normal hearing male students. All the participants had normal IQ and visual status, and came from an average socioeconomic background. None were diagnosed with a particular learning or motor disability. The language spoken in the homes of all participants was Persian. Two tests of word processing were developed and presented to the participants using OpenSesame software, in order to measure the speed and accuracy of their performance at the two perceptual and conceptual levels. In the third offline test of reading comprehension which comprised of semantically plausible and semantically implausible subject relative clauses, the participants had to select the correct answer out of two choices. The data derived from the statistical analysis using SPSS software indicated that hearing and deaf participants had a similar word processing performance both in terms of speed and accuracy of their responses. The results also showed that there was no significant difference between the performance of the deaf and hearing participants in comprehending semantically plausible sentences (p > 0/05). However, a significant difference between the performances of the two groups was observed with respect to their comprehension of semantically implausible sentences (p < 0/05). In sum, the findings revealed that the seriously impoverished sentence reading ability characterizing the profound deaf subjects of the present research, exhibited their reliance on reading strategies that are based on insufficient or deviant structural knowledge, in particular in processing semantically implausible sentences, rather than a failure to efficiently process written words at the lexical level. This conclusion, of course, does not mean to say that deaf individuals may never experience deficits at the word processing level, deficits that impede their understanding of written texts. However, as stated in previous researches, it sounds reasonable to assume that the more deaf individuals get familiar with written words, the better they can recognize them, despite having a profound phonological weakness.

Keywords: deafness, reading comprehension, reading strategy, word processing, subject and object relative sentences

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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: Nikitha Francis, Anjana Hoode, Vinitha George, Jayashree S. Bhat

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The interaction between cognition and language, referred as cognitive-communication, is very intricate, involving several mental processes such as perception, memory, attention, lexical retrieval, decision making, motor planning, self-monitoring and knowledge. Cognitive-communication disorders are difficulties in communicative competencies that result from underlying cognitive impairments of attention, memory, organization, information processing, problem solving, and executive functions. Traumatic brain injury (TBI) is an acquired, non - progressive condition, resulting in distinct deficits of cognitive communication abilities such as naming, word-finding, self-monitoring, auditory recognition, attention, perception and memory. Cognitive-communication intervention in TBI is individualized, in order to enhance the person’s ability to process and interpret information for better functioning in their family and community life. The present case report illustrates the cognitive-communicative behaviors and the intervention outcomes of an adult with TBI, who was brought to the Department of Audiology and Speech Language Pathology, with cognitive and communicative disturbances, consequent to road traffic accident. On a detailed assessment, she showed naming deficits along with perseverations and had severe difficulty in recalling the details of the accident, her house address, places she had visited earlier, names of people known to her, as well as the activities she did each day, leading to severe breakdowns in her communicative abilities. She had difficulty in initiating, maintaining and following a conversation. She also lacked orientation to time and place. On administration of the Manipal Manual of Cognitive Linguistic Abilities (MMCLA), she exhibited poor performance on tasks related to visual and auditory perception, short term memory, working memory and executive functions. She attended 20 sessions of cognitive-communication intervention which followed a domain-general, adaptive training paradigm, with tasks relevant to everyday cognitive-communication skills. Compensatory strategies such as maintaining a dairy with reminders of her daily routine, names of people, date, time and place was also recommended. MMCLA was re-administered and her performance in the tasks showed significant improvements. Occurrence of perseverations and word retrieval difficulties reduced. She developed interests to initiate her day-to-day activities at home independently, as well as involve herself in conversations with her family members. Though she lacked awareness about her deficits, she actively involved herself in all the therapy activities. Rehabilitation of moderate to severe head injury patients can be done effectively through a holistic cognitive retraining with a focus on different cognitive-linguistic domains. Selection of goals and activities should have relevance to the functional needs of each individual with TBI, as highlighted in the present case report.

Keywords: cognitive-communication, executive functions, memory, traumatic brain injury

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Authors: Tom S. Owens, Tom A. Calverley, Benjamin S. Stacey, Christopher J. Marley, George Rose, Lewis Fall, Gareth L. Jones, Priscilla Williams, John P. R. Williams, Martin Steggall, Damian M. Bailey

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Introduction and aims: Sports-related concussion (SRC) represents a significant and growing public health concern in rugby union, yet remains one of the least understood injuries facing the health community today. Alongside increasing SRC incidence rates, there is concern that prior recurrent concussion may contribute to long-term neurologic sequelae in later-life. This may be due to an accelerated decline in cerebral perfusion, a major risk factor for neurocognitive decline and neurodegeneration, though the underlying mechanisms remain to be established. The present study hypothesised that recurrent concussion in current professional rugby union players would result in elevated systemic oxidative-nitrosative stress, reflected by a free radical-mediated reduction in nitric oxide (NO) bioavailability and impaired cerebrovascular and cognitive function. Methodology: A longitudinal study design was adopted across the 2017-2018 rugby union season. Ethical approval was obtained from the University of South Wales Ethics Committee. Data collection is ongoing, and therefore the current report documents result from the pre-season and first half of the in-season data collection. Participants were initially divided into two subgroups; 23 professional rugby union players (aged 26 ± 5 years) and 22 non-concussed controls (27 ± 8 years). Pre-season measurements were performed for cerebrovascular function (Doppler ultrasound of middle cerebral artery velocity (MCAv) in response to hypocapnia/normocapnia/hypercapnia), cephalic venous concentrations of the ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), NO (ozone-based chemiluminescence) and cognition (neuropsychometric tests). Notational analysis was performed to assess contact in the rugby group throughout each competitive game. Results: 1001 tackles and 62 injuries, including three concussions were observed across the first half of the season. However, no associations were apparent between number of tackles and any injury type (P > 0.05). The rugby group expressed greater oxidative stress as indicated by increased A•- (P < 0.05 vs. control) and a subsequent decrease in NO bioavailability (P < 0.05 vs. control). The rugby group performed worse in the Ray Auditory Verbal Learning Test B (RAVLT-B, learning, and memory) and the Grooved Pegboard test using both the dominant and non-dominant hands (visuomotor coordination, P < 0.05 vs. control). There were no between-group differences in cerebral perfusion at baseline (MCAv: 54 ± 13 vs. 59 ± 12, P > 0.05). Likewise, no between-group differences in CVRCO2Hypo (2.58 ± 1.01 vs. 2.58 ± 0.75, P > 0.05) or CVRCO2Hyper (2.69 ± 1.07 vs. 3.35 ± 1.28, P > 0.05) were observed. Conclusion: The present study identified that the rugby union players are characterized by impaired cognitive function subsequent to elevated systemic-oxidative-nitrosative stress. However, this appears to be independent of any functional impairment in cerebrovascular function. Given the potential long-term trajectory towards accelerated cognitive decline in populations exposed to SRC, prophylaxis to increase NO bioavailability warrants consideration.

Keywords: cognition, concussion, mild traumatic brain injury, rugby

Procedia PDF Downloads 176

Authors: Nadeesha Sewwandi, Dilini Shashikala, R. Kanapathy, S. Viyasan, R. M. S. Kumara, Duminda Guruge

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Early childhood development is important to the emotional, social, and physical development of young children and it has a direct effect on their overall development and on the adult they become. Play is so important to optimal child developments including skill development, social development, imagination, creativity and it fulfills a baby’s inborn need to learn. So, health promotion approach empowers people about the development of early childhood. Play area is a new concept and this study focus how this play areas helps to the development of early childhood of children in rural villages in Sri Lanka. This study was conducted with a children society in a rural village called Welankulama in Sri Lanka. Survey was conducted with children society about emotional, social and physical development of young children (Under age eight) in this village using questionnaires. It described most children under eight years age have poor level of emotional, social and physical development in this village. Then children society wanted to find determinants for this problem and among them they prioritized determinants like parental interactions, learning environment and social interaction and address them using an innovative concept called play area. In this village there is a common place as play area under a big tamarind tree. It consists of a playhouse, innovative playing toys, mobile library, etc. Twice a week children, parents, grandparents gather to this nice place. Collective feeding takes place in this area once a week and it was conducted by several mothers groups in this village. Mostly grandparents taught about handicrafts and this is a very nice place to share their experiences with all. Healthy competitions were conducted in this place through playing to motivate the children. Happy calendar (mood of the children) was marked by children before and after coming to the play area. In terms of results qualitative changes got significant place in this study. By learning about colors and counting through playing the thinking and reasoning skills got developed among children. Children were widening their imagination by means of storytelling. We observed there were good developments of fine and gross motor skills of two differently abled children in this village. Children learn to empathize with other people, sharing, collaboration, team work and following of rules. And also children gain knowledge about fairness, through role playing, obtained insight on the right ways of displaying emotions such as stress, fear, anger, frustration, and develops knowledge of how they can manage their feelings. The reading and writing ability of the children got improved by 83% because of the mobile library. The weight of children got increased by 81% in the village. Happiness was increased by 76% among children in the society. Playing is very important for learning during early childhood period of a person. Health promotion interventions play a major role to the development of early childhood and it help children to adjust to the school setting and even to enhance children’s learning readiness, learning behaviors and problem solving skills.

Keywords: early childhood development, health promotion approach, play and learning, working with children

Procedia PDF Downloads 139

Authors: Ashley L. Freeman, Jessica D. Watkins

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TeleEmergency Medicine (TeleEM) is an innovative approach leveraging virtual technology to deliver specialized emergency medical care across diverse healthcare settings, including internal acute care and critical access hospitals, remote patient monitoring, and nurse triage escalation, in addition to external emergency departments, skilled nursing facilities, and community health centers. TeleEM represents a significant advancement in the delivery of emergency medical care, providing healthcare professionals the capability to deliver expertise that closely mirrors in-person emergency medicine, exceeding geographical boundaries. Through qualitative research, the extension of timely, high-quality care has proven to address the critical needs of patients in remote and underserved areas. TeleEM’s service design allows for the expansion of existing services and the establishment of new ones in diverse geographic locations. This ensures that healthcare institutions can readily scale and adapt services to evolving community requirements by leveraging on-demand (non-scheduled) telemedicine visits through the deployment of multiple video solutions. In terms of financial management, TeleEM currently employs billing suppression and subscription models to enhance accessibility for a wide range of healthcare facilities. Plans are in motion to transition to a billing system routing charges through a third-party vendor, further enhancing financial management flexibility. To address state licensure concerns, a patient location verification process has been integrated through legal counsel and compliance authorities' guidance. The TeleEM workflow is designed to terminate if the patient is not physically located within licensed regions at the time of the virtual connection, alleviating legal uncertainties. A distinctive and pivotal feature of TeleEM is the introduction of the TeleEmergency Medicine Care Team Assistant (TeleCTA) role. TeleCTAs collaborate closely with TeleEM Physicians, leading to enhanced service activation, streamlined coordination, and workflow and data efficiencies. In the last year, more than 800 TeleEM sessions have been conducted, of which 680 were initiated by internal acute care and critical access hospitals, as evidenced by quantitative research. Without this service, many of these cases would have necessitated patient transfers. Barriers to success were examined through thorough medical record review and data analysis, which identified inaccuracies in documentation leading to activation delays, limitations in billing capabilities, and data distortion, as well as the intricacies of managing varying workflows and device setups. TeleEM represents a transformative advancement in emergency medical care that nurtures collaboration and innovation. Not only has advanced the delivery of emergency medicine care virtual technology through focus group participation with key stakeholders, rigorous attention to legal and financial considerations, and the implementation of robust documentation tools and the TeleCTA role, but it’s also set the stage for overcoming geographic limitations. TeleEM assumes a notable position in the field of telemedicine by enhancing patient outcomes and expanding access to emergency medical care while mitigating licensure risks and ensuring compliant billing.

Keywords: emergency medicine, TeleEM, rural healthcare, telemedicine

Procedia PDF Downloads 82

Authors: S. J. Addinell, T. Richard, B. Evans

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The Deep Exploration Technologies Cooperative Research Centre (DET CRC) is researching and developing a new coiled tubing based greenfields mineral exploration drilling system utilising downhole water powered percussive drill tooling. This new drilling system is aimed at significantly reducing the costs associated with identifying mineral resource deposits beneath deep, barron cover. This system has shown superior rates of penetration in water-rich hard rock formations at depths exceeding 500 meters. Several key challenges exist regarding the deployment and use of these bottom hole assemblies for mineral exploration, and this paper discusses some of the key technical challenges. This paper presents experimental results obtained from the research program during laboratory and field testing of the prototype drilling system. A study of the morphological aspects of the cuttings generated during the percussive drilling process is presented and shows a strong power law relationship for particle size distributions. Several percussive drilling parameters such as RPM, applied fluid pressure and weight on bit have been shown to influence the particle size distributions of the cuttings generated. This has direct influence on other drilling parameters such as flow loop performance, cuttings dewatering, and solids control. Real-time, accurate knowledge of percussive system operating parameters will assist the driller in maximising the efficiency of the drilling process. The applied fluid flow, fluid pressure, and rock properties are known to influence the natural oscillating frequency of the percussive hammer, but this paper also shows that drill bit design, drill bit wear and the applied weight on bit can also influence the oscillation frequency. Due to the changing drilling conditions and therefore changing operating parameters, real-time understanding of the natural operating frequency is paramount to achieving system optimisation. Several techniques to understand the oscillating frequency have been investigated and presented. With a conventional top drive drilling rig, spectral analysis of applied fluid pressure, hydraulic feed force pressure, hold back pressure and drill string vibrations have shown the presence of the operating frequency of the bottom hole tooling. Unfortunately, however, with the implementation of a coiled tubing drilling rig, implementing a positive displacement downhole motor to provide drill bit rotation, these signals are not available for interrogation at the surface and therefore another method must be considered. The investigation and analysis of ground vibrations using geophone sensors, similar to seismic-while-drilling techniques have indicated the presence of the natural oscillating frequency of the percussive hammer. This method is shown to provide a robust technique for the determination of the downhole percussive oscillation frequency when used with a coiled tubing drill rig.

Keywords: cuttings characterization, drilling optimization, oscillation frequency, percussive drilling, spectral analysis

Procedia PDF Downloads 230

Authors: Victor Kang, Sirene Bellahnid, Amy Al-Simaani

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Efficient documentation and completion of clerical tasks are pillars of efficient patient-centered care in acute settings such as the emergency department (ED). Medical scribes aid physicians with documentation, navigation of electronic health records, results gathering, and communication coordination with other healthcare teams. However, the use of medical scribes is not widespread, with some hospitals even continuing to discontinue their programs. One reason for this could be the lack of studies that have outlined concrete improvements in efficiency and patient and provider satisfaction in emergency departments before and after incorporating scribes. Methods: We conducted a review of the literature concerning the implementation of a medical scribe program and emergency department performance. For this review, a narrative synthesis accompanied by textual commentaries was chosen to present the selected papers. PubMed was searched exclusively. Initially, no date limits were set, but seeing as the electronic medical record was officially implemented in Canada in 2013, studies published after this date were preferred as they provided insight into the interplay between its implementation and scribes on quality improvement. Results: Throughput, efficiency, and cost-effectiveness were the most commonly used parameters in evaluating scribes in the Emergency Department. Important throughput metrics, specifically door-to-doctor and disposition time, were significantly decreased in emergency departments that utilized scribes. Of note, this was shown to be the case in community hospitals, where the burden of documentation and clerical tasks would fall directly upon the attending physician. Academic centers differ in that they rely heavily on residents and students; so the implementation of scribes has been shown to have limited effect on these metrics. However, unique to academic centers was the provider’s perception of incrased time for teaching was unique to academic centers. Consequently, providers express increased work satisfaction in relation to time spent with patients and in teaching. Patients, on the other hand, did not demonstrate a decrease in satisfaction in regards to the care that was provided, but there was no significant increase observed either. Of the studies we reviewed, one of the biggest limitations was the lack of significance in the data. While many individual studies reported that medical scribes in emergency rooms improved relative value units, patient satisfaction, provider satisfaction, and increased number of patients seen, there was no statistically significant improvement in the above criteria when compiled in a systematic review. There is also a clear publication bias; very few studies with negative results were published. To prove significance, data from more emergency rooms with scribe programs would need to be compiled which also includes emergency rooms who did not report noticeable benefits. Furthermore, most data sets focused only on scribes in academic centers. Conclusion: Ultimately, the literature suggests that while emergency room physicians who have access to medical scribes report higher satisfaction due to lower clerical burdens and can see more patients per shift, there is still variability in terms of patient and provider satisfaction. Whether or not this variability exists due to differences in training (in-house trainees versus contractors), population profile (adult versus pediatric), setting (academic versus community), or which shifts scribe work cannot be determined based on the studies that exist. Ultimately, more scribe programs need to be evaluated to determine whether these variables affect outcomes and prove whether scribes significantly improve emergency room efficiency.

Keywords: emergency medicine, medical scribe, scribe, documentation

Procedia PDF Downloads 90

Authors: Asem Alhnity, Nicholas Pickett

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The leisure home industry is experiencing an increase in sales due to the rise in popularity of staycations. However, there is also a demand for improvements in thermal and structural behaviour from customers. Existing standards and codes of practice outline the requirements for leisure home design. However, there is a lack of expertise in applying Finite Element Analysis (FEA) to complex structures in this industry. As a result, manufacturers rely on standardized design approaches, which often lead to excessively engineered or inadequately designed products. This study aims to address this issue by investigating the impact of the habitation structure on chassis performance in leisure homes. The aim of this research is to comprehensively analyse the impact of the habitation structure on chassis performance in leisure homes. By employing FEA on the entire unit, including both the habitation structure and the chassis, this study seeks to develop a novel framework for designing and analysing leisure homes. The objectives include material reduction, enhancing structural stability, resolving existing design issues, and developing innovative modular and wooden chassis designs. The methodology used in this research is quantitative in nature. The study utilizes FEA to analyse the performance of leisure home chassis under various loads. The analysis procedures involve running the FEA simulations on the numerical model of the leisure home chassis. Different load scenarios are applied to assess the stress and deflection performance of the chassis under various conditions. FEA is a numerical method that allows for accurate analysis of complex systems. The research utilizes flexible mesh sizing to calculate small deflections around doors and windows, with large meshes used for macro deflections. This approach aims to minimize run-time while providing meaningful stresses and deflections. Moreover, it aims to investigate the limitations and drawbacks of the popular approach of applying FEA only to the chassis and replacing the habitation structure with a distributed load. The findings of this study indicate that the popular approach of applying FEA only to the chassis and replacing the habitation structure with a distributed load overlooks the strengthening generated from the habitation structure. By employing FEA on the entire unit, it is possible to optimize stress and deflection performance while achieving material reduction and enhanced structural stability. The study also introduces innovative modular and wooden chassis designs, which show promising weight reduction compared to the existing heavily fabricated lattice chassis. In conclusion, this research provides valuable insights into the impact of the habitation structure on chassis performance in leisure homes. By employing FEA on the entire unit, the study demonstrates the importance of considering the strengthening generated from the habitation structure in chassis design. The research findings contribute to advancements in material reduction, structural stability, and overall performance optimization. The novel framework developed in this study promotes sustainability, cost-efficiency, and innovation in leisure home design.

Keywords: static homes, caravans, motor homes, holiday homes, finite element analysis (FEA)

Procedia PDF Downloads 101

Authors: Meherun Nahar

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Background:The Chittagong Hill Tracts (CHT) is one of the most diverse regions in Bangladesh in terms of geography, ethnicity, culture and traditions of the people and home of thirteen indigenous ethnic people. In Bangladesh indigenous children aged 6-10 years remain out of school, and the majority of those who do enroll drop out before completing primary school. According to different study that the dropout rate of indigenous children is much higher than the estimated national rate, children dropping out especially in the early years of primary school. One of the most critical barriers for these children is that they do not understand the national language in the government pre-primary school. And also their school readiness and development become slower. In this situation, indigenous children excluded from the mainstream quality education. To address this issue Save the children in Bangladesh and other organizations are implementing community-based Mother Tongue-Based Multilingual Education program (MTBMLE) in the Chittagong Hill Tracts (CHT) for improving the enrolment rate in Government Primary Schools (GPS) reducing dropout rate as well as quality education. In connection with that Save the children conducted comparative research in Chittagong hill tracts on children readiness through Mother tongue-based and Non-mother tongue ECCD center. Objectives of the Study To assess Mother Language based ECCD centers and Non-Mother language based ECCD centers children’s school readiness and development. To assess the community perception over Mother Language based and Non-Mother Language based ECCD center. Methodology: The methodology of the study was FGD, KII, In-depth Interview and observation. Both qualitative and quantitative research methods were followed. The quantitative part has three components, School Readiness, Classroom observation and Headteacher interview and qualitative part followed FGD technique. Findings: The interviews with children under school readiness component showed that in general, Mother Language (ML) based ECCD children doing noticeably better in all four areas (Knowledge, numeracy, fine motor skill and communication) than their peers from Non-mother language based children. ML students seem to be far better skilled in concepts about print as most of them could identify cover and title of the book that was shown to them. They could also know from where to begin to read the book or could correctly point the letter that was read. A big difference was found in the area of identifying letters as 89.3% ML students of could identify letters correctly whereas for Non mother language 30% could do the same. The class room observation data shows that ML children are more active and remained engaged in the classroom than NML students. Also, teachers of ML appeared to have more engaged in explaining issues relating to general knowledge or leading children in rhyming/singing other than telling something from text books. The participants of FGDs were very enthusiastic on using mother language as medium of teaching in pre-schools. They opined that this initiative elates children to attend school and enables them to continue primary schooling without facing any language barrier.

Keywords: Chittagong hill tracts, early childhood care and development (ECCD), indigenous, mother language

Procedia PDF Downloads 117

Authors: Sarah Niklas, Lynne Chester, Mark Diesendorf

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Geopolitical tensions, climate change and recent movements favouring a transformative shift in institutional power structures have influenced the economics of conventional energy supply for decades. This study takes a multi-dimensional approach to illustrate the potential of renewable energy (RE) technology to provide a pathway to a low-carbon economy driven by ecologically sustainable, independent and socially just energy. This comparative analysis identifies economic, political and social drivers that shaped the adoption of RE policy in two significantly different economies, Germany and Australia, with strong and weak commitments to RE respectively. Two complementary political-economy theories frame the document-based analysis. Régulation Theory, inspired by Marxist ideas and strongly influenced by contemporary economic problems, provides the background to explore the social relationships contributing the adoption of RE within the macro-economy. Varieties of Capitalism theory, a more recently developed micro-economic approach, examines the nature of state-firm relationships. Together these approaches provide a comprehensive lens of analysis. Germany’s energy policy transformed substantially over the second half of the last century. The development is characterised by the coordination of societal, environmental and industrial demands throughout the advancement of capitalist regimes. In the Fordist regime, mass production based on coal drove Germany’s astounding economic recovery during the post-war period. Economic depression and the instability of institutional arrangements necessitated the impulsive seeking of national security and energy independence. During the postwar Flexi-Fordist period, quality-based production, innovation and technology-based competition schemes, particularly with regard to political power structures in and across Europe, favoured the adoption of RE. Innovation, knowledge and education were institutionalized, leading to the legislation of environmental concerns. Lastly the establishment of government-industry-based coordinative programs supported the phase out of nuclear power and the increased adoption of RE during the last decade. Australia’s energy policy is shaped by the country’s richness in mineral resources. Energy policy largely served coal mining, historically and currently one of the most capital-intense industry. Assisted by the macro-economic dimensions of institutional arrangements, social and financial capital is orientated towards the export-led and strongly demand-oriented economy. Here energy policy serves the maintenance of capital accumulation in the mining sector and the emerging Asian economies. The adoption of supportive renewable energy policy would challenge the distinct role of the mining industry within the (neo)-liberal market economy. The state’s protective role of the mining sector has resulted in weak commitment to RE policy and investment uncertainty in the energy sector. Recent developments, driven by strong public support for RE, emphasize the sense of community in urban and rural areas and the emergence of a bottom-up approach to adopt renewables. Thus, political economy frameworks on both the macro-economic (Regulation Theory) and micro-economic (Varieties of Capitalism theory) scales can together explain the strong commitment to RE in Germany vis-à-vis the weak commitment in Australia.

Keywords: political economy, regulation theory, renewable energy, social relationships, energy transitions

Procedia PDF Downloads 381

Authors: Sharon Millen, Sarah Miller, Laura Dunne, Clare McGeady, Laura Neeson

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This paper presents the findings from a randomised controlled trial (RCT) and process evaluation of the Lifestart parenting programme. Lifestart is a structured child-centred programme of information and practical activity for parents of children aged from birth to five years of age. It is delivered to parents in their own homes by trained, paid family visitors and it is offered to parents regardless of their social, economic or other circumstances. The RCT evaluated the effectiveness of the programme and the process evaluation documented programme delivery and included a qualitative exploration of parent and child outcomes. 424 parents and children participated in the RCT: 216 in the intervention group and 208 in the control group across the island of Ireland. Parent outcomes included: parental knowledge of child development, parental efficacy, stress, social support, parenting skills and embeddedness in the community. Child outcomes included cognitive, language and motor development and social-emotional and behavioural development. Both groups were tested at baseline (when children were less than 1 year old), mid-point (aged 3) and at post-test (aged 5). Data were collected during a home visit, which took two hours. The process evaluation consisted of interviews with parents (n=16 at baseline and end-point), and focus groups with Lifestart Coordinators (n=9) and Family Visitors (n=24). Quantitative findings from the RCT indicated that, compared to the control group, parents who received the Lifestart programme reported reduced parenting-related stress, increased knowledge of their child’s development, and improved confidence in their parenting role. These changes were statistically significant and consistent with the hypothesised pathway of change depicted in the logic model. There was no evidence of any change in parents’ embeddedness in the community. Although four of the five child outcomes showed small positive change for children who took part in the programme, these were not statistically significant and there is no evidence that the programme improves child cognitive and non-cognitive skills by immediate post-test. The qualitative process evaluation highlighted important challenges related to conducting trials of this magnitude and design in the general population. Parents reported that a key incentive to take part in study was receiving feedback from the developmental assessment, which formed part of the data collection. This highlights the potential importance of appropriate incentives in relation to recruitment and retention of participants. The interviews with intervention parents indicated that one of the first changes they experienced as a result of the Lifestart programme was increased knowledge and confidence in their parenting ability. The outcomes and pathways perceived by parents and described in the interviews are also consistent with the findings of the RCT and the theory of change underpinning the programme. This hypothesises that improvement in parental outcomes, arising as a consequence of the programme, mediate the change in child outcomes. Parents receiving the Lifestart programme reported great satisfaction with and commitment to the programme, with the role of the Family Visitor being identified as one of the key components of the programme.

Keywords: parent-child relationship, parental self-efficacy, parental stress, school readiness

Procedia PDF Downloads 444

Authors: Jiri Cecrdle

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This paper describes the concept of the W-WING whirl flutter aeroelastic demonstrator. Whirl flutter is the specific case of flutter that accounts for the additional dynamic and aerodynamic influences of the engine rotating parts. The instability is driven by motion-induced unsteady aerodynamic propeller forces and moments acting in the propeller plane. Whirl flutter instability is a serious problem that may cause the unstable vibration of a propeller mounting, leading to the failure of an engine installation or an entire wing. The complicated physical principle of whirl flutter required the experimental validation of the analytically gained results. W-WING aeroelastic demonstrator has been designed and developed at Czech Aerospace Research Centre (VZLU) Prague, Czechia. The demonstrator represents the wing and engine of the twin turboprop commuter aircraft. Contrary to the most of past demonstrators, it includes a powered motor and thrusting propeller. It allows the changes of the main structural parameters influencing the whirl flutter stability characteristics. Propeller blades are adjustable at standstill. The demonstrator is instrumented by strain gauges, accelerometers, revolution-counting impulse sensor, sensor of airflow velocity, and the thrust measurement unit. Measurement is supported by the in house program providing the data storage and real-time depiction in the time domain as well as pre-processing into the form of the power spectral densities. The engine is linked with a servo-drive unit, which enables maintaining of the propeller revolutions (constant or controlled rate ramp) and monitoring of immediate revolutions and power. Furthermore, the program manages the aerodynamic excitation of the demonstrator by the aileron flapping (constant, sweep, impulse). Finally, it provides the safety guard to prevent any structural failure of the demonstrator hardware. In addition, LMS TestLab system is used for the measurement of the structure response and for the data assessment by means of the FFT- and OMA-based methods. The demonstrator is intended for the experimental investigations in the VZLU 3m-diameter low-speed wind tunnel. The measurement variant of the model is defined by the structural parameters: pitch and yaw attachment stiffness, pitch and yaw hinge stations, balance weight station, propeller type (duralumin or steel blades), and finally, angle of attack of the propeller blade 75% section (). The excitation is provided either by the airflow turbulence or by means of the aerodynamic excitation by the aileron flapping using a frequency harmonic sweep. The experimental results are planned to be utilized for validation of analytical methods and software tools in the frame of development of the new complex multi-blade twin-rotor propulsion system for the new generation regional aircraft. Experimental campaigns will include measurements of aerodynamic derivatives and measurements of stability boundaries for various configurations of the demonstrator.

Keywords: aeroelasticity, flutter, whirl flutter, W WING demonstrator

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Authors: E Tambo, O. O. Olalubi, E. C. Ugwu, J. Y. Ngogang

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Despite the World Health Organization (WHO) declaration of international health emergency concern, the status quo of responses and efforts to stem the worst-recorded Ebola epidemic Ebola outbreak is still precariously inadequate in most of the affected in West. Mining natural resources have been shown to play a key role in both motivating and fuelling ethnic, civil and armed conflicts that have plagued a number of African countries over the last decade. Revenues from the exploitation of natural resources are not only used in sustaining the national economy but also armies, personal enrichment and building political support. Little is documented on the mining and ecological impact on the emergence and geographical distribution of Ebola in Africa over time and space. We aimed to provide a better understanding of the interconnectedness among issues of mining natural, resource management, mining conflict and post-conflict on Ebola outbreak and how wealth generated from abundant natural resources could be better managed in promoting research and development towards strengthening environmental, socioeconomic and health systems sustainability on Ebola outbreak and other emerging diseases surveillance and responses systems prevention and control, early warning alert, durable peace and sustainable development rather than to fuel conflicts, resurgence and emerging diseases epidemics in the perspective of community and national/regional approach. Our results showed the first assessment of systematic impact of all major minerals conflict events diffusion over space and time and mining activities on nine Ebola genesis and geo-distribution in affected countries across Africa. We demonstrate how, where and when mining activities in Africa increase ecological degradation, conflicts at the local level and then spreads violence across territory and time by enhancing the financial capacities of fighting groups/ethnics and diseases onset. In addition, led process of developing minimum standards for natural resource governance; improving governmental and civil society capacity for natural resource management, including the strengthening of monitoring and enforcement mechanisms; understanding the post-mining and conflicts community or national reconstruction and rehabilitation programmes in strengthening or developing community health systems and regulatory mechanisms. In addition the quest for the control over these resources and illegal mining across the landscape forest incursion provided increase environmental and ecological instability and displacement and disequilibrium, therefore affecting the intensity and duration of mining and conflict/wars and episode of Ebola outbreaks over time and space. We highlight the key findings and lessons learnt in promoting country or community-led process in transforming natural resource wealth from a peace liability to a peace asset. The imperative necessity for advocacy and through facilitating intergovernmental deliberations on critical issues and challenges affecting Africa community transforming exploitation of natural resources from a peace liability to outbreak prevention and control. The vital role of mining in increasing government revenues and expenditures, equitable distribution of wealth and health to all stakeholders, in particular local communities requires coordination, cooperative leadership and partnership in fostering sustainable developmental initiatives from mining context to outbreak and other infectious diseases surveillance responses systems in prevention and control, and judicious resource management.

Keywords: mining, mining conflicts, mines, ecological, Ebola, outbreak, mining companies, miners, impact

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Authors: Milada Krejci, Martin Hill, Vaclav Hosek, Dobroslava Jandova, Jiri Kajzar, Pavel Blaha

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The paper declares effects of exercise intervention of the research project “Basic research of balance changes in seniors”, granted by the Czech Science Foundation. The objective of the presented study is to define predictors, which influence bio-psycho-social consequences and effects of balance ability in senior 65 years old and above. We focused on the Fall-Efficacy Scale changes evaluation in seniors. Comprehensive hypothesis of the project declares, that motion uncertainty (dyskinesia) can negatively affect the well-being of a senior in bio-psycho-social context. In total, random selection and testing of 100 seniors (30 males, 70 females) from Prague and Central Bohemian region was provided. The sample was divided by stratified random selection into experimental and control groups, who underwent input and output testing. For diagnostics the methods of Medical Anamnesis, Functional anthropological examinations, Tinetti Balance Assessment Tool, SF-36 Health Survey, Anamnestic comparative self-assessment scale were used. Intervention method called "Life in Balance" based on yoga techniques was applied in four-week cycle. Results of multivariate regression were verified by repeated measures ANOVA: subject factor, phase of intervention (between-subject factor), body fluid (within-subject factor) and phase of intervention × body fluid interaction). ANOVA was performed with a repetition involving the factors of subjects, experimental/control group, phase of intervention (independent variable), and x phase interaction followed by Bonferroni multiple comparison assays with a test strength of at least 0.8 on the probability level p < 0.05. In the paper results of the first-year investigation of the three years running project are analysed. Results of balance tests confirmed no significant difference between females and males in pre-test. Significant improvements in balance and walking ability were observed in experimental group in females comparing to males (F = 128.4, p < 0.001). In the females control group, there was no significant change in post- test, while in the female experimental group positive changes in posture and spine flexibility in post-tests were found. It seems that females even in senior age react better to incentives of intervention in balance and spine flexibility. On the base of results analyses, we can declare the significant improvement in social balance markers after intervention in the experimental group (F = 10.5, p < 0.001). In average, seniors are used to take four drugs daily. Number of drugs can contribute to allergy symptoms and balance problems. It can be concluded that static balance and walking ability of seniors according Tinetti Balance scale correlate significantly with psychic and social monitored markers.

Keywords: exercises, balance, seniors 65+, health, mental and social balance

Procedia PDF Downloads 137

Authors: Yusuf Hesham Mohamed

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Introduction: Three-dimensional printing technology includes multiple procedures that fabricate three-dimensional objects through consecutively layering two-dimensional cross-sections on top of each other. 3D bioprinting is a promising field of 3D printing, which fabricates tissues and organs by accurately controlling the proper arrangement of diverse biological components. 3D bioprinting uses software and prints biological materials and their supporting components layer-by-layer on a substrate or in a tissue culture plate to produce complex live tissues and organs. 3D food printing is an emerging field of 3D bioprinting in which the 3D printed products are food products that are cheap, require less effort to produce, and have more desirable traits. The Aim of the Study is the development of an affordable 3D bioprinter by altering a locally made CNC instrument with an open-source platform to suit the 3D bio-printer purposes. Later, we went through applying the prototype in several applications regarding food technology and drug testing, including the organ-On-Chip. Materials and Methods: An off-the-shelf 3D printer was modified by designing and fabricating the syringe unit, which was designed on the basis of the Milli-fluidics system. Sodium alginate and gelatin hydrogels were prepared, followed by leaf cell suspension preparation from narrow sections of Fragaria’s viable leaves. The desired 3D structure was modeled, and 3D printing preparations took place. Cell-free and cell-laden hydrogels were printed at room temperature under sterile conditions. Post printing curing process was performed. The printed structure was further studied. Results: Positive results have been achieved using the altered 3D bioprinter where a 3D hydrogel construct of two layers made of the combination of sodium alginate to gelatin (15%: 0.5%) has been printed. DLP 3D printer was used to design the syringe component with a transparent PLA-Pro resin for the creation of a microfluidics system having two channels altered to the double extruder. The hydrogel extruder’s design was based on peristaltic pumps, which utilized a stepper motor. The design and fabrication were made using DIY-3D printed parts. Hard plastic PLA was the material utilized for printing. SEM was used to carry out the porous 3D construct imaging. Multiple physical and chemical tests were performed in order to ensure that the cell line was suitable for hosting. Fragaria plant was developed by suspending Fragaria’s cells from its leaves using the 3D bioprinter. Conclusion: 3D bioprinting is considered to be an emerging scientific field that can facilitate and improve many scientific tests and studies. Thus, having a 3D bioprinter in labs is considered to be an essential requirement. 3D bioprinters are very expensive; however, the fabrication of a 3D printer into a 3D bioprinter can lower the cost of the bioprinter. The 3D bioprinter implemented made use of peristaltic pumps instead of syringe-based pumps in order to extend the ability to print multiple types of materials and cells.

Keywords: scaffold, eco on chip, 3D bioprinter, DLP printer

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Authors: N. Schneider, M. Bruchhage, M. Hartweg, G. Mutungi, J. O Regan, S. Deoni

Abstract:

Observational neuroimaging studies suggest differences between breast-fed and formula-fed infants in developmental myelination, a key brain process for learning and cognitive development. However, the possible effects of a nutrient formulation on myelin development in healthy term infants in an intervention study have not been investigated. Objective was, therefore, to investigate the efficacy of a nutrient formulation with higher levels of myelin-relevant nutrients as compared to a control formulation with lower levels of the same nutrients on brain myelination and cognitive development in the first 6 months of life. The study is an ongoing randomized, controlled, double-blind, two-center, parallel-group clinical trial with a nonrandomized, non-blinded arm of exclusively breastfed infants. The current findings result from a staged statistical analysis at 6 months; the recruitment and intervention period has been completed for all participants. Follow-up visits at 12, 18 and 24 months are still ongoing. N= 81 enrolled full term, neurotypical infants of both sexes were randomized into either the investigational (N= 42) or the control group (N= 39), and N= 108 children in the breast-fed arm served as a natural reference group. The effect of a blend of docosahexaenoic acid, arachidonic acid, iron, vitamin B12, folic acid as well as sphingomyelin from a uniquely proceed whey protein concentrate enriched in alpha-lactalbumin and phospholipids in an infant nutrition product matrix was investigated. The main outcomes for the staged statistical analyses at 6 months included brain myelination measures derived from MRI. Additional outcomes were brain volume, cognitive development and safety. The full analyses set at 6 months comprised N= 66 infants. Higher levels of myelin-relevant nutrients compared to lower levels resulted in significant differences in myelin structure, volume, and rate of myelination as early as 3 and 6 months of life. The cross-sectional change of means between groups for whole-brain myelin volume was 8.4% for investigational versus control formulation (3.5% versus the breastfeeding reference) group at 3 months and increased to 36.4% for investigational versus control formulation (14.1% versus breastfeeding reference) at 6 months. No statistically significant differences were detected for early cognition scores. Safety findings were largely similar across groups. This is the first pediatric nutritional neuroimaging study demonstrating the efficacy of a myelin nutrient blend on developmental myelination in well-nourished term infants. Myelination is a critical process in learning and development. The effects were demonstrated across the brain, particularly in temporal and parietal regions, known to be functionally involved in sensory, motor and language skills. These first results add to the field of nutritional neuroscience by demonstrating early life nutrition benefits for brain architecture which may be foundational for later cognitive and behavioral outcomes. ClinicalTrials.gov Identifier: NCT03111927 (Infant Nutrition and Brain Development - Full-Text View - ClinicalTrials.gov).

Keywords: brain development, infant nutrition, MRI, myelination

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Authors: Ziara Carmelli G. Tan, Irene Carmelle S. Tan

Abstract:

Background: Trichotillomania (TTM) and Major Depressive Disorder (MDD) are two psychiatric conditions that frequently co-occur, presenting a significant challenge for treatment due to their complex interplay. TTM involves repetitive hair-pulling, leading to noticeable hair loss and distress, while MDD is characterized by persistent low mood and loss of interest or pleasure, leading to dysfunctionality. This case report examines the intricate relationship between TTM and MDD in a young adult female, emphasizing the need for a comprehensive, multifaceted therapeutic approach to address both disorders effectively. Case Presentation: The patient is a 21-year-old female college student and youth church leader who presented with chronic hair-pulling and depressive symptoms. Her premorbid personality was marked by low self-esteem and a strong need for external validation. Despite her academic and social responsibilities and achievements, she struggled with managing her emotional distress, which was exacerbated by her family dynamics and her role within her church community. Her hair-pulling and mood symptoms were particularly triggered by self-esteem threats and feelings of inadequacy. She was diagnosed with Trichotillomania, Scalp and Major Depressive Disorder. Intervention/Management: The patient’s treatment plan was comprehensive, incorporating both pharmacological and non-pharmacological interventions. Initial pharmacologic management was Fluoxetine 20mg/day up, titrated to 40mg/day with no improvement; hence, shifted to Escitalopram 20mg/day and started with N-acetylcysteine 600mg/day with noted significant improvement in symptoms. Psychotherapeutic strategies played a crucial role in her treatment. These included supportive-expressive psychodynamic psychotherapy, which helped her explore and understand underlying emotional conflicts. Cognitive-behavioral techniques were employed to modify her maladaptive thoughts and behaviors. Grief processing was integrated to help her cope with significant losses. Family therapy was done to address conflicts and collaborate with the treatment process. Psychoeducation was provided to enhance her understanding of her condition and to empower her in her treatment journey. A suicide safety plan was developed to ensure her safety during critical periods. An interprofessional approach, which involved coordination with the Dermatology service for co-management, was also a key component of her treatment. Outcome: Over the course of 15 therapy sessions, the patient demonstrated significant improvement in both her depressive symptoms and hair-pulling behavior. Her active engagement in therapy, combined with pharmacological support, facilitated better emotional regulation and a more cohesive sense of self. Her adherence to the treatment plan, along with the collaborative efforts of the interprofessional team, contributed to her positive outcomes. Discussion: This case underscores the significance of addressing both TTM and its comorbid conditions to achieve effective treatment outcomes. The intricate interplay between TTM and MDD in the patient’s case highlights the importance of a comprehensive treatment plan that includes both pharmacological and psychotherapeutic approaches. Supportive-expressive psychodynamic psychotherapy, Cognitive-behavioral techniques, and Family therapy were particularly beneficial in addressing the complex emotional and behavioral aspects of her condition. The involvement of an interprofessional team, including dermatology co-management, was crucial in providing holistic care. Future practice should consider the benefits of such a multidisciplinary approach to managing complex cases like this, ensuring that both the psychological and physiological aspects of the disorders are adequately addressed.

Keywords: cognitive-behavioral therapy, interprofessional approach, major depressive disorder, psychodynamic psychotherapy, trichotillomania

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Authors: Giuliana Murfet, Heidi Behrens

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Chronic disease is Australia’s biggest health concern and obesity the leading risk factor for many. Obesity and chronic disease have a higher representation in rural Tasmania, where levels of socio-disadvantage are also higher. People living outside major cities have less access to health services and poorer health outcomes. To help primary healthcare professionals manage obesity, the Australian NHMRC evidence-based clinical practice guidelines for management of overweight and obesity in adults were developed. They include recommendations for practice and models for obesity management. To our knowledge there has been no research conducted that investigates translation of these guidelines into practice in rural-regional areas; where implementation can be complicated by limited financial and staffing resources. Also, the systematic review that informed the guidelines revealed a lack of evidence for chronic disease models of obesity care. The aim was to establish and evaluate a multidisciplinary model for obesity management in a group of adult people with type 2 diabetes in a dispersed rural population in Australia. Extensive stakeholder engagement was undertaken to both garner support for an obesity clinic and develop a sustainable model of care. A comprehensive nurse practitioner-led outpatient model for obesity care was designed. Multidisciplinary obesity clinics for adults with type 2 diabetes including a dietitian, psychologist, physiotherapist and nurse practitioner were set up in the north-west of Tasmania at two geographically-rural towns. Implementation was underpinned by the NHMRC guidelines and recommendations focused on: assessment approaches; promotion of health benefits of weight loss; identification of relevant programs for individualising care; medication and bariatric surgery options for obesity management; and, the importance of long-term weight management. A clinical pathway for adult weight management is delivered by the multidisciplinary team with recognition of the impact of and adjustments needed for other comorbidities. The model allowed for intensification of intervention such as bariatric surgery according to recommendations, patient desires and suitability. A randomised controlled trial is ongoing, with the aim to evaluate standard care (diabetes-focused management) compared with an obesity-related approach with additional dietetic, physiotherapy, psychology and lifestyle advice. Key barriers and enablers to guideline implementation were identified that fall under the following themes: 1) health care delivery changes and the project framework development; 2) capacity and team-building; 3) stakeholder engagement; and, 4) the research project and partnerships. Engagement of not only local hospital but also state-wide health executives and surgical services committee were paramount to the success of the project. Staff training and collective development of the framework allowed for shared understanding. Staff capacity was increased with most taking on other activities (e.g., surgery coordination). Barriers were often related to differences of opinions in focus of the project; a desire to remain evidenced based (e.g., exercise prescription) without adjusting the model to allow for consideration of comorbidities. While barriers did exist and challenges overcome; the development of critical partnerships did enable the capacity for a potential model of obesity care for rural regional areas. Importantly, the findings contribute to the evidence base for models of diabetes and obesity care that coordinate limited resources.

Keywords: diabetes, interdisciplinary, model of care, obesity, rural regional

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Authors: V. K. Tewari, M. Hussain, H. K. D. Gupta

Abstract:

Background: Nitric Oxide Donars (NODs) (intrathecal sodium nitroprusside (ITSNP) and oral tadalafil 20mg post ITSNP) has been studied in this context in cerebral palsy patients for fast recovery. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a) Retrograde Neurotransmission (acute cases): 1) Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2) Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b) Vasopasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c) Long-Term Potentiation (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Design: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat cerebral palsy cases. Case-control prospective study. Materials and Methods: The experimental population included 82 cerebral palsy patients (10 patients were given control treatments without NOD or with 5% dextrose superfusion, and 72 patients comprised the NOD group). The mean time for superfusion was 5 months post-cerebral palsy. Pre- and post-NOD status was monitored by Gross Motor Function Classification System for Cerebral Palsy (GMFCS), MRI, and TCD studies. Results: After 7 days in the NOD group, the mean change in the GMFCS score was an increase of 1.2 points mean; after 3 months, there was an increase of 3.4 points mean, compared to the control-group increase of 0.1 points at 3 months. MRI and TCD documented the improvements. Conclusions: NOD (ITSNP boosts up the recovery and oral tadalafil maintains the recovery to a well-desired level) acts swiftly in the treatment of CP, acting within 7 days on 5 months post-cerebral palsy either of the three mechanisms.

Keywords: cerebral palsy, intrathecal sodium nitroprusside, oral tadalafil, perforators, vasodilations, retrograde transmission, the 10, 000-fold effect, long-term potantiation

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Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

Abstract:

Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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