Search results for: Kate Parkinson
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 164

Search results for: Kate Parkinson

44 Dwindling the Stability of DNA Sequence by Base Substitution at Intersection of COMT and MIR4761 Gene

Authors: Srishty Gulati, Anju Singh, Shrikant Kukreti

Abstract:

The manifestation of structural polymorphism in DNA depends on the sequence and surrounding environment. Ample of folded DNA structures have been found in the cellular system out of which DNA hairpins are very common, however, are indispensable due to their role in the replication initiation sites, recombination, transcription regulation, and protein recognition. We enumerate this approach in our study, where the two base substitutions and change in temperature embark destabilization of DNA structure and misbalance the equilibrium between two structures of a sequence present at the overlapping region of the human COMT gene and MIR4761 gene. COMT and MIR4761 gene encodes for catechol-O-methyltransferase (COMT) enzyme and microRNAs (miRNAs), respectively. Environmental changes and errors during cell division lead to genetic abnormalities. The COMT gene entailed in dopamine regulation fosters neurological diseases like Parkinson's disease, schizophrenia, velocardiofacial syndrome, etc. A 19-mer deoxyoligonucleotide sequence 5'-AGGACAAGGTGTGCATGCC-3' (COMT19) is located at exon-4 on chromosome 22 and band q11.2 at the intersection of COMT and MIR4761 gene. Bioinformatics studies suggest that this sequence is conserved in humans and few other organisms and is involved in recognition of transcription factors in the vicinity of 3'-end. Non-denaturating gel electrophoresis and CD spectroscopy of COMT sequences indicate the formation of hairpin type DNA structures. Temperature-dependent CD studies revealed an unusual shift in the slipped DNA-Hairpin DNA equilibrium with the change in temperature. Also, UV-thermal melting techniques suggest that the two base substitutions on the complementary strand of COMT19 did not affect the structure but reduces the stability of duplex. This study gives insight about the possibility of existing structurally polymorphic transient states within DNA segments present at the intersection of COMT and MIR4761 gene.

Keywords: base-substitution, catechol-o-methyltransferase (COMT), hairpin-DNA, structural polymorphism

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43 The Influence of the Visual and the Direct Physical Accessibility on the Sense of Control of Saudi Women in the Home Environment

Authors: Ahdab H. Mahdaly, Debajyoti Pati, Sharran Parkinson, Lee S. Duemer

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The importance of providing employed mothers with the right physical environment inside the home is not an easy task, especially when the culture is involved. This study examines the typical Saudi home as a personal, emotional, social and cultural setting, especially on the interactions between the physical design and perceived control of working mothers. However, owing to the scarcity of published literature on Saudi homes, American employed mothers were included in the study to provide a baseline. With the ongoing transformations in women’s role in Saudi Arabia, there is a perception that traditional home designs may not afford the appropriate sense of control inside the home. Saudi Arabia has numerous interacting layers of socio-cultural-religious forces that affect residential design, and understanding the moderating role of the Saudi home is vital to the ongoing national policy transition on women. The study investigated one narrow, albeit critical, influence of home design on ones sense of control – direct visual and physical accessibility between sets of rooms. Ten subjects, five Saudis and five American, examined visual and physical access between 171 room sets, and provided qualitative responses on how each access influences their sense of control. Three main themes emerged, with potential effects on control: 1- Openness, 2- Proximity, and 3- Separation. Data suggest that although the Saudi home is a substantially more complex setting than the American ones, a class of spaces that can be termed as ‘Neutral Rooms’ serving as cultural separators may represent the ideal solution for optimizing sense of control, without ignoring cultural-religious traditions, during the transition of the Saudi women.

Keywords: direct physical accessibility, home environment, sense of control, visual accessibility, working mothers

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42 Formulation of the N-Acylethanolamine, Linoleoylethanolamide into Cubosomes for Delivery across the Blood-Brain Barrier

Authors: Younus Mohammad, Anita B. Fallah, Ben J. Boyd, Shakila B. Rizwan

Abstract:

N-acylethanolamines (NAEs) are endogenous lipids, which have neuromodulatory properties. NAEs have shown neuroprotective properties in various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and ischemic stroke. However, NAEs are eliminated rapidly in vivo by enzymatic hydrolysis. We propose to encapsulate NAEs in liquid crystalline nanoparticles (cubosomes) to increase their biological half-life and explore their therapeutic potential. Recently, we have reported the co-formulation and nanostructural characterization of cubosomes containing the NAE, oleoylethanolamide and a synthetic cubosome forming lipid phytantriol. Here, we report on the formulation of cubosomes with the NAE, linoleoylethanolamide (LEA) as the core cubosome forming lipid. LEA-cubosomes were formulated in the presence of three different steric stabilisers: two brain targeting ligands, Tween 80 and Pluronic P188 and a control, Pluronic F127. Size, morphology and internal structure of formulations were characterized by dynamic light scattering (DLS), cryogenic transmission electron microscopy (Cryo–TEM) and small angle X–ray scattering (SAXS), respectively. Chemical stability of LEA in formulations was investigated using high-performance liquid chromatography (HPLC). Cytotoxicity of formulations towards human cerebral microvascular endothelial cell line (hCMEC/D3) was also investigated using an MTT (3-[4, 5- dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay. All cubosome formulations had mean particle size of less than 250 nm and were uniformly distributed with polydispersity indices less than 0.2. Cubosomes produced had a bicontinuous cubic internal structure with an Im3m space group but different lattice parameters, indicating the different modes of interaction between the stabilisers and LEA. LEA in formulations was found to be chemically stable. At concentrations of up to 20 µg/mL LEA in the presence of all the stabilisers, greater than 80% cell viability was observed.

Keywords: blood-brain barrier, cubosomes, linoleoyl ethanolamide, N-acylethanolamines (NAEs)

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41 Predicting Returns Volatilities and Correlations of Stock Indices Using Multivariate Conditional Autoregressive Range and Return Models

Authors: Shay Kee Tan, Kok Haur Ng, Jennifer So-Kuen Chan

Abstract:

This paper extends the conditional autoregressive range (CARR) model to multivariate CARR (MCARR) model and further to the two-stage MCARR-return model to model and forecast volatilities, correlations and returns of multiple financial assets. The first stage model fits the scaled realised Parkinson volatility measures using individual series and their pairwise sums of indices to the MCARR model to obtain in-sample estimates and forecasts of volatilities for these individual and pairwise sum series. Then covariances are calculated to construct the fitted variance-covariance matrix of returns which are imputed into the stage-two return model to capture the heteroskedasticity of assets’ returns. We investigate different choices of mean functions to describe the volatility dynamics. Empirical applications are based on the Standard and Poor 500, Dow Jones Industrial Average and Dow Jones United States Financial Service Indices. Results show that the stage-one MCARR models using asymmetric mean functions give better in-sample model fits than those based on symmetric mean functions. They also provide better out-of-sample volatility forecasts than those using CARR models based on two robust loss functions with the scaled realised open-to-close volatility measure as the proxy for the unobserved true volatility. We also find that the stage-two return models with constant means and multivariate Student-t errors give better in-sample fits than the Baba, Engle, Kraft, and Kroner type of generalized autoregressive conditional heteroskedasticity (BEKK-GARCH) models. The estimates and forecasts of value-at-risk (VaR) and conditional VaR based on the best MCARR-return models for each asset are provided and tested using Kupiec test to confirm the accuracy of the VaR forecasts.

Keywords: range-based volatility, correlation, multivariate CARR-return model, value-at-risk, conditional value-at-risk

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40 Neuropalliative Care in Patients with Progressive Neurological Disease in Czech Republic: Study Protocol

Authors: R. Bužgová, R. Kozáková, M. Škutová, M. Bar, P. Ressner, P. Bártová

Abstract:

Introduction: Currently, there has been an increasing concern about the provision of palliative care in non-oncological patients in both professional literature and clinical practice. However, there is not much scientific information on how to provide neurological and palliative care together. The main objective of the project is to create and to verify a concept of neuro-palliative and rehabilitative care for patients with selected neurological diseases in an advanced stage of the disease and also to evaluate bio-psychosocial and spiritual needs of these patients and their caregivers related to the quality of life using created standardized tools. Methodology: Triangulation of research methods (qualitative and quantitative) will be used. A concept of care and assessment tools will be developed by analyzing interviews and focus groups. Qualitative data will be analyzed using grounded theory. The concept of care will be tested in the context of the intervention study. Using quantitative analysis, we will assess the effect of an intervention provided on the saturation of needs, quality of life, and quality of care. A research sample will be made up of the patients with selected neurological diseases (Parkinson´s syndrome, motor neuron disease, multiple sclerosis, Huntington’s disease), together with patients´ family members. Based on the results, educational materials and a certified course for health care professionals will be created. Findings: Based on qualitative data analysis, we will propose the concept of integrated care model combining neurological, rehabilitative and specialist palliative care for patients with selected neurological diseases in different settings of care and services. Patients´ needs related to quality of life will be described by newly created and validated measuring tools before the start of intervention (application of neuro-palliative and palliative approach) and then in the time interval. Conclusion: Based on the results, educational materials and a certified course for doctors and health care professionals will be created.

Keywords: multidisciplinary approach, neuropalliative care, research, quality of life

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39 A Radioprotective Effect of Nanoceria (CNPs), Magnetic Flower-Like Iron Oxide Microparticles (FIOMPs), and Vitamins C and E on Irradiated BSA Protein

Authors: Hajar Zarei, AliAkbar Zarenejadatashgah, Vuk Uskoković, Hiroshi Watabe

Abstract:

The reactive oxygen species (ROS) generated by radiation in nuclear diagnostic imaging and radiotherapy could damage the structure of the proteins in noncancerous cells surrounding the tumor. The critical factor in many age-related diseases, such as Alzheimer, Parkinson, or Huntington diseases, is the oxidation of proteins by the ROS as molecular triggers of the given pathologies. Our studies by spectroscopic experiments showed doses close to therapeutic ones (1 to 5 Gy) could lead to changes of secondary and tertiary structures in BSA protein macromolecule as a protein model as well as the aggregation of polypeptide chain but without the fragmentation. For this reason, we investigated the radioprotective effects of natural (vitamin C and E) and synthetic materials (CNPs and FIOMPs) on the structural changes in BSA protein induced by gamma irradiation at a therapeutic dose (3Gy). In the presence of both vitamins and synthetic materials, the spectroscopic studies revealed that irradiated BSA was protected from the structural changes caused by ROS, according to in vitro research. The radioprotective property of CNPs and FIOMPs arises from enzyme mimetic activities (catalase, superoxide dismutase, and peroxidase) and their antioxidant capability against hydroxyl radicals. In the case of FIOMPs, a porous structure also leads to increased ROS recombination with each other in the same radiolytic track and subsequently decreased encounters with BSA. The hydrophilicity of vitamin C resulted in the major scavenging of ROS in the solvent, whereas hydrophobic vitamin E localized on the nonpolar patches of the BSA surface, where it did not only neutralize them thanks to the moderate BSA binding constant but also formed a barrier for diffusing ROS. To the best of our knowledge, there has been a persistent lack of studies investigating the radioactive effect of mentioned materials on proteins. Therefore, the results of our studies can open a new widow for application of these common dietary ingredients and new synthetic NPs in improving the safety of radiotherapy.

Keywords: reactive oxygen species, spectroscopy, bovine serum albumin, gamma radiation, radioprotection

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38 Diversity and Distribution of Cytochrome P450 2C9 Genes Related with Medical Cannabis in Thai Patients

Authors: Tanakrit Doltanakarn

Abstract:

Introduction: These days, cannabis is being accepted in many countries due to the fact that cannabis could be use in medical. The medical cannabis is used to treat and reduce the pain many diseases. For example, neuropathic pain, Parkinson, autism disorders, cancer pain reduce the adverse effect of chemotherapy, diabetes, and migraine. Active ingredients in cannabis that modulate patients' perceptions of their conditions include Δ9‐tetrahydrocannabinol (THC), cannabidiol (CBD), flavonoids, and terpenes. However, there is an adverse effect of cannabis, cardiovascular effects, psychosis, schizophrenia, mood disorder, and cognitive alternation. These effects are from the THC and CBD ingredients in the cannabis. The metabolize processes of delta-9 THC to 11-OH-delta 9 -THC (inactive form), THC were cause of adverse effects. Interestingly, the distributions of CYP2C9 gene (CYP2C9*2 and CYP2C9*3, poor metabolizer) that might affect incidences of adverse effects in patients who treated with medical cannabis. Objective: The aim of this study we want to investigate the association between genetic polymorphism of CYP2C9 frequency and Thai patients who treated with medical cannabis. Materials and Methods:We recruited sixty-five unrelated Thai patients from the College of Pharmacy, Rangsit University. DNA were extracted using Genomic DNA Mini Kit. Genotyping of CYP2C9*2 (430C>T, rs1799853) and CYP2C9*3 (1075A>C, rs1057910) were genotyped by the TaqMan Real-time PCR assay. Results: Among these 31 medicals cannabis-induced ADRs patients, they were diagnosed with 22 (33.85%) tachycardia and 3 (4.62%) arrhythmia. There were 34 (52.31%) medical cannabis-tolerant controls who were included in this study.40 (61.53%) Thai patients were female, and 25 (38.46%) were male, with median age of 57 (range 27 – 87) years. In this study, we found none of the medical cannabis-induced ADRs carried CYP2C9*2 variant along with medical cannabis-tolerant control group. CYP2C9*3 variant (intermediate metabolizer, IM) was found just only one of thirty-one (3.23%) in the medical cannabis-induced ADRs and two of thirty-fourth (5.88%) in the tolerant controls. Conclusions: Thus, the distribution of CYP2C9 alleles offer a comprehensive view of pharmacogenomics marker in Thai population that could be used as a reference for worldwide to investigate the pharmacogenomics application.

Keywords: medical cannabis, adverse effect, CYP2C9, thai patients

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37 Structural Correlates of Reduced Malicious Pleasure in Huntington's Disease

Authors: Sandra Baez, Mariana Pino, Mildred Berrio, Hernando Santamaria-Garcia, Lucas Sedeno, Adolfo Garcia, Sol Fittipaldi, Agustin Ibanez

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Schadenfreude refers to the perceiver’s experience of pleasure at another’s misfortune. This is a multidetermined emotion which can be evoked by hostile feelings and envy. The experience of Schadenfreude engages mechanisms implicated in diverse social cognitive processes. For instance, Schadenfreude involves heightened reward processing, accompanied by increased striatal engagement and it interacts with mentalizing and perspective-taking abilities. Patients with Huntington's disease (HD) exhibit reductions of Schadenfreude experience, suggesting a role of striatal degeneration in such an impairment. However, no study has directly assessed the relationship between regional brain atrophy in HD and reduced Schadenfreude. This study investigated whether gray matter (GM) atrophy in HD patients correlates with ratings of Schadenfreude. First, we compared the performance of 20 HD patients and 23 controls on an experimental task designed to trigger Schadenfreude and envy (another social emotion acting as a control condition). Second, we compared GM volume between groups. Third, we examined brain regions where atrophy might be associated with specific impairments in the patients. Results showed that while both groups showed similar ratings of envy, HD patients reported lower Schadenfreude. The latter pattern was related to atrophy in regions of the reward system (ventral striatum) and the mentalizing network (precuneus and superior parietal lobule). Our results shed light on the intertwining of reward and socioemotional processes in Schadenfreude, while offering novel evidence about their neural correlates. In addition, our results open the door to future studies investigating social emotion processing in other clinical populations characterized by striatal or mentalizing network impairments (e.g., Parkinson’s disease, schizophrenia, autism spectrum disorders).

Keywords: envy, Gray matter atrophy, Huntigton's disease, Schadenfreude, social emotions

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36 Obesity and Cancer: Current Scientific Evidence and Policy Implications

Authors: Martin Wiseman, Rachel Thompson, Panagiota Mitrou, Kate Allen

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Since 1997 World Cancer Research Fund (WCRF) International and the American Institute for Cancer Research (AICR) have been at the forefront of synthesising and interpreting the accumulated scientific literature on the link between diet, nutrition, physical activity and cancer, and deriving evidence-based Cancer Prevention Recommendations. The 2007 WCRF/AICR 2nd Expert Report was a landmark in the analysis of evidence linking diet, body weight and physical activity to cancer and led to the establishment of the Continuous Update Project (CUP). In 2018, as part of the CUP, WCRF/AICR will publish a new synthesis of the current evidence and update the Cancer Prevention Recommendations. This will ensure that everyone - from policymakers and health professionals to members of the public - has access to the most up-to-date information on how to reduce the risk of developing cancer. Overweight and obesity play a significant role in cancer risk, and rates of both are increasing in many parts of the world. This session will give an overview of new evidence relating obesity to cancer since the 2007 report. For example, since the 2007 Report, the number of cancers for which obesity is judged to be a contributory cause has increased from seven to eleven. The session will also shed light on the well-established mechanisms underpinning obesity and cancer links. Additionally, the session will provide an overview of diet and physical activity related factors that promote positive energy imbalance, leading to overweight and obesity. Finally, the session will highlight how policy can be used to address overweight and obesity at a population level, using WCRF International’s NOURISHING Framework. NOURISHING formalises a comprehensive package of policies to promote healthy diets and reduce obesity and non-communicable diseases; it is a tool for policymakers to identify where action is needed and assess if an approach is sufficiently comprehensive. The framework brings together ten policy areas across three domains: food environment, food system, and behaviour change communication. The framework is accompanied by a regularly updated database providing an extensive overview of implemented government policy actions from around the world. In conclusion, the session will provide an overview of obesity and cancer, highlighting the links seen in the epidemiology and exploring the mechanisms underpinning these, as well as the influences that help determine overweight and obesity. Finally, the session will illustrate policy approaches that can be taken to reduce overweight and obesity worldwide.

Keywords: overweight, obesity, nutrition, cancer, mechanisms, policy

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35 Reaching the Goals of Routine HIV Screening Programs: Quantifying and Implementing an Effective HIV Screening System in Northern Nigeria Facilities Based on Optimal Volume Analysis

Authors: Folajinmi Oluwasina, Towolawi Adetayo, Kate Ssamula, Penninah Iutung, Daniel Reijer

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Objective: Routine HIV screening has been promoted as an essential component of efforts to reduce incidence, morbidity, and mortality. The objectives of this study were to identify the optimal annual volume needed to realize the public health goals of HIV screening in the AIDS Healthcare Foundation supported hospitals and establish an implementation process to realize that optimal annual volume. Methods: Starting in 2011 a program was established to routinize HIV screening within communities and government hospitals. In 2016 Five-years of HIV screening data were reviewed to identify the optimal annual proportions of age-eligible patients screened to realize the public health goals of reducing new diagnoses and ending late-stage diagnosis (tracked as concurrent HIV/AIDS diagnosis). Analysis demonstrated that rates of new diagnoses level off when 42% of age-eligible patients were screened, providing a baseline for routine screening efforts; and concurrent HIV/AIDS diagnoses reached statistical zero at screening rates of 70%. Annual facility based targets were re-structured to meet these new target volumes. Restructuring efforts focused on right-sizing HIV screening programs to align and transition programs to integrated HIV screening within standard medical care and treatment. Results: Over one million patients were screened for HIV during the five years; 16, 033 new HIV diagnoses and access to care and treatment made successfully for 82 % (13,206), and concurrent diagnosis rates went from 32.26% to 25.27%. While screening rates increased by 104.7% over the 5-years, volume analysis demonstrated that rates need to further increase by 62.52% to reach desired 20% baseline and more than double to reach optimal annual screening volume. In 2011 facility targets for HIV screening were increased to reflect volume analysis, and in that third year, 12 of the 19 facilities reached or exceeded new baseline targets. Conclusions and Recommendation: Quantifying targets against routine HIV screening goals identified optimal annual screening volume and allowed facilities to scale their program size and allocate resources accordingly. The program transitioned from utilizing non-evidence based annual volume increases to establishing annual targets based on optimal volume analysis. This has allowed efforts to be evaluated on the ability to realize quantified goals related to the public health value of HIV screening. Optimal volume analysis helps to determine the size of an HIV screening program. It is a public health tool, not a tool to determine if an individual patient should receive screening.

Keywords: HIV screening, optimal volume, HIV diagnosis, routine

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34 Preliminary Efficacy of a Pilot Paediatric Day Hospital Program Project to Address Severe Mental Illness, Obesity, and Binge Eating

Authors: Alene Toulany, Elizabeth Dettmer, Seena Grewal, Kaley Roosen, Andrea Regina, Cathleen Steinegger, Kate Stadelman, Melissa Chambers, Lindsay Lochhead, Kelsey Gallagher, Alissa Steinberg, Andrea Leyser, Allison Lougheed, Jill Hamilton

Abstract:

Obesity and psychiatric disorders occur together so frequently that the combination has been coined an epidemic within an epidemic. Youth living with obesity are at increased risk for trauma, depression, anxiety and disordered eating. Although symptoms of binge eating disorder are common in paediatric obesity management programs, they are often not identified or addressed within treatment. At The Hospital for Sick Children (SickKids), a tertiary care paediatric hospital in Toronto, Canada, adolescents with obesity are treated in an interdisciplinary outpatient clinic (1-2 hours/week). This intensity of care is simply not enough to help these extremely complex patients. Existing day treatment programs for eating, and psychiatric disorders are not well suited for patients with obesity. In order to address this identified care gap, a unique collaboration was formed between the obesity, psychiatry, and eating disorder programs at SickKids in 2015. The aim of this collaboration was to provide an enhanced treatment arm to our general psychiatry day hospital program that addresses both the mental health issues and the lifestyle challenges common to youth with obesity and binge eating. The program is currently in year-one of a two-year pilot project and is designed for a length of stay of approximately 6 months. All youth participate in daily group therapy, academics, and structured mealtimes. The groups are primarily skills-based and are informed by cognitive/dialectical behavioural therapies. Weekly family therapy and individual therapy, as well as weekly medical appointments with a psychiatrist and a nurse, are provided. Youth in the enhanced treatment arm also receive regular sessions with a dietitian to establish normalized eating behaviours and monthly multifamily meal sessions to address challenges related to behaviour change and mealtimes in the home. Outcomes that will be evaluated include measures of mental health, anthropometrics, metabolic status, and healthcare satisfaction. At the end of the two years, it is expected that we will have had about 16 youth participants. This model of care delivery will be the first of its kind in Canada and is expected to inform future paediatric treatment practices.

Keywords: adolescent, binge eating, mental illness, obesity

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33 Diagnostic Contribution of the MMSE-2:EV in the Detection and Monitoring of the Cognitive Impairment: Case Studies

Authors: Cornelia-Eugenia Munteanu

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The goal of this paper is to present the diagnostic contribution that the screening instrument, Mini-Mental State Examination-2: Expanded Version (MMSE-2:EV), brings in detecting the cognitive impairment or in monitoring the progress of degenerative disorders. The diagnostic signification is underlined by the interpretation of the MMSE-2:EV scores, resulted from the test application to patients with mild and major neurocognitive disorders. The original MMSE is one of the most widely used screening tools for detecting the cognitive impairment, in clinical settings, but also in the field of neurocognitive research. Now, the practitioners and researchers are turning their attention to the MMSE-2. To enhance its clinical utility, the new instrument was enriched and reorganized in three versions (MMSE-2:BV, MMSE-2:SV and MMSE-2:EV), each with two forms: blue and red. The MMSE-2 was adapted and used successfully in Romania since 2013. The cases were selected from current practice, in order to cover vast and significant neurocognitive pathology: mild cognitive impairment, Alzheimer’s disease, vascular dementia, mixed dementia, Parkinson’s disease, conversion of the mild cognitive impairment into Alzheimer’s disease. The MMSE-2:EV version was used: it was applied one month after the initial assessment, three months after the first reevaluation and then every six months, alternating the blue and red forms. Correlated with age and educational level, the raw scores were converted in T scores and then, with the mean and the standard deviation, the z scores were calculated. The differences of raw scores between the evaluations were analyzed from the point of view of statistic signification, in order to establish the progression in time of the disease. The results indicated that the psycho-diagnostic approach for the evaluation of the cognitive impairment with MMSE-2:EV is safe and the application interval is optimal. The alternation of the forms prevents the learning phenomenon. The diagnostic accuracy and efficient therapeutic conduct derive from the usage of the national test norms. In clinical settings with a large flux of patients, the application of the MMSE-2:EV is a safe and fast psycho-diagnostic solution. The clinicians can draw objective decisions and for the patients: it doesn’t take too much time and energy, it doesn’t bother them and it doesn’t force them to travel frequently.

Keywords: MMSE-2, dementia, cognitive impairment, neuropsychology

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32 Development of Positron Emission Tomography (PET) Tracers for the in-Vivo Imaging of α-Synuclein Aggregates in α-Synucleinopathies

Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi

Abstract:

There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.

Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development

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31 Pioneering Technology of Night Photo-Stimulation of the Brain Lymphatic System: Therapy of Brain Diseases during Sleep

Authors: Semyachkina-Glushkovskaya Oxana, Fedosov Ivan, Blokhina Inna, Terskov Andrey, Evsukova Arina, Elovenko Daria, Adushkina Viktoria, Dubrovsky Alexander, Jürgen Kurths

Abstract:

In modern neurobiology, sleep is considered a novel biomarker and a promising therapeutic target for brain diseases. This is due to recent discoveries of the nighttime activation of the brain lymphatic system (BLS), playing an important role in the removal of wastes and toxins from the brain and contributes neuroprotection of the central nervous system (CNS). In our review, we discuss that night stimulation of BLS might be a breakthrough strategy in a new treatment of Alzheimer’s and Parkinson’s disease, stroke, brain trauma, and oncology. Although this research is in its infancy, however, there are pioneering and promising results suggesting that night transcranial photostimulation (tPBM) stimulates more effectively lymphatic removal of amyloid-beta from mouse brain than daily tPBM that is associated with a greater improvement of the neurological status and recognition memory of animals. In our previous study, we discovered that tPBM modulates the tone and permeability of the lymphatic endothelium by stimulating NO formation, promoting lymphatic clearance of wastes and toxins from the brain tissues. We also demonstrate that tPBM can also lead to angio- and lymphangiogenesis, which is another mechanism underlying tPBM-mediated stimulation of BLS. Thus, photo-augmentation of BLS might be a promising therapeutic target for preventing or delaying brain diseases associated with BLS dysfunction. Here we present pioneering technology for simultaneous tPBM in humans and sleep monitoring for stimulation of BLS to remove toxins from CNS and modulation of brain immunity. The wireless-controlled gadget includes a flexible organic light-emitting diode (LED) source that is controlled directly by a sleep-tracking device via a mobile application. The designed autonomous LED source is capable of providing the required therapeutic dose of light radiation at a certain region of the patient’s head without disturbing of sleeping patient. To minimize patients' discomfort, advanced materials like flexible organic LEDs were used. Acknowledgment: This study was supported by RSF project No. 23-75-30001.

Keywords: brain diseases, brain lymphatic system, phototherapy, sleep

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30 The Relationship between Wasting and Stunting in Young Children: A Systematic Review

Authors: Susan Thurstans, Natalie Sessions, Carmel Dolan, Kate Sadler, Bernardette Cichon, Shelia Isanaka, Dominique Roberfroid, Heather Stobagh, Patrick Webb, Tanya Khara

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For many years, wasting and stunting have been viewed as separate conditions without clear evidence supporting this distinction. In 2014, the Emergency Nutrition Network (ENN) examined the relationship between wasting and stunting and published a report highlighting the evidence for linkages between the two forms of undernutrition. This systematic review aimed to update the evidence generated since this 2014 report to better understand the implications for improving child nutrition, health and survival. Following PRISMA guidelines, this review was conducted using search terms to describe the relationship between wasting and stunting. Studies related to children under five from low- and middle-income countries that assessed both ponderal growth/wasting and linear growth/stunting, as well as the association between the two, were included. Risk of bias was assessed in all included studies using SIGN checklists. 45 studies met the inclusion criteria- 39 peer reviewed studies, 1 manual chapter, 3 pre-print publications and 2 published reports. The review found that there is a strong association between the two conditions whereby episodes of wasting contribute to stunting and, to a lesser extent, stunting leads to wasting. Possible interconnected physiological processes and common risk factors drive an accumulation of vulnerabilities. Peak incidence of both wasting and stunting was found to be between birth and three months. A significant proportion of children experience concurrent wasting and stunting- Country level data suggests that up to 8% of children under 5 may be both wasted and stunted at the same time, global estimates translate to around 16 million children. Children with concurrent wasting and stunting have an elevated risk of mortality when compared to children with one deficit alone. These children should therefore be considered a high-risk group in the targeting of treatment. Wasting, stunting and concurrent wasting and stunting appear to be more prevalent in boys than girls and it appears that concurrent wasting and stunting peaks between 12- 30 months of age with younger children being the most affected. Seasonal patterns in prevalence of both wasting and stunting are seen in longitudinal and cross sectional data and in particular season of birth has been shown to have an impact on a child’s subsequent experience of wasting and stunting. Evidence suggests that the use of mid-upper-arm circumference combined with weight-for-age Z-score might effectively identify children most at risk of near-term mortality, including those concurrently wasted and stunted. Wasting and stunting frequently occur in the same child, either simultaneously or at different moments through their life course. Evidence suggests there is a process of accumulation of nutritional deficits and therefore risk over the life course of a child demonstrates the need for a more integrated approach to prevention and treatment strategies to interrupt this process. To achieve this, undernutrition policies, programmes, financing and research must become more unified.

Keywords: Concurrent wasting and stunting, Review, Risk factors, Undernutrition

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29 Development of a One Health and Comparative Medicine Curriculum for Medical Students

Authors: Aliya Moreira, Blake Duffy, Sam Kosinski, Kate Heckman, Erika Steensma

Abstract:

Introduction: The One Health initiative promotes recognition of the interrelatedness between people, animals, plants, and their shared environment. The field of comparative medicine studies the similarities and differences between humans and animals for the purpose of advancing medical sciences. Currently, medical school education is narrowly focused on human anatomy and physiology, but as the COVID-19 pandemic has demonstrated, a holistic understanding of health requires comprehension of the interconnection between health and the lived environment. To prepare future physicians for unique challenges from emerging zoonoses to climate change, medical students can benefit from exposure to and experience with One Health and Comparative Medicine content. Methods: In January 2020, an elective course for medical students on One Health and Comparative Medicine was created to provide medical students with the background knowledge necessary to understand the applicability of animal and environmental health in medical research and practice. The 2-week course was continued in January 2021, with didactic and experiential activities taking place virtually due to the COVID-19 pandemic. In response to student feedback, lectures were added to expand instructional content on zoonotic and wildlife diseases for the second iteration of the course. Other didactic sessions included interprofessional lectures from 20 physicians, veterinarians, public health professionals, and basic science researchers. The first two cohorts of students were surveyed regarding One Health and Comparative Medicine concepts at the beginning and conclusion of the course. Results: 16 medical students have completed the comparative medicine course thus far, with 87.5% (n=14) completing pre-and post-course evaluations. 100% of student respondents indicated little to no exposure to comparative medicine or One Health concepts during medical school. Following the course, 100% of students felt familiar or very familiar with comparative medicine and One Health concepts. To assess course efficacy, questions were evaluated on a five-point Likert scale. 100% agreed or strongly agreed that learning Comparative Medicine and One Health topics augmented their medical education. 100% agreed or strongly agreed that a course covering this content should be regularly offered to medical students. Conclusions: Data from the student evaluation surveys demonstrate that the Comparative Medicine course was successful in increasing medical student knowledge of Comparative Medicine and One Health. Results also suggest that interprofessional training in One Health and Comparative Medicine is applicable and useful for medical trainees. Future iterations of this course could capitalize on the inherently interdisciplinary nature of these topics by enrolling students from veterinary and public health schools into a longitudinal course. Such recruitment may increase the course’s value by offering multidisciplinary student teams the opportunity to conduct research projects, thereby strengthening both the individual learning experience as well as sparking future interprofessional research ventures. Overall, these efforts to educate medical students in One Health topics should be reproducible at other institutions, preparing more future physicians for the diverse challenges they will encounter in practice.

Keywords: medical education, interprofessional instruction, one health, comparative medicine

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28 The Effect of Emotional Stimuli Related to Body Imbalance in Postural Control and the Phenomenological Experience of Young Healthy Adults

Authors: David Martinez-Pernia, Alvaro Rivera-Rei, Alejandro Troncoso, Gonzalo Forno, Andrea Slachevsky, David Huepe, Victoria Silva-Mack, Jorge Calderon, Mayte Vergara, Valentina Carrera

Abstract:

Background: Recent theories in the field of emotions have taken the relevance of motor control beyond a system related to personal autonomy (walking, running, grooming), and integrate it into the emotional dimension. However, to our best knowledge, there are no studies that specifically investigate how emotional stimuli related to motor control modify emotional states in terms of postural control and phenomenological experience. Objective: The main aim of this work is to investigate the emotions produced by stimuli of bodily imbalance (neutral, pleasant and unpleasant) in the postural control and the phenomenological experience of young, healthy adults. Methodology: 46 healthy young people are shown emotional videos (neutral, pleasant, motor unpleasant, and non-motor unpleasant) related to the body imbalance. During the period of stimulation of each of the videos (60 seconds) the participant is standing on a force platform to collect temporal and spatial data of postural control. In addition, the electrophysiological activity of the heart and electrodermal activity is recorded. In relation to the two unpleasant conditions (motor versus non-motor), a phenomenological interview is carried out to collect the subjective experience of emotion and body perception. Results: Pleasant and unpleasant emotional videos have significant changes with respect to the neutral condition in terms of greater area, higher mean velocity, and greater mean frequency power on the anterior-posterior axis. The results obtained with respect to the electrodermal response was that the pleasurable and unpleasant conditions produced a significant increase in the phasic component with respect to the neutral condition. Regarding the electrophysiology of the heart, no significant change was found in any condition. Phenomenological experiences in the two unpleasant conditions differ in body perception and the emotional meaning of the experience. Conclusion: Emotional stimuli related to bodily imbalance produce changes in postural control, electrodermal activity, and phenomenological experience. This experimental setting could be relevant to be implemented in people with motor disorders (Parkinson, Stroke, TBI) to know how emotions affect motor control.

Keywords: body imbalance stimuli, emotion, phenomenological experience, postural control

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27 Development of Solar Poly House Tunnel Dryer (STD) for Medicinal Plants

Authors: N. C. Shahi, Anupama Singh, E. Kate

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Drying is practiced to enhance the storage life, to minimize losses during storage, and to reduce transportation costs of agricultural products. Drying processes range from open sun drying to industrial drying. In most of the developing countries, use of fossil fuels for drying of agricultural products has not been practically feasible due to unaffordable costs to majority of the farmers. On the other hand, traditional open sun drying practiced on a large scale in the rural areas of the developing countries suffers from high product losses due to inadequate drying, fungal growth, encroachment of insects, birds and rodents, etc. To overcome these problems a middle technology dryer having low cost need to be developed for farmers. In case of mechanical dryers, the heated air is the main driving force for removal of moisture. The air is heated either electrically or by burning wood, coal, natural gas etc. using heaters. But, all these common sources have finite supplies. The lifetime is estimated to range from 15 years for a natural gas to nearly 250 years for coal. So, mankind must turn towards its safe and reliable utilization and may have undesirable side effects. The mechanical drying involves higher cost of drying and open sun drying deteriorates the quality. The solar tunnel dryer is one of promising option for drying various agricultural and agro-industrial products on large scale. The advantage of Solar tunnel dryer is its relatively cheaper cost of construction and operation. Although many solar dryers have been developed, still there is a scope of modification in them. Therefore, an attempt was made to develop Solar tunnel dryer and test its performance using highly perishable commodity i.e. leafy vegetables (spinach). The effect of air velocity, loading density and shade net on performance parameters namely, collector efficiency, drying efficiency, overall efficiency of dryer and specific heat energy consumption were also studied. Thus, the need for an intermediate level technology was realized and an effort was made to develop a small scale Solar Tunnel Dryer . A dryer consisted of base frame, semi cylindrical drying chamber, solar collector and absorber, air distribution system with chimney and auxiliary heating system, and wheels for its mobility were the main functional components. Drying of fenugreek was carried out to analyze the performance of the dryer. The Solar Tunnel Dryer temperature was maintained using the auxiliary heating system. The ambient temperature was in the range of 12-33oC. The relative humidity was found inside and outside the Solar Tunnel Dryer in the range of 21-75% and 35-79%, respectively. The solar radiation was recorded in the range of 350-780W/m2 during the experimental period. Studies revealed that total drying time was in range of 230 to 420 min. The drying time in Solar Tunnel Dryer was considerably reduced by 67% as compared to sun drying. The collector efficiency, drying efficiency, overall efficiency and specific heat consumption were determined and were found to be in the range of 50.06- 38.71%, 15.53-24.72%, 4.25 to 13.34% and 1897.54-3241.36 kJ/kg, respectively.

Keywords: overall efficiency, solar tunnel dryer, specific heat consumption, sun drying

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26 Integration, a Tool to Develop Critical Thinking Skills of Undergraduate Veterinary Students

Authors: M. L. W. P. De Silva, R. A. C. Rabel, N. Smith, L. McIntyre, T. J Parkinson, K. A. N. Wijayawardhane

Abstract:

Curricular integration is an important concept in medical education for developing students’ ability to create connections between different medical disciplines. Problem-Based Learning (PBL) is one of the vehicles through which such integration can be achieved. During the recent review of the veterinary curriculum at the University of Peradeniya, a series of courses in Integrative Veterinary Science (IVS) were introduced, in which PBL was the primary teaching methodology. The objectives of this study were to evaluate students’ opinions on PBL as a teaching method: it should be noted that, within the context of secondary and tertiary education in Sri Lanka, this would be an entirely novel learning experience for the students. Opinions were sought at the conclusion of IVS sessions where students of semesters 2, 4, 6, and 7 (of an 8-semester program) were exposed to a two, 2-hour PBL-based case scenario. The PBL-based case scenario in semesters 2, 4, and 7 were delivered using material previously developed by an experienced PBL practitioner, whilst material for semester 6 was prepared de novo by a less experienced practitioner. Each student (semesters 2: n=38, 4: n=37, 6: n=55, and 7: n=40) completed a questionnaire which asked whether: (i) the course had improved their critical thinking skills; (ii) the learning environment was sufficiently comfortable to express/share student’s opinion; (iii) there was sufficient facilitator guidance; (iv) the online study environment enhanced learning; and (v) the students were overall satisfied with the PBL approach and IVS concept. Responses were given on a 5-point Likert-scale (strongly agree (SA), agree (A), neutral (N), disagree (D), and strongly disagree (SD)). SA and A responses were summed to provide an overall ‘satisfactory’ response. Results were subjected to frequency-distribution statistical analysis. A total of 88.5% of students gave SA+A scores to their overall satisfaction. The proportion of SA+A scores differed between different semesters, such that 95% of semester 2, 4, and 7 students gave SA+A scores, whereas only 69% of semester 6 students did so for their respective sessions. Overall, 96% of the students gave SA+A scores to the question relating to the improvement of critical thinking skills: semester 6 students’ scores were marginally, but not significantly, lower (91% SA+A) than those in other semesters. The difference of scores between semester 6 and the other semesters may be attributed to the different PBL-material used and/or the different experience levels of the practitioners that developed the study material. The use of PBL as a means of teaching IVS curriculum-integration courses was well-received by the students in terms of their overall satisfaction and their perceptions of improved critical thinking skills. Importantly, this was achieved in the face of a methodology that was entirely novel to the students. Finally, the delivery of the PBL medium was readily mastered by the practitioner to whom it was also a novel methodology.

Keywords: critical thinking skills, integration, problem based learning, veterinary education

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25 Hydration of Three-Piece K Peptide Fragments Studied by Means of Fourier Transform Infrared Spectroscopy

Authors: Marcin Stasiulewicz, Sebastian Filipkowski, Aneta Panuszko

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Background: The hallmark of neurodegenerative diseases, including Alzheimer's and Parkinson's diseases, is an aggregation of the abnormal forms of peptides and proteins. Water is essential to functioning biomolecules, and it is one of the key factors influencing protein folding and misfolding. However, the hydration studies of proteins are complicated due to the complexity of protein systems. The use of model compounds can facilitate the interpretation of results involving larger systems. Objectives: The goal of the research was to characterize the properties of the hydration water surrounding the two three-residue K peptide fragments INS (Isoleucine - Asparagine - Serine) and NSR (Asparagine - Serine - Arginine). Methods: Fourier-transform infrared spectra of aqueous solutions of the tripeptides were recorded on Nicolet 8700 spectrometer (Thermo Electron Co.) Measurements were carried out at 25°C for varying molality of solute. To remove oscillation couplings from water spectra and, consequently, obtain narrow O-D semi-heavy water bands (HDO), the isotopic dilution method of HDO in H₂O was used. The difference spectra method allowed us to isolate the tripeptide-affected HDO spectrum. Results: The structural and energetic properties of water affected by the tripeptides were compared to the properties of pure water. The shift of the values of the gravity center of bands (related to the mean energy of water hydrogen bonds) towards lower values with respect to the ones corresponding to pure water suggests that the energy of hydrogen bonds between water molecules surrounding tripeptides is higher than in pure water. A comparison of the values of the mean oxygen-oxygen distances in water affected by tripeptides and pure water indicates that water-water hydrogen bonds are shorter in the presence of these tripeptides. The analysis of differences in oxygen-oxygen distance distributions between the tripeptide-affected water and pure water indicates that around the tripeptides, the contribution of water molecules with the mean energy of hydrogen bonds decreases, and simultaneously the contribution of strong hydrogen bonds increases. Conclusions: It was found that hydrogen bonds between water molecules in the hydration sphere of tripeptides are shorter and stronger than in pure water. It means that in the presence of the tested tripeptides, the structure of water is strengthened compared to pure water. Moreover, it has been shown that in the vicinity of the Asparagine - Serine - Arginine, water forms stronger and shorter hydrogen bonds. Acknowledgments: This work was funded by the National Science Centre, Poland (grant 2017/26/D/NZ1/00497).

Keywords: amyloids, K-peptide, hydration, FTIR spectroscopy

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24 Supporting a Moral Growth Mindset Among College Students

Authors: Kate Allman, Heather Maranges, Elise Dykhuis

Abstract:

Moral Growth Mindset (MGM) is the belief that one has the capacity to become a more moral person, as opposed to a fixed conception of one’s moral ability and capacity (Han et al., 2018). Building from Dweck’s work in incremental implicit theories of intelligence (2008), Moral Growth Mindset (Han et al., 2020) extends growth mindsets into the moral dimension. The concept of MGM has the potential to help researchers understand how both mindsets and interventions can impact character development, and it has even been shown to have connections to voluntary service engagement (Han et al., 2018). Understanding the contexts in which MGM might be cultivated could help to promote the further cultivation of character, in addition to prosocial behaviors like service engagement, which may, in turn, promote larger scale engagement in social justice-oriented thoughts, feelings, and behaviors. In particular, college may be a place to intentionally cultivate a growth mindset toward moral capacities, given the unique developmental and maturational components of the college experience, including contextual opportunity (Lapsley & Narvaez, 2006) and independence requiring the constant consideration, revision, and internalization of personal values (Lapsley & Woodbury, 2016). In a semester-long, quasi-experimental study, we examined the impact of a pedagogical approach designed to cultivate college student character development on participants’ MGM. With an intervention (n=69) and a control group (n=97; Pre-course: 27% Men; 66% Women; 68% White; 18% Asian; 2% Black; <1% Hispanic/Latino), we investigated whether college courses that intentionally incorporate character education pedagogy (Lamb, Brant, Brooks, 2021) affect a variety of psychosocial variables associated with moral thoughts, feelings, identity, and behavior (e.g. moral growth mindset, honesty, compassion, etc.). The intervention group consisted of 69 undergraduate students (Pre-course: 40% Men; 52% Women; 68% White; 10.5% Black; 7.4% Asian; 4.2% Hispanic/Latino) that voluntarily enrolled in five undergraduate courses that encouraged students to engage with key concepts and methods of character development through the application of research-based strategies and personal reflection on goals and experiences. Moral Growth Mindset was measured using the four-item Moral Growth Mindset scale (Han et al., 2020), with items such as You can improve your basic morals and character considerably on a six-point Likert scale from 1 (strongly disagree) to 6 (strongly agree). Higher scores of MGM indicate a stronger belief that one can become a more moral person with personal effort. Reliability at Time 1 was Cronbach’s ɑ= .833, and at Time 2 Cronbach’s ɑ= .772. An Analysis of Covariance (ANCOVA) was conducted to explore whether post-course MGM scores were different between the intervention and control when controlling for pre-course MGM scores. The ANCOVA indicated significant differences in MGM between groups post-course, F(1,163) = 8.073, p = .005, R² = .11, where descriptive statistics indicate that intervention scores were higher than the control group at post-course. Results indicate that intentional character development pedagogy can be leveraged to support the development of Moral Growth Mindset and related capacities in undergraduate settings.

Keywords: moral personality, character education, incremental theories of personality, growth mindset

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23 Controlling the Release of Cyt C and L- Dopa from pNIPAM-AAc Nanogel Based Systems

Authors: Sulalit Bandyopadhyay, Muhammad Awais Ashfaq Alvi, Anuvansh Sharma, Wilhelm R. Glomm

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Release of drugs from nanogels and nanogel-based systems can occur under the influence of external stimuli like temperature, pH, magnetic fields and so on. pNIPAm-AAc nanogels respond to the combined action of both temperature and pH, the former being mostly determined by hydrophilic-to-hydrophobic transitions above the volume phase transition temperature (VPTT), while the latter is controlled by the degree of protonation of the carboxylic acid groups. These nanogels based systems are promising candidates in the field of drug delivery. Combining nanogels with magneto-plasmonic nanoparticles (NPs) introduce imaging and targeting modalities along with stimuli-response in one hybrid system, thereby incorporating multifunctionality. Fe@Au core-shell NPs possess optical signature in the visible spectrum owing to localized surface plasmon resonance (LSPR) of the Au shell, and superparamagnetic properties stemming from the Fe core. Although there exist several synthesis methods to control the size and physico-chemical properties of pNIPAm-AAc nanogels, yet, there is no comprehensive study that highlights the dependence of incorporation of one or more layers of NPs to these nanogels. In addition, effective determination of volume phase transition temperature (VPTT) of the nanogels is a challenge which complicates their uses in biological applications. Here, we have modified the swelling-collapse properties of pNIPAm-AAc nanogels, by combining with Fe@Au NPs using different solution based methods. The hydrophilic-hydrophobic transition of the nanogels above the VPTT has been confirmed to be reversible. Further, an analytical method has been developed to deduce the average VPTT which is found to be 37.3°C for the nanogels and 39.3°C for nanogel coated Fe@Au NPs. An opposite swelling –collapse behaviour is observed for the latter where the Fe@Au NPs act as bridge molecules pulling together the gelling units. Thereafter, Cyt C, a model protein drug and L-Dopa, a drug used in the clinical treatment of Parkinson’s disease were loaded separately into the nanogels and nanogel coated Fe@Au NPs, using a modified breathing-in mechanism. This gave high loading and encapsulation efficiencies (L Dopa: ~9% and 70µg/mg of nanogels, Cyt C: ~30% and 10µg/mg of nanogels respectively for both the drugs. The release kinetics of L-Dopa, monitored using UV-vis spectrophotometry was observed to be rather slow (over several hours) with highest release happening under a combination of high temperature (above VPTT) and acidic conditions. However, the release of L-Dopa from nanogel coated Fe@Au NPs was the fastest, accounting for release of almost 87% of the initially loaded drug in ~30 hours. The chemical structure of the drug, drug incorporation method, location of the drug and presence of Fe@Au NPs largely alter the drug release mechanism and the kinetics of these nanogels and Fe@Au NPs coated with nanogels.

Keywords: controlled release, nanogels, volume phase transition temperature, l-dopa

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22 Emergency Department Utilisation of Older People Presenting to Four Emergency Departments

Authors: M. Fry, L. Fitzpatrick, Julie Considine, R. Z. Shaban, Kate Curtis

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Introduction: The vast majority of older Australians lives independently and are self-managing at home, despite a growing number living with a chronic illness that requires health intervention. Evidence shows that between 50% and 80% of people presenting to the emergency department (ED) are in pain. Australian EDs manage 7.2 million attendances every year and 1.4 million of these are people aged 65 years or more. Research shows that 28% of ED patients aged 65 years or more have Cognitive impairment (CI) associated with dementia, delirium and neurological conditions. Background: Traditional ED service delivery may not be suitable for older people who present with multiple, complex and ongoing illnesses. Likewise, ED clinical staff often perceive that their role should be focused more on immediate and potential lifethreatening illness and conditions which are episodic in nature. Therefore, the needs of older people and their family/carers may not be adequately addressed in the context of an ED presentation. Aim: We aimed to explore the utilisation and characteristics of older people presenting to four metropolitan EDs. Method: The findings being presented are part of a program of research exploring pain management practices for older persons with long bone fractures. The study was conducted across four metropolitan emergency departments of older patients (65years and over) and involved a 12-month randomised medical record audit (n=255). Results: ED presentations across four ED sites in 2012 numbered 168021, with 44778 (26.6%) patients aged 65 and over. Of the 44778 patients, the average age was 79.1 years (SD 8.54). There were more females 23932 (53.5%). The majority (26925: 85.0%) of older persons self-referred to the ED and lived independently. The majority arrived by ambulance (n=18553: 41.4%) and were allocated triage category was 3 (n=19,507:43.65%) or Triage category 4 at (n=15,389: 34.43%). The top five triage symptom presentations involved pain (n=8088; 18.25%), dyspnoea (n=4735; 10.7%), falls (n=4032; 9.1%), other (n=3984; 9.0%), cardiac (n=2987; 6.7%). The top five system based diagnostic presentations involved musculoskeletal (n=8902; 20.1%), cardiac (n=6704:15.0%), respiratory (n=4933; 11.0%), neurological (n=4909; 11.0%), gastroenterology (n=4321; 9.7%). On review of one tertiary hospital database the vital signs on average at time triage: Systolic Blood Pressure 143.6mmHg. Heart Rate 83.4 beats/minute; Respiratory Rate 18.5 breaths/ minute; Oxygen saturation 97.0% and Tympanic temperature 36.7 and Blood Glucose Level 7.4mmols/litre. The majority presented with a Glasgow Coma Score of 14 or higher. On average the older person stayed in the ED 4:56 (SD 3:28minutes).The average time to be seen was 39 minutes (SD 48 minutes). The majority of older persons were admitted (n=27562: 61.5%), did not wait for treatment (n= 8879: 0.02%) discharged home (n=16256: 36.0%). Conclusion: The vast majority of older persons are living independently, although many require admission on arrival to the ED. Many arrived in pain and with musculoskeletal injuries and or conditions. New models of care need to be considered, which may better support self-management and independent living of the older person and the National Emergency Access Targets.

Keywords: chronic, older person, aged care, emergency department

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21 Reframing Physical Activity for Health

Authors: M. Roberts

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We Are Undefeatable - is a mass marketing behaviour change campaign that aims to support the least active people living with long term health conditions to be more active. This is an important issue to address because people with long term conditions are an historically underserved community for the sport and physical activity sector and the least active of those with long term conditions have the most to gain in health and wellbeing benefits. The campaign has generated a significant change in the way physical activity is communicated and people with long term conditions are represented in the media and marketing. The goal is to create a social norm around being active. The campaign is led by a unique partnership of organisations: the Richmond Group of Charities (made up of Age UK, Alzheimer’s Society, Asthma + Lung UK, Breast Cancer Now, British Heart Foundation, British Red Cross, Diabetes UK, Macmillan Cancer Support, Rethink Mental Illness, Royal Voluntary Service, Stroke Association, Versus Arthritis) along with Mind, MS Society, Parkinson’s UK and Sport England, with National Lottery Funding. It is underpinned by the COM-B model of behaviour change. It draws on the lived experience of people with multiple long term conditions to shape the look and feel of the campaign and all the resources available. People with long term conditions are the campaign messengers, central to the ethos of the campaign by telling their individual stories of overcoming barriers to be active with their health conditions. The central messaging is about finding a way to be active that works for the individual. We Are Undefeatable is evaluated through a multi-modal approach, including regular qualitative focus groups and a quantitative evaluation tracker undertaken three times a year. The campaign has highlighted the significant barriers to physical activity for people with long term conditions. This has changed the way our partnership talks about physical activity but has also had an impact on the wider sport and physical activity sector, prompting an increasing departure from traditional messaging and marketing approaches for this audience of people with long term conditions. The campaign has reached millions of people since its launch in 2019, through multiple marketing and partnership channels including primetime TV advertising and promotion through health professionals and in health settings. Its diverse storytellers make it relatable to its target audience and the achievable activities highlighted and inclusive messaging inspire our audience to take action as a result of seeing the campaign. The We Are Undefeatable campaign is a blueprint for physical activity campaigns; it not only addresses individual behaviour change but plays a role in addressing systemic barriers to physical activity by sharing the lived experience insight to shape policy and professional practice.

Keywords: behaviour change, long term conditions, partnership, relatable

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20 Fabrication of High-Aspect Ratio Vertical Silicon Nanowire Electrode Arrays for Brain-Machine Interfaces

Authors: Su Yin Chiam, Zhipeng Ding, Guang Yang, Danny Jian Hang Tng, Peiyi Song, Geok Ing Ng, Ken-Tye Yong, Qing Xin Zhang

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Brain-machine interfaces (BMI) is a ground rich of exploration opportunities where manipulation of neural activity are used for interconnect with myriad form of external devices. These research and intensive development were evolved into various areas from medical field, gaming and entertainment industry till safety and security field. The technology were extended for neurological disorders therapy such as obsessive compulsive disorder and Parkinson’s disease by introducing current pulses to specific region of the brain. Nonetheless, the work to develop a real-time observing, recording and altering of neural signal brain-machine interfaces system will require a significant amount of effort to overcome the obstacles in improving this system without delay in response. To date, feature size of interface devices and the density of the electrode population remain as a limitation in achieving seamless performance on BMI. Currently, the size of the BMI devices is ranging from 10 to 100 microns in terms of electrodes’ diameters. Henceforth, to accommodate the single cell level precise monitoring, smaller and denser Nano-scaled nanowire electrode arrays are vital in fabrication. In this paper, we would like to showcase the fabrication of high aspect ratio of vertical silicon nanowire electrodes arrays using microelectromechanical system (MEMS) method. Nanofabrication of the nanowire electrodes involves in deep reactive ion etching, thermal oxide thinning, electron-beam lithography patterning, sputtering of metal targets and bottom anti-reflection coating (BARC) etch. Metallization on the nanowire electrode tip is a prominent process to optimize the nanowire electrical conductivity and this step remains a challenge during fabrication. Metal electrodes were lithographically defined and yet these metal contacts outline a size scale that is larger than nanometer-scale building blocks hence further limiting potential advantages. Therefore, we present an integrated contact solution that overcomes this size constraint through self-aligned Nickel silicidation process on the tip of vertical silicon nanowire electrodes. A 4 x 4 array of vertical silicon nanowires electrodes with the diameter of 290nm and height of 3µm has been successfully fabricated.

Keywords: brain-machine interfaces, microelectromechanical systems (MEMS), nanowire, nickel silicide

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19 Drones, Rebels and Bombs: Explaining the Role of Private Security and Expertise in a Post-piratical Indian Ocean

Authors: Jessica Kate Simonds

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The last successful hijacking perpetrated by Somali pirates in 2012 represented a critical turning point for the identity and brand of Indian Ocean (IO) insecurity, coined in this paper as the era of the post-piratical. This paper explores the broadening of the PMSC business model to account and contribute to the design of a new IO security environment that prioritises foreign and insurgency drone activity and Houthi rebel operations as the main threat to merchant shipping in the post-2012 era. This study is situated within a longer history of analysing maritime insecurity and also contributes a bespoke conceptual framework that understands the sea as a space that is produced and reproduced relative to existing and emerging threats to merchant shipping based on bespoke models of information sharing and intelligence acquisition. This paper also makes a prominent empirical contribution by drawing on a post-positivist methodology, data drawn from original semi-structured interviews with senior maritime insurers and active merchant seafarers that is triangulated with industry-produced guidance such as the BMP series as primary data sources. Each set is analysed through qualitative discourse and content analysis and supported by the quantitative data sets provided by the IMB Piracy Reporting center and intelligence networks. This analysis reveals that mechanisms such as the IGP&I Maritime Security Committee and intelligence divisions of PMSC’s have driven the exchanges of knowledge between land and sea and thus the reproduction of the maritime security environment through new regulations and guidance to account dones, rebels and bombs as the key challenges in the IO, beyond piracy. A contribution of this paper is the argument that experts who may not be in the highest-profile jobs are the architects of maritime insecurity based on their detailed knowledge and connections to vessels in transit. This paper shares the original insights of those who have served in critical decision making spaces to demonstrate that the development and refinement of industry produced deterrence guidance that has been accredited to the mitigation of piracy, have shaped new editions such as BMP 5 that now serve to frame a new security environment that prioritises the mitigation of risks from drones and WBEID’s from both state and insurgency risk groups. By highlighting the experiences and perspectives of key players on both land and at sea, the key finding of this paper is outlining that as pirates experienced a financial boom by profiteering from their bespoke business model during the peak of successful hijackings, the private security market encountered a similar level of financial success and guaranteed risk environment in which to prospect business. Thus, the reproduction of the Indian Ocean as a maritime security environment reflects a new found purpose for PMSC’s as part of the broader conglomerate of maritime insurers, regulators, shipowners and managers who continue to redirect the security consciousness and IO brand of insecurity.

Keywords: maritime security, private security, risk intelligence, political geography, international relations, political economy, maritime law, security studies

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18 The Adaptive Role of Negative Emotions in Optimal Functioning

Authors: Brianne Nichols, John A. Parkinson

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Positive Psychology has provided a rich understanding of the beneficial effects of positive emotions in relation to optimal functioning, and research has been devoted to promote states of positive feeling and thinking. While this is a worthwhile pursuit, positive emotions are not useful in all contexts - some situations may require the individual to make use of their negative emotions to reach a desired end state. To account for the potential value of a wider range of emotional experiences that are common to the human condition, Positive Psychology needs to expand its horizons and investigate how individuals achieve positive outcomes using varied means. The current research seeks to understand the positive psychology of fear of failure (FF), which is a commonly experienced negative emotion relevant to most life domains. On the one hand, this emotion has been linked with avoidance motivation and self-handicap behaviours, on the other; FF has been shown to act as a drive to move the individual forward. To fully capture the depth of this highly subjective emotional experience and understand the circumstances under which FF may be adaptive, this study adopted a mixed methods design using SenseMaker; a web-based tool that combines the richness of narratives with the objectivity of numerical data. Two hundred participants consisting mostly of undergraduate university students shared a story of a time in the recent past when they feared failure of achieving a valued goal. To avoid researcher bias in the interpretation of narratives, participants self-signified their stories in a tagging system that was based on researchers’ aim to explore the role of past failures, the cognitive, emotional and behavioural profile of individuals high and low in FF, and the relationship between these factors. In addition, the role of perceived personal control and self-esteem were investigated in relation to FF using self-report questionnaires. Results from quantitative analyses indicated that individuals with high levels of FF, compared to low, were strongly influenced by past failures and preoccupied with their thoughts and emotions relating to the fear. This group also reported an unwillingness to accept their internal experiences, which in turn was associated with withdrawal from goal pursuit. Furthermore, self-esteem was found to mediate the relationship between perceived control and FF, suggesting that self-esteem, with or without control beliefs, may have the potential to buffer against high FF. It is hoped that the insights provided by the current study will inspire future research to explore the ways in which ‘acceptance’ may help individuals keep moving towards a goal despite the presence of FF, and whether cultivating a non-contingent self-esteem is the key to resilience in the face of failures.

Keywords: fear of failure, goal-pursuit, negative emotions, optimal functioning, resilience

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17 Determinants of Quality of Life in Patients with Atypical Prarkinsonian Syndromes: 1-Year Follow-Up Study

Authors: Tatjana Pekmezovic, Milica Jecmenica-Lukic, Igor Petrovic, Vladimir Kostic

Abstract:

Background: A group of atypical parkinsonian syndromes (APS) includes a variety of rare neurodegenerative disorders characterized by reduced life expectancy, increasing disability, and considerable impact on health-related quality of life (HRQoL). Aim: In this study we wanted to answer two questions: a) which demographic and clinical factors are main contributors of HRQoL in our cohort of patients with APS, and b) how does quality of life of these patients change over 1-year follow-up period. Patients and Methods: We conducted a prospective cohort study in hospital settings. The initial study comprised all consecutive patients who were referred to the Department of Movement Disorders, Clinic of Neurology, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade (Serbia), from January 31, 2000 to July 31, 2013, with the initial diagnoses of ‘Parkinson’s disease’, ‘parkinsonism’, ‘atypical parkinsonism’ and ‘parkinsonism plus’ during the first 8 months from the appearance of first symptom(s). The patients were afterwards regularly followed in 4-6 month intervals and eventually the diagnoses were established for 46 patients fulfilling the criteria for clinically probable progressive supranuclear palsy (PSP) and 36 patients for probable multiple system atrophy (MSA). The health-related quality of life was assessed by using the SF-36 questionnaire (Serbian translation). Hierarchical multiple regression analysis was conducted to identify predictors of composite scores of SF-36. The importance of changes in quality of life scores of patients with APS between baseline and follow-up time-point were quantified using Wilcoxon Signed Ranks Test. The magnitude of any differences for the quality of life changes was calculated as an effect size (ES). Results: The final models of hierarchical regression analysis showed that apathy measured by the Apathy evaluation scale (AES) score accounted for 59% of the variance in the Physical Health Composite Score of SF-36 and 14% of the variance in the Mental Health Composite Score of SF-36 (p<0.01). The changes in HRQoL were assessed in 52 patients with APS who completed 1-year follow-up period. The analysis of magnitude for changes in HRQoL during one-year follow-up period have shown sustained medium ES (0.50-0.79) for both Physical and Mental health composite scores, total quality of life as well as for the Physical Health, Vitality, Role Emotional and Social Functioning. Conclusion: This study provides insight into new potential predictors of HRQoL and its changes over time in patients with APS. Additionally, identification of both prognostic markers of a poor HRQoL and magnitude of its changes should be considered when developing comprehensive treatment-related strategies and health care programs aimed at improving HRQoL and well-being in patients with APS.

Keywords: atypical parkinsonian syndromes, follow-up study, quality of life, APS

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16 The Solid-Phase Sensor Systems for Fluorescent and SERS-Recognition of Neurotransmitters for Their Visualization and Determination in Biomaterials

Authors: Irina Veselova, Maria Makedonskaya, Olga Eremina, Alexandr Sidorov, Eugene Goodilin, Tatyana Shekhovtsova

Abstract:

Such catecholamines as dopamine, norepinephrine, and epinephrine are the principal neurotransmitters in the sympathetic nervous system. Catecholamines and their metabolites are considered to be important markers of socially significant diseases such as atherosclerosis, diabetes, coronary heart disease, carcinogenesis, Alzheimer's and Parkinson's diseases. Currently, neurotransmitters can be studied via electrochemical and chromatographic techniques that allow their characterizing and quantification, although these techniques can only provide crude spatial information. Besides, the difficulty of catecholamine determination in biological materials is associated with their low normal concentrations (~ 1 nM) in biomaterials, which may become even one more order lower because of some disorders. In addition, in blood they are rapidly oxidized by monoaminooxidases from thrombocytes and, for this reason, the determination of neurotransmitter metabolism indicators in an organism should be very rapid (15—30 min), especially in critical states. Unfortunately, modern instrumental analysis does not offer a complex solution of this problem: despite its high sensitivity and selectivity, HPLC-MS cannot provide sufficiently rapid analysis, while enzymatic biosensors and immunoassays for the determination of the considered analytes lack sufficient sensitivity and reproducibility. Fluorescent and SERS-sensors remain a compelling technology for approaching the general problem of selective neurotransmitter detection. In recent years, a number of catecholamine sensors have been reported including RNA aptamers, fluorescent ribonucleopeptide (RNP) complexes, and boronic acid based synthetic receptors and the sensor operated in a turn-off mode. In this work we present the fluorescent and SERS turn-on sensor systems based on the bio- or chemorecognizing nanostructured films {chitosan/collagen-Tb/Eu/Cu-nanoparticles-indicator reagents} that provide the selective recognition, visualization, and sensing of the above mentioned catecholamines on the level of nanomolar concentrations in biomaterials (cell cultures, tissue etc.). We have (1) developed optically transparent porous films and gels of chitosan/collagen; (2) ensured functionalization of the surface by molecules-'recognizers' (by impregnation and immobilization of components of the indicator systems: biorecognizing and auxiliary reagents); (3) performed computer simulation for theoretical prediction and interpretation of some properties of the developed materials and obtained analytical signals in biomaterials. We are grateful for the financial support of this research from Russian Foundation for Basic Research (grants no. 15-03-05064 a, and 15-29-01330 ofi_m).

Keywords: biomaterials, fluorescent and SERS-recognition, neurotransmitters, solid-phase turn-on sensor system

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15 Fluorescence-Based Biosensor for Dopamine Detection Using Quantum Dots

Authors: Sylwia Krawiec, Joanna Cabaj, Karol Malecha

Abstract:

Nowadays, progress in the field of the analytical methods is of great interest for reliable biological research and medical diagnostics. Classical techniques of chemical analysis, despite many advantages, do not permit to obtain immediate results or automatization of measurements. Chemical sensors have displaced the conventional analytical methods - sensors combine precision, sensitivity, fast response and the possibility of continuous-monitoring. Biosensor is a chemical sensor, which except of conventer also possess a biologically active material, which is the basis for the detection of specific chemicals in the sample. Each biosensor device mainly consists of two elements: a sensitive element, where is recognition of receptor-analyte, and a transducer element which receives the signal and converts it into a measurable signal. Through these two elements biosensors can be divided in two categories: due to the recognition element (e.g immunosensor) and due to the transducer (e.g optical sensor). Working of optical sensor is based on measurements of quantitative changes of parameters characterizing light radiation. The most often analyzed parameters include: amplitude (intensity), frequency or polarization. Changes in the optical properties one of the compound which reacts with biological material coated on the sensor is analyzed by a direct method, in an indirect method indicators are used, which changes the optical properties due to the transformation of the testing species. The most commonly used dyes in this method are: small molecules with an aromatic ring, like rhodamine, fluorescent proteins, for example green fluorescent protein (GFP), or nanoparticles such as quantum dots (QDs). Quantum dots have, in comparison with organic dyes, much better photoluminescent properties, better bioavailability and chemical inertness. These are semiconductor nanocrystals size of 2-10 nm. This very limited number of atoms and the ‘nano’-size gives QDs these highly fluorescent properties. Rapid and sensitive detection of dopamine is extremely important in modern medicine. Dopamine is very important neurotransmitter, which mainly occurs in the brain and central nervous system of mammals. Dopamine is responsible for the transmission information of moving through the nervous system and plays an important role in processes of learning or memory. Detection of dopamine is significant for diseases associated with the central nervous system such as Parkinson or schizophrenia. In developed optical biosensor for detection of dopamine, are used graphene quantum dots (GQDs). In such sensor dopamine molecules coats the GQD surface - in result occurs quenching of fluorescence due to Resonance Energy Transfer (FRET). Changes in fluorescence correspond to specific concentrations of the neurotransmitter in tested sample, so it is possible to accurately determine the concentration of dopamine in the sample.

Keywords: biosensor, dopamine, fluorescence, quantum dots

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