Search results for: efficacy prediction

Authors: Markéta Chmelíková, David Ullrich, Iva Burešová

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The paper maps the possibilities and limits of diagnosing selected personality and performance characteristics of military leadership and psychology students in the context of coping with challenging situations. Individuals vary greatly inter-individually in their ability to effectively manage extreme situations, yet existing diagnostic tools are often criticized mainly for their low predictive power. Nowadays, every modern army focuses primarily on the systematic minimization of potential risks, including the prediction of desirable forms of behavior and the performance of military commanders. The context of military leadership is well known for its life-threatening nature. Therefore, it is crucial to research stress load in the specific context of military leadership for the purpose of possible anticipation of human failure in managing extreme situations of military leadership. The aim of the submitted pilot study, using an experiment of 24 hours duration, is to verify the possibilities of a specific combination of psychodiagnostic to predict people who possess suitable equipment for coping with increased stress load. In our pilot study, we conducted an experiment of 24 hours duration with an experimental group (N=13) in the bomb shelter and a control group (N=11) in a classroom. Both groups were represented by military leadership students (N=11) and psychology students (N=13). Both groups were equalized in terms of study type and gender. Participants were administered the following test battery of personality characteristics: Big Five Inventory 2 (BFI-2), Short Dark Triad (SD-3), Emotion Regulation Questionnaire (ERQ), Fatigue Severity Scale (FSS), and Impulsive Behavior Scale (UPPS-P). This test battery was administered only once at the beginning of the experiment. Along with this, they were administered a test battery consisting of the Test of Attention (d2) and the Bourdon test four times overall with 6 hours ranges. To better simulate an extreme situation – we tried to induce sleep deprivation - participants were required to try not to fall asleep throughout the experiment. Despite the assumption that a stay in an underground bomb shelter will manifest in impaired cognitive performance, this expectation has been significantly confirmed in only one measurement, which can be interpreted as marginal in the context of multiple testing. This finding is a fundamental insight into the issue of stress management in extreme situations, which is crucial for effective military leadership. The results suggest that a 24-hour stay in a shelter, together with sleep deprivation, does not seem to simulate sufficient stress for an individual, which would be reflected in the level of cognitive performance. In the context of these findings, it would be interesting in future to extend the diagnostic battery with physiological indicators of stress, such as: heart rate, stress score, physical stress, mental stress ect.

Keywords: bomb shelter, extreme situation, military leadership, psychodiagnostic

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Authors: Laura Roe

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This study draws on twelve months of ethnographic fieldwork conducted in 2017 with heroin and poly-substance users in Scotland and explores experiences of time and temporality as factors in continuing drug use. The research largely took place over the year in which drug-related deaths in Scotland reached a record high, and were statistically recorded as the highest in Europe. This qualitative research is therefore significant in understanding both evolving patterns of drug use and the experiential lifeworlds of those who use heroin and other substances in high doses. Methodologies included participant observation, structured and semi-structured interviews, and unstructured conversations with twenty-two regular participants. The fieldwork was conducted in two needle exchanges, a community recovery group and in the community. The initial aim of the study was to assess evolving patterns of drug preferences in order to explore a clinical and user-reported rise in the use of novel psychoactive substances (NPS), which are typically considered to be highly potent, synthetic substances, often available at a low cost. It was found, however, that while most research participants had experimented with NPS with varying intensity, those who used every day regularly consumed heroin, methadone, and alcohol with benzodiazepines such as diazepam or anticonvulsants such as gabapentin. The research found that many participants deliberately pursued the non-fatal effects of overdose, aiming to induce states of dissociation, detachment and uneven consciousness, and did so by both mixing substances and experimenting with novel modes of consumption. Temporality was significant in the decision to consume cocktails of substances, as users described wishing to sever themselves from time; entering into states of ‘non-time’ and insensibility through specific modes of intoxication. Time and temporality similarly impacted other aspects of addicted life. Periods of attempted abstinence witnessed a slowing of time’s passage that was tied to affective states of boredom and melancholy, in addition to a disruptive return of distressing and difficult memories. Abject past memories frequently dominated and disrupted the present, which otherwise could be highly immersive due to the time and energy-consuming nature of seeking drugs while in financial difficulty. There was furthermore a discordance between individual user temporalities and the strict time-based regimes of recovery services and institutional bodies, and the study aims to highlight the impact of such a disjuncture on the efficacy of treatment programs. Many participants had difficulty in adhering to set appointments or temporal frameworks due to their specific temporal situatedness. Overall, exploring increasing tendencies of heroin users in Scotland towards poly-substance use, this study draws on experiences and perceptions of time, analysing how temporality comes to bear on the ways drugs are sought and consumed, and how recovery is imagined and enacted. The study attempts to outline the experiential, intimate and subjective worlds of heroin and poly-substance users while explicating the structural and historical factors that shape them.

Keywords: addiction, poly-substance use, temporality, timelessness

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Authors: Patrick Louie Robles, Jerry Suls, Ciaran Friel, Mark Butler, Samantha Gordon, Frank Vicari, Joan Duer-Hefele, Karina W. Davidson

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Physical activity guidelines focus on increasing moderate-intensity activity for older adults, but adherence to recommendations remains low. This is despite the fact that scientific evidence finds increasing physical activity is positively associated with health benefits. Behavior change techniques (BCTs) have demonstrated some effectiveness in reducing sedentary behavior and promoting physical activity. This pilot study uses a personalized trials (N-of-1) design, delivered virtually, to evaluate the efficacy of using five BCTs in increasing low-intensity physical activity (by 2,000 steps of walking per day) in adults aged 45-75 years old. The 5 BCTs described in habit formation theory are goal setting, action planning, rehearsal, rehearsal in a consistent context, and self-monitoring. The study recruited health system employees in the target age range who had no mobility restrictions and expressed interest in increasing their daily activity by a minimum of 2,000 steps per day at least five days per week. Participants were sent a Fitbit Charge 4 fitness tracker with an established study account and password. Participants were recommended to wear the Fitbit device 24/7 but were required to wear it for a minimum of ten hours per day. Baseline physical activity was measured by Fitbit for two weeks. Participants then engaged remotely with a clinical research coordinator to establish a “walking plan” that included a time and day interval (e.g., between 7am -8am on Monday-Friday), a location for the walk (e.g., park), and how much time the plan would need to achieve a minimum of 2,000 steps over their baseline average step count (20 minutes). All elements of the walking plan were required to remain consistent throughout the study. In the 10-week intervention phase of the study, participants received all five BCTs in a single, time-sensitive text message. The text message was delivered 30 minutes prior to the established walk time and signaled participants to begin walking when the context (i.e., day of the week, time of day) they pre-selected is encountered. Participants were asked to log both the start and conclusion of their activity session by pressing a button on the Fitbit tracker. Within 30 minutes of the planned conclusion of the activity session, participants received a text message with a link to a secure survey. Here, they noted whether they engaged in the BCTs when prompted and completed an automaticity survey to identify how “automatic” their walking behavior had become. At the end of their trial, participants received a personalized summary of their step data over time, helping them learn more about their responses to the five BCTs. Whether the use of these 5 ‘habit formation’ BCTs in combination elicits a change in physical activity behavior among older adults will be reported. This study will inform the feasibility of a virtually-delivered N-of-1 study design to effectively promote physical activity as a component of healthy aging.

Keywords: aging, exercise, habit, walking

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Authors: Ifeoma Anozie, Teka Apalata, Dominic Abaver

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Introduction: Despite use of Anti-retroviral therapy to reduce the incidence of opportunistic infections among HIV/AIDS patients, rapid episodes of re-infection after deworming are still common occurrences because pharmaceutical intervention alone does not prevent reinfection. Unsafe water and inadequate personal hygiene and parasitic infections are widely expected to accelerate the progression of HIV infection. This is because the chronic immunosuppression of HIV infection encourages susceptibility to opportunistic (including parasitic) infections which is linked to CD4+ cell count of <200 cells/μl. Intestinal parasites such as G. intestinalis and Entamoeba spp are ubiquitous protozoa that remain infectious over a long time in an environment and show resistance to standard disinfection. To control re-infection, the social factors that underpin the prevention need to be controlled. This study aims at prevention of intestinal parasites in people living with HIV/AIDS by using a treatment, hygiene education and sanitation (THEdS) bundle approach. Methods: This study was conducted in four clinics (Ngangelizwe health centre, Tsolo gateway clinic, Idutywa health centre and Nqamakwe health centre) across the seven districts in Eastern cape, South Africa. The four clinics were divided in two: experimental and control, for the purpose of intervention. Data was collected from March 2019 to February 2020. Six hundred participants were screened for intestinal parasitic infections. Stool samples were collected and analysed twice: before (Pre-test infection screening) and after (Post-test re-infection) THEdS bundle intervention. The experimental clinics received full intervention package, which include therapeutic treatment, health education on personal hygiene and sanitation training, while the control clinics received only therapeutic treatment for those found with intestinal parasitic infections. Results: Baseline prevalence of Intestinal Parasites isolated shows 12 intestinal parasites with overall frequency of 65, with Ascaris lumbricoides having most frequency (44.6%). The intervention had a cure rate of 60%, with odd ratio of 1.42, which indicates that the intervention group is 1.42 times more likely of parasite clearing as compared to the control group. The relative risk ratio of 1.17 signifies that there is 1.17 times more likelihood to clear intestinal parasite if there no intervention. Discussion and conclusion: Infection with multiple parasites can cause health defects, especially among HIV/AIDS patients. Efficiency of some HIV vaccines in HIV/AIDS patients is affected because treatment of re-infection amplifies drug resistance, affects the efficacy of the front-line drugs, and still permits transmission. In South Africa, treatment of intestinal parasites is usually offered to clinic attending HIV/AIDS patients upon suspicion but not as a mandate for patients being initiated into Antiretroviral (ART) program. The effectiveness of THEdS bundle advocates for inclusiveness of mandatory screening for intestinal parasitic infections among attendees of HIV/Aids clinics on regular basis.

Keywords: cure rate, , HIV/AIDS patients, intestinal parasites, intervention studies, reinfection rate

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Authors: Wen Liu, Errol Haarhoff, Lee Beattie

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In 2010, New Zealand’s central government re-organise the local governments arrangements in Auckland, New Zealand by amalgamating its previous regional council and seven supporting local government units into a single unitary council, the Auckland Council. The Auckland Council is charged with providing local government services to approximately 1.5 million people (a third of New Zealand’s total population). This includes addressing Auckland’s strategic urban growth management and setting its urban planning policy directions for the next 40 years. This is expressed in the first ever spatial plan in the region – the Auckland Plan (2012). The Auckland plan supports implementing a compact city model by concentrating the larger part of future urban growth and development in, and around, existing and proposed transit centres, with the intention of Auckland to become globally competitive city and achieving ‘the most liveable city in the world’. Turning that vision into reality is operatized through the statutory land use plan, the Auckland Unitary Plan. The Unitary plan replaced the previous regional and local statutory plans when it became operative in 2016, becoming the ‘rule book’ on how to manage and develop the natural and built environment, using land use zones and zone standards. Common to the broad range of literature on urban growth management, one significant issue stands out about intensification. The ‘gap’ between strategic planning and what has been achieved is evident in the argument for the ‘compact’ urban form. Although the compact city model may have a wide range of merits, the extent to which these are actualized largely rely on how intensification actually is delivered. The transformation of the rhetoric of the residential intensification model into reality is of profound influence, yet has enjoyed limited empirical analysis. In Auckland, the establishment of the Auckland Plan set up the strategies to deliver intensification into diversified arenas. Nonetheless, planning policy itself does not necessarily achieve the envisaged objectives, delivering the planning system and high capacity to enhance and sustain plan implementation is another demanding agenda. Though the Auckland Plan provides a wide ranging strategic context, its actual delivery is beholden on the Unitary Plan. However, questions have been asked if the Unitary Plan has the necessary statutory tools to deliver the Auckland Plan’s policy outcomes. In Auckland, there is likely to be continuing tension between the strategies for intensification and their envisaged objectives, and made it doubtful whether the main principles of the intensification strategies could be realized. This raises questions over whether the Auckland Plan’s policy goals can be achieved in practice, including delivering ‘quality compact city’ and residential intensification. Taking Auckland as an example of traditionally sprawl cities, this article intends to investigate the efficacy plan making and implementation directed towards higher density development. This article explores the process of plan development, plan making and implementation frameworks of the first ever spatial plan in Auckland, so as to explicate the objectives and processes involved, and consider whether this will facilitate decision making processes to realize the anticipated intensive urban development.

Keywords: urban intensification, sustainable development, plan making, governance and implementation

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Authors: Ran Goldblatt, Nicholas Jones, Jennifer Mannix, Brad Bottoms

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Accurate, complete, and up-to-date geospatial information is the foundation of successful disaster management. When the 2010 Haiti Earthquake struck, accurate and timely information on the distribution of critical infrastructure was essential for the disaster response community for effective search and rescue operations. Existing geospatial datasets such as Google Maps did not have comprehensive coverage of these features. In the days following the earthquake, many organizations released high-resolution satellite imagery, catalyzing a worldwide effort to map Haiti and support the recovery operations. Of these organizations, OpenStreetMap (OSM), a collaborative project to create a free editable map of the world, used the imagery to support volunteers to digitize roads, buildings, and other features, creating the most detailed map of Haiti in existence in just a few weeks. However, large portions of the island are still not fully covered by OSM. There is an increasing need for a tool to automatically identify which areas in Haiti, as well as in other countries vulnerable to disasters, that are not fully mapped. The objective of this project is to leverage different types of remote sensing measurements, together with machine learning approaches, in order to identify geographical areas where OSM coverage of building footprints is incomplete. Several remote sensing measures and derived products were assessed as potential predictors of OSM building footprints coverage, including: intensity of light emitted at night (based on VIIRS measurements), spectral indices derived from Sentinel-2 satellite (normalized difference vegetation index (NDVI), normalized difference built-up index (NDBI), soil-adjusted vegetation index (SAVI), urban index (UI)), surface texture (based on Sentinel-1 SAR measurements)), elevation and slope. Additional remote sensing derived products, such as Hansen Global Forest Change, DLR`s Global Urban Footprint (GUF), and World Settlement Footprint (WSF), were also evaluated as predictors, as well as OSM street and road network (including junctions). Using a supervised classification with a random forest classifier resulted in the prediction of 89% of the variation of OSM building footprint area in a given cell. These predictions allowed for the identification of cells that are predicted to be covered but are actually not mapped yet. With these results, this methodology could be adapted to any location to assist with preparing for future disastrous events and assure that essential geospatial information is available to support the response and recovery efforts during and following major disasters.

Keywords: disaster management, Haiti, machine learning, OpenStreetMap, remote sensing

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Authors: G. Magalhães-Mota, C. Magro, S. Sério, E. Mateus, P. A. Ribeiro, A. B. Ribeiro, M. Raposo

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Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol], belonging to the class of Pharmaceuticals and Personal Care Products (PPCPs), is a broad-spectrum antimicrobial agent and bactericide. Because of its antimicrobial efficacy, it is widely used in personal health and skin care products, such as soaps, detergents, hand cleansers, cosmetics, toothpastes, etc. However, it has been considered to disrupt the endocrine system, for instance, thyroid hormone homeostasis and possibly the reproductive system. Considering the widespread use of triclosan, it is expected that environmental and food safety problems regarding triclosan will increase dramatically. Triclosan has been found in river water samples in both North America and Europe and is likely widely distributed wherever triclosan-containing products are used. Although significant amounts are removed in sewage plants, considerable quantities remain in the sewage effluent, initiating widespread environmental contamination. Triclosan undergoes bioconversion to methyl-triclosan, which has been demonstrated to bio accumulate in fish. In addition, triclosan has been found in human urine samples from persons with no known industrial exposure and in significant amounts in samples of mother's milk, demonstrating its presence in humans. The action of sunlight in river water is known to turn triclosan into dioxin derivatives and raises the possibility of pharmacological dangers not envisioned when the compound was originally utilized. The aim of this work is to detect low concentrations of triclosan in an aqueous complex matrix through the use of a sensor array system, following the electronic tongue concept based on impedance spectroscopy. To achieve this goal, we selected the appropriate molecules to the sensor so that there is a high affinity for triclosan and whose sensitivity ensures the detection of concentrations of at least nano-molar. Thin films of organic molecules and oxides have been produced by the layer-by-layer (LbL) technique and sputtered onto glass solid supports already covered by gold interdigitated electrodes. By submerging the films in complex aqueous solutions with different concentrations of triclosan, resistance and capacitance values were obtained at different frequencies. The preliminary results showed that an array of interdigitated electrodes sensor coated or uncoated with different LbL and films, can be used to detect TCS traces in aqueous solutions in a wide range concentration, from 10⁻¹² to 10⁻⁶ M. The PCA method was applied to the measured data, in order to differentiate the solutions with different concentrations of TCS. Moreover, was also possible to trace a curve, the plot of the logarithm of resistance versus the logarithm of concentration, which allowed us to fit the plotted data points with a decreasing straight line with a slope of 0.022 ± 0.006 which corresponds to the best sensitivity of our sensor. To find the sensor resolution near of the smallest concentration (Cs) used, 1pM, the minimum measured value which can be measured with resolution is 0.006, so the ∆logC =0.006/0.022=0.273, and, therefore, C-Cs~0.9 pM. This leads to a sensor resolution of 0.9 pM for the smallest concentration used, 1pM. This attained detection limit is lower than the values obtained in the literature.

Keywords: triclosan, layer-by-layer, impedance spectroscopy, electronic tongue

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Authors: R. Christopher, C. Brandt, N. Damons

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Background: The sequence of prevention model states that by constant assessment of injury, injury mechanisms and risk factors are identified, highlighting that collecting and recording of data is a core approach for preventing injuries. Several screening tools are available for use in the clinical setting. These screening techniques only recently received research attention, hence there is a dearth of inconsistent and controversial data regarding their applicability, validity, and reliability. Several systematic reviews related to common soccer injuries have been conducted; however, none of them addressed the screening tools for common soccer injuries. Objectives: The purpose of this study was to conduct a review of screening tools and their accuracy for common injuries in soccer. Methods: A systematic scoping review was performed based on the Joanna Briggs Institute procedure for conducting systematic reviews. Databases such as SPORT Discus, Cinahl, Medline, Science Direct, PubMed, and grey literature were used to access suitable studies. Some of the key search terms included: injury screening, screening, screening tool accuracy, injury prevalence, injury prediction, accuracy, validity, specificity, reliability, sensitivity. All types of English studies dating back to the year 2000 were included. Two blind independent reviewers selected and appraised articles on a 9-point scale for inclusion as well as for the risk of bias with the ACROBAT-NRSI tool. Data were extracted and summarized in tables. Plot data analysis was done, and sensitivity and specificity were analyzed with their respective 95% confidence intervals. I² statistic was used to determine the proportion of variation across studies. Results: The initial search yielded 95 studies, of which 21 were duplicates, and 54 excluded. A total of 10 observational studies were included for the analysis: 3 studies were analysed quantitatively while the remaining 7 were analysed qualitatively. Seven studies were graded low and three studies high risk of bias. Only high methodological studies (score > 9) were included for analysis. The pooled studies investigated tools such as the Functional Movement Screening (FMS™), the Landing Error Scoring System (LESS), the Tuck Jump Assessment, the Soccer Injury Movement Screening (SIMS), and the conventional hamstrings to quadriceps ratio. The accuracy of screening tools was of high reliability, sensitivity and specificity (calculated as ICC 0.68, 95% CI: 52-0.84; and 0.64, 95% CI: 0.61-0.66 respectively; I² = 13.2%, P=0.316). Conclusion: Based on the pooled results from the included studies, the FMS™ has a good inter-rater and intra-rater reliability. FMS™ is a screening tool capable of screening for common soccer injuries, and individual FMS™ scores are a better determinant of performance in comparison with the overall FMS™ score. Although meta-analysis could not be done for all the included screening tools, qualitative analysis also indicated good sensitivity and specificity of the individual tools. Higher levels of evidence are, however, needed for implication in evidence-based practice.

Keywords: accuracy, screening tools, sensitivity, soccer injuries, specificity

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Authors: Iliana Georganta, Clare Deehan, Marysia Thomson, Miriam McDonald, Kerrie McNulty, Anna Strachan, Elizabeth Anderson, Alyaa Mostafa

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Context: A meta-analysis of randomized controlled trials (RCTs) comparing hysterectomy versus endometrial ablation and resection in the management of heavy menstrual bleeding. Objective: To evaluate the clinical efficacy, satisfaction rates and adverse events of hysterectomy compared to more minimally invasive techniques in the treatment of HMB. Evidence Acquisition: A literature search was performed for all RCTs and quasi-RCTs comparing hysterectomy with either endometrial ablation endometrial resection of both. The search had no language restrictions and was last updated in June 2020 using MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials, PubMed, Google Scholar, PsycINFO, Clinicaltrials.gov and Clinical trials. EU. In addition, a manual search of the abstract databases of the European Haemophilia Conference on women's health was performed and further studies were identified from references of acquired papers. The primary outcomes were patient-reported and objective reduction in heavy menstrual bleeding up to 2 years and after 2 years. Secondary outcomes included satisfaction rates, pain, adverse events short and long term, quality of life and sexual function, further surgery, duration of surgery and hospital stay and time to return to work and normal activities. Data were analysed using RevMan software. Evidence synthesis: 12 studies and a total of 2028 women were included (hysterectomy: n = 977 women vs endometrial ablation or resection: n = 1051 women). Hysterectomy was compared with endometrial ablation only in five studies (Lin, Dickersin, Sesti, Jain, Cooper) and endometrial resection only in five studies (Gannon, Schulpher, O’Connor, Crosignani, Zupi) and a mixture of the Ablation and Resection in two studies (Elmantwe, Pinion). Of the 1² studies, 10 reported women’s perception of bleeding symptoms as improved. Meta-analysis showed that women in the hysterectomy group were more likely to show improvement in bleeding symptoms when compared with endometrial ablation or resection up to 2-year follow-up (RR 0.75, 95% CI 0.71 to 0.79, I² = 95%). Objective outcomes of improvement in bleeding also favored hysterectomy. Patient satisfaction was higher after hysterectomy within the 2 years follow-up (RR: 0.90, 95%CI: 0.86 to 0.94, I²:58%), however, there was no significant difference between the two groups at more than 2 years follow up. Sepsis (RR: 0.03, 95% CI 0.002 to 0.56; 1 study), wound infection (RR: 0.05, 95% CI: 0.01 to 0.28, I²: 0%, 3 studies) and Urinary tract infection (UTI) (RR: 0.20, 95% CI: 0.10 to 0.42, I²: 0%, 4 studies) all favoured hysteroscopic techniques. Fluid overload (RR: 7.80, 95% CI: 2.16 to 28.16, I² :0%, 4 studies) and perforation (RR: 5.42, 95% CI: 1.25 to 23.45, I²: 0%, 4 studies) however favoured hysterectomy in the short term. Conclusions: This meta-analysis has demonstrated that endometrial ablation and endometrial resection are both viable options when compared with hysterectomy for the treatment of heavy menstrual bleeding. Hysteroscopic procedures had better outcomes in the short term with fewer adverse events including wound infection, UTI and sepsis. The hysterectomy performed better when measuring more long-term impacts such as recurrence of symptoms, overall satisfaction at two years and the need for further treatment or surgery.

Keywords: menorrhagia, hysterectomy, ablation, resection

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Authors: Gary Peach, Furqan Hameed

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Musaimeer outfall tunnel is one of the longest storm water tunnels in the world, with a total length of 10.15 km. The tunnel will accommodate surface and rain water received from the drainage networks from 270 km of urban areas in southern Doha with a pumping capacity of 19.7m³/sec. The tunnel is excavated by Tunnel Boring Machine (TBM) through Rus Formation, Midra Shales, and Simsima Limestone. Water inflows at high pressure, complex mixed ground, and weaker ground strata prone to karstification with the presence of vertical and lateral fractures connected to the sea bed were also encountered during mining. In addition to pre-tender geotechnical investigations, the Contractor carried out a supplementary offshore geophysical investigation in order to fine-tune the existing results of geophysical and geotechnical investigations. Electric resistivity tomography (ERT) and Seismic Reflection survey was carried out. Offshore geophysical survey was performed, and interpretations of rock mass conditions were made to provide an overall picture of underground conditions along the tunnel alignment. This allowed the critical tunnelling area and cutter head intervention to be planned accordingly. Karstification was monitored with a non-intrusive radar system facility installed on the TBM. The Boring Electric Ahead Monitoring(BEAM) was installed at the cutter head and was able to predict the rock mass up to 3 tunnel diameters ahead of the cutter head. BEAM system was provided with an online system for real time monitoring of rock mass condition and then correlated with the rock mass conditions predicted during the interpretation phase of offshore geophysical surveys. The further correlation was carried by Samples of the rock mass taken from tunnel face inspections and excavated material produced by the TBM. The BEAM data was continuously monitored to check the variations in resistivity and percentage frequency effect (PFE) of the ground. This system provided information about rock mass condition, potential karst risk, and potential of water inflow. BEAM system was found to be more than 50% accurate in picking up the difficult ground conditions and faults as predicted in the geotechnical interpretative report before the start of tunnelling operations. Upon completion of the project, it was concluded that the combined use of different geophysical investigation results can make the execution stage be carried out in a more confident way with the less geotechnical risk involved. The approach used for the prediction of rock mass condition in Geotechnical Interpretative Report (GIR) and Geophysical Reflection and electric resistivity tomography survey (ERT) Geophysical Reflection surveys were concluded to be reliable as the same rock mass conditions were encountered during tunnelling operations.

Keywords: tunnel boring machine (TBM), subsea, karstification, seismic reflection survey

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Authors: Bill D. Geis

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Suicide wrongful death forensic cases are the fastest rising tort in mental health law. It is estimated that suicide-related cases have accounted for 15% of U.S. malpractice claims since 2006. Most suicide-related personal injury claims fall into the legal category of “wrongful death.” Though mental health experts may be called on to address a range of forensic questions in wrongful death cases, the central consultation that most experts provide is about the negligence element—specifically, the issue of whether the clinician met the clinical standard of care in assessing, treating, and managing the deceased person’s mental health care. Standards of care, varying from U.S. state to state, are broad and address what a reasonable clinician might do in a similar circumstance. This fact leaves the issue of the suicide standard of care, in each case, up to forensic experts to put forth a reasoned estimate of what the standard of care should have been in the specific case under litigation. Because the general state guidelines for standard of care are broad, forensic experts are readily retained to provide scientific and clinical opinions about whether or not a clinician met the standard of care in their suicide assessment, treatment, and management of the case. In the past and in much of current practice, the assessment of suicide has centered on the elicitation of verbalized suicide ideation. Research in recent years, however, has indicated that the majority of persons who end their lives do not say they are suicidal at their last medical or psychiatric contact. Near-term risk assessment—that goes beyond verbalized suicide ideation—is needed. Our previous research employed structural equation modeling to predict lethal suicide risk--eight negative thought patterns (feeling like a burden on others, hopelessness, self-hatred, etc.) mediated by nine transdiagnostic clinical factors (mental torment, insomnia, substance abuse, PTSD intrusions, etc.) were combined to predict acute lethal suicide risk. This structural equation model, the Lethal Suicide Risk Pattern (LSRP), Acute model, had excellent goodness-of-fit [χ2(df) = 94.25(47)***, CFI = .98, RMSEA = .05, .90CI = .03-.06, p(RMSEA = .05) = .63. AIC = 340.25, ***p < .001.]. A further SEQ analysis was completed for this paper, adding a measure of Acute Suicide Ideation to the previous SEQ. Acceptable prediction model fit was no longer achieved [χ2(df) = 3.571, CFI > .953, RMSEA = .075, .90% CI = .065-.085, AIC = 529.550].This finding suggests that, in this additional study, immediate verbalized suicide ideation information was unhelpful in the assessment of lethal risk. The LSRP and other dynamic, near-term risk models (such as the Acute Suicide Affective Disorder Model and the Suicide Crisis Syndrome Model)—going beyond elicited suicide ideation—need to be incorporated into current clinical suicide assessment training. Without this training, the standard of care for suicide assessment is out of sync with current research—an emerging dilemma for the forensic evaluation of suicide wrongful death cases.

Keywords: forensic evaluation, standard of care, suicide, suicide assessment, wrongful death

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Authors: Mai Sirhan, Arieh Sidess

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Asphaltic mixture is a heterogeneous material composed of three main components: aggregates; bitumen and air voids. The professional experience and scientific literature categorize asphaltic mixture as a viscoelastic material, whose behavior is determined by temperature and loading rate. Properties characterization of the asphaltic mixture used under the service conditions is done by compacting and testing cylindric asphalt samples in the laboratory. These samples must resemble in a high degree internal structure of the mixture achieved in service, and the mechanical characteristics of the compacted asphalt layer in the pavement. The laboratory samples are usually compacted in temperatures between 140 and 160 degrees Celsius. In this temperature range, the asphalt has a low degree of strength. The laboratory samples are compacted using the dynamic or vibrational compaction methods. In the compaction process, the aggregates tend to align themselves in certain directions that lead to anisotropic behavior of the asphaltic mixture. This issue has been studied in the Strategic Highway Research Program (SHRP) research, that recommended using the gyratory compactor based on the assumption that this method is the best in mimicking the compaction in the service. In Israel, the Netivei Israel company is considering adopting the Gyratory Method as a replacement for the Marshall method used today. Therefore, the compatibility of the Gyratory Method for the use with Israeli asphaltic mixtures should be investigated. In this research, we aimed to examine the impact of the compaction method used on the mechanical characteristics of the asphaltic mixtures and to evaluate the degree of anisotropy in relation to the compaction method. In order to carry out this research, samples have been compacted in the vibratory and gyratory compactors. These samples were cylindrically cored both vertically (compaction wise) and horizontally (perpendicular to compaction direction). These models were tested under dynamic modulus and permanent deformation tests. The comparable results of the tests proved that: (1) specimens compacted by the vibratory compactor had higher dynamic modulus values than the specimens compacted by the gyratory compactor (2) both vibratory and gyratory compacted specimens had anisotropic behavior, especially in high temperatures. Also, the degree of anisotropy is higher in specimens compacted by the gyratory method. (3) Specimens compacted by the vibratory method that were cored vertically had the highest resistance to rutting. On the other hand, specimens compacted by the vibratory method that were cored horizontally had the lowest resistance to rutting. Additionally (4) these differences between the different types of specimens rise mainly due to the different internal arrangement of aggregates resulting from the compaction method. (5) Based on the initial prediction of the performance of the flexible pavement containing an asphalt layer having characteristics based on the results achieved in this research. It can be concluded that there is a significant impact of the compaction method and the degree of anisotropy on the strains that develop in the pavement, and the resistance of the pavement to fatigue and rutting defects.

Keywords: anisotropy, asphalt compaction, dynamic modulus, gyratory compactor, mechanical properties, permanent deformation, vibratory compactor

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Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

Procedia PDF Downloads 135

Authors: Ibtissem Hosni, Lilia Bennaceur Farah, Saber Mohamed Naceur

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In order to assess the water availability in the soil, it is crucial to have information about soil distributed moisture content; this parameter helps to understand the effect of humidity on the exchange between soil, plant cover and atmosphere in addition to fully understanding the surface processes and the hydrological cycle. On the other hand, aerodynamic roughness length is a surface parameter that scales the vertical profile of the horizontal component of the wind speed and characterizes the surface ability to absorb the momentum of the airflow. In numerous applications of the surface hydrology and meteorology, aerodynamic roughness length is an important parameter for estimating momentum, heat and mass exchange between the soil surface and atmosphere. It is important on this side, to consider the atmosphere factors impact in general, and the natural erosion in particular, in the process of soil evolution and its characterization and prediction of its physical parameters. The study of the induced movements by the wind over soil vegetated surface, either spaced plants or plant cover, is motivated by significant research efforts in agronomy and biology. The known major problem in this side concerns crop damage by wind, which presents a booming field of research. Obviously, most models of soil surface require information about the aerodynamic roughness length and its temporal and spatial variability. We have used a bi-dimensional multi-scale (2D MLS) roughness description where the surface is considered as a superposition of a finite number of one-dimensional Gaussian processes each one having a spatial scale using the wavelet transform and the Mallat algorithm to describe natural surface roughness. We have introduced multi-layer aspect of the humidity of the soil surface, to take into account a volume component in the problem of backscattering radar signal. As humidity increases, the dielectric constant of the soil-water mixture increases and this change is detected by microwave sensors. Nevertheless, many existing models in the field of radar imagery, cannot be applied directly on areas covered with vegetation due to the vegetation backscattering. Thus, the radar response corresponds to the combined signature of the vegetation layer and the layer of soil surface. Therefore, the key issue of the numerical estimation of soil moisture is to separate the two contributions and calculate both scattering behaviors of the two layers by defining the scattering of the vegetation and the soil blow. This paper presents a synergistic methodology, and it is for estimating roughness and soil moisture from C-band radar measurements. The methodology adequately represents a microwave/optical model which has been used to calculate the scattering behavior of the aerodynamic vegetation-covered area by defining the scattering of the vegetation and the soil below.

Keywords: aerodynamic, bi-dimensional, vegetation, synergistic

Procedia PDF Downloads 243

Authors: Chevonne Reynolds, Res Altwegg, Andrew Balmford, Claire N. Spottiswoode

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Modern agriculture has revolutionised the planet’s capacity to support humans, yet has simultaneously had a greater negative impact on biodiversity than any other human activity. Balancing the demand for food with the conservation of biodiversity is one of the most pressing issues of our time. Biodiversity-friendly farming (‘land sharing’), or alternatively, separation of conservation and production activities (‘land sparing’), are proposed as two strategies for mediating the trade-off between agriculture and biodiversity. However, there is much debate regarding the efficacy of each strategy, as this trade-off has typically been addressed by short term studies at fine spatial scales. These studies ignore processes that are relevant to biodiversity at larger scales, such as meta-population dynamics and landscape connectivity. Therefore, to better understand species response to agricultural land-use and provide evidence to underpin the planning of better production landscapes, we need to determine the merits of each strategy at larger scales. In South Africa, a remarkable citizen science project - the South African Bird Atlas Project 2 (SABAP2) – collates an extensive dataset describing the occurrence of birds at a 5-min by 5-min grid cell resolution. We use these data, along with fine-resolution data on agricultural land-use, to determine which strategy optimises the agriculture-biodiversity trade-off in a southern African context, and at a spatial scale never considered before. To empirically test this trade-off, we model bird species population density, derived for each 5-min grid cell by Royle-Nicols single-species occupancy modelling, against both the amount and configuration of different types of agricultural production in the same 5-min grid cell. In using both production amount and configuration, we can show not only how species population densities react to changes in yield, but also describe the production landscape patterns most conducive to conservation. Furthermore, the extent of both the SABAP2 and land-cover datasets allows us to test this trade-off across multiple regions to determine if bird populations respond in a consistent way and whether results can be extrapolated to other landscapes. We tested the land sparing/sharing trade-off for 281 bird species across three different biomes in South Africa. Overall, a higher proportion of species are classified as losers, and would benefit from land sparing. However, this proportion of loser-sparers is not consistent and varies across biomes and the different types of agricultural production. This is most likely because of differences in the intensity of agricultural land-use and the interactions between the differing types of natural vegetation and agriculture. Interestingly, we observe a higher number of species that benefit from agriculture than anticipated, suggesting that agriculture is a legitimate resource for certain bird species. Our results support those seen at smaller scales and across vastly different agricultural systems, that land sparing benefits the most species. However, our analysis suggests that land sparing needs to be implemented at spatial scales much larger than previously considered. Species persistence in agricultural landscapes will require the conservation of large tracts of land, and is an important consideration in developing countries, which are undergoing rapid agricultural development.

Keywords: agriculture, birds, land sharing, land sparing

Procedia PDF Downloads 185

Authors: Swati Srivastava, Mattia Lauriola, Yuval Gilad, Adi Kimchi, Yosef Yarden

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The glucocorticoid receptor (GR) has been proposed to play important, but incompletely understood roles in cancer. Glucocorticoids (GCs) are widely used as co-medication of various carcinomas, due to their ability to reduce the toxicity of chemotherapy. Furthermore, GR antagonism has proven to be a strategy to treat triple negative breast cancer and castration-resistant prostate cancer. These observations suggest differential GR involvement in cancer subtypes. The goal of our study has been to elaborate the current understanding of GR signaling in tumor progression and metastasis. Our study involves two cellular models, non-tumorigenic breast epithelial cells (MCF10A) and Ewing sarcoma cells (CHLA9). In our breast cell model, the results indicated that the GR agonist dexamethasone inhibits EGF-induced mammary cell migration, and this effect was blocked when cells were stimulated with a GR antagonist, namely RU486. Microarray analysis for gene expression revealed that the mechanism underlying inhibition involves dexamenthasone-mediated repression of well-known activators of EGFR signaling, alongside with enhancement of several EGFR’s negative feedback loops. Because GR mainly acts primarily through composite response elements (GREs), or via a tethering mechanism, our next aim has been to find the transcription factors (TFs) which can interact with GR in MCF10A cells.The TF-binding motif overrepresented at the promoter of dexamethasone-regulated genes was predicted by using bioinformatics. To validate the prediction, we performed high-throughput Protein Complementation Assays (PCA). For this, we utilized the Gaussia Luciferase PCA strategy, which enabled analysis of protein-protein interactions between GR and predicted TFs of mammary cells. A library comprising both nuclear receptors (estrogen receptor, mineralocorticoid receptor, GR) and TFs was fused to fragments of GLuc, namely GLuc(1)-X, X-GLuc(1), and X-GLuc(2), where GLuc(1) and GLuc(2) correspond to the N-terminal and C-terminal fragments of the luciferase gene.The resulting library was screened, in human embryonic kidney 293T (HEK293T) cells, for all possible interactions between nuclear receptors and TFs. By screening all of the combinations between TFs and nuclear receptors, we identified several positive interactions, which were strengthened in response to dexamethasone and abolished in response to RU486. Furthermore, the interactions between GR and the candidate TFs were validated by co-immunoprecipitation in MCF10A and in CHLA9 cells. Currently, the roles played by the uncovered interactions are being evaluated in various cellular processes, such as cellular proliferation, migration, and invasion. In conclusion, our assay provides an unbiased network analysis between nuclear receptors and other TFs, which can lead to important insights into transcriptional regulation by nuclear receptors in various diseases, in this case of cancer.

Keywords: epidermal growth factor, glucocorticoid receptor, protein complementation assay, transcription factor

Procedia PDF Downloads 203

Authors: Vrushali Guhe, Shailza Singh

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Cutaneous leishmaniasis is neglected tropical disease present worldwide caused by the protozoan parasite Leishmania major, the therapeutic armamentarium for leishmaniasis are showing several limitations as drugs are showing toxic effects with increasing resistance by a parasite. Thus identification of novel therapeutic targets is of paramount importance. Previous studies have shown that autophagy, a cellular process, can either facilitate infection or aid in the elimination of the parasite, depending on the specific parasite species and host background in leishmaniasis. In the present study, our objective was to target the essential autophagy protein ATG8, which plays a crucial role in the survival, infection dynamics, and differentiation of the Leishmania parasite. ATG8 in Leishmania major and its homologue, LC3, in Homo sapiens, act as autophagic markers. Present study manifested the crucial role of ATG8 protein as a potential target for combating Leishmania major infection. Through bioinformatics analysis, we identified non-conserved motifs within the ATG8 protein of Leishmania major, which are not present in LC3 of Homo sapiens. Against these two non-conserved motifs, we generated a peptide library of 60 peptides on the basis of physicochemical properties. These peptides underwent a filtering process based on various parameters, including feasibility of synthesis and purification, compatibility with Selective Reaction Monitoring (SRM)/Multiple reaction monitoring (MRM), hydrophobicity, hydropathy index, average molecular weight (Mw average), monoisotopic molecular weight (Mw monoisotopic), theoretical isoelectric point (pI), and half-life. Further filtering criterion shortlisted three peptides by using molecular docking and molecular dynamics simulations. The direct interaction between ATG8 and the shortlisted peptides was confirmed through Surface Plasmon Resonance (SPR) experiments. Notably, these peptides exhibited the remarkable ability to penetrate the parasite membrane and exert profound effects on Leishmania major. The treatment with these peptides significantly impacted parasite survival, leading to alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, suggesting their involvement in disrupting the regulation of autophagy within Leishmania major. In vitro, studies demonstrated that the selected peptides effectively reduced the parasite load within infected host cells. Encouragingly, these findings were corroborated by in vivo experiments, which showed a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II within host cells. In conclusion, our findings highlight the efficacy of these novel peptides in targeting Leishmania major’s ATG8 and disrupting parasite survival. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis via targeting autophagy protein ATG8 of Leishmania major.

Keywords: ATG8, leishmaniasis, surface plasmon resonance, MD simulation, molecular docking, peptide designing, therapeutics

Procedia PDF Downloads 53

Authors: Andreas Kohlhepp, Gerrit Schatte, Wieland Christoph, Spliethoff Hartmut

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In recent years the research of heat transfer phenomena of water and other working fluids near the critical point experiences a growing interest for power engineering applications. To match the highly volatile characteristics of renewable energies, conventional power plants need to shift towards flexible operation. This requires speeding up the load change dynamics of steam generators and their heating surfaces near the critical point. In dynamic load transients, both a high heat flux with an unfavorable ratio to the mass flux and a high difference in fluid and wall temperatures, may cause problems. It may lead to deteriorated heat transfer (at supercritical pressures), dry-out or departure from nucleate boiling (at subcritical pressures), all cases leading to an extensive rise of temperatures. For relevant technical applications, the heat transfer coefficients need to be predicted correctly in case of transient scenarios to prevent damage to the heated surfaces (membrane walls, tube bundles or fuel rods). In transient processes, the state of the art method of calculating the heat transfer coefficients is using a multitude of different steady-state correlations for the momentarily existing local parameters for each time step. This approach does not necessarily reflect the different cases that may lead to a significant variation of the heat transfer coefficients and shows gaps in the individual ranges of validity. An algorithm was implemented to calculate the transient behavior of steam generators during load changes. It is used to assess existing correlations for transient heat transfer calculations. It is also desirable to validate the calculation using experimental data. By the use of a new full-scale supercritical thermo-hydraulic test rig, experimental data is obtained to describe the transient phenomena under dynamic boundary conditions as mentioned above and to serve for validation of transient steam generator calculations. Aiming to improve correlations for the prediction of the onset of deteriorated heat transfer in both, stationary and transient cases the test rig was specially designed for this task. It is a closed loop design with a directly electrically heated evaporation tube, the total heating power of the evaporator tube and the preheater is 1MW. To allow a big range of parameters, including supercritical pressures, the maximum pressure rating is 380 bar. The measurements contain the most important extrinsic thermo-hydraulic parameters. Moreover, a high geometric resolution allows to accurately predict the local heat transfer coefficients and fluid enthalpies.

Keywords: departure from nucleate boiling, deteriorated heat transfer, dryout, supercritical working fluid, transient operation of steam generators

Procedia PDF Downloads 199

Authors: Olga Kokoulina

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Today, algorithms are assuming a leading role in various areas of decision-making. Prompted by a promise to provide increased economic efficiency and fuel solutions for pressing societal challenges, algorithmic decision-making is often celebrated as an impartial and constructive substitute for human adjudication. But in the face of this implied objectivity and efficiency, the application of algorithms is also marred with mounting concerns about embedded biases, discrimination, and exclusion. In Europe, vigorous debates on risks and adverse implications of algorithmic decision-making largely revolve around the potential of data protection laws to tackle some of the related issues. For example, one of the often-cited venues to mitigate the impact of potentially unfair decision-making practice is a so-called 'right to explanation'. In essence, the overall right is derived from the provisions of the General Data Protection Regulation (‘GDPR’) ensuring the right of data subjects to access and mandating the obligation of data controllers to provide the relevant information about the existence of automated decision-making and meaningful information about the logic involved. Taking corresponding rights and obligations in the context of the specific provision on automated decision-making in the GDPR, the debates mainly focus on efficacy and the exact scope of the 'right to explanation'. In essence, the underlying logic of the argued remedy lies in a transparency imperative. Allowing data subjects to acquire as much knowledge as possible about the decision-making process means empowering individuals to take control of their data and take action. In other words, forewarned is forearmed. The related discussions and debates are ongoing, comprehensive, and, often, heated. However, they are also frequently misguided and isolated: embracing the data protection law as ultimate and sole lenses are often not sufficient. Mandating the disclosure of technical specifications of employed algorithms in the name of transparency for and empowerment of data subjects potentially encroach on the interests and rights of IPR holders, i.e., business entities behind the algorithms. The study aims at pushing the boundaries of the transparency debate beyond the data protection regime. By systematically analysing legal requirements and current judicial practice, it assesses the limits of the transparency requirement and right to access posed by intellectual property law, namely by copyrights and trade secrets. It is asserted that trade secrets, in particular, present an often-insurmountable obstacle for realising the potential of the transparency requirement. In reaching that conclusion, the study explores the limits of protection afforded by the European Trade Secrets Directive and contrasts them with the scope of respective rights and obligations related to data access and portability enshrined in the GDPR. As shown, the far-reaching scope of the protection under trade secrecy is evidenced both through the assessment of its subject matter as well as through the exceptions from such protection. As a way forward, the study scrutinises several possible legislative solutions, such as flexible interpretation of the public interest exception in trade secrets as well as the introduction of the strict liability regime in case of non-transparent decision-making.

Keywords: algorithms, public interest, trade secrets, transparency

Procedia PDF Downloads 103

Authors: Jo Mitchell, Daniel Johnson

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MindMax is a digital community and learning platform built to maximise the wellbeing and resilience of AFL Players and Australian men. The MindMax application engages men, via their existing connection with sport and video games, in a range of wellbeing ideas, stories and actions, because we believe fit minds, kick goals. MindMax is an AFL Players Association led project, supported by a Movember Foundation grant, to improve the mental health of Australian males aged between 16-35 years. The key engagement and delivery strategy for the project was digital technology, sport (AFL) and video games, underpinned by evidenced based wellbeing science. The project commenced April 2015, and the expected completion date is March 2017. This paper describes the conceptual model underpinning product development, including progress, key learnings and challenges, as well as the research agenda. Evaluation of the MindMax project is a multi-pronged approach of qualitative and quantitative methods, including participatory design workshops, online reference groups, longitudinal survey methods, a naturalistic efficacy trial and evaluation of the social and economic return on investment. MindMax is focused on the wellness pathway and maximising our mind's capacity for fitness by sharing and promoting evidence-based actions that support this. A range of these ideas (from ACT, mindfulness and positive psychology) are already being implemented in AFL programs and services, mostly in face-to-face formats, with strong engagement by players. Player's experience features strongly as part of the product content. Wellbeing science is a discipline of psychology that explores what helps individuals and communities to flourish in life. Rather than ask questions about illness and poor functioning, wellbeing scientists and practitioners ask questions about wellness and optimal functioning. While illness and wellness are related, they operate as separate constructs and as such can be influenced through different pathways. The essential idea was to take the evidence-based wellbeing science around building psychological fitness to the places and spaces that men already frequent, namely sport and video games. There are 800 current senior AFL players, 5000+ past players, and 11 million boys and men that are interested in the lives of AFL Players; what they think and do to be their best both on and off field. AFL Players are also keen video gamers – using games as one way to de-stress, connect and build wellbeing. There are 9.5 million active gamers in Australia with 93% of households having a device for playing games. Video games in MindMax will be used as an engagement and learning tool. Gamers (including AFL players) can also share their personal experience of how games help build their mental fitness. Currently available games (i.e., we are not in the game creation business) will also be used to motivate and connect MindMax participants. The MindMax model is built with replication by other sport codes (e.g., Cricket) in mind. It is intended to not only support our current crop of athletes but also the community that surrounds them, so they can maximise their capacity for health and wellbeing.

Keywords: Australian football league, digital application, positive psychology, wellbeing

Procedia PDF Downloads 205

Authors: Sonika Sharma, Mohan G. Vairale, Sibnarayan Datta, Soumya Chatterjee, Dharmendra Dubey, Rajesh Prasad, Raghvendra Budhauliya, Bidisha Das, Vijay Veer

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Bacteriophages are viruses that parasitize specific bacteria and multiply in metabolising host bacteria. Bacteriophages hunt for a single or a subset of bacterial species, making them potential antibacterial agents. Utilizing the ability of phages to control bacterial populations has several applications from medical to the fields of agriculture, aquaculture and the food industry. However, harnessing phage based techniques in wastewater treatments to improve quality of effluent and sludge release into the environment is a potential area for R&D application. Phage mediated bactericidal effect in any wastewater treatment process has many controlling factors that lead to treatment performance. In laboratory conditions, titer of bacteriophages (coliphages) isolated from effluent water of a specially designed anaerobic digester of human night soil (DRDO Biotoilet) was successfully increased with a modified protocol of the classical double layer agar technique. Enrichment of the same was carried out and efficacy of the phage enriched medium was evaluated at different conditions (specific media, temperature, storage conditions). Growth optimization study was carried out on different media like soybean casein digest medium (Tryptone soya medium), Luria-Bertani medium, phage deca broth medium and MNA medium (Modified nutrient medium). Further, temperature-phage yield relationship was also observed at three different temperatures 27˚C, 37˚C and 44˚C at laboratory condition. Results showed the higher activity of coliphage 27˚C and at 37˚C. Further, addition of divalent ions (10mM MgCl2, 5mM CaCl2) and 5% glycerol resulted in a significant increase in phage titer. Besides this, effect of antibiotics addition like ampicillin and kanamycin at different concentration on plaque formation was analysed and reported that ampicillin at a concentration of 1mg/ml ampicillin stimulates phage infection and results in more number of plaques. Experiments to test viability of phage showed that it can remain active for 6 months at 4˚C in fresh tryptone soya broth supplemented with fresh culture of coliforms (early log phase). The application of bacteriophages (especially coliphages) for treatment of effluent of human faecal matter contaminated effluent water is unique. This environment-friendly treatment system not only reduces the pathogenic coliforms, but also decreases the competition between nuisance bacteria and functionally important microbial populations. Therefore, the phage based cocktail to treat fecal pathogenic bacteria present in black water has many implication in wastewater treatment processes including ‘DRDO Biotoilet’, which is an ecofriendly appropriate and affordable human faecal matter treatment technology for different climates and situations.

Keywords: wastewater, microbes, virus, biotoilet, phage viability

Procedia PDF Downloads 403

Authors: Hassan Younis

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Purpose: The objective of this study is to review influential papers in the sustainability and supply chain studies domain, leveraging insights from this review to develop a structured framework for academics and researchers. This framework aims to assist scholars in identifying the most impactful publications for their scholarly pursuits. Subsequently, the study will apply and trial the developed framework on selected scholarly articles within the sustainability and supply chain studies domain to evaluate its efficacy, practicality, and reliability. Design/Methodology/Approach: Utilizing the "Publish or Perish" tool, a search was conducted to locate papers incorporating "sustainability" and "supply chain" in their titles. After rigorous filtering steps, a panel of university professors identified five crucial criteria for evaluating research robustness: average yearly citation counts (25%), scholarly contribution (25%), alignment of findings with objectives (15%), methodological rigor (20%), and journal impact factor (15%). These five evaluation criteria are abbreviated as “ACMAJ" framework. Each paper then received a tiered score (1-3) for each criterion, normalized within its category, and summed using weighted averages to calculate a Final Normalized Score (FNS). This systematic approach allows for objective comparison and ranking of the research based on its impact, novelty, rigor, and publication venue. Findings: The study's findings highlight the lack of structured frameworks for assessing influential sustainability research in supply chain management, which often results in a dependence on citation counts. A complete model that incorporates five essential criteria has been suggested as a response. By conducting a methodical trial on specific academic articles in the field of sustainability and supply chain studies, the model demonstrated its effectiveness as a tool for identifying and selecting influential research papers that warrant additional attention. This work aims to fill a significant deficiency in existing techniques by providing a more comprehensive approach to identifying and ranking influential papers in the field. Practical Implications: The developed framework helps scholars identify the most influential sustainability and supply chain publications. Its validation serves the academic community by offering a credible tool and helping researchers, students, and practitioners find and choose influential papers. This approach aids field literature reviews and study suggestions. Analysis of major trends and topics deepens our grasp of this critical study area's changing terrain. Originality/Value: The framework stands as a unique contribution to academia, offering scholars an important and new tool to identify and validate influential publications. Its distinctive capacity to efficiently guide scholars, learners, and professionals in selecting noteworthy publications, coupled with the examination of key patterns and themes, adds depth to our understanding of the evolving landscape in this critical field of study.

Keywords: supply chain management, sustainability, framework, model

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Authors: Navid Kaboudi, Ali Shayanfar

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Introduction: Feeding infants with safe milk from the beginning of their life is an important issue. Drugs which are used by mothers can affect the composition of milk in a way that is not only unsuitable, but also toxic for infants. Consuming permeable drugs during that sensitive period by mother could lead to serious side effects to the infant. Due to the ethical restrictions of drug testing on humans, especially women, during their lactation period, computational approaches based on structural parameters could be useful. The aim of this study is to develop mechanistic models to predict the M/P ratio of drugs during breastfeeding period based on their structural descriptors. Methods: Two hundred and nine different chemicals with their M/P ratio were used in this study. All drugs were categorized into two groups based on their M/P value as Malone classification: 1: Drugs with M/P>1, which are considered as high risk 2: Drugs with M/P>1, which are considered as low risk Thirty eight chemical descriptors were calculated by ACD/labs 6.00 and Data warrior software in order to assess the penetration during breastfeeding period. Later on, four specific models based on the number of hydrogen bond acceptors, polar surface area, total surface area, and number of acidic oxygen were established for the prediction. The mentioned descriptors can predict the penetration with an acceptable accuracy. For the remaining compounds (N= 147, 158, 160, and 174 for models 1 to 4, respectively) of each model binary regression with SPSS 21 was done in order to give us a model to predict the penetration ratio of compounds. Only structural descriptors with p-value<0.1 remained in the final model. Results and discussion: Four different models based on the number of hydrogen bond acceptors, polar surface area, and total surface area were obtained in order to predict the penetration of drugs into human milk during breastfeeding period About 3-4% of milk consists of lipids, and the amount of lipid after parturition increases. Lipid soluble drugs diffuse alongside with fats from plasma to mammary glands. lipophilicity plays a vital role in predicting the penetration class of drugs during lactation period. It was shown in the logistic regression models that compounds with number of hydrogen bond acceptors, PSA and TSA above 5, 90 and 25 respectively, are less permeable to milk because they are less soluble in the amount of fats in milk. The pH of milk is acidic and due to that, basic compounds tend to be concentrated in milk than plasma while acidic compounds may consist lower concentrations in milk than plasma. Conclusion: In this study, we developed four regression-based models to predict the penetration class of drugs during the lactation period. The obtained models can lead to a higher speed in drug development process, saving energy, and costs. Milk/plasma ratio assessment of drugs requires multiple steps of animal testing, which has its own ethical issues. QSAR modeling could help scientist to reduce the amount of animal testing, and our models are also eligible to do that.

Keywords: logistic regression, breastfeeding, descriptors, penetration

Procedia PDF Downloads 43

Authors: Hazel James P. Agngarayngay, Arnold R. Elepaño

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Mango is the third most important export fruit in the Philippines. Despite the expanding mango trade in world market, problems on postharvest losses caused by pests and diseases are still prevalent. Many disease control and pest disinfestation methods have been studied and adopted. Heat treatment is necessary to eliminate pests and diseases to be able to pass the quarantine requirements of importing countries. During heat treatments, temperature and time are critical because fruits can easily be damaged by over-exposure to heat. Modeling the process enables researchers and engineers to study the behaviour of temperature distribution within the fruit over time. Understanding physical processes through modeling and simulation also saves time and resources because of reduced experimentation. This research aimed to simulate the heat transfer mechanism and predict the temperature distribution in ‘Carabao' mangoes during hot water treatment (HWT) and extended hot water treatment (EHWT). The simulation was performed in ANSYS CFD Software, using ANSYS CFX Solver. The simulation process involved model creation, mesh generation, defining the physics of the model, solving the problem, and visualizing the results. Boundary conditions consisted of the convective heat transfer coefficient and a constant free stream temperature. The three-dimensional energy equation for transient conditions was numerically solved to obtain heat flux and transient temperature values. The solver utilized finite volume method of discretization. To validate the simulation, actual data were obtained through experiment. The goodness of fit was evaluated using mean temperature difference (MTD). Also, t-test was used to detect significant differences between the data sets. Results showed that the simulations were able to estimate temperatures accurately with MTD of 0.50 and 0.69 °C for the HWT and EHWT, respectively. This indicates good agreement between the simulated and actual temperature values. The data included in the analysis were taken at different locations of probe punctures within the fruit. Moreover, t-tests showed no significant differences between the two data sets. Maximum heat fluxes obtained at the beginning of the treatments were 394.15 and 262.77 J.s-1 for HWT and EHWT, respectively. These values decreased abruptly at the first 10 seconds and gradual decrease was observed thereafter. Data on heat flux is necessary in the design of heaters. If underestimated, the heating component of a certain machine will not be able to provide enough heat required by certain operations. Otherwise, over-estimation will result in wasting of energy and resources. This study demonstrated that the simulation was able to estimate temperatures accurately. Thus, it can be used to evaluate the influence of various treatment conditions on the temperature-time history in mangoes. When combined with information on insect mortality and quality degradation kinetics, it could predict the efficacy of a particular treatment and guide appropriate selection of treatment conditions. The effect of various parameters on heat transfer rates, such as the boundary and initial conditions as well as the thermal properties of the material, can be systematically studied without performing experiments. Furthermore, the use of ANSYS software in modeling and simulation can be explored in modeling various systems and processes.

Keywords: heat transfer, heat treatment, mango, modeling and simulation

Procedia PDF Downloads 227

Authors: G. Kontochristopoulos, T. Spiliopoulos, V. Markantoni, E. Platsidaki, A. Kouris, E. Balamoti, C. Bokotas, G. Haidemenos

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Introduction: There is a high patient demand for periorbital rejuvenation since the facial area is often the first to show visible signs of aging. With advancing age, there are sometimes marked changes that occur in the skin, fat, muscle and bone of the periorbital region, resulting to wrinkles and skin laxity. These changes are among the easiest areas to correct using several minimally invasive techniques, which have become increasingly popular over the last decade. Lasers, radiofrequency, botulinum toxin, fat grafting and fillers are available treatments sometimes in combination to traditional blepharoplasty. This study attempts to show the benefits of a minimally invasive approach to periorbital wrinkles and skin laxity that combine microneedling and 10% trichloroacetic acid (TCA) peels. Method: Eleven female patients aged 34-72 enrolled in the study. They all gave informed consent after receiving detailed information regarding the treatment procedure. Exclusion criteria in the study were previous treatment for the same condition in the past six months, pregnancy, allergy or hypersensitivity to the components, infection, inflammation and photosensitivity on the affected region. All patients had diffuse periorbital wrinkles and mild to moderate upper or lower eyelid skin laxity. They were treated with Automatic Microneedle Therapy System-Handhold and topical application of 10% trichloroacetic acid solution to each periorbital area for five minutes. Needling at a 0,25 mm depth was performed in both latelar (x-y) directions. Subsequently, the peeling agent was applied to each periorbital area for five minutes. Patients were subjected to the above combination every two weeks for a series of four treatments. Subsequently they were followed up regularly every month for two months. The effect was photo-documented. A Physician's and a Patient's Global Assessment Scale was used to evaluate the efficacy of the treatment (0-25% indicated poor response, 25%-50% fair, 50%-75% good and 75%-100% excellent response). Safety was assessed by monitoring early and delayed adverse events. Results: At the end of the study, almost all patients demonstrated significant aesthetic improvement. Physicians assessed a fair and a good improvement in 9(81.8% of patients) and 2(18.1% of patients) participants respectively. Patients Global Assessment rated a fair and a good response in 6 (54.5%) and 5 (45.4%) participants respectively. The procedure was well tolerated and all patients were satisfied. Mild discomfort and transient erythema were quite common during or immediately after the procedure, however only temporary. During the monthly follow up, no complications or scars were observed. Conclusions: Microneedling is known as a simple, office–based collagen induction therapy. Low concentration TCA solution applied to the epidermis that has been more permeable by microneedling, can reach the dermis more effectively. In the present study, chemical peels with 10% TCA acted as an adjuvant to microneedling, as it causes controlled skin damage, promoting regeneration and rejuvenation of tissues. This combined therapy improved periorbital fine lines, wrinkles, and overall appearance of the skin. Thus it constitutes an alternative treatment of periorbital skin aging, with encouraging results and minor side-effects.

Keywords: chemical peels, microneedling, periorbital wrinkles, skin laxity

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Authors: Karen Koellner, Nanette Seago, Jennifer Jacobs, Helen Garnier

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Although studies of teacher professional development (PD) are prevalent, surprisingly most have only produced incremental shifts in teachers’ learning and their impact on students. There is a critical need to understand what teachers take up and use in their classroom practice after attending PD and why we often do not see greater changes in learning and practice. This paper is based on a mixed methods efficacy study of the Learning and Teaching Geometry (LTG) video-based mathematics professional development materials. The extent to which the materials produce a beneficial impact on teachers’ mathematics knowledge, classroom practices, and their students’ knowledge in the domain of geometry through a group-randomized experimental design are considered. Included is a close-up examination of a small group of teachers to better understand their interpretations of the workshops and their classroom uptake. The participants included 103 secondary mathematics teachers serving grades 6-12 from two US states in different regions. Randomization was conducted at the school level, with 23 schools and 49 teachers assigned to the treatment group and 18 schools and 54 teachers assigned to the comparison group. The case study examination included twelve treatment teachers. PD workshops for treatment teachers began in Summer 2016. Nine full days of professional development were offered to teachers, beginning with the one-week institute (Summer 2016) and four days of PD throughout the academic year. The same facilitator-led all of the workshops, after completing a facilitator preparation process that included a multi-faceted assessment of fidelity. The overall impact of the LTG PD program was assessed from multiple sources: two teacher content assessments, two PD embedded assessments, pre-post-post videotaped classroom observations, and student assessments. Additional data were collected from the case study teachers including additional videotaped classroom observations and interviews. Repeated measures ANOVA analyses were used to detect patterns of change in the treatment teachers’ content knowledge before and after completion of the LTG PD, relative to the comparison group. No significant effects were found across the two groups of teachers on the two teacher content assessments. Teachers were rated on the quality of their mathematics instruction captured in videotaped classroom observations using the Math in Common Observation Protocol. On average, teachers who attended the LTG PD intervention improved their ability to engage students in mathematical reasoning and to provide accurate, coherent, and well-justified mathematical content. In addition, the LTG PD intervention and instruction that engaged students in mathematical practices both positively and significantly predicted greater student knowledge gains. Teacher knowledge was not a significant predictor. Twelve treatment teachers self-selected to serve as case study teachers to provide additional videotapes in which they felt they were using something from the PD they learned and experienced. Project staff analyzed the videos, compared them to previous videos and interviewed the teachers regarding their uptake of the PD related to content knowledge, pedagogical knowledge and resources used. The full paper will include the case study of Ana to illustrate the factors involved in what teachers take up and use from participating in the LTG PD.

Keywords: geometry, mathematics professional development, pedagogical content knowledge, teacher learning

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Authors: Asif Ali, Daud Salim Faruquie

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With the advancement of knowledge about the utility and impact of sustainability, its feasibility has been explored into different walks of life. Scientists, however; have established their knowledge in four areas viz environmental, economic, social and cultural, popularly termed as four pillars of sustainability. Aspects of environmental and economic sustainability have been rigorously researched and practiced and huge volume of strong evidence of effectiveness has been founded for these two sub-areas. For the social and cultural aspects of sustainability, dependable evidence of effectiveness is still to be instituted as the researchers and practitioners are developing and experimenting methods across the globe. Therefore, the present research aimed to identify globally used practices of social and cultural sustainability and through evidence synthesis assess their outcomes to determine the effectiveness of those practices. A PICO format steered the methodology which included all populations, popular sustainability practices including walkability/cycle tracks, social/recreational spaces, privacy, health & human services and barrier free built environment, comparators included ‘Before’ and ‘After’, ‘With’ and ‘Without’, ‘More’ and ‘Less’ and outcomes included Social well-being, cultural co-existence, quality of life, ethics and morality, social capital, sense of place, education, health, recreation and leisure, and holistic development. Search of literature included major electronic databases, search websites, organizational resources, directory of open access journals and subscribed journals. Grey literature, however, was not included. Inclusion criteria filtered studies on the basis of research designs such as total randomization, quasi-randomization, cluster randomization, observational or single studies and certain types of analysis. Studies with combined outcomes were considered but studies focusing only on environmental and/or economic outcomes were rejected. Data extraction, critical appraisal and evidence synthesis was carried out using customized tabulation, reference manager and CASP tool. Partial meta-analysis was carried out and calculation of pooled effects and forest plotting were done. As many as 13 studies finally included for final synthesis explained the impact of targeted practices on health, behavioural and social dimensions. Objectivity in the measurement of health outcomes facilitated quantitative synthesis of studies which highlighted the impact of sustainability methods on physical activity, Body Mass Index, perinatal outcomes and child health. Studies synthesized qualitatively (and also quantitatively) showed outcomes such as routines, family relations, citizenship, trust in relationships, social inclusion, neighbourhood social capital, wellbeing, habitability and family’s social processes. The synthesized evidence indicates slight effectiveness and efficacy of social and cultural sustainability on the targeted outcomes. Further synthesis revealed that such results of this study are due weak research designs and disintegrated implementations. If architects and other practitioners deliver their interventions in collaboration with research bodies and policy makers, a stronger evidence-base in this area could be generated.

Keywords: built environment, cultural sustainability, social sustainability, sustainable architecture

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Authors: Rahbel Rahman, Rogério Meireles Pinto, Margareth Santos Zanchetta

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Background: Existing shortcomings of current health-service delivery include poor teamwork, competencies that do not address consumer needs, and episodic rather than continuous care. Brazil’s Sistema Único de Saúde (Unified Health System, UHS) is acknowledged worldwide as a model for delivering community-based care through Estratégia Saúde da Família (FHS; Family Health Strategy) interdisciplinary teams, comprised of Community Health Agents (in Portuguese, Agentes Comunitário de Saude, ACS), nurses, and physicians. FHS teams are mandated to collectively offer clinical care, disease prevention services, vector control, health surveillance and social services. Our study compares medical providers (nurses and physicians) and community-based providers (ACS) on their perceptions of work environment, professional skills, cognitive capacities and job context. Global health administrators and policy makers can leverage on similarities and differences across care providers to develop interprofessional training for community-based primary care. Methods: Cross-sectional data were collected from 168 ACS, 62 nurses and 32 physicians in Brazil. We compared providers’ demographic characteristics (age, race, and gender) and job context variables (caseload, work experience, work proximity to community, the length of commute, and familiarity with the community). Providers perceptions were compared to their work environment (work conditions and work resources), professional skills (consumer-input, interdisciplinary collaboration, efficacy of FHS teams, work-methods and decision-making autonomy), and cognitive capacities (knowledge and skills, skill variety, confidence and perseverance). Descriptive and bi-variate analysis, such as Pearson Chi-square and Analysis of Variance (ANOVA) F-tests, were performed to draw comparisons across providers. Results: Majority of participants were ACS (64%); 24% nurses; and 12% physicians. Majority of nurses and ACS identified as mixed races (ACS, n=85; nurses, n=27); most physicians identified as males (n=16; 52%), and white (n=18; 58%). Physicians were less likely to incorporate consumer-input and demonstrated greater decision-making autonomy than nurses and ACS. ACS reported the highest levels of knowledge and skills but the least confidence compared to nurses and physicians. ACS, nurses, and physicians were efficacious that FHS teams improved the quality of health in their catchment areas, though nurses tend to disagree that interdisciplinary collaboration facilitated their work. Conclusion: To our knowledge, there has been no study comparing key demographic and cognitive variables across ACS, nurses and physicians in the context of their work environment and professional training. We suggest that global health systems can leverage upon the diverse perspectives of providers to implement a community-based primary care model grounded in interprofessional training. Our study underscores the need for in-service trainings to instill reflective skills of providers, improve communication skills of medical providers and curative skills of ACS. Greater autonomy needs to be extended to community based providers to offer care integral to addressing consumer and community needs.

Keywords: global health systems, interdisciplinary health teams, community health agents, community-based care

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Authors: Anantha S. Babbili

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This paper analyzes the current media practices dominant in global journalistic practices within the framework of world press theories of Libertarian, Authoritarian, Communist, and Social Responsibility to evaluate their efficacy in addressing their role in the coverage of the coronavirus, also known as COVID-19. The global media flows, determinants of news coverage, and international awareness and the Western view of the world will be critically analyzed within the context of the prevalent news values that underpin free press and media coverage of the world. While evaluating the global discourse paramount to a sustained and dispassionate understanding of world events, this paper proposes an ethical framework that brings clarity devoid of sensationalism, partisanship, right-wing and left-wing interpretations to a breaking and dangerous development of a pandemic. As the world struggles to contain the coronavirus pandemic with death climbing close to 6,000 from late January to mid-March, 2020, the populations of the developed as well as the developing nations are beset with news media renditions of the crisis that are contradictory, confusing and evoking anxiety, fear and hysteria. How are we to understand differing news standards and news values? What lessons do we as journalism and mass media educators, researchers, and academics learn in order to construct a better news model and structure of media practice that addresses science, health, and media literacy among media practitioners, journalists, and news consumers? As traditional media struggles to cover the pandemic to its audience and consumers, social media from which an increasing number of consumers get their news have exerted their influence both in a positive way and in a negative manner. Even as the world struggles to grasp the full significance of the pandemic, the World Health Organization (WHO) has been feverishly battling an additional challenge related to the pandemic in what it termed an 'infodemic'—'an overabundance of information, some accurate and some not, that makes it hard for people to find trustworthy sources and reliable guidance when they need it.' There is, indeed, a need for journalism and news coverage in times of pandemics that reflect social responsibility and ethos of public service journalism. Social media and high-tech information corporations, collectively termed GAMAF—Google, Apple, Microsoft, Amazon, and Facebook – can team up with reliable traditional media—newspapers, magazines, book publishers, radio and television corporates—to ease public emotions and be helpful in times of a pandemic outbreak. GAMAF can, conceivably, weed out sensational and non-credible sources of coronavirus information, exotic cures offered for sale on a quick fix, and demonetize videos that exploit peoples’ vulnerabilities at the lowest ebb. Credible news of utility delivered in a sustained, calm, and reliable manner serves people in a meaningful and helpful way. The world’s consumers of news and information, indeed, deserve a healthy and trustworthy news media – at least in the time of pandemic COVID-19. Towards this end, the paper will propose a practical model for news media and journalistic coverage during times of a pandemic.

Keywords: COVID-19, international news flow, social media, social responsibility

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Authors: Yujie Yuan, Yiyang Fan, Hong Fan

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Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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