Search results for: Monte Carlo methods

Authors: Aleksandra Rajewska-Rager, Maria Skibinska, Monika Dmitrzak-Weglarz, Natalia Lepczynska, Pawel Kapelski, Joanna Pawlak, Joanna Hauser

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Introduction: Inflammation and cytokines have emerged as a promising target in mood disorders research; however there are still very limited numbers of study regarding inflammatory alterations among adolescents and young adults with mood disorders. The Macrophage Migration Inhibitory Factor (MIF) and Stem Cell Factor (SCF) are the pleiotropic cytokines which may play an important role in mood disorders pathophysiology. The aim of this study was to investigate levels of these factors in serum of adolescent and young adults with mood disorders compared to healthy controls. Subjects: We involved 79 patients aged 12-24 years in 2-year follow-up study with a primary diagnosis of mood disorders: bipolar disorder (BP) and unipolar disorder with BP spectrum. Study group includes 23 males (mean age 19.08, SD 3.3) and 56 females (18.39, SD 3.28). Control group consisted 35 persons: 7 males (20.43, SD 4.23) and 28 females (21.25, SD 2.11). Clinical diagnoses according to DSM-IV-TR criteria were assessed using Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL) and Structured Clinical Interview for the Diagnostic and Statistical Manual (SCID) in young adults respectively. Clinical assessment includes evaluation of clinical factors and symptoms severity (rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale). Clinical and biological evaluations were made at control visits respectively at baseline (week 0), euthymia (at month 3 or 6) and after 12 and 24 months. Methods: Serum protein concentration was determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Human MIF and SCF DuoSet ELISA kits were used. In the analyses non-parametric tests were used: Mann-Whitney U test, Kruskal-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation. We defined statistical significance as p < 0.05. Results: Comparing MIF and SCF levels between acute episode of depression/hypo/mania at baseline and euthymia (at month 3 or 6) we did not find any statistical differences. At baseline patients with age above 18 years old had decreased MIF level compared to patients younger than 18 years. MIF level at baseline positively correlated with age (p=0.004). Positive correlations of SCF level at month 3 and 6 with depression or mania occurrence at month 24 (p=0.03 and p=0.04, respectively) was detected. Strong correlations between MIF and SCF levels at baseline (p=0.0005) and month 3 (p=0.03) were observed. Discussion: Our results did not show any differences in MIF and SCF levels between acute episode of depression/hypo/mania and euthymia in young patients. Further studies on larger groups are recommended. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.

Keywords: cytokines, MIF, mood disorders, SCF

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Authors: Jessie Rapoza, Petr Moroshkin, Jimmy Xu

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Chirality is omnipresent, in nature, in life, and in the field of physics. One intriguing example is the homochirality that has remained a great secret of life. Another is the pairs of mirror-image molecules – enantiomers. They are identical in atomic composition and therefore indistinguishable in the scalar physical properties. Yet, they can be either therapeutic or toxic, depending on their chirality. Recent studies suggest a potential link between abnormal levels of certain D-amino acids and some serious health impairments, including schizophrenia, amyotrophic lateral sclerosis, and potentially cancer. Although indistinguishable in their scalar properties, the chirality of a molecule reveals itself in interaction with the surrounding of a certain chirality, or more generally, a broken mirror-symmetry. In this work, we report on a system for chiral molecule detection, in which the mirror-symmetry is doubly broken, first by asymmetric structuring a nanopatterned plasmonic surface than by the incidence of circularly polarized light (CPL). In this system, the incident circularly-polarized light induces a surface plasmon polariton (SPP) wave, propagating along the asymmetric plasmonic surface. This SPP field itself is chiral, evanescently bound to a near-field zone on the surface (~10nm thick), but with an amplitude greatly intensified (by up to 104) over that of the incident light. It hence probes just the molecules on the surface instead of those in the volume. In coupling to molecules along its path on the surface, the chiral SPP wave favors one chirality over the other, allowing for chirality detection via the change in an optical rectification current measured at the edges of the sample. The asymmetrically structured surface converts the high-frequency electron plasmonic-oscillations in the SPP wave into a net DC drift current that can be measured at the edge of the sample via the mechanism of optical rectification. The measured results validate these design concepts and principles. The observed optical rectification current exhibits a clear differentiation between a pair of enantiomers. Experiments were performed by focusing a 1064nm CW laser light at the sample - a gold grating microchip submerged in an approximately 1.82M solution of either L-arabinose or D-arabinose and water. A measurement of the current output was then recorded under both rights and left circularly polarized lights. Measurements were recorded at various angles of incidence to optimize the coupling between the spin-momentums of the incident light and that of the SPP, that is, spin-momentum locking. In order to suppress the background, the values of the photocurrent for the right CPL are subtracted from those for the left CPL. Comparison between the two arabinose enantiomers reveals a preferential signal response of one enantiomer to left CPL and the other enantiomer to right CPL. In sum, this work reports on the first experimental evidence of the feasibility of chiral molecule detection via optical rectification in a metal meta-grating. This nanoscale interfaced electrical detection technology is advantageous over other detection methods due to its size, cost, ease of use, and integration ability with read-out electronic circuits for data processing and interpretation.

Keywords: Chirality, detection, molecule, spin

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Authors: Pauline Calleja, Brooke Alexander

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In 2010 the College of Emergency Nursing Australasia (CENA) undertook sole administration of the Trauma Nursing Program (TNP) across Australia. The original TNP was developed from recommendations by the Review of Trauma and Emergency Services-Victoria. While participant and faculty feedback about the program was positive, issues were identified that were common for industry training programs in Australia. These issues included didactic approaches, with many lectures and little interaction/activity for participants. Participants were not necessarily encouraged to undertake deep learning due to the teaching and learning principles underpinning the course, and thus participants described having to learn by rote, and only gain a surface understanding of principles that were not always applied to their working context. In Australia, a trauma or emergency nurse may work in variable contexts that impact on practice, especially where resources influence scope and capacity of hospitals to provide trauma care. In 2011, a program review was undertaken resulting in major changes to the curriculum, teaching, learning and assessment approaches. The aim was to improve learning including a greater emphasis on pre-program preparation for participants, the learning environment and clinically applicable contextualized outcomes participants experienced. Previously if participants wished to undertake assessment, they were given a take home examination. The assessment had poor uptake and return, and provided no rigor since assessment was not invigilated. A new assessment structure was enacted with an invigilated examination during course hours. These changes were implemented in early 2012 with great improvement in both faculty and participant satisfaction. This presentation reports on a comparison of participant evaluations collected from courses post implementation in 2012 and in 2015 to evaluate if positive changes were sustained. Methods: Descriptive statistics were applied in analyzing evaluations. Since all questions had more than 20% of cells with a count of <5, Fisher’s Exact Test was used to identify significance (p = <0.05) between groups. Results: A total of fourteen group evaluations were included in this analysis, seven CENA TNP groups from 2012 and seven from 2015 (randomly chosen). A total of 173 participant evaluations were collated (n = 81 from 2012 and 92 from 2015). All course evaluations were anonymous, and nine of the original 14 questions were applicable for this evaluation. All questions were rated by participants on a five-point Likert scale. While all items showed improvement from 2012 to 2015, significant improvement was noted in two items. These were in regard to the content being delivered in a way that met participant learning needs and satisfaction with the length and pace of the program. Evaluation of written comments supports these results. Discussion: The aim of redeveloping the CENA TNP was to improve learning and satisfaction for participants. These results demonstrate that initial improvements in 2012 were able to be maintained and in two essential areas significantly improved. Changes that increased participant engagement, support and contextualization of course materials were essential for CENA TNP evolution.

Keywords: emergency nursing education, industry training programs, teaching and learning, trauma education

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Authors: Mohammad Javaherian, Siamak Bashardoust Tajali, Monavvar Hadizadeh

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Objective: This systematic review study was conducted to evaluate the effects of Pulsed Electromagnetic (PEMF) and Static Magnetic Fields (SMG) on pain relief and functional improvement in patients with musculoskeletal Low Back Pain (LBP). Methods: Seven electronic databases were searched by two researchers independently to identify the published Randomized Controlled Trials (RCTs) on the efficacy of pulsed electromagnetic, static magnetic, and therapeutic nuclear magnetic fields. The identified databases for systematic search were Ovid Medline®, Ovid Cochrane RCTs and Reviews, PubMed, Web of Science, Cochrane Library, CINAHL, and EMBASE from 1968 to February 2016. The relevant keywords were selected by Mesh. After initial search and finding relevant manuscripts, all references in selected studies were searched to identify second hand possible manuscripts. The published RCTs in English would be included to the study if they reported changes on pain and/or functional disability following application of magnetic fields on chronic musculoskeletal low back pain. All studies with surgical patients, patients with pelvic pain, and combination of other treatment techniques such as acupuncture or diathermy were excluded. The identified studies were critically appraised and the data were extracted independently by two raters (M.J and S.B.T). Probable disagreements were resolved through discussion between raters. Results: In total, 1505 abstracts were found following the initial electronic search. The abstracts were reviewed to identify potentially relevant manuscripts. Seventeen possibly appropriate studies were retrieved in full-text of which 48 were excluded after reviewing their full-texts. Ten selected articles were categorized into three subgroups: PEMF (6 articles), SMF (3 articles), and therapeutic nuclear magnetic fields (tNMF) (1 article). Since one study evaluated tNMF, we had to exclude it. In the PEMF group, one study of acute LBP did not show significant positive results and the majority of the other five studies on Chronic Low Back Pain (CLBP) indicated its efficacy on pain relief and functional improvement, but one study with the lowest sessions (6 sessions during 2 weeks) did not report a significant difference between treatment and control groups. In the SMF subgroup, two articles reported near significant pain reduction without any functional improvement although more studies are needed. Conclusion: The PEMFs with a strength of 5 to 150 G or 0.1 to 0.3 G and a frequency of 5 to 64 Hz or sweep 7 to 7KHz can be considered as an effective modality in pain relief and functional improvement in patients with chronic low back pain, but there is not enough evidence to confirm their effectiveness in acute low back pain. To achieve the appropriate effectiveness, it is suggested to perform this treatment modality 20 minutes per day for at least 9 sessions. SMFs have not been reported to be substantially effective in decreasing pain or improving the function in chronic low back pain. More studies are necessary to achieve more reliable results.

Keywords: pulsed electromagnetic field, static magnetic field, magnetotherapy, low back pain

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Authors: Antonio Piga

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The issue of European cultural identity has become a prominent topic of discussion among political actors in the wake of the unsuccessful referenda held in France and the Netherlands in May and June 2006. The „period of reflection‟ announced by the European Council at the conclusion of June 2006 has provided an opportunity for the implementation of several initiatives and programmes designed to „bridge the gap‟ between the EU institutions and its citizens. Specific programmes were designed with the objective of enhancing the European Commission‟s external communication of its activities. Subsequently, further plans for democracy, debate, and dialogue were devised with the objective of fostering open and extensive discourse between EU institutions and citizens. Further documentation on communication policy emphasised the necessity of developing linguistic techniques to re-engage disenchanted or uninformed citizens with the European project. It was observed that the European Union is perceived as a „faceless‟ entity, which is attributed to the absence of a distinct public identity vis-à-vis its institutions. This contribution presents an analysis of a collection of informative publications regarding the European Union, entitled “Europe on the Move”. This collection of booklets provides comprehensive information about the European Union, including its historical origins, core values, and historical development, as well as its achievements, strategic objectives, policies, and operational procedures. The theoretical framework adopted for the longitudinal linguistic analysis of EU discourse is that of Systemic Functional Linguistics (SFL). In more detail, this study considers two basic systems of relations between clauses: firstly, the degree of interdependency (or taxis) and secondly, the logico-semantic relation of expansion. The former refers to the structural markers of grammatical relations between clauses within sentences, namely paratactic, hypotactic and embedded relations. The latter pertains to various logicosemantic relationships existing between the primary and secondary members of the clause nexus. These relationships include how the secondary clause expands the primary clause, which may be achieved by (a) elaborating it, (b) extending it or (c) enhancing it. This study examines the impact of the European Commission‟s post-referendum communication methods on the portrayal of Europe, its role in facilitating the EU institutional process, and its articulation of a specific EU identity linked to distinct values. The research reveals that the language employed by the EU is evidently grounded in an explanatory logic, elucidating the rationale behind their institutionalised acts. Nevertheless, the minimal use of hypotaxis in the post-referendum booklets, coupled with the inconsistent yet increasing ratio of parataxis to hypotaxis, may suggest a potential shift towards a logic of appearance, characterised by a predominant reliance on coordination and additive, and elaborative logico-semantic relations.

Keywords: systemic functional linguistics, logic of appearance, explanatory logic, interdependency, logico-semantic relation

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Authors: Z. Yousefniayejahr, S. Bolognini, A. Bonini, C. Campobasso, N. Poma, F. Vivaldi, M. Di Luca, A. Tavanti, F. Di Francesco

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Pathogenic bacteria represent a threat to healthcare systems and the food industry because their rapid detection remains challenging. Electrochemical biosensors are gaining prominence as a novel technology for the detection of pathogens due to intrinsic features such as low cost, rapid response time, and portability, which make them a valuable alternative to traditional methodologies. These sensors use biorecognition elements that are crucial for the identification of specific bacteria. In this context, bacteriophages are promising tools for their inherent high selectivity towards bacterial hosts, which is of fundamental importance when detecting bacterial pathogens in complex biological samples. In this study, we present the development of a low-cost and portable sensor based on the Zeno phage for the rapid detection of Staphylococcus aureus. Screen-printed gold electrodes functionalized with the Zeno phage were used, and electrochemical impedance spectroscopy was applied to evaluate the change of the charge transfer resistance (Rct) as a result of the interaction with S. aureus MRSA ATCC 43300. The phage-based biosensor showed a linear range from 101 to 104 CFU/mL with a 20-minute response time and a limit of detection (LOD) of 1.2 CFU/mL under physiological conditions. The biosensor’s ability to recognize various strains of staphylococci was also successfully demonstrated in the presence of clinical isolates collected from different geographic areas. Assays using S. epidermidis were also carried out to verify the species-specificity of the phage sensor. We only observed a remarkable change of the Rct in the presence of the target S. aureus bacteria, while no substantial binding to S. epidermidis occurred. This confirmed that the Zeno phage sensor only targets S. aureus species within the genus Staphylococcus. In addition, the biosensor's specificity with respect to other bacterial species, including gram-positive bacteria like Enterococcus faecium and the gram-negative bacterium Pseudomonas aeruginosa, was evaluated, and a non-significant impedimetric signal was observed. Notably, the biosensor successfully identified S. aureus bacterial cells in a complex matrix such as a nasal swab, opening the possibility of its use in a real-case scenario. We diluted different concentrations of S. aureus from 108 to 100 CFU/mL with a ratio of 1:10 in the nasal swap matrices collected from healthy donors. Three different sensors were applied to measure various concentrations of bacteria. Our sensor indicated high selectivity to detect S. aureus in biological matrices compared to time-consuming traditional methods, such as enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and radioimmunoassay (RIA), etc. With the aim to study the possibility to use this biosensor to address the challenge associated to pathogen detection, ongoing research is focused on the assessment of the biosensor’s analytical performances in different biological samples and the discovery of new phage bioreceptors.

Keywords: electrochemical impedance spectroscopy, bacteriophage, biosensor, Staphylococcus aureus

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Authors: Sam Bartlett, Thomas Bacquart, Arul Murugan, Abigail Morris

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Fuel cell electric vehicles provide the potential to decarbonise road transport, create new economic opportunities, diversify national energy supply, and significantly reduce the environmental impacts of road transport. A potential issue, however, is that the catalyst used at the fuel cell cathode is susceptible to degradation by impurities, especially sulphur-containing compounds. A recent European Directive (2014/94/EU) stipulates that, from November 2017, all hydrogen provided to fuel cell vehicles in Europe must comply with the hydrogen purity specifications listed in ISO 14687-2; this includes reactive and toxic chemicals such as ammonia and total sulphur-containing compounds. This requirement poses great analytical challenges due to the instability of some of these compounds in calibration gas standards at relatively low amount fractions and the difficulty associated with undertaking measurements of groups of compounds rather than individual compounds. Without the available reference materials and analytical infrastructure, hydrogen refuelling stations will not be able to demonstrate compliance to the ISO 14687 specifications. The hydrogen purity laboratory at NPL provides world leading, accredited purity measurements to allow hydrogen refuelling stations to evidence compliance to ISO 14687. Utilising state-of-the-art methods that have been developed by NPL’s hydrogen purity laboratory, including a novel method for measuring total sulphur compounds at 4 nmol/mol and a hydrogen impurity enrichment device, we provide the capabilities necessary to achieve these goals. An overview of these capabilities will be given in this paper. As part of the EMPIR Hydrogen co-normative project ‘Metrology for sustainable hydrogen energy applications’, NPL are developing a validated analytical methodology for the measurement of speciated sulphur-containing compounds in hydrogen at low amount fractions pmol/mol to nmol/mol) to allow identification and measurement of individual sulphur-containing impurities in real samples of hydrogen (opposed to a ‘total sulphur’ measurement). This is achieved by producing a suite of stable gravimetrically-prepared primary reference gas standards containing low amount fractions of sulphur-containing compounds (hydrogen sulphide, carbonyl sulphide, carbon disulphide, 2-methyl-2-propanethiol and tetrahydrothiophene have been selected for use in this study) to be used in conjunction with novel dynamic dilution facilities to enable generation of pmol/mol to nmol/mol level gas mixtures (a dynamic method is required as compounds at these levels would be unstable in gas cylinder mixtures). Method development and optimisation are performed using gas chromatographic techniques assisted by cryo-trapping technologies and coupled with sulphur chemiluminescence detection to allow improved qualitative and quantitative analyses of sulphur-containing impurities in hydrogen. The paper will review the state-of-the art gas standard preparation techniques, including the use and testing of dynamic dilution technologies for reactive chemical components in hydrogen. Method development will also be presented highlighting the advances in the measurement of speciated sulphur compounds in hydrogen at low amount fractions.

Keywords: gas chromatography, hydrogen purity, ISO 14687, sulphur chemiluminescence detector

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Authors: Kamal Tolani, Sandeep Kumar, Rohit Luthra, Ankit Dadhania, Krishnaprasad K., Ram Gupta, Deepa Joshi

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Background: Post-operative analgesia remains a clinical challenge, with central and peripheral sensitization playing a pivotal role in treatment-related complications and impaired quality of life. Centrally acting opioids offer poor risk benefit profile with increased intensity of gastrointestinal or central side effects and slow onset of clinical analgesia. The objective of this study was to assess the clinical feasibility of induction and maintenance therapy with Tapentadol Nasal Spray (NS) in moderate to severe acute post-operative pain. Methods: Phase III, randomized, active-controlled, non-inferiority clinical trial involving 294 cases who had undergone surgical procedures under general anesthesia or regional anesthesia. Post-surgery patients were randomized to receive either Tapentadol NS 45 mg or Tramadol 100mg IV as a bolus and subsequent 50 mg or 100 mg dose over 2-3 minutes. The frequency of administration of NS was at every 4-6 hours. At the end of 24 hrs, patients in the tramadol group who had a pain intensity score of ≥4 were switched to oral tramadol immediate release 100mg capsule until the pain intensity score reduced to <4. All patients who had achieved pain intensity ≤ 4 were shifted to a lower dose of either Tapentadol NS 22.5 mg or oral Tramadol immediate release 50mg capsule. The statistical analysis plan was envisaged as a non-inferiority trial involving comparison with Tramadol for Pain intensity difference at 60 minutes (PID60min), Sum of Pain intensity difference at 60 minutes (SPID60min), and Physician Global Assessment at 24 hrs (PGA24 hrs). Results: The per-protocol analyses involved 255 hospitalized cases undergoing surgical procedures. The median age of patients was 38.0 years. For the primary efficacy variables, Tapentadol NS was non-inferior to Inj/Oral Tramadol in relief of moderate to severe post-operative pain. On the basis of SPID60min, no clinically significant difference was observed between Tapentadol NS and Tramadol IV (1.73±2.24 vs. 1.64± 1.92, -0.09 [95% CI, -0.43, 0.60]). In the co-primary endpoint PGA24hrs, Tapentadol NS was non–inferior to Tramadol IV (2.12 ± 0.707 vs. 2.02 ±0.704, - 0.11[95% CI, -0.07, 0.28). However, on further assessment at 48hr, 72 hrs, and 120hrs, clinically superior pain relief was observed with the Tapentadol NS formulation that was statistically significant (p <0.05) at each of the time intervals. Secondary efficacy measures, including the onset of clinical analgesia and TOTPAR, showed non-inferiority to Tramadol. The safety profile and need for rescue medication were also similar in both the groups during the treatment period. The most common concomitant medications were anti-bacterial (98.3%). Conclusion: Tapentadol NS is a clinically feasible option for improved compliance as induction and maintenance therapy while offering a sustained and persistent patient response that is clinically meaningful in post-surgical settings.

Keywords: tapentadol nasal spray, acute pain, tramadol, post-operative pain

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Authors: Tavee Cheausuwantavee

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: COVID-19 pandemic significantly has impacted everyone’s life. Persons with disabilities (PWDs) in Thailand have been also effected by COVID-19 situation in many aspects of their lives, while there have been no more appropriate services of the government and providers. Research projects had been only focused on health precaution and protection. Rapid need assessments on populations and vulnerable groups were limited and conducted via social media and an online survey. However, little is known about the real problems and needs of Thai PWDs during the COVID-19 pandemic for an effective plan and integral services for those PWDs. Therefore, this study aims to explore the diverse problems and needs of Thai PWDs in the COVID -19 pandemic. Results from the study can be used by the government and other stakeholders for further effective services. Methods: This study was used a mixed-method design that consisted of both quantitative and qualitative measures. In terms of the quantitative approach, there were 744 PWDs and caregivers of all types of PWDs selected by proportional multistage stratified random sampling according to their disability classification and geographic location. Questionnaires with 59 items regarding participant characteristics, problems, and needs in health, education, employment, and other social inclusion, were distributed to all participants and some caregivers completed questionnaires when PWDs were not able to due to limited communication and/or literacy skills. Completed questionnaires were analyzed by descriptive statistics. For qualitative design, 62 key informants who were PWDs or caregivers were selected by purposive sampling. Ten focus groups, each consisting of 5-6 participants and 7 in-depth interviews from all the groups identified above, were conducted by researchers across five regions. Focus group and in-depth interview guidelines with 6 items regarding problems and needs in health, education, employment, other social inclusion, and their coping during COVID -19 pandemic. Data were analyzed using a modification of thematic content analysis. Results: Both quantitative and qualitative studies showed that PWDs and their caregivers had significant problems and needs all aspects of their life, including income and employment opportunity, daily living and social inclusion, health, and education, respectively. These problems and needs were related to each other, forming a vicious cycle. Participants also learned from negative pandemic to more positive life aspects, including their health protection, financial plan, family cohesion, and virtual technology literacy and innovation. Conclusion and implications: There have been challenges facing all life aspects of PWDs in Thailand during the COVID -19 pandemic, particularly incomes and daily living. All challenges have been the vicious cycle and complicated. There have been also a positive lesson learned of participants from the pandemic. Recommendations for government and stakeholders in the COVID-19 pandemic for PWDs are the following. First, the health protection strategy and policy of PWDs should be promoted together with other quality of life development including income generation, education and social inclusion. Second, virtual technology and alternative innovation should be enhanced for proactive service providers. Third, accessible information during the pandemic for all PWDs must be concerned. Forth, lesson learned from the pandemic should be shared and disseminated for crisis preparation and a positive mindset in the disruptive world.

Keywords: challenge, COVID-19, disability, Thailand

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Authors: Jia Li, Xing Wei, Yuchen Hong, Yang Lu

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Detecting vehicle behavior has always been the focus of intelligent transportation, but with the explosive growth of the number of vehicles and the complexity of the road environment, the vehicle behavior videos captured by traditional surveillance have been unable to satisfy the study of vehicle behavior. The traditional method of manually labeling vehicle behavior is too time-consuming and labor-intensive, but the existing object detection and tracking algorithms have poor practicability and low behavioral location detection rate. This paper proposes a vehicle behavior detection algorithm based on the dual-stream convolution network and the multi-dimensional video dynamic detection network. In the videos, the straight-line behavior of the vehicle will default to the background behavior. The Changing lanes, turning and turning around are set as target behaviors. The purpose of this model is to automatically mark the target behavior of the vehicle from the untrimmed videos. First, the target behavior proposals in the long video are extracted through the dual-stream convolution network. The model uses a dual-stream convolutional network to generate a one-dimensional action score waveform, and then extract segments with scores above a given threshold M into preliminary vehicle behavior proposals. Second, the preliminary proposals are pruned and identified using the multi-dimensional video dynamic detection network. Referring to the hierarchical reinforcement learning, the multi-dimensional network includes a Timer module and a Spacer module, where the Timer module mines time information in the video stream and the Spacer module extracts spatial information in the video frame. The Timer and Spacer module are implemented by Long Short-Term Memory (LSTM) and start from an all-zero hidden state. The Timer module uses the Transformer mechanism to extract timing information from the video stream and extract features by linear mapping and other methods. Finally, the model fuses time information and spatial information and obtains the location and category of the behavior through the softmax layer. This paper uses recall and precision to measure the performance of the model. Extensive experiments show that based on the dataset of this paper, the proposed model has obvious advantages compared with the existing state-of-the-art behavior detection algorithms. When the Time Intersection over Union (TIoU) threshold is 0.5, the Average-Precision (MP) reaches 36.3% (the MP of baselines is 21.5%). In summary, this paper proposes a vehicle behavior detection model based on multi-dimensional dynamic detection network. This paper introduces spatial information and temporal information to extract vehicle behaviors in long videos. Experiments show that the proposed algorithm is advanced and accurate in-vehicle timing behavior detection. In the future, the focus will be on simultaneously detecting the timing behavior of multiple vehicles in complex traffic scenes (such as a busy street) while ensuring accuracy.

Keywords: vehicle behavior detection, convolutional neural network, long short-term memory, deep learning

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Authors: Marzieh Nojomi, Azadeh Mottaghi, Arghavan Haj-Sheykholeslami, Narjes Khalili, Arash Tehrani Banihashemi

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Background and objectives: Domestic violence is a global problem with severe consequences throughout the life of the victims. Iran’s Ministry of Health has launched an intimate partner violence (IPV) prevention program, integrated in the primary health care services since 2016. The present study is a part of this national program’s evaluation. In this section, we aimed to examine spousal abuse victims’ knowledge and attitude towards domestic violence before and after receivingthese services. Methods: To assess the knowledge and attitudes of victims, a questionnaire designed by Ahmadzadand colleagues in 2013 was used. This questionnaire includes 15 questions regarding knowledge in the fields of definition, epidemiology, and effects on children, outcomes, and prevention of domestic violence. To assess the attitudes, this questionnaire has 10 questions regarding the attitudes toward the causes, effects, and legal or protective support services of domestic violence. To assess the satisfaction and the effect of the program on prevention or reduction of spousal violence episodes, two more questions were also added. Since domestic violence prevalence differs in different parts of the country, we chose nine areas with the highest, the lowest, and moderate prevalence of IPVfor the study. The link to final electronic version of the questionnaire was sent to the randomly selected public rural or urban health centers in the nine chosen areas. Since the study had to be completed in one month, we used newly identified victims as pre-intervention group and people who had at least received one related service from the program (like psychiatric consultation, education about safety measures, supporting organizations and etc.) during the previous year, as our post- intervention group. Results: A hundred and ninety-two newly identified IPV victims and 267 victims who had at least received one related program service during the previous year entered the study. All of the victims were female. Basic characteristics of the two groups, including age, education, occupation, addiction, spouses’ age, spouses’ addiction, duration of the current marriage, and number of children, were not statistically different. In knowledge questions, post- intervention group had statistically better scores in the fields of domestic violence outcomes and its effects on children; however, in the remaining areas, the scores of both groups were similar. The only significant difference in the attitude across the two groups was in the field of legal or protective support services. From the 267 women who had ever received a service from the program, 91.8% were satisfied with the services, and 74% reported a decrease in the number of violent episodes. Conclusion: National IPV prevention program integrated in the primary health care services in Iran is effective in improving the knowledge of victims about domestic violence outcomes and its effects on children. Improving the attitude and knowledge of domestic violence victims about its causes and preventive measures needs more effective interventions. This program can reduce the number of IPV episodes between the spouses, and satisfaction among the service users is high.

Keywords: intimate partner violence, assessment, health services, efficacy

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Authors: Gideon Nyuimbe Gasu

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Sub Saharan Africa is at a critical point, experiencing rapid population growth, particularly in urban areas and young growing force. At the same time, the growing risk of catastrophic global climate change threatens to weaken food production system, increase intensity and frequency of drought, flood, and fires and undermine gains on development and poverty reduction. Although the region has the lowest per capital greenhouse gas emission level in the world, it will need to join global efforts to address climate change, including action to avoid significant increases and to encourage a green economy. Thus, there is a need for the concept of 'greening the economy' as was prescribed at Rio Summit of 1992. Renewable energy is one of the criterions to achieve this laudable goal of maintaining a green economy. There is need to address climate change while facilitating continued economic growth and social progress as energy today is critical to economic growth. Fossil fuels remain the major contributor of greenhouse gas emission. Thus, cleaner technologies such as carbon capture storage, renewable energy have emerged to be commercially competitive. This paper sets out to examine how to achieve a low carbon economy with minimal emission of carbon dioxide and other greenhouse gases which is one of the outcomes of implementing a green economy. Also, the paper examines the different renewable energy sources such as nuclear, wind, hydro, biofuel, and solar voltaic as a panacea to the looming climate change menace. Finally, the paper assesses the different renewable energy and energy efficiency as a propeller to generating new sources of income and jobs and in turn reduces carbon emission. The research shall engage qualitative, evaluative and comparative methods. The research will employ both primary and secondary sources of information. The primary sources of information shall be drawn from the sub Saharan African region and the global environmental organizations, energy legislation, policies and related industries and the judicial processes. The secondary sources will be made up of some books, journal articles, commentaries, discussions, observations, explanations, expositions, suggestions, prescriptions and other material sourced from the internet on renewable energy as a panacea to climate change. All information obtained from these sources will be subject to content analysis. The research result will show that the entire planet is warming as a result of the activities of mankind which is clear evidence that the current development is fundamentally unsustainable. Equally, the study will reveal that a low carbon development pathway in the sub Saharan African region should be embraced to minimize emission of greenhouse gases such as using renewable energy rather than coal, oil, and gas. The study concludes that until adequate strategies are devised towards the use of renewable energy the region will continue to add and worsen the current climate change menace and other adverse environmental conditions.

Keywords: carbon dioxide, climate change, legislation/law, renewable energy

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Authors: Tali Neta

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Humans’ impact on the environment has been incredibly brutal, with enormous plastic- and other pollutants (e.g., cigarette buds, paper cups, tires) worldwide. On land, litter costs taxpayers a fortune. Most of the litter pollution comes from the land, yet it is one of the greatest hazards to marine environments. Due to spatial and temporal limitations, previous litter data covered very small areas. Currently, smartphones can be used to obtain information on various pollutants (through citizen science), and they can greatly assist in acknowledging and mitigating the environmental impact of litter. Litter app data, such as the Litterati, are available for study through a global map only; these data are not available for download, and it is not clear whether irrelevant hashtags have been eliminated. Instagram and Twitter open-source geospatial data are available for download; however, these are considered inaccurate, computationally challenging, and impossible to quantify. Therefore, the resulting data are of poor quality. Other downloadable geospatial data (e.g., Marine Debris Tracker8 and Clean Swell10) are focused on marine- rather than terrestrial litter. Therefore, accurate terrestrial geospatial documentation of litter distribution is needed to improve environmental awareness. The current research employed citizen science to examine litter distribution in Lethbridge, Alberta, Canada, using the OpenLitterMap (OLM) app. The OLM app is an application used to track litter worldwide, and it can mark litter locations through photo georeferencing, which can be presented through GIS-designed maps. The OLM app provides open-source data that can be downloaded. It also offers information on various litter types and “hot-spots” areas where litter accumulates. In this study, Lethbridge College students collected litter data with the OLM app. The students produced GIS Story Maps (interactive web GIS illustrations) and presented these to school children to improve awareness of litter's impact on environmental health. Preliminary results indicate that towards the Lethbridge Coulees’ (valleys) East edges, the amount of litter significantly increased due to shrubs’ presence, that acted as litter catches. As wind generally travels from west to east in Lethbridge, litter in West-Lethbridge often finds its way down in the east part of the coulees. The students’ documented various litter types, while the majority (75%) included plastic and paper food packaging. The students also found metal wires, broken glass, plastic bottles, golf balls, and tires. Presentations of the Story Maps to school children had a significant impact, as the children voluntarily collected litter during school recess, and they were looking into solutions to reduce litter. Further litter distribution documentation through Citizen Science is needed to improve public awareness. Additionally, future research will be focused on Drone imagery of highly concentrated litter areas. Finally, a time series analysis of litter distribution will help us determine whether public education through Citizen Science and Story Maps can assist in reducing litter and reaching a cleaner and healthier environment.

Keywords: citizen science, litter pollution, Open Litter Map, GIS Story Map

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Authors: Susmita Ghosh

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Catchment area of Damodar River, India experiences seasonal rains due to the south-west monsoon every year and depending upon the intensity of the storms, floods occur. During the monsoon season, the rainfall in the area is mainly due to active monsoon conditions. The upstream reach of Damodar river system has five dams store the water for utilization for various purposes viz, irrigation, hydro-power generation, municipal supplies and last but not the least flood moderation. But, in the downstream reach of Damodar River, known as Lower Damodar region, is severely and frequently suffering from flood due to heavy monsoon rainfall and also release from upstream reservoirs. Therefore, an effective flood management study is required to know in depth the nature and extent of flood, water logging, and erosion related problems, affected area, and damages in the Lower Damodar region, by conducting mathematical model study. The design flood or discharge is needed to decide to assign the respective model for getting several scenarios from the simulation runs. The ultimate aim is to achieve a sustainable flood management scheme from the several alternatives. there are various methods for estimating flood discharges to be carried through the rivers and their tributaries for quick drainage from inundated areas due to drainage congestion and excess rainfall. In the present study, the flood frequency analysis is performed to decide the design flood discharge of the study area. This, on the other hand, has limitations in respect of availability of long peak flood data record for determining long type of probability density function correctly. If sufficient past records are available, the maximum flood on a river with a given frequency can safely be determined. The floods of different frequency for the Damodar has been calculated by five candidate distributions i.e., generalized extreme value, extreme value-I, Pearson type III, Log Pearson and normal. Annual peak discharge series are available at Durgapur barrage for the period of 1979 to 2013 (35 years). The available series are subjected to frequency analysis. The primary objective of the flood frequency analysis is to relate the magnitude of extreme events to their frequencies of occurrence through the use of probability distributions. The design flood for return periods of 10, 15 and 25 years return period at Durgapur barrage are estimated by flood frequency method. It is necessary to develop flood hydrographs for the above floods to facilitate the mathematical model studies to find the depth and extent of inundation etc. Null hypothesis that the distributions fit the data at 95% confidence is checked with goodness of fit test, i.e., Chi Square Test. It is revealed from the goodness of fit test that the all five distributions do show a good fit on the sample population and is therefore accepted. However, it is seen that there is considerable variation in the estimation of frequency flood. It is therefore considered prudent to average out the results of these five distributions for required frequencies. The inundated area from past data is well matched using this flood.

Keywords: design discharge, flood frequency, goodness of fit, sustainable flood management

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Authors: Dalia Ambrazaitienė, Monika Vilkienė, Danute Karcauskienė, Gintaras Siaudinis

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The soil is a complex ecosystem that is part of our biosphere. The ability of soil to provide ecosystem services is dependent on microbial diversity. T Tillage is one of the major factors that affect soil properties. The no-till systems or shallow ploughless tillage are opposite of traditional deep ploughing, no-tillage systems, for instance, increase soil organic matter by reducing mineralization rates and stimulating litter concentrations of the top soil layer, whereas deep ploughing increases the biological activity of arable soil layer and reduces the incidence of weeds. The role of soil organisms is central to soil processes. Although the number of microbial species in soil is still being debated, the metagenomic approach to estimate microbial diversity predicted about 2000 – 18 000 bacterial genomes in 1 g of soil. Despite the key role of bacteria in soil processes, there is still lack of information about the bacterial diversity of soils as affected by tillage practices. This study focused on metagenomic analysis of bacterial diversity in long-term experimental plots of Dystric Epihypogleyic Albeluvisols in western part of Lithuania. The experiment was set up in 2013 and had a split-plot design where the whole-plot treatments were laid out in a randomized design with three replicates. The whole-plot treatments consisted of two tillage methods - deep ploughing (22-25 cm) (DP), ploughless tillage (7-10 cm) (PT). Three subsamples (0-20 cm) were collected on October 22, 2015 for each of the three replicates. Subsamples from the DP and PT systems were pooled together wise to make two composition samples, one representing deep ploughing (DP) and the other ploughless tillage (PT). Genomic DNA from soil sample was extracted from approximately 200 mg field-moist soil by using the D6005 Fungal/Bacterial Miniprep set (Zymo Research®) following the manufacturer’s instructions. To determine bacterial diversity and community composition, we employed a culture – independent approach of high-throughput pyrosequencing of the 16S rRNA gene. Metagenomic sequencing was made with Illumina MiSeq platform in Base Clear Company. The microbial component of soil plays a crucial role in cycling of nutrients in biosphere. Our study was a preliminary attempt at observing bacterial diversity in soil under two common but contrasting tillage practices. The number of sequenced reads obtained for PT (161 917) was higher than DP (131 194). The 10 most abundant genus in soil sample were the same (Arthrobacter, Candidatus Saccharibacteria, Actinobacteria, Acidobacterium, Mycobacterium, Bacillus, Alphaproteobacteria, Longilinea, Gemmatimonas, Solirubrobacter), just the percent of community part was different. In DP the Arthrobacter and Acidobacterium consist respectively 8.4 % and 2.5%, meanwhile in PT just 5.8% and 2.1% of all community. The Nocardioides and Terrabacter were observed just in PT. This work was supported by the project VP1-3.1-ŠMM-01-V-03-001 NKPDOKT and National Science Program: The effect of long-term, different-intensity management of resources on the soils of different genesis and on other components of the agro-ecosystems [grant number SIT-9/2015] funded by the Research Council of Lithuania.

Keywords: deep ploughing, metagenomics, ploughless tillage, soil community analysis

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Authors: Luisa Kynast

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It is obvious that buildings and infrastructure are highly impacted by climate change (CC). Both, design and material of buildings need to be resilient to weather events in order to shelter humans, animals, or goods. As well as buildings and infrastructure are exposed to weather events, the construction process itself is generally carried out outdoors without being protected from extreme temperatures, heavy rain, or storms. The production process is restricted by technical limitations for processing materials with machines and physical limitations due to human beings (“outdoor-worker”). In future due to CC, average weather patterns are expected to change as well as extreme weather events are expected to occur more frequently and more intense and therefore have a greater impact on production processes and on the construction businesses itself. This research aims to examine this impact by analyzing an association between responses to CC and financial performance of businesses within the construction industry. After having embedded the above depicted field of research into the resource dependency theory, a literature review was conducted to expound the state of research concerning a contingent relation between climate change adaptation measures (CCAM) and corporate financial performance for construction businesses. The examined studies prove that this field is rarely investigated, especially for construction businesses. Therefore, reports of the Carbon Disclosure Project (CDP) were analyzed by applying content analysis using the software tool MAXQDA. 58 construction companies – located worldwide – could be examined. To proceed even more systematically a coding scheme analogous to findings in literature was adopted. Out of qualitative analysis, data was quantified and a regression analysis containing corporate financial data was conducted. The results gained stress adaptation measures as a response to CC as a crucial proxy to handle climate change impacts (CCI) by mitigating risks and exploiting opportunities. In CDP reports the majority of answers stated increasing costs/expenses as a result of implemented measures. A link to sales/revenue was rarely drawn. Though, CCAM were connected to increasing sales/revenues. Nevertheless, this presumption is supported by the results of the regression analysis where a positive effect of implemented CCAM on construction businesses´ financial performance in the short-run was ascertained. These findings do refer to appropriate responses in terms of the implemented number of CCAM. Anyhow, still businesses show a reluctant attitude for implementing CCAM, which was confirmed by findings in literature as well as by findings in CDP reports. Businesses mainly associate CCAM with costs and expenses rather than with an effect on their corporate financial performance. Mostly companies underrate the effect of CCI and overrate the costs and expenditures for the implementation of CCAM and completely neglect the pay-off. Therefore, this research shall create a basis for bringing CC to the (financial) attention of corporate decision-makers, especially within the construction industry.

Keywords: climate change adaptation measures, construction businesses, financial implication, resource dependency theory

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Authors: Ifeyinwa Victor-Uadiale, Georgina Pearson, Sophie Witter, D. Reidpath

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Introduction: Smoking, alcohol misuse, unhealthy diet, and physical inactivity are the primary drivers of noncommunicable diseases (NCD), including cardiovascular diseases, cancers, respiratory diseases, and diabetes, worldwide. Collectively, these diseases are the leading cause of all global deaths, most of which are premature, affecting people between 30 and 70 years. Empirical evidence suggests that these risk behaviors can be modified by community-based interventions (CBI). However, there is little insight into the mechanisms and contextual factors of successful community interventions that impact risk behaviours for chronic diseases. This study examined “Under what circumstances, for whom, and how, do community-based interventions modify smoking, alcohol use, unhealthy diet, and physical inactivity among adults”. Adopting the Capability (C), Opportunity (O), Motivation (M), Behavior (B) (COM-B) framework for behaviour change, it sought to: (1) identify the mechanisms through which CBIs could reduce tobacco use and alcohol consumption and increase physical activity and the consumption of healthy diets and (2) examine the contextual factors that trigger the impact of these mechanisms on these risk behaviours among adults. Methods: Pawson’s realist review method was used to examine the literature. Empirical evidence and theoretical understanding were combined to develop a realist program theory that explains how CBIs influence NCD risk behaviours. Documents published between 2002 and 2020 were systematically searched in five electronic databases (CINAHL, Cochrane Library, Medline, ProQuest Central, and PsycINFO). They were included if they reported on community-based interventions aimed at cardiovascular diseases, cancers, respiratory diseases, and diabetes in a global context; and had an outcome targeted at smoking, alcohol, physical activity, and diet. Findings: Twenty-nine scientific documents were retrieved and included in the review. Over half of them (n = 18; 62%) focused on three of the four risk behaviours investigated in this review. The review identified four mechanisms: capability, opportunity, motivation, and social support that are likely to change the dietary and physical activity behaviours in adults given certain contexts. There were weak explanations of how the identified mechanisms could likely change smoking and alcohol consumption habits. In addition, eight contextual factors that may affect how these mechanisms impact physical activity and dietary behaviours were identified: suitability to work and family obligations, risk status awareness, socioeconomic status, literacy level, perceived need, availability and access to resources, culture, and group format. Conclusion: The findings suggest that CBIs are likely to improve the physical activity and dietary habits of adults if the intervention function seeks to educate, incentivize, change the environment, and model the right behaviours. The review applies and advances theory, realist research, and the design and implementation of community-based interventions for NCD prevention.

Keywords: community-based interventions, noncommunicable disease, realist program theory, risk behaviors

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Authors: Mohammed Alhamed

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This research examines the factors influencing the acceptance and adoption of digital technologies in Saudi Arabia’s government sector by focusing on government employees' attitudes toward digital transformation initiatives. As digital technologies increasingly integrate into public sectors worldwide, there is a requirement to enhance citizen empowerment and government-public interactions as well as understand their impact in unique socio-political contexts like Saudi Arabia. The study aims to explore user attitudes, identify the main challenges, and investigate factors that affect the intention to use digital applications in governmental settings. The study employs a mixed-methods approach by combining quantitative and qualitative data collection to provide a comprehensive view of digital government application adoption. Data was collected through two online surveys administered to 870 government employees and face-to-face semi-structured interviews with 24 participants. This dual approach allows for both statistical analysis and thematic exploration, which provides a deeper understanding of user behaviour, perceived benefits, challenges and attitudes toward these digital applications. Quantitative data were analyzed to identify significant variables influencing adoption, while qualitative responses were coded thematically to uncover recurring themes related to user trust, security, usability and socio-political influences. The results indicate that digital government applications are largely valued for their ability to increase efficiency and accessibility and streamline processes like online documentation and inter-departmental coordination. However, the study highlights that security, privacy, and confidentiality concerns constitute substantial barriers to adoption, with participants calling for stronger cybersecurity measures and data protection policies. Moreover, usability emerged as a key theme that intuitively interfaces in encouraging adoption as respondents emphasized the importance of user-friendly. Additionally, the study found that Saudi Arabia’s unique cultural and organizational dynamics impact acceptance levels with factors like hierarchical structures and varying levels of digital literacy shaping user attitudes. A significant limitation of the study is its exclusive focus on government employees, which may limit the generalizability of the findings to other stakeholder groups, such as the general public. Despite this, the study offers valuable views for policymakers. This, in turn, suggests best practices and guidelines that could enhance the design and implementation of digital government projects. By addressing the identified barriers and leveraging the factors that drive adoption, the study underscores the potential for digital government initiatives to improve efficiency, transparency and responsiveness in Saudi Arabia's public sector. Furthermore, these findings may provide a roadmap for similar countries aiming to adopt digital government solutions within comparable socio-political and economic contexts.

Keywords: acceptance, adoption, digital technologies, digital government, Saudi Arabia

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Authors: Shao-Huang Wu, Ai-Yun Wu, Meng-Chen Wu, Chun-Liang Wu, Kai-Ping Shaw, Hsiao-Ting Chen

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Objective: To analyze the forensic autopsy data of known passengers and compare it with the National database of the autopsy report in 2017, and obtain the special patterned injuries, which can be used as the reference for the reconstruction of hit-and-run motor vehicle accidents. Methods: Analyze the items of the Motor Vehicle Accident Report, including Date of accident, Time occurred, Day, Acc. severity, Acc. Location, Acc. Class, Collision with Vehicle, Motorcyclists Codes, Safety equipment use, etc. Analyzed the items of the Autopsy Report included, including General Description, Clothing and Valuables, External Examination, Head and Neck Trauma, Trunk Trauma, Other Injuries, Internal Examination, Associated Items, Autopsy Determinations, etc. Materials: Case 1. The process of injury formation: the car was chased forward and collided with the scooter. The passenger wearing the helmet fell to the ground. The helmet crashed under the bottom of the sedan, and the bottom of the sedan was raised. Additionally, the sedan was hit on the left by the other sedan behind, resulting in the front sedan turning 180 degrees on the spot. The passenger’s head was rotated, and the cervical spine was fractured. Injuries: 1. Fracture of atlantoaxial joint 2. Fracture of the left clavicle, scapula, and proximal humerus 3. Fracture of the 1-10 left ribs and 2-7 right ribs with lung contusion and hemothorax 4. Fracture of the transverse process of 2-5 lumbar vertebras 5. Comminuted fracture of the right femur 6. Suspected subarachnoid space and subdural hemorrhage 7. Laceration of the spleen. Case 2. The process of injury formation: The motorcyclist wearing the helmet fell to the left by himself, and his chest was crushed by the car going straight. Only his upper body was under the car and the helmet finally fell off. Injuries: 1. Dislocation of atlantoaxial joint 2. Laceration on the left posterior occipital 3. Laceration on the left frontal 4. Laceration on the left side of the chin 5. Strip bruising on the anterior neck 6. Open rib fracture of the right chest wall 7. Comminuted fracture of both 1-12 ribs 8. Fracture of the sternum 9. Rupture of the left lung 10. Rupture of the left and right atria, heart tip and several large vessels 11. The aortic root is nearly transected 12. Severe rupture of the liver. Results: The common features of the two cases were the fracture or dislocation of the atlantoaxial joint and both helmets that were crashed. There were no atlantoaxial fractures or dislocations in 27 pedestrians (without wearing a helmet) versus motor vehicle accidents in 2017 the National database of an autopsy report, but there were two atlantoaxial fracture or dislocation cases in the database, both of which were cases of falling from height. Conclusion: The cervical spine fracture injury of the motorcyclist, who was wearing a helmet, is very likely to be a patterned injury caused by his/her fall and rollover under the sedan. It could provide a reference for forensic peers.

Keywords: patterned injuries, atlantoaxial fracture or dislocation, accident reconstruction, motorcycle accident with helmet, forensic autopsy data

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Authors: Azza A. Ali, Asmaa Abdelaty, Mona G. Khalil, Mona M. Kamal, Karema Abu-Elfotuh

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Background: Aluminium (Al) is known as a neurotoxin environmental pollutant that can cause certain diseases as Dementia, Alzheimer's disease, and Parkinsonism. It is widely used in antacid drugs as well as in food additives and toothpaste. Stresses have been linked to cognitive impairment; Social isolation (SI) may exacerbate memory deficits while protein malnutrition (PM) increases oxidative damage in cortex, hippocampus and cerebellum. The risk of cognitive decline may be lower by maintaining social connections. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and has antioxidant, anti-inflammatory and anti-atherogenic effects as well as health-promoting effects in CNS. Objective: To study the influence of different stressful conditions as social isolation, electric shock (EC) and inadequate Nutritional condition as PM on neurotoxicity induced by Al in rats as well as to investigate the possible protective effect of EGCG in these stressful and PM conditions. Methods: Rats were divided into two major groups; protected group which was daily treated during three weeks of the experiment by EGCG (10 mg/kg, IP) or non-treated. Protected and non-protected groups included five subgroups as following: One normal control received saline and four Al toxicity groups injected daily for three weeks by ALCl3 (70 mg/kg, IP). One of them served as Al toxicity model, two groups subjected to different stresses either by isolation as mild stressful condition (SI-associated Al toxicity model) or by electric shock as high stressful condition (EC- associated Al toxicity model). The last was maintained on 10% casein diet (PM -associated Al toxicity model). Isolated rats were housed individually in cages covered with black plastic. Biochemical changes in the brain as acetyl cholinesterase (ACHE), Aβ, brain derived neurotrophic factor (BDNF), inflammatory mediators (TNF-α, IL-1β), oxidative parameters (MDA, SOD, TAC) were estimated for all groups. Histopathological changes in different brain regions were also evaluated. Results: Rats exposed to Al for three weeks showed brain neurotoxicity and neuronal degenerations. Both mild (SI) and high (EC) stressful conditions as well as inadequate nutrition (PM) enhanced Al-induced neurotoxicity and brain neuronal degenerations; the enhancement induced by stresses especially in its higher conditions (ES) was more pronounced than that of inadequate nutritional conditions (PM) as indicated by the significant increase in Aβ, ACHE, MDA, TNF-α, IL-1β together with the significant decrease in SOD, TAC, BDNF. On the other hand, EGCG showed more pronounced protection against hazards of Al in both stressful conditions (SI and EC) rather than in PM .The protective effects of EGCG were indicated by the significant decrease in Aβ, ACHE, MDA, TNF-α, IL-1β together with the increase in SOD, TAC, BDNF and confirmed by brain histopathological examinations. Conclusion: Neurotoxicity and brain neuronal degenerations induced by Al were more severe with stresses than with PM. EGCG can protect against Al-induced brain neuronal degenerations in all conditions. Consequently, administration of EGCG together with socialization as well as adequate protein nutrition is advised especially on excessive Al-exposure to avoid the severity of its neuronal toxicity.

Keywords: environmental pollution, aluminum, social isolation, protein malnutrition, neuronal degeneration, epigallocatechin-3-gallate, rats

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Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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Authors: Rajkumar Ghosh, Bhabani Prasad Mukhopadhay

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Groundwater contamination with fluoride has emerged as a global concern affecting millions of people, leading to the widespread occurrence of fluorosis. It affects bones and teeth, leading to dental and skeletal fluorosis. This study presents a comprehensive analysis of the relationship between groundwater contamination and fluorosis. It delves into the causes of fluoride contamination in groundwater, its spatial distribution, and adverse health impacts of fluorosis on affected communities. Fluoride contamination in groundwater can be attributed to both natural and anthropogenic sources. Geogenic sources involve the dissolution of fluoride-rich minerals present in the aquifer materials. On the other hand, anthropogenic activities such as industrial discharges, agricultural practices, and improper disposal of fluoride-containing waste contribute to the contamination of groundwater. The spatial distribution of fluoride contamination varies widely across different regions and geological formations. High fluoride levels are commonly observed in areas with fluorine-rich geological deposits. Additionally, agricultural and industrial centres often exhibit elevated fluoride concentrations due to anthropogenic contributions. Excessive fluoride ingestion during tooth development leads to dental fluorosis, characterized by enamel defects, discoloration, and dental caries. The severity of dental fluorosis varies based on fluoride exposure levels during tooth development. Long-term consumption of fluoride-contaminated water causes skeletal fluorosis, resulting in bone and joint pain, decreased joint mobility, and skeletal deformities. In severe cases, skeletal fluorosis can lead to disability and reduced quality of life. Various defluoridation techniques such as activated alumina, bone char, and reverse osmosis have been employed to reduce fluoride concentrations in drinking water. These methods effectively remove fluoride, but their implementation requires careful consideration of cost, maintenance, and sustainability. Diversifying water sources, such as rainwater harvesting and surface water supply, can reduce the reliance on fluoride-contaminated groundwater, especially in regions with high fluoride concentrations. Groundwater contamination with fluoride remains a significant public health challenge, leading to the widespread occurrence of fluorosis globally. This scientific report emphasizes the importance of understanding the relationship between groundwater contamination and fluorosis. Implementing effective mitigation strategies and preventive measures is crucial to combat fluorosis and ensure sustainable access to safe drinking water for communities worldwide. Collaborative efforts between government agencies, local communities, and scientific researchers are essential to address this issue and safeguard the health of vulnerable populations. Additionally, the report explores various mitigation strategies and preventive measures to address the issue and offers recommendations for sustainable management of groundwater resources to combat fluorosis effectively.

Keywords: fluorosis, fluoride contamination, groundwater contamination, groundwater resources

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Authors: Nicole A. Alford

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The study of online graduate education started just 30 years ago, with the first online graduate program in the 1990s. Institutions are looking for ways to increase retention and support the needs of students with the rapid expansion of online higher education due to the global pandemic. Online education provides access and opportunities to those who otherwise would be unable to pursue an advanced degree for logistical reasons. Thus, the objective of the critical literature review is to survey current research of student experiences given the expanding role of online doctoral programs. The guiding research questions are: What are the personal, professional, and student life practices of graduate students who enrolled in a fully online university doctoral program or course? and How do graduate students who enrolled in a fully online doctoral program or course describe the factors that contributed to their continued study? The systematic literature review was conducted employing a variety of databases to locate articles using key Boolean terms and synonyms within three categories of the e-learning, doctoral education, and student perspectives. Inclusion criteria for the literature review consisted of empirical peer-reviewed studies with original data sources that focused on doctoral programs and courses within a fully online environment and centered around student experiences. A total of 16 articles were selected based on the inclusion criteria and systemically analyzed through coding using the Boote and Beile criteria. Major findings suggest that doctoral students face stressors related to social and emotional wellbeing in the online environment. A lack of social connection, isolation, and burnout were the main challenges experienced by students. Students found support from their colleagues, advisors, and faculty to persist. Communities and cohorts of online doctoral students were found to guard against these challenges. Moreover, in the methods section of the articles, there was a lack of specificity related to student demographics, general student information, and insufficient detail about the online doctoral program. Additionally, descriptions regarding the experiences of cohorts and communities in the online environment were vague and not easily replicable with the given details. This literature review reveals that doctoral students face social and emotional challenges related to isolation and the rigor of the academic process and lean on others for support to continue in their studies. Given the lack of current knowledge about online doctoral students, it proves to be a challenge to identify effective practices and create high-retention doctoral programs in online environments. The paucity of information combined with the dramatic transition to e-learning due to the global pandemic can provide a perfect storm for attrition in these programs. Several higher education institutions have transitioned graduate studies online, thus providing an opportunity for further exploration. Given the new necessity of online learning, this work provides insight into examining current practices in online doctoral programs that have moved to this modality during the pandemic. The significance of the literature review provides a springboard for research into online doctoral programs as the solution to continue advanced education amongst a global pandemic.

Keywords: e-learning, experiences, higher education, literature review

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Authors: Gabriel P. Fife, Saeyong Lee, David M. O'Sullivan

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Introduction: Although investigations into injury characteristics are represented well in the literature, few have investigated the biomechanical characteristics associated with head impacts in Taekwondo. Therefore, the purpose of this study was to identify the kinematic characteristics of head impacts due to taekwondo kicks among non-elite practitioners. Participants: Male participants (n= 11, 175 + 5.3 cm, 71 + 8.3 kg) with 7.5 + 3.6 years of taekwondo training volunteered for this study. Methods: Participants were asked to perform five repetitions of each technique (i.e., turning kick, spinning hook kick, spinning back kick, front axe kick, and clench axe kick) aimed at the Hybrid III head with their dominant kicking leg. All participants wore a protective foot pad (thickness = 12 mm) that is commonly used in competition and training. To simulate head impact in taekwondo, the target consisted of a Hybrid III 50th Percentile Crash Test Dummy (Hybrid III) head (mass = 5.1 kg) and neck (fitted with taekwondo headgear) secured to an aluminum support frame and positioned to each athlete’s standing height. The Hybrid III head form was instrumented with a 500 g tri-axial accelerometer (PCB Piezotronics) mounted to the head center of gravity to obtain resultant linear accelerations (RLA). Rotational accelerations were collected using three angular rate sensors mounted orthogonally to each other (Diversified Technical Systems ARS-12 K Angular Rate Sensor). The accelerometers were interfaced via a 3-channel, battery-powered integrated circuit piezoelectric sensor signal conditioner (PCB Piezotronics) and connected to a desktop computer for analysis. Acceleration data were captured using LABVIEW Signal Express and processed in accordance with SAE J211-1 channel frequency class 1000. Head injury criteria values (HIC) were calculated using the VSRSoftware. A one-way analysis of variance was used to determine differences between kicks, while the Tukey HSD test was employed for pairwise comparisons. The level of significance was set to an effect size of 0.20. All statistical analyses were done using R 3.1.0. Results: A statistically significant difference was observed in RLA (p = 0.00075); however, these differences were not clinically meaningful (η² = 0.04, 95% CI: -0.94 to 1.03). No differences were identified with ROTA (p = 0.734, η² = 0.0004, 95% CI: -0.98 to 0.98). A statistically significant difference (p < 0.001) between kicks in HIC was observed, with a medium effect (η2= 0.08, 95% CI: -0.98 to 1.07). However, the confidence interval of this difference indicates uncertainty. Tukey HSD test identified differences (p < 0.001) between kicking techniques in RLA and HIC. Conclusion: This study observed head impact levels that were comparable to previous studies of similar objectives and methodology. These data are important as impact measures from this study may be more representative of impact levels experienced by non-elite competitors. Although the clench axe kick elicited a lower RLA, the ROTA of this technique was higher than levels from other techniques (although not large differences in reference to effect sizes). As the axe kick has been reported to cause severe head injury, future studies may consider further study of this kick important.

Keywords: Taekwondo, head injury, biomechanics, kicking

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Authors: Kenechukwu Ikebuaku

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Entrepreneurship has long been offered as the panacea for poor economic growth and high rate of unemployment. Business incubation is considered an effective means for enhancing entrepreneurial actitivities while engendering socio-economic development. Information Technology Developers Entrepreneurship Accelerator (iDEA), is a software business incubation programme established by the Nigerian government as a means of boosting digital entrepreneurship activities and reducing unemployment in the country. This study assessed the contribution of iDEA Nigeria’s entrepreneurship programmes towards enhancing the capabilities of its tenants. Using the capability approach and the sustainable livelihoods approach, the study analysed iDEA programmes’ contribution towards the expansion of participants’ entrepreneurial capabilities. Apart from identifying a set of entrepreneurial capabilities from both the literature and empirical analysis, the study went further to ascertain how iDEA incubation has helped to enhance those capabilities for its tenants. It also examined digital entrepreneurship as a valued functioning and as an intermediate functioning leading to other valuable functioning. Furthermore, the study examined gender as a conversion factor in digital entrepreneurship. Both qualitative and quantitative research methods were used for the study, and measurement of key variables was made. While the entire population was utilised to collect data for the quantitative research, purposive sampling was used to select respondents for semi-structured interviews in the qualitative research. However, only 40 beneficiaries agreed to take part in the survey while 10 respondents were interviewed for the study. Responses collected from questionnaires administered were subjected to statistical analysis using SPSS. The study developed indexes to measure the perception of the respondents, on how iDEA programmes have enhanced their entrepreneurial capabilities. The Capabilities Enhancement Perception Index (CEPI) computed indicated that the respondents believed that iDEA programmes enhanced their entrepreneurial capabilities. While access to power supply and reliable internet have the highest positive deviations around mean, negotiation skills and access to customers/clients have the highest negative deviation. These were well supported by the findings of the qualitative analysis in which the participants unequivocally narrated how the resources provided by iDEA aid them in their entrepreneurial endeavours. It was also found that iDEA programmes have a significant effect on the tenants’ access to networking opportunities, both with other emerging entrepreneurs and established entrepreneurs. While assessing gender as a conversion factor, it was discovered that there was very low female participation within the digital entrepreneurship ecosystem. The root cause of this gender disparity was found in unquestioned cultural beliefs and social norms which relegate women to a subservient position and household duties. The findings also showed that many of the entrepreneurs could be considered opportunity-based entrepreneurs rather than necessity entrepreneurs, and that digital entrepreneurship is a valued functioning for iDEA tenants. With regards to challenges facing digital entrepreneurship in Nigeria, infrastructural/institutional inadequacies, lack of funding opportunities, and unfavourable government policies, were considered inimical to entrepreneurial capabilities in the country.

Keywords: entrepreneurial capabilities, unemployment, business incubators, development

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Authors: Deniz Peksen

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This thesis aims to predict trend movement of closing price of stock and to maximize portfolio by utilizing the predictions. In this context, the study aims to define a stock portfolio strategy from models created by using Logistic Regression, Gradient Boosting and Random Forest. Recently, predicting the trend of stock price has gained a significance role in making buy and sell decisions and generating returns with investment strategies formed by machine learning basis decisions. There are plenty of studies in the literature on the prediction of stock prices in capital markets using machine learning methods but most of them focus on closing prices instead of the direction of price trend. Our study differs from literature in terms of target definition. Ours is a classification problem which is focusing on the market trend in next 20 trading days. To predict trend direction, fourteen years of data were used for training. Following three years were used for validation. Finally, last three years were used for testing. Training data are between 2002-06-18 and 2016-12-30 Validation data are between 2017-01-02 and 2019-12-31 Testing data are between 2020-01-02 and 2022-03-17 We determine Hold Stock Portfolio, Best Stock Portfolio and USD-TRY Exchange rate as benchmarks which we should outperform. We compared our machine learning basis portfolio return on test data with return of Hold Stock Portfolio, Best Stock Portfolio and USD-TRY Exchange rate. We assessed our model performance with the help of roc-auc score and lift charts. We use logistic regression, Gradient Boosting and Random Forest with grid search approach to fine-tune hyper-parameters. As a result of the empirical study, the existence of uptrend and downtrend of five stocks could not be predicted by the models. When we use these predictions to define buy and sell decisions in order to generate model-based-portfolio, model-based-portfolio fails in test dataset. It was found that Model-based buy and sell decisions generated a stock portfolio strategy whose returns can not outperform non-model portfolio strategies on test dataset. We found that any effort for predicting the trend which is formulated on stock price is a challenge. We found same results as Random Walk Theory claims which says that stock price or price changes are unpredictable. Our model iterations failed on test dataset. Although, we built up several good models on validation dataset, we failed on test dataset. We implemented Random Forest, Gradient Boosting and Logistic Regression. We discovered that complex models did not provide advantage or additional performance while comparing them with Logistic Regression. More complexity did not lead us to reach better performance. Using a complex model is not an answer to figure out the stock-related prediction problem. Our approach was to predict the trend instead of the price. This approach converted our problem into classification. However, this label approach does not lead us to solve the stock prediction problem and deny or refute the accuracy of the Random Walk Theory for the stock price.

Keywords: stock prediction, portfolio optimization, data science, machine learning

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Authors: Yuli Hou, Jianping Sun, Mengdan Gao, Hui Liu, Ling Qin, Ang Li, Dongfu Li, Yonghong Zhang, Yan Zhao

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Background and Aims: Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. IFITM3 has been recognized as a key signal molecule regulating cell growth in some tumors. However, the function of IFITM3 rs12252-CC genotype in the hepatocellular carcinoma (HCC) remains unknown to author’s best knowledge. A cohort study was employed to clarify the relationship between IFITM3 rs12252-CC genotype and HCC progression, and cellular experiments were used to investigate the correlation of function of IFITM3 and the progress of HCC. Methods: 336 candidates were enrolled in study, including 156 with HBV related HCC and 180 with chronic Hepatitis B infections or liver cirrhosis. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3. The functions of IFITM3 were detected in PLC/PRF/5 cell with different treated:LV-IFITM3 transfected with lentivirus to knockdown the expression of IFITM3 and LV-NC transfected with empty lentivirus as negative control. The IFITM3 expression, proliferation and migration were detected by Quantitative reverse transcription polymerase chain reaction (qRT-PCR), QuantiGene Plex 2.0 assay, western blotting, immunohistochemistry, Cell Counting Kit(CCK)-8 and wound healing respectively. Six samples (three infected with empty lentiviral as control; three infected with LV-IFITM3 vector lentiviral as experimental group ) of PLC/PRF/5 were sequenced at BGI (Beijing Genomics Institute, Shenzhen,China) using RNA-seq technology to identify the IFITM3-related signaling pathways and chose PI3K/AKT pathway as related signaling to verify. Results: The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC compared with the patients with chronic HBV infection or liver cirrhosis. The distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Patients with CC genotype found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes. The expression of IFITM3 was higher in HCC tissues than adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic than high/medium differentiation and without metastatic. Higher RNA level of IFITM3 was found in CC genotype than TT genotype. In PLC/PRF/5 cell with knockdown, the ability of cell proliferation and migration was inhibited. Analysis RNA sequencing and verification of RT-PCR found out the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) pathway was associated with knockdown IFITM3.With the inhibition of IFITM3, the expression of PI3K/AKT/mTOR signaling pathway was blocked and the expression of vimentin was decreased. Conclusions: IFITM3 rs12252-CC with the higher expression plays a vital role in the progress of HCC by regulating HCC cell proliferation and migration. These effects are associated with PI3K/AKT/mTOR signaling pathway.

Keywords: IFITM3, interferon-induced transmembrane protein 3, HCC, hepatocellular carcinoma, PI3K/ AKT/mTOR, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin

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Authors: Harriet Bothwell, Lowri Evans, Kevin Jones

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Background: The University of Bristol provides all medical students the opportunity to undertake student selected components (SSCs) at multiple stages of the undergraduate programme. SSCs enable students to explore areas of interest that are not necessarily covered by the curriculum. Students are required to produce a written report and most use SSCs as an opportunity to undertake an audit or small research project. In 2013 Swindon Academy, based at the Great Western Hospital, offered eight students the opportunity of a global health SSC which included a two week trip to rural hospital in Uganda. This SSC has since expanded and in 2017 a total of 20 students had the opportunity to undertake small research projects at two hospitals in rural Uganda. 'Tomorrows Doctors' highlights the importance of understanding healthcare from a 'global perspective' and student feedback from previous SSCs suggests that self-assessed knowledge of global health increases as a result of this SSC. Through the most recent version of this SSC students had the opportunity to undertake projects in a wide range of specialties including paediatrics, palliative care, surgery and medical education. Methods: An anonymous online questionnaire was made available to students following the SSC. There was a response rate of 80% representing 16 out of the 20 students. This questionnaire surveyed students’ satisfaction and experience of the SSC including the level of academic, project and spiritual support provided as well as perceived challenges in completing the project and barriers to healthcare delivery in the low resource setting. This survey had multiple open questions allowing the collection of qualitative data. Further qualitative data was collected from the students’ project report. The suggested format included a reflection and all students completed these. All qualitative data underwent thematic analysis. Results: All respondents rated the overall experience of the SSC as 'good' or 'excellent'. Preliminary data suggest that students’ confidence in their knowledge of global health, diagnosis of tropical diseases and management of tropical diseases improved after completing this SSC. Thematic analysis of students' reflection is ongoing but suggests that students gain far more than improved knowledge of tropical diseases. Students reflect positively on having the opportunity to research in a low resource setting and feel that by completing these projects they will be 'useful' to the hospital. Several students reflect the stark contrast to healthcare delivery in the UK and recognise the 'privilege' of having a healthcare system that is free at the point of access. Some students noted the different approaches that clinicians in Uganda had to train in 'taking ownership' of their own learning. Conclusions: Students completing this SSC report increased knowledge of global health and tropical medicine. However, their reflections reveal much broader learning outcomes and demonstrate considerable insight in multiple topics including conducting research in the low resource setting, training and healthcare inequality.

Keywords: global health, medical education, student feedback, undergraduate

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Authors: Isaac Martin, Abigail Lark, Sandra Morales, Eric W. Alton, Jane C. Davies

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Objectives: The cystic fibrosis (CF) lung is a unique microbiological niche, wherein harmful bacteria persist for many years despite antibiotic therapy. Pseudomonas aeruginosa (Pa), the major culprit leading to lung decline and increased mortality, thrives in the lungs of patients with CF due to several factors that have been linked with poor antibiotic performance. Our group is investigating alternative therapies including bacteriophage cocktails with which we have previously demonstrated efficacy against planktonic organisms. In this study, we explored the effects of a 4-phage cocktail on Pa grown in two different conditions, intended to mirror the CF lung: a) alongside standard antibiotic treatment in pre-formed biofilms (structures formed by Pa-secreted exopolysaccharides which provide both physical and cell division barriers to antimicrobials and host defenses and b) in an acidic environment postulated to be present in the CF airway due both to the primary defect in bicarbonate secretion and secondary effects of inflammation. Methods: 16 Pa strains from CF patients at the Royal Brompton Hospital were selected based on sensitivity to a) ceftazidime/ tobramycin and b) the phage cocktail in a conventional plaque assay. To assess efficacy of phage in biofilms, 96 well plates with Pa (5x10⁷ CFU/ ml) were incubated in static conditions, allowing adherent bacterial colonies to form for 24 hr. Ceftazidime and tobramycin (both at 2 × MIC) were added, +/- bacteriophage (4x10⁸ PFU/mL) for a further 24 hr. Cell viability and biomass were estimated using fluorescent resazurin and crystal violet assays, respectively. To evaluate the effect of pH, strains were grown planktonically in shaking 96 well plates at pH 6.0, 6.6, 7.0 and 7.5 with tobramycin or phage, at varying concentrations. Cell viability was quantified by fluorescent resazurin assay. Results: For the biofilm assay, treatment groups were compared with untreated controls and expressed as percent reduction in cell viability and biomass. Addition of the 4-phage cocktail resulted in a 1.3-fold reduction in cell viability and 1.7-fold reduction in biomass (p < 0.001) when compared to standard antibiotic treatment alone. Notably, there was a 50 ± 15% reduction in cell viability and 60 ± 12% reduction in biomass (95% CI) for the 4 biofilms demonstrating the most resistance to antibiotic treatment. 83% of strains tested (n=6) showed decreased bacterial killing by tobramycin at acidic pHs (p < 0.01). However, 25% of strains (n=12) showed improved phage killing at acidic pHs (p < 0.05), with none showing the pattern of reduced efficacy at acidic pH demonstrated by tobramycin. Conclusion: The 4-phage anti-Pa cocktail tested against Pa performs well in pre-formed biofilms and in acidic environments; two conditions intended to mimic the CF lung. To our knowledge, these are the first data looking at the effects of subtle pH changes on phage-mediated bacterial killing in the context of Pa infection. These findings contribute to a growing body of evidence supporting the use of nebulised lytic bacteriophage as a treatment in the context of lung infection.

Keywords: biofilm, cystic fibrosis, pH, Pseudomonas aeruginosa, lytic bacteriophage

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Authors: Valentina A. Mikhailova, Serguei V. Feskov, Anatoly I. Ivanov

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In the last decade the nonequilibrium charge transfer have attracted considerable interest from the scientific community. Examples of such processes are the charge recombination in excited donor-acceptor complexes and the intramolecular electron transfer from the second excited electronic state. In these reactions the charge transfer proceeds predominantly in the nonequilibrium mode. In the excited donor-acceptor complexes the nuclear nonequilibrium is created by the pump pulse. The intramolecular electron transfer from the second excited electronic state is an example where the nuclear nonequilibrium is created by the forward electron transfer. The kinetics of these nonequilibrium reactions demonstrate a number of peculiar properties. Most important from them are: (i) the absence of the Marcus normal region in the free energy gap law for the charge recombination in excited donor-acceptor complexes, (ii) extremely low quantum yield of thermalized charge separated state in the ultrafast charge transfer from the second excited state, (iii) the nonexponential charge recombination dynamics in excited donor-acceptor complexes, (iv) the dependence of the charge transfer rate constant on the excitation pulse frequency. This report shows that most of these kinetic features can be well reproduced in the framework of stochastic point-transition multichannel model. The model involves an explicit description of the nonequilibrium excited state formation by the pump pulse and accounts for the reorganization of intramolecular high-frequency vibrational modes, for their relaxation as well as for the solvent relaxation. The model is able to quantitatively reproduce complex nonequilibrium charge transfer kinetics observed in modern experiments. The interpretation of the nonequilibrium effects from a unified point of view in the terms of the multichannel point transition stochastic model allows to see similarities and differences of electron transfer mechanism in various molecular donor-acceptor systems and formulates general regularities inherent in these phenomena. The nonequilibrium effects in photoinduced ultrafast charge transfer which have been studied for the last 10 years are analyzed. The methods of suppression of the ultrafast charge recombination, similarities and dissimilarities of electron transfer mechanism in different molecular donor-acceptor systems are discussed. The extremely low quantum yield of the thermalized charge separated state observed in the ultrafast charge transfer from the second excited state in the complex consisting of 1,2,4-trimethoxybenzene and tetracyanoethylene in acetonitrile solution directly demonstrates that its effectiveness can be close to unity. This experimental finding supports the idea that the nonequilibrium charge recombination in the excited donor-acceptor complexes can be also very effective so that the part of thermalized complexes is negligible. It is discussed the regularities inherent to the equilibrium and nonequilibrium reactions. Their fundamental differences are analyzed. Namely the opposite dependencies of the charge transfer rates on the dynamical properties of the solvent. The increase of the solvent viscosity results in decreasing the thermal rate and vice versa increasing the nonequilibrium rate. The dependencies of the rates on the solvent reorganization energy and the free energy gap also can considerably differ. This work was supported by the Russian Science Foundation (Grant No. 16-13-10122).

Keywords: Charge recombination, higher excited states, free energy gap law, nonequilibrium

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