Search results for: clinical outcomes

Authors: Elham Abbas Aljaaly, Nahlaa Abdulwahab Khalifa

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The active method of disease prevention is seen as the most affordable and sustainable action to deal with risks of non-communicable diseases such as obesity. This eight-week project aimed to pilot the feasibility and acceptability of a school-based programme, which is proposed to prevent and modify overweight status and possible related risk factors among student girls 'at the intermediate level' in Jeddah city. The programme was conducted through comprehensible approach targeting physical environment and school policies (nutritional/exercise/behavioural approach). The programme was designed to cultivate the personal and environmental awareness in schools for girls. This was applied by promoting healthy eating and physical activity through policies, physical education, healthier options for school canteens, and the creation of school health teams. The prevention programme was applied on 68 students (who agreed to participate) from grades 7th, 8th and 9th. A pre and post assessment questionnaire was employed on 66 students. The questionnaires were designed to obtain information on students' knowledge about health, nutrition and physical activity. Survey questions included information about nutrients, food consumption patterns, food intake and lifestyle. Physical education included training sessions for new opportunities for physical activities to be performed during school or after school hours. A running competition 'to enhance students’ performance for physical activities' was also conducted during the school visit. A visit to the school canteen was conducted to check, observe, record and assess all available food/beverage items and meals. The assessment method was a subjective method for the type of food/beverages if high in saturated fat, salt and sugar (HFSS) or non-HFSS. The school canteen administrators were encouraged to provide healthy food/beverage items and a sample healthy canteen was provided for implementation. Two healthy options were introduced to the school canteen. A follow up for students’ preferences for the introduced options and the purchasing power were assessed. Thirty-eight percent of young girls (n=26) were not participating in any form of physical activities inside or outside school. Skipping breakfast was stated by 42% (n=28) of students with no daily consumption (19%, n=13) for fruit/vegetables. Significant changes were noticed in students’ (n=66) overall responses to the pre and post questions (P value=.001). All students had participated in the conducted running competition sessions and reported satisfaction and enjoyment about the sessions. No absence was reported by the research team for attending physical education and activity sessions throughout the delivered programme. The purchasing power of the introduced healthy options of 'Salad and oatmeal' was increased to 18% in 8 weeks at the school canteen, and slightly affected the purchase for other less healthy options. The piloted programme indorsed better health and nutrition knowledge, healthy eating and lifestyle attitude, which could help young girls to obtain sustainable changes. It is expected that the outcomes of the programme will be a cornerstone for the futuristic national study that will assist policy makers and participants to build a knowledgeable health promotion scenario and make sure that school students have access to healthy foods, physical exercise and healthy lifestyle.

Keywords: adolescents, diet, exercise, behaviours, overweight/obesity, prevention-intervention programme, Saudi Arabia, schoolgirls

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Authors: Humaira Saeed Malik, Salma Saad

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Introduction: Fowler's syndrome, first described by Clare Fowler in 1985, is a rare urological condition characterized by difficulty in urination due to the abnormal function of the urethral sphincter. It predominantly affects young women and leads to chronic urinary retention. The main concern in managing this condition is ensuring regular bladder emptying. Clam cystoplasty is a bladder augmentation surgery in which the bladder is clam-shelled open, and a segment of the intestine is used to increase the bladder's capacity and reduce bladder pressure. The Mitrofanoff procedure, a surgical creation of a continent urinary diversion, is often performed in patients with Fowler's syndrome who require long-term catheterization. This procedure involves creating a conduit (from the appendix or a segment of the small intestine) between the bladder and the skin, allowing for intermittent self-catheterization to manage urinary retention. Study: This case study examines a 39-year-old gravida 3, para 0+2 woman with a BMI of 40, Fowler's syndrome, type I diabetes, and post-traumatic stress disorder (PTSD), presenting at Dumfries and Galloway Royal Infirmary at 8 weeks of gestation. Diagnosed with Fowler's syndrome at 23, . A sacral nerve stimulator (SNS) device was initially placed but was subsequently removed after one year due to malfunction caused by trauma, subsequently she had undergone clam cystoplasty and the Mitrofanoff procedure for bladder management. Her pregnancy was complicated by vaginal bleeding at 10 weeks, treated with progesterone pessaries, and a urinary tract infection at 14 weeks, managed with antibiotics. Despite these challenges, she continued self-catheterization through the Mitrofanoff stoma and was placed on prophylactic antibiotics. Her diabetes was well-controlled on insulin, and a 20-week fetal anomaly scan was normal. The multidisciplinary team, including an obstetrician and a urologist, planned for serial growth scans and the initiation of low molecular weight heparin (LMWH) from 28 weeks due to the intermediate risk of venous thromboembolism (VTE) and to continue six weeks after delivery. A planned cesarean delivery at 37 weeks was arranged, with an MRI scan scheduled later in the pregnancy to assist in surgical planning, ensuring the preservation of the Mitrofanoff stoma's function. The surgery will occur in an elective setting and include a consultant urologist. Conclusion: Pregnancy in women with Fowler's syndrome who have undergone Clam cystoplasty and the Mitrofanoff procedure is rare, and management requires careful planning and a multidisciplinary approach. This case highlights the importance of individualized care plans and close monitoring of both mother and fetus. The patient's risk of recurrent UTIs, coupled with her diabetes and high BMI, necessitated coordinated care across specialties to ensure the best possible outcomes. The Mitrofanoff procedure proved effective in managing her urinary retention, allowing her to maintain self-catheterization during pregnancy. The multidisciplinary team approach was crucial in addressing her complex medical needs, involving obstetrics, urology, and endocrinology. This case adds valuable information to the limited literature on pregnancy management in patients with Fowler's syndrome who have undergone the Mitrofanoff procedure, highlighting the need for comprehensive, individualized care and the involvement of a multidisciplinary team to achieve the best results.

Keywords: fowler's syndrome, clam cystoplasty, mitrofanoff procedure, pregnancy

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Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

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Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

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Authors: Nils Haglund, Svenolof Dahlgren, Maria Rastam, Peik Gustafsson, Karin Kalien

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In Sweden, like in most developed countries, there is a substantial increase of children diagnosed with autism and other conditions within the autism spectrum (ASD). The rapid increase of ASD rates stresses the importance of developing care programs to provide support and comprehensive interventions for affected families. The current observational study was conducted in order to evaluate an ongoing Comprehensive Intensive Early Intervention (CIEI) program for children with autism in southern Sweden. The change in autism symptoms among children participating in CIEI (intervention group, n=67) was compared with children who received traditional habilitation services only (comparison group, n=27). Children of parents who accepted the offered CIEI-program, constituted the intervention group, whereas children, whose parents (for some reason) were not interested in the offered CIEI-program, constituted the comparison group. The CIEI-program was individualized to each child by experienced applied behavior analysis (ABA) specialists with different backgrounds as psychologists, speech pathologists or special education teachers, in cooperation with parents and preschool staff. Due to the individualization, the intervention could vary in intensity and techniques. The intensity was calculated to 15-25 hours each week at home and the preschool altogether. Each child was assigned one 'trainer', who was often employed as a preschool teacher but could have another educational background. An agreement between supervisor- parents and preschool staff was reached to confirm the intensity and content of the CIEI- program over an approximately two-year intervention period. Symptom changes were measured as evaluation-ADOS-2-scores, total- and severity-scores, minus the corresponding baseline-scores, divided by the time between baseline and evaluation. The difference between the study-groups regarding change of ADOS-2-scores was estimated using ANCOVA. In the current study, children in the CIEI-group improved their ADOS-2-total scores between baseline and evaluation (-0.8 scores per year; 95%CI: -1.2 to -0.4), whereas no such improvement was detected in the comparison group (+0.1 scores per year; 95%CI: -0.7 to +0.9). The change difference (change in the CIEI-group vs. change in the comparison group) was statistically significant, both crude and after adjusting for possible confounders (-1.1; 95%CI -1.9 to -0.4). Children in the CIEI-group also significantly improved their ADOS-calibrated severity scores, but not significantly differently so from the comparison group. The results from the current study indicate that the CIEI program significantly improves social and communicative skills among children with autism and that children with developmental delay could benefit to a similar degree as other children. The results support earlier studies reporting on the improvement of autism symptoms after early intensive interventions. The results from observational studies are difficult to interpret, but it is nevertheless of uttermost importance to evaluate costly autism intervention programs. Such results may be of immediate importance to healthcare organizations when allocating the already strained resources to different patient groups. Albeit the obvious limitation of the current naturalistic study, the results support previous positive studies and indicate that children with autism benefit from participating in early comprehensive, intensive programs and that investments in these programs may be highly justifiable.

Keywords: autism symptoms, ADOS-scores, evaluation, intervention program

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Authors: Jun Wang, Chenglei Diao, Emanuele Pagone, Jialuo Ding, Stewart Williams

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As a crucial component in aircraft, landing gear systems are responsible for supporting the plane during parking, taxiing, takeoff, and landing. Given the need for high load-bearing capacity over extended periods, 300M ultra-high strength steel (UHSS) is often the material of choice for crafting these systems due to its exceptional strength, toughness, and fatigue resistance. In the quest for cost-effective and sustainable manufacturing solutions, Wire Arc Additive Manufacturing (WAAM) emerges as a promising alternative for fabricating 300M UHSS landing gears. This is due to its advantages in near-net-shape forming of large components, cost-efficiency, and reduced lead times. Cranfield University has conducted an extensive preliminary study on WAAM 300M UHSS, covering feature deposition, interface analysis, and post-heat treatment. Both Gas Metal Arc (GMA) and Plasma Transferred Arc (PTA)-based WAAM methods were explored, revealing their feasibility for defect-free manufacturing. However, as-deposited 300M features showed lower strength but higher ductility compared to their forged counterparts. Subsequent post-heat treatments were effective in normalising the microstructure and mechanical properties, meeting qualification standards. A 300M UHSS landing gear demonstrator was successfully created using PTA-based WAAM, showcasing the method's precision and cost-effectiveness. The demonstrator, measuring Ф200mm x 700mm, was completed in 16 hours, using 7 kg of material at a deposition rate of 1.3kg/hr. This resulted in a significant reduction in the Buy-to-Fly (BTF) ratio compared to traditional manufacturing methods, further validating WAAM's potential for this application. A "cradle-to-gate" environmental impact assessment, which considers the cumulative effects from raw material extraction to customer shipment, has revealed promising outcomes. Utilising Wire Arc Additive Manufacturing (WAAM) for landing gear components significantly reduces the need for raw material extraction and refinement compared to traditional subtractive methods. This, in turn, lessens the burden on subsequent manufacturing processes, including heat treatment, machining, and transportation. Our estimates indicate that the carbon footprint of the component could be halved when switching from traditional machining to WAAM. Similar reductions are observed in embodied energy consumption and other environmental impact indicators, such as emissions to air, water, and land. Additionally, WAAM offers the unique advantage of part repair by redepositing only the necessary material, a capability not available through conventional methods. Our research shows that WAAM-based repairs can drastically reduce environmental impact, even when accounting for additional transportation for repairs. Consequently, WAAM emerges as a pivotal technology for reducing environmental impact in manufacturing, aiding the industry in its crucial and ambitious journey towards Net Zero. This study paves the way for transformative benefits across the aerospace industry, as we integrate manufacturing into a hybrid solution that offers substantial savings and access to more sustainable technologies for critical component production.

Keywords: WAAM, aircraft landing gear, microstructure, mechanical performance, life cycle assessment

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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: Fernanda Piculo, Giovana Vesentini, Gabriela Marini, Debora Cristina Damasceno, Angelica Mercia Pascon Barbosa, Marilza Vieira Cunha Rudge

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Introduction: Women with previous gestational diabetes mellitus (GDM) were significantly more likely to have urinary incontinence (UI) and pelvic floor muscle dysfunction compared to non-diabetic women two years after a cesarean section. Additional results demonstrated that induced diabetes causes detrimental effects on pregnant rat urethral muscle. These results indicate the need for exploration of the mechanistic role of a recovery factor in female UI. Chemokine ligand 7 (CCL7) was significantly over expressed in rat serum, urethral and vaginal tissues immediately following induction of stress UI in a rat model simulating birth trauma. CCL7 over expression has shown potency for stimulating targeted stem cell migration and provide a translational link (clinical measurement) which further provide opportunities for treatment. The aim of this study was to investigate the CCL7 levels profile in diabetic pregnant women with urinary incontinence during pregnancy over the first year postpartum. Methods: This study was conducted in the Perinatal Diabetes Research Center of the Botucatu Medical School/UNESP, and was approved by the Research Ethics Committee of the Institution (CAAE: 20639813.0.0000.5411). The diagnosis of GDM was established between 24th and 28th gestational weeks, by the 75 g-OGTT test according to ADA’s criteria. Urinary incontinence was defined according to the International Continence Society and the CCL7 levels was measured by ELISA (R&D Systems, Catalog Number DCC700). Two hundred twelve women were classified into four study groups: normoglycemic continent (NC), normoglycemic incontinent (NI), diabetic continent (DC) and diabetic incontinent (DI). They were evaluated at six-time-points: 12-18, 24-28 and 34-38 gestational weeks, 24-48 hours, 6 weeks and 6-12 months postpartum. Results: At 12-18 weeks, it was possible to consider only two groups, continent and incontinent, because at this early gestational period has not yet been the diagnosis of GDM. The group with GDM and UI (DI group) showed lower levels of CCL7 in all time points during pregnancy and postpartum, compared to normoglycemic groups (NC and NI), indicating that these women have not recovered from child birth induced UI during the 6-12 months postpartum compared to their controls, and that the progression of UI and/or lack of recovery throughout the first postpartum year can be related with lower levels of CCL7. Instead, serum CCL7 was significantly increased in the NC group. Taken together, these findings of overexpression of CCL7 in the NC group and decreased levels in the DI group, could confirm that diabetes delays the recovery from child birth induced UI, and that CCL7 could potentially be used as a serum marker of injury. Conclusion: This study demonstrates lower levels of CCL7 in the DI group during pregnancy and postpartum and suggests that the progression of UI in diabetic women and/or lack of recovery throughout the first postpartum year can be related with low levels of CCL7. This provides a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery. Successful controlled CCL7 mediated stem cell homing to the lower urinary tract could one day introduce the potential for non-operative treatment or prevention of stress urinary incontinence.

Keywords: CCL7, gestational diabetes, pregnancy, urinary incontinence

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Authors: Javier E. García-Gallo, Nelson J. Fonseca-Ruiz, John F. Duitama-Munoz

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Sepsis is a syndrome that occurs with physiological and biochemical abnormalities induced by severe infection and carries a high mortality and morbidity, therefore the severity of its condition must be interpreted quickly. After patient admission in an intensive care unit (ICU), it is necessary to synthesize the large volume of information that is collected from patients in a value that represents the severity of their condition. Traditional severity of illness scores seeks to be applicable to all patient populations, and usually assess in-hospital mortality. However, the use of machine learning techniques and the data of a population that shares a common characteristic could lead to the development of customized mortality prediction scores with better performance. This study presents the development of a score for the one-year mortality prediction of the patients that are admitted to an ICU with a sepsis diagnosis. 5650 ICU admissions extracted from the MIMICIII database were evaluated, divided into two groups: 70% to develop the score and 30% to validate it. Comorbidities, demographics and clinical information of the first 24 hours after the ICU admission were used to develop a mortality prediction score. LASSO (least absolute shrinkage and selection operator) and SGB (Stochastic Gradient Boosting) variable importance methodologies were used to select the set of variables that make up the developed score; each of this variables was dichotomized and a cut-off point that divides the population into two groups with different mean mortalities was found; if the patient is in the group that presents a higher mortality a one is assigned to the particular variable, otherwise a zero is assigned. These binary variables are used in a logistic regression (LR) model, and its coefficients were rounded to the nearest integer. The resulting integers are the point values that make up the score when multiplied with each binary variables and summed. The one-year mortality probability was estimated using the score as the only variable in a LR model. Predictive power of the score, was evaluated using the 1695 admissions of the validation subset obtaining an area under the receiver operating characteristic curve of 0.7528, which outperforms the results obtained with Sequential Organ Failure Assessment (SOFA), Oxford Acute Severity of Illness Score (OASIS) and Simplified Acute Physiology Score II (SAPSII) scores on the same validation subset. Observed and predicted mortality rates within estimated probabilities deciles were compared graphically and found to be similar, indicating that the risk estimate obtained with the score is close to the observed mortality, it is also observed that the number of events (deaths) is indeed increasing as the outcome go from the decile with the lowest probabilities to the decile with the highest probabilities. Sepsis is a syndrome that carries a high mortality, 43.3% for the patients included in this study; therefore, tools that help clinicians to quickly and accurately predict a worse prognosis are needed. This work demonstrates the importance of customization of mortality prediction scores since the developed score provides better performance than traditional scoring systems.

Keywords: intensive care, logistic regression model, mortality prediction, sepsis, severity of illness, stochastic gradient boosting

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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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Authors: Thomas Rockstuhl, Kok Yee Ng, Guido Gianasso, Soon Ang

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Two meta-analyses show that intercultural experience is not related to intercultural adaptation or performance in international assignments. These findings have prompted calls for a deeper grounding of research on international experience in the phenomenon of global work. Two issues, in particular, may limit current understanding of the relationship between international experience and global work performance. First, intercultural experience is too broad a construct that may not sufficiently capture the essence of global work, which to a large part involves sensemaking and managing intercultural conflicts. Second, the psychological mechanisms through which intercultural experience affects performance remains under-explored, resulting in a poor understanding of how experience is translated into learning and performance outcomes. Drawing on recognition primed decision-making (RPD) research, the current study advances a cognitive processing model to highlight the importance of intercultural conflict familiarity. Compared to intercultural experience, intercultural conflict familiarity is a more targeted construct that captures individuals’ previous exposure to dealing with intercultural conflicts. Drawing on RPD theory, we argue that individuals’ intercultural conflict familiarity enhances their ability to make accurate judgments and generate effective responses when intercultural conflicts arise. In turn, the ability to make accurate situation judgements and effective situation responses is an important predictor of global work performance. A relocation program within a multinational enterprise provided the context to test these hypotheses using a time-lagged, multi-source field study. Participants were 165 employees (46% female; with an average of 5 years of global work experience) from 42 countries who relocated from country to regional offices as part a global restructuring program. Within the first two weeks of transfer to the regional office, employees completed measures of their familiarity with intercultural conflicts, cultural intelligence, cognitive ability, and demographic information. They also completed an intercultural situational judgment test (iSJT) to assess their situation judgment and situation response. The iSJT comprised four validated multimedia vignettes of challenging intercultural work conflicts and prompted employees to provide protocols of their situation judgment and situation response. Two research assistants, trained in intercultural management but blind to the study hypotheses, coded the quality of employee’s situation judgment and situation response. Three months later, supervisors rated employees’ global work performance. Results using multilevel modeling (vignettes nested within employees) support the hypotheses that greater familiarity with intercultural conflicts is positively associated with better situation judgment, and that situation judgment mediates the effect of intercultural familiarity on situation response quality. Also, aggregated situation judgment and situation response quality both predicted supervisor-rated global work performance. Theoretically, our findings highlight the important but under-explored role of familiarity with intercultural conflicts; a shift in attention from the general nature of international experience assessed in terms of number and length of overseas assignments. Also, our cognitive approach premised on RPD theory offers a new theoretical lens to understand the psychological mechanisms through which intercultural conflict familiarity affects global work performance. Third, and importantly, our study contributes to the global talent identification literature by demonstrating that the cognitive processes engaged in resolving intercultural conflicts predict actual performance in the global workplace.

Keywords: intercultural conflict familiarity, job performance, judgment and decision making, situational judgment test

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Authors: Vinodhini Elangovan, Jen Heng Pek

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Background: An ectopic pregnancy is defined as any pregnancy implanted outside of the endometrial cavity. Cornual pregnancy, a rare variety of ectopic pregnancies, is seen in about 2-4% of ectopic pregnancies. It develops in the interstitial portion of the fallopian tube and invades through the uterine wall. This case describes a third-trimester cornual pregnancy that resulted in a uterine rupture. Case: A 38-year old Chinese lady was brought to the Emergency Department (ED) as a standby case for hypotension. She was 30+6 weeks pregnant (Gravida 3, Parous 1). Her past obstetric history included a live birth delivered via lower segment Caesarean section due to non-reassuring fetal status in 2002 and a miscarriage in 2012. She developed generalized abdominal pain. There was no per vaginal bleeding or leaking liquor. There was also no fever, nausea, vomiting, constipation, diarrhea, or urinary symptoms. On arrival in the ED, she was pale, diaphoretic, and lethargic. She had generalized tenderness with guarding and rebound over her abdomen. Point of care ultrasound was performed and showed a large amount of intra-abdominal free fluid, and the fetal heart rate was 170 beats per minute. The point of care hemoglobin was 7.1 g/dL, and lactate was 6.8 mmol/L. The patient’s blood pressure dropped precipitously to 50/36 mmHg, and her heart rate went up to 141 beats per minute. The clinical impression was profound shock secondary to uterine rupture. Intra-operatively, there was extensive haemoperitoneum, and the fetus was seen in the abdominal cavity. The fetus was delivered immediately and handed to the neonatal team. On exploration of the uterus, the point of rupture was at the left cornual region where the placenta was attached to. Discussion: Cornual pregnancies are difficult to diagnose pre-operatively with low ultrasonographic sensitivity and hence are commonly confused with normal intrauterine pregnancies. They pose a higher risk of rupture and hemorrhage compared to other types of ectopic pregnancies. In very rare circumstances, interstitial pregnancies can result in a viable fetus. Uterine rupture resulting in hemorrhagic shock is a true obstetric emergency that can result in significant morbidity and mortality for the patient and the fetus, and early diagnosis in the emergency department is crucial. The patient in this case presented with known risk factors of multiparity, advanced maternal age, and previous lower segment cesarean section, which increased the suspicion of uterine rupture. Ultrasound assessment may be beneficial to any patient who presents with symptoms and a history of uterine surgery to assess the possibility of uterine dehiscence or rupture. Management of a patient suspected of uterine rupture should be systematic in the emergency department and follow an ABC approach. Conclusion: This case demonstrates the importance for an emergency physician to maintain the suspicion for ectopic pregnancy even at advanced gestational ages. It also highlights how even though all emergency physicians may not be qualified to do a detailed pelvic ultrasound, it is essential for them to be competent with a point of care ultrasound to make a prompt diagnosis of conditions such as uterine rupture.

Keywords: cornual ectopic , ectopic pregnancy, emergency medicine, obstetric emergencies

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Bitewulign Mekonnen

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Context: This scientific paper focuses on the use of near-infrared (NIR) spectroscopy to determine glucose concentration in aqueous solutions accurately and rapidly. The study compares six different machine learning methods for predicting glucose concentration and also explores the development of a deep learning model for classifying NIR spectra. The objective is to optimize the detection model and improve the accuracy of glucose prediction. This research is important because it provides a comprehensive analysis of various machine-learning techniques for estimating aqueous glucose concentrations. Research Aim: The aim of this study is to compare and evaluate different machine-learning methods for predicting glucose concentration from NIR spectra. Additionally, the study aims to develop and assess a deep-learning model for classifying NIR spectra. Methodology: The research methodology involves the use of machine learning and deep learning techniques. Six machine learning regression models, including support vector machine regression, partial least squares regression, extra tree regression, random forest regression, extreme gradient boosting, and principal component analysis-neural network, are employed to predict glucose concentration. The NIR spectra data is randomly divided into train and test sets, and the process is repeated ten times to increase generalization ability. In addition, a convolutional neural network is developed for classifying NIR spectra. Findings: The study reveals that the SVMR, ETR, and PCA-NN models exhibit excellent performance in predicting glucose concentration, with correlation coefficients (R) > 0.99 and determination coefficients (R²)> 0.985. The deep learning model achieves high macro-averaging scores for precision, recall, and F1-measure. These findings demonstrate the effectiveness of machine learning and deep learning methods in optimizing the detection model and improving glucose prediction accuracy. Theoretical Importance: This research contributes to the field by providing a comprehensive analysis of various machine-learning techniques for estimating glucose concentrations from NIR spectra. It also explores the use of deep learning for the classification of indistinguishable NIR spectra. The findings highlight the potential of machine learning and deep learning in enhancing the prediction accuracy of glucose-relevant features. Data Collection and Analysis Procedures: The NIR spectra and corresponding references for glucose concentration are measured in increments of 20 mg/dl. The data is randomly divided into train and test sets, and the models are evaluated using regression analysis and classification metrics. The performance of each model is assessed based on correlation coefficients, determination coefficients, precision, recall, and F1-measure. Question Addressed: The study addresses the question of whether machine learning and deep learning methods can optimize the detection model and improve the accuracy of glucose prediction from NIR spectra. Conclusion: The research demonstrates that machine learning and deep learning methods can effectively predict glucose concentration from NIR spectra. The SVMR, ETR, and PCA-NN models exhibit superior performance, while the deep learning model achieves high classification scores. These findings suggest that machine learning and deep learning techniques can be used to improve the prediction accuracy of glucose-relevant features. Further research is needed to explore their clinical utility in analyzing complex matrices, such as blood glucose levels.

Keywords: machine learning, signal processing, near-infrared spectroscopy, support vector machine, neural network

Procedia PDF Downloads 94

Authors: Miroslava Cuperlovic-Culf, Lipu Wang, Ketty Boyle, Nadine Makley, Ian Burton, Anissa Belkaid, Mohamed Touaibia, Marc E. Surrette

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Metabolic changes are one of the major factors in the development of a variety of diseases in various species. Metabolism of agricultural plants is altered the following infection with pathogens sometimes contributing to resistance. At the same time, pathogens use metabolites for infection and progression. In humans, metabolism is a hallmark of cancer development for example. Quantified metabolomics data combined with other omics or clinical data and analyzed using various unsupervised and supervised methods can lead to better diagnosis and prognosis. It can also provide information about resistance as well as contribute knowledge of compounds significant for disease progression or prevention. In this work, different methods for metabolomics quantification and analysis from Nuclear Magnetic Resonance (NMR) measurements that are used for investigation of disease development in wheat and human cells will be presented. One-dimensional 1H NMR spectra are used extensively for metabolic profiling due to their high reliability, wide range of applicability, speed, trivial sample preparation and low cost. This presentation will describe a new method for metabolite quantification from NMR data that combines alignment of spectra of standards to sample spectra followed by multivariate linear regression optimization of spectra of assigned metabolites to samples’ spectra. Several different alignment methods were tested and multivariate linear regression result has been compared with other quantification methods. Quantified metabolomics data can be analyzed in the variety of ways and we will present different clustering methods used for phenotype determination, network analysis providing knowledge about the relationships between metabolites through metabolic network as well as biomarker selection providing novel markers. These analysis methods have been utilized for the investigation of fusarium head blight resistance in wheat cultivars as well as analysis of the effect of estrogen receptor and carbonic anhydrase activation and inhibition on breast cancer cell metabolism. Metabolic changes in spikelet’s of wheat cultivars FL62R1, Stettler, MuchMore and Sumai3 following fusarium graminearum infection were explored. Extensive 1D 1H and 2D NMR measurements provided information for detailed metabolite assignment and quantification leading to possible metabolic markers discriminating resistance level in wheat subtypes. Quantification data is compared to results obtained using other published methods. Fusarium infection induced metabolic changes in different wheat varieties are discussed in the context of metabolic network and resistance. Quantitative metabolomics has been used for the investigation of the effect of targeted enzyme inhibition in cancer. In this work, the effect of 17 β -estradiol and ferulic acid on metabolism of ER+ breast cancer cells has been compared to their effect on ER- control cells. The effect of the inhibitors of carbonic anhydrase on the observed metabolic changes resulting from ER activation has also been determined. Metabolic profiles were studied using 1D and 2D metabolomic NMR experiments, combined with the identification and quantification of metabolites, and the annotation of the results is provided in the context of biochemical pathways.

Keywords: metabolic biomarkers, metabolic network, metabolomics, multivariate linear regression, NMR quantification, quantified metabolomics, spectral alignment

Procedia PDF Downloads 338

Authors: Aisling Gough, Ruth F. Hunter, Jianjun Tang, Sarah F. Brennan, Oliver Smith, Mark A. Tully, Chris Patterson, Alberto Longo, George Hutchinson, Lindsay Prior, David French, Jean Adams, Emma McIntosh, Frank Kee

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Background: As a large proportion of the UK workforce is employed in sedentary occupations, worksite interventions have the potential to contribute significantly to the health of the population. The UK Government is currently encouraging the use of financial incentives to promote healthier lifestyles but there is a dearth of evidence regarding the effectiveness and sustainability of incentive schemes to promote physical activity in the workplace. Methods: A large cluster RCT is currently underway, incorporating nested behavioural economic field experiments and process evaluation, to evaluate the effectiveness of a Physical Activity Loyalty Scheme. Office-based employees were recruited from large public sector organisations in Lisburn and Belfast (Northern Ireland) and randomised to an Intervention or Control group. Participants in the Intervention Group were encouraged to take part in 150 minutes of physical activity per week through provision of financial incentives (retailer vouchers) to those who met physical activity targets throughout the course of the 6 month intervention. Minutes of physical activity were monitored when participants passed by sensors (holding a keyfob) placed along main walking routes, parks and public transport stops nearby their workplace. Participants in the Control Group will complete the same outcome assessments (waiting-list control). The primary outcome is steps per day measured via pedometers (7 days). Secondary outcomes include health and wellbeing (Short Form-8, EuroQol-5D-5L, Warwick Edinburgh Mental Well Being Scale), and work absenteeism and presenteeism. Data will be collected at baseline, 6, 12 and 18 months. Information on PAL card & website usage, voucher downloads and redemption of vouchers will also be collected as part of a comprehensive process evaluation. Results: In total, 853 participants have been recruited from 9 workplaces in Lisburn, 12 buildings within the Stormont Estate, Queen’s University Belfast and Belfast City Hospital. Participants have been randomised to intervention and control groups. Baseline and 6-month data for the Physical Activity Loyalty Scheme has been collected. Findings regarding the effectiveness of the intervention from the 6-month follow-up data will be presented. Discussion: This study will address the gap in knowledge regarding the effectiveness and cost-effectiveness of a workplace-based financial incentive scheme to promote a healthier lifestyle. As the UK workforce is increasingly sedentary, workplace-based physical activity interventions have significant potential in terms of encouraging employees to partake in physical activity during the working day which could lead to substantial improvements in physical activity levels overall. Implications: If a workplace based physical activity intervention such as this proves to be both effective and cost-effective, there is great potential to contribute significantly to the health and wellbeing of the workforce in the future. Workplace-based physical activity interventions have the potential to improve the physical and mental health of employees which may in turn lead to economic benefits for the employer, such as reduction in rates of absenteeism and increased productivity.

Keywords: behaviour change, cluster randomised controlled trial, loyalty scheme, physical activity

Procedia PDF Downloads 325

Authors: Rahel Birhane Eshetu

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This research investigates the complex landscape of project management practices and operational challenges in conflict-affected areas, with a specific focus on Kewot Woreda in the North Shewa Zone of the Amhara region in Ethiopia. The study aims to identify essential project management methodologies, the significant operational hurdles faced, and the adaptive strategies employed by project managers in these challenging environments. Utilizing a mixed-methods approach, the research combines qualitative and quantitative data collection. Initially, a comprehensive literature review was conducted to establish a theoretical framework. This was followed by the administration of questionnaires to gather empirical data, which was then analyzed using statistical software. This sequential approach ensures a robust understanding of the context and challenges faced by project managers. The findings reveal that project managers in conflict zones encounter a range of escalating challenges. Initially, they must contend with immediate security threats and the presence of displaced populations, which significantly disrupt project initiation and execution. As projects progress, additional challenges arise, including limited access to essential resources and environmental disruptions such as natural disasters. These factors exacerbate the operational difficulties that project managers must navigate. In response to these challenges, the study highlights the necessity for project managers to implement formal project plans while simultaneously adopting adaptive strategies that evolve over time. Key adaptive strategies identified include flexible risk management frameworks, change management practices, and enhanced stakeholder engagement approaches. These strategies are crucial for maintaining project momentum and ensuring that objectives are met despite the unpredictable nature of conflict environments. The research emphasizes that structured scope management, clear documentation, and thorough requirements analysis are vital components for effectively navigating the complexities inherent in conflict-affected regions. However, the ongoing threats and logistical barriers necessitate a continuous adjustment to project management methodologies. This adaptability is not only essential for the immediate success of projects but also for fostering long-term resilience within the community. Concluding, the study offers actionable recommendations aimed at improving project management practices in conflict zones. These include the adoption of adaptive frameworks specifically tailored to the unique conditions of conflict environments and targeted training for project managers. Such training should focus on equipping managers with the skills to better address the dynamic challenges presented by conflict situations. The insights gained from this research contribute significantly to the broader field of project management, providing a practical guide for practitioners operating in high-risk areas. By emphasizing sustainable and resilient project outcomes, this study underscores the importance of adaptive management strategies in ensuring the success of projects in conflict-affected regions. The findings serve not only to enhance the understanding of project management practices in Kewot Woreda but also to inform future research and practice in similar contexts, ultimately aiming to promote stability and development in areas beset by conflict.

Keywords: project management practices, operational challenges, conflict zones, adaptive strategies

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

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

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

Procedia PDF Downloads 236

Authors: Phenphak Horadee, Rodchares Hanrinth, Saithip Suttiruksa

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Inappropriate use of antibiotics has happened in several hospitals, Thailand. Drug use evaluation (DUE) is one strategy to overcome this difficulty. However, most community hospitals still encounter incomplete evaluation resulting overuse of antibiotics with high cost. Consequently, drug-resistant bacteria have been rising due to inappropriate antibiotic use. The aim of this study was to involve stakeholders in conceptualizing, developing, and prioritizing a feasible intervention strategy to promote and support appropriate antibiotic prescribing in a community hospital, Thailand. Study antibiotics included four antibiotics such as Meropenem, Piperacillin/tazobactam, Amoxicillin/clavulanic acid, and Vancomycin. The study was conducted for the 1-year period between March 1, 2018, and March 31, 2019, in a community hospital in the northeastern part of Thailand. Concept mapping was used in a purposive sample, including doctors (one was an administrator), pharmacists, and nurses who involving drug use evaluation of antibiotics. In-depth interviews for each participant and survey research were conducted to seek the problems for inappropriate use of antibiotics based on drug use evaluation system. Seventy-seven percent of DUE reported appropriate antibiotic prescribing, which still did not reach the goal of 80 percent appropriateness. Meropenem led other antibiotics for inappropriate prescribing. The causes of the unsuccessful DUE program were classified into three themes such as personnel, lack of public relation and communication, and unsupported policy and impractical regulations. During the first meeting, stakeholders (n = 21) expressed the generation of interventions. During the second meeting, participants who were almost the same group of people in the first meeting (n = 21) were requested to independently rate the feasibility and importance of each idea and to categorize them into relevant clusters to facilitate multidimensional scaling and hierarchical cluster analysis. The outputs of analysis included the idealist, cluster list, point map, point rating map, cluster map, and cluster rating map. All of these were distributed to participants (n = 21) during the third meeting to reach consensus on an intervention model. The final proposed intervention strategy included 29 feasible and crucial interventions in seven clusters: development of information technology system, establishing policy and taking it into the action plan, proactive public relations of the policy, action plan and workflow, in cooperation of multidisciplinary teams in drug use evaluation, work review and evaluation with performance reporting, promoting and developing professional and clinical skill for staff with training programs, and developing practical drug use evaluation guideline for antibiotics. These interventions are relevant and fit to several intervention strategies for antibiotic stewardship program in many international organizations such as participation of the multidisciplinary team, developing information technology to support antibiotic smart use, and communication. These interventions were prioritized for implementation over a 1-year period. Once the possibility of each activity or plan is set up, the proposed program could be applied and integrated into hospital policy after evaluating plans. Effectiveness of each intervention could be promoted to other community hospitals to promote and support antibiotic smart use.

Keywords: antibiotic, concept mapping, drug use evaluation, multidisciplinary teams

Procedia PDF Downloads 118

Authors: Eylem Tas

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This empirical study aims to explore the development of students' entrepreneurial skills through problem-based learning within the context of university-industry collaborations (UICs) in curriculum co-design and co-delivery (CDD). The research question guiding this study is: "How do problem-based learning and university-industry collaborations influence the development of students' entrepreneurial skills in the context of curriculum co-design and co-delivery?” To address this question, the study was conducted in a big city in Germany and involved interviews with stakeholders from various industries, including the private sector, government agencies (govt), and non-governmental organizations (NGOs). These stakeholders had established collaborative partnerships with the targeted university for projects encompassing entrepreneurial development aspects in CDD. The study sought to gain insights into the intricacies and subtleties of UIC dynamics and their impact on fostering entrepreneurial skills. Qualitative content analysis, based on Mayring's guidelines, was employed to analyze the interview transcriptions. Through an iterative process of manual coding, 442 codes were generated, resulting in two main sections: "the role of problem-based learning and UIC in fostering entrepreneurship" and "challenges and requirements of problem-based learning within UIC for systematical entrepreneurship development.” The chosen experimental approach of semi-structured interviews was justified by its capacity to provide in-depth perspectives and rich data from stakeholders with firsthand experience in UICs in CDD. By enlisting participants with diverse backgrounds, industries, and company sizes, the study ensured a comprehensive and heterogeneous sample, enhancing the credibility of the findings. The first section of the analysis delved into problem-based learning and entrepreneurial self-confidence to gain a deeper understanding of UIC dynamics from an industry standpoint. It explored factors influencing problem-based learning, alignment of students' learning styles and preferences with the experiential learning approach, specific activities and strategies, and the role of mentorship from industry professionals in fostering entrepreneurial self-confidence. The second section focused on various interactions within UICs, including communication, knowledge exchange, and collaboration. It identified key elements, patterns, and dynamics of interaction, highlighting challenges and limitations. Additionally, the section emphasized success stories and notable outcomes related to UICs' positive impact on students' entrepreneurial journeys. Overall, this research contributes valuable insights into the dynamics of UICs and their role in fostering students' entrepreneurial skills. UICs face challenges in communication and establishing a common language. Transparency, adaptability, and regular communication are vital for successful collaboration. Realistic expectation management and clearly defined frameworks are crucial. Responsible data handling requires data assurance and confidentiality agreements, emphasizing the importance of trust-based relationships when dealing with data sharing and handling issues. The identified key factors and challenges provide a foundation for universities and industrial partners to develop more effective UIC strategies for enhancing students' entrepreneurial capabilities and preparing them for success in today's digital age labor market. The study underscores the significance of collaborative learning and transparent communication in UICs for entrepreneurial development in CDD.

Keywords: collaborative learning, curriculum co-design and co-delivery, entrepreneurial skills, problem-based learning, university-industry collaborations

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Authors: Mohammad Al-Refai, Majed Wakid

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Introduction: Soil-transmitted diseases (STD) are caused by intestinal worms that are transmitted via various routes into the human body resulting in various clinical manifestations. The intestinal worms causing these infections are known as soil transmitted helminths (STH), including Hook worms, Ascaris lumbricoides (A. lumbricoides), Trichuris trichiura (T. trichiura), and Strongyloides sterocoralis (S. sterocoralis). Objectives: The aim of this study was to investigate the prevalence of STH among newly arrived expatriate labors in Jeddah city, Saudi Arabia, using three different techniques (direct smears, sedimentation concentration, and real-time PCR). Methods: A total of 188 stool specimens were collected and investigated at the parasitology laboratory in the Special Infectious Agents Unit at King Fahd Medical Research Center, King Abdulaziz University in Jeddah, Saudi Arabia. Microscopic examination of wet mount preparations using normal saline and Lugols Iodine was carried out, followed by the formal ether sedimentation method. In addition, real-time PCR was used as a molecular tool to detect several STH and hookworm speciation. Results: Out of 188 stool specimens analyzed, in addition to STH parasite, several other types were detected. 9 samples (4.79%) were positive for Entamoeba coli, 7 samples (3.72%) for T. trichiura, 6 samples (3.19%) for Necator americanus, 4 samples (2.13%) for S. sterocoralis, 4 samples (2.13%) for A. lumbricoides, 4 samples (2.13%) for E. histolytica, 3 samples (1.60%) for Blastocystis hominis, 2 samples (1.06%) for Ancylostoma duodenale, 2 samples (1.06%) for Giardia lamblia, 1 sample (0.53%) for Iodamoeba buetschlii, 1 sample (0.53%) for Hymenolepis nana, 1 sample (0.53%) for Endolimax nana, and 1 sample (0.53%) for Heterophyes heterophyes. Out of the 35 infected cases, 26 revealed single infection, 8 with double infections, and only one triple infection of different STH species and other intestinal parasites. Higher rates of STH infections were detected among housemaids (11 cases) followed by drivers (7 cases) when compared to other occupations. According to educational level, illiterate participants represent the majority of infected workers (12 cases). The majority of workers' positive cases were from the Philippines. In comparison between laboratory techniques, out of the 188 samples screened for STH, real-time PCR was able to detect the DNA in (19/188) samples followed by Ritchie sedimentation technique (18/188), and direct wet smear (7/188). Conclusion: STH infections are a major public health issue to healthcare systems around the world. Communities must be educated on hygiene practices and the severity of such parasites to human health. As far as drivers and housemaids come to close contact with families, including children and elderlies. This may put family members at risk of developing serious side effects related to STH, especially as the majority of workers were illiterate, lacking the basic hygiene knowledge and practices. We recommend the official authority in Jeddah and around the kingdom of Saudi Arabia to revise the standard screening tests for newly arrived workers and enforce regular follow-up inspections to minimize the chances of the spread of STH from expatriate workers to the public.

Keywords: expatriate labors, Jeddah, prevalence, soil transmitted helminths

Procedia PDF Downloads 149

Authors: Sugam Kale, Arif Uzair Bin Mohammed Roslan, Cindy Lee, Syed Beevee Mohammed Ismail

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Preemptive analgesia is an established concept in the modern practice of anaesthesia. To be most effective, it is best instituted earlier than the surgical stimulus and should last beyond the offset of surgically induced pain till healing is complete. Whereas the start of afferent pain blockade with regional anaesthesia is common, its effect often falls short to cover the entire period of pain impulses making their way to CNS in the post-operative period. We tried to use a combination of two regional anaesthetic techniques used sequentially to overcome this handicap. Madam S., a 56 year old lady, was scheduled for elective surgery for pancreatic cancer. She underwent laparotomy and distal pancreatectomy, splenectomy, bilateral salpingo oophorectomy, and sigmoid colectomy. Surgery was expected to be extensive, and it was presumed that the standard pain relief with PCA with opiates and oral analgesics would not be adequate. After counselling the patient pre-operative about the technique of regional anaesthesia techniques, including epidural catheterization and rectus sheath catheter placement, their benefits, and potential complications, informed consent was obtained. Epidural catheter was placed awake, and general anaesthesia was then induced. Epidural infusion of local anaesthetics was started prior to surgical incision and was continued till 60 hours into the postoperative period. Before skin closure, the surgeons inserted commercially available rectus sheath catheters bilaterally along the midline incision used for laparotomy. After 46 hours post-op, local anaesthetic infusion via these was started as bridging while the epidural infusion rate was tapered off. The epidural catheter was removed at 75 hours. Elastomeric pumps were used to provide local anaesthetic infusion with the ability to vary infusion rates. Acute pain service followed up the patient’s vital signs and effectiveness of pain relief twice daily or more frequently as required. Rectus sheath catheters were removed 137 hours post-op. The patient had good post-op analgesia with the minimal additional analgesic requirement. For the most part, the visual analog score (VAS) for pain remained at 1-3 on a scale of 1 to 10. Haemodynamics remained stable, and surgical recovery was as expected. Minimal opiate requirement after an extensive laparotomy also translates to the early return of intestinal motility. Our experience was encouraging, and we are hoping to extend this combination of two regional anaesthetic techniques to patients undergoing similar surgeries. Epidural analgesia is denser and offers excellent pain relief for both visceral and somatic pain in the first few days after surgery. As the pain intensity grows weaker, rectus sheath block and oral analgesics provide almost the same degree of pain relief after the epidural catheter is removed. We discovered that the background infusion of local anaesthetic down the rectus sheath catherter largely reduced the requirement for other classes of analgesics. We aim to study this further with a larger patient cohort and hope that it may become an established clinical practice that benefits patients everywhere.

Keywords: rectus sheath, epidural infusion, post operative analgesia, elastomeric

Procedia PDF Downloads 134

Authors: Chung Yan Natalia Yeung, Man Kit Indy Ho, Kin Yu Stan Chan, Ho Pui Kipper Lam, Man Wah Genie Tong, Tze Chung Jim Luk

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Excessive foot pronation is a well-known risk factor of knee and foot injuries such as patellofemoral pain, patellar and Achilles tendinopathy, and plantar fasciitis. Low-Dye taping (LDT) application is not uncommon for basketball players to control excessive foot pronation for pain control and injury prevention. The primary potential benefits of using LDT include providing additional supports to medial longitudinal arch and restricting the excessive midfoot and subtalar motion in weight-bearing activities such as running and landing. Meanwhile, restrictions provided by the rigid tape may also potentially limit functional joint movements and sports performance. Coaches and athletes need to weigh the potential benefits and harmful effects before making a decision if applying LDT technique is worthwhile or not. However, the influence of using LDT on basketball-related performance such as explosive and reactive strength is not well understood. Therefore, the purpose of this study was to investigate the change of drop jump (DJ) and countermovement jump (CMJ) performance before and after LDT application for collegiate male basketball players. In this within-subject crossover study, 12 healthy male basketball players (age: 21.7 ± 2.5 years) with at least 3-year regular basketball training experience were recruited. Navicular drop (ND) test was adopted as the screening and only those with excessive pronation (ND ≥ 10mm) were included. Participants with recent lower limb injury history were excluded. Recruited subjects were required to perform both ND, DJ (on a platform of 40cm height) and CMJ (without arms swing) tests in series during taped and non-taped conditions in the counterbalanced order. Reactive strength index (RSI) was calculated by using the flight time divided by the ground contact time measured. For DJ and CMJ tests, the best of three trials was used for analysis. The difference between taped and non-taped conditions for each test was further calculated through standardized effect ± 90% confidence intervals (CI) with clinical magnitude-based inference (MBI). Paired samples T-test showed significant decrease in ND (-4.68 ± 1.44mm; 95% CI: -3.77, -5.60; p < 0.05) while MBI demonstrated most likely beneficial and large effect (standardize effect: -1.59 ± 0.27) in LDT condition. For DJ test, significant increase in both flight time (25.25 ± 29.96ms; 95% CI: 6.22, 44.28; p < 0.05) and RSI (0.22 ± 0.22; 95% CI: 0.08, 0.36; p < 0.05) were observed. In taped condition, MBI showed very likely beneficial and moderate effect (standardized effect: 0.77 ± 0.49) in flight time, possibly beneficial and small effect (standardized effect: -0.26 ± 0.29) in ground contact time and very likely beneficial and moderate effect (standardized effect: 0.77 ± 0.42) in RSI. No significant difference in CMJ was observed (95% CI: -2.73, 2.08; p > 0.05). For basketball players with pes planus, applying LDT could substantially support the foot by elevating the navicular height and potentially provide acute beneficial effects in reactive strength performance. Meanwhile, no significant harmful effect on CMJ was observed. Basketball players may consider applying LDT before the game or training to enhance the reactive strength performance. However since the observed effects in this study could not generalize to other players without excessive foot pronation, further studies on players with normal foot arch or navicular height are recommended.

Keywords: flight time, pes planus, pronated foot, reactive strength index

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Authors: Ashley L. Freeman, Jessica D. Watkins

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

Keywords: emergency medicine, TeleEM, rural healthcare, telemedicine

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Authors: Sree Bash Chandra Debnath, Didier Tonneau, Carole Fauquet, Agnes Tallet, Julien Darreon

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Purpose: Inorganic scintillating dosimetry is the most recent promising technique to solve several dosimetric issues and provide quality assurance in radiation therapy. Despite several advantages, the major issue of using scintillating detectors is the Cerenkov effect, typically induced in the visible emission range. In this context, the purpose of this research work is to evaluate the performance of a novel infrared inorganic scintillator detector (IR-ISD) in the radiation therapy treatment to ensure Cerenkov free signal and the best matches between the delivered and prescribed doses during treatment. Methods: A simple and small-scale infrared inorganic scintillating detector of 100 µm diameter with a sensitive scintillating volume of 2x10-6 mm3 was developed. A prototype of the dose verification system has been introduced based on PTIR1470/F (provided by Phosphor Technology®) material used in the proposed novel IR-ISD. The detector was tested on an Elekta LINAC system tuned at 6 MV/15MV and a brachytherapy source (Ir-192) used in the patient treatment protocol. The associated dose rate was measured in count rate (photons/s) using a highly sensitive photon counter (sensitivity ~20ph/s). Overall measurements were performed in IBATM water tank phantoms by following international Technical Reports series recommendations (TRS 381) for radiotherapy and TG43U1 recommendations for brachytherapy. The performance of the detector was tested through several dosimetric parameters such as PDD, beam profiling, Cerenkov measurement, dose linearity, dose rate linearity repeatability, and scintillator stability. Finally, a comparative study is also shown using a reference microdiamond dosimeter, Monte-Carlo (MC) simulation, and data from recent literature. Results: This study is highlighting the complete removal of the Cerenkov effect especially for small field radiation beam characterization. The detector provides an entire linear response with the dose in the 4cGy to 800 cGy range, independently of the field size selected from 5 x 5 cm² down to 0.5 x 0.5 cm². A perfect repeatability (0.2 % variation from average) with day-to-day reproducibility (0.3% variation) was observed. Measurements demonstrated that ISD has superlinear behavior with dose rate (R2=1) varying from 50 cGy/s to 1000 cGy/s. PDD profiles obtained in water present identical behavior with a build-up maximum depth dose at 15 mm for different small fields irradiation. A low dimension of 0.5 x 0.5 cm² field profiles have been characterized, and the field cross profile presents a Gaussian-like shape. The standard deviation (1σ) of the scintillating signal remains within 0.02% while having a very low convolution effect, thanks to lower sensitive volume. Finally, during brachytherapy, a comparison with MC simulations shows that considering energy dependency, measurement agrees within 0.8% till 0.2 cm source to detector distance. Conclusion: The proposed scintillating detector in this study shows no- Cerenkov radiation and efficient performance for several radiation therapy measurement parameters. Therefore, it is anticipated that the IR-ISD system can be promoted to validate with direct clinical investigations, such as appropriate dose verification and quality control in the Treatment Planning System (TPS).

Keywords: IR-Scintillating detector, dose measurement, micro-scintillators, Cerenkov effect

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Authors: Annika J. Meyer, Tom Piechotta

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Unmanned Aerial Vehicles (UAVs) have increasingly become vital tools in various applications, including surveillance, search and rescue, and environmental monitoring. One common approach to ensure redundant communication systems when flying beyond visual line of sight is for UAVs to employ multiple mobile data modems by different providers. Although widely adopted, this approach suffers from several drawbacks, such as high costs, added weight and potential increases in signal interference. In light of these challenges, this paper proposes a communication framework intermeshing mobile networks and LoRa (Long Range) technology—a low-power, long-range communication protocol. LoRaWAN (Long Range Wide Area Network) is commonly used in Internet of Things applications, relying on stationary gateways and Internet connectivity. This paper, however, utilizes the underlying LoRa protocol, taking advantage of the protocol’s low power and long-range capabilities while ensuring efficiency and reliability. Conducted in collaboration with the Potsdam Fire Department, the implementation of mobile network technology in combination with the LoRa protocol in small UAVs (take-off weight < 0.4 kg), specifically designed for search and rescue and area monitoring missions, is explored. This research aims to test the viability of LoRa as an additional redundant communication system during UAV flights as well as its intermeshing with the primary, mobile network-based controller. The methodology focuses on direct UAV-to-UAV and UAV-to-ground communications, employing different spreading factors optimized for specific operational scenarios—short-range for UAV-to-UAV interactions and long-range for UAV-to-ground commands. This explored use case also dramatically reduces one of the major drawbacks of LoRa communication systems, as a line of sight between the modules is necessary for reliable data transfer. Something that UAVs are uniquely suited to provide, especially when deployed as a swarm. Additionally, swarm deployment may enable UAVs that have lost contact with their primary network to reestablish their connection through another, better-situated UAV. The experimental setup involves multiple phases of testing, starting with controlled environments to assess basic communication capabilities and gradually advancing to complex scenarios involving multiple UAVs. Such a staged approach allows for meticulous adjustment of parameters and optimization of the communication protocols to ensure reliability and effectiveness. Furthermore, due to the close partnership with the Fire Department, the real-world applicability of the communication system is assured. The expected outcomes of this paper include a detailed analysis of LoRa's performance as a communication tool for UAVs, focusing on aspects such as signal integrity, range, and reliability under different environmental conditions. Additionally, the paper seeks to demonstrate the cost-effectiveness and operational efficiency of using a single type of communication technology that reduces UAV payload and power consumption. By shifting from traditional cellular network communications to a more robust and versatile cellular and LoRa-based system, this research has the potential to significantly enhance UAV capabilities, especially in critical applications where reliability is paramount. The success of this paper could pave the way for broader adoption of LoRa in UAV communications, setting a new standard for UAV operational communication frameworks.

Keywords: LoRa communication protocol, mobile network communication, UAV communication systems, search and rescue operations

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Authors: Marthinus Conradie

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The conversational dynamics of democratically orientated deliberation continue to stimulate critical scholarship for its potential to bolster robust engagement between different sections of pluralist societies. Several axes of deliberation that have attracted academic attention include face-to-face vs. online interaction, and citizen-to-citizen communication vs. engagement between citizens and political elites. In all these areas, numerous researchers have explored deliberative procedures aimed at achieving instrumental goals such a securing consensus on policy issues, against procedures that prioritise expressive outcomes such as broadening the range of argumentative repertoires that discursively construct and mediate specific political issues. The study that informs this paper, works in the latter stream. Drawing its data from the reader-comments section of a South African broadsheet newspaper, the study investigates online, citizen-to-citizen deliberation by analysing the discursive practices through which competing understandings of social problems are articulated and contested. To advance this agenda, the paper deals specifically with user-generated comments posted in response to news stories on questions of race and racism in South Africa. The analysis works to discern and interpret the various sets of discourse practices that shape how citizens deliberate contentious political issues, especially racism. Since the website in question is designed to encourage the critical comparison of divergent interpretations of news events, without feeding directly into national policymaking, the study adopts an analytic framework that traces how citizens articulate arguments, rather than the instrumental effects that citizen deliberations might exert on policy. The paper starts from the argument that such expressive interactions are particularly crucial to current trends in South African politics, given that the precise nature of race and racism remain contested and uncertain. Centred on a sample of 2358 conversational moves in 814 posts to 18 news stories emanating from issues of race and racism, the analysis proceeds in a two-step fashion. The first stage conducts a qualitative content analysis that offers insights into the levels of reciprocity among commenters (do readers engage with each other or simply post isolated opinions?), as well as the structures of argumentation (do readers support opinions by citing evidence?). The second stage involves a more fine-grained discourse analysis, based on a theorisation of argumentation that delineates it into three components: opinions/conclusions, evidence/data to support opinions/conclusions and warrants that explicate precisely how evidence/data buttress opinions/conclusions. By tracing the manifestation and frequency of specific argumentative practices, this study contributes to the archive of research currently aggregating around the practices that characterise South Africans’ engagement with provocative political questions, especially racism and racial inequity. Additionally, the study also contributes to recent scholarship on the affordances of Web 2.0 software by eschewing a simplistic bifurcation between cyber-optimist vs. pessimism, in favour of a more nuanced and context-specific analysis of the patterns that structure online deliberation.

Keywords: online deliberation, discourse analysis, qualitative content analysis, racism

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Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

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Authors: E. Tan, O. McKay, T. Clarnette T., D. Croagh

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Background: Historically with pancreatic trauma, complete disruption of the main pancreatic duct (MPD), classified as Grade IV-V by the American Association for the Surgery of Trauma (AAST), necessitated a damage-control laparotomy. This was to avoid mortality, shorten diet upgrade timeframe, and hence shorter length of stay. However, acute pancreatic resection entailed complications of pancreatic fistulas and leaks. With the advance of imaging-guided interventions, non-operative management such as percutaneous and transpapillary drainage of traumatic peripancreatic collections have been trialled favourably. The aim of this case series is to evaluate the efficacy of endoscopic ultrasound-guided (EUS) transmural drainage in managing traumatic peripancreatic collections as a less invasive alternative to traditional approaches. This study also highlights the importance of anatomical knowledge regarding peripancreatic collection’s common location in the lesser sac, the pancreas relationship to adjacent organs, and the formation of the main pancreatic duct in regards to the feasibility of therapeutic internal drainage. Methodology: A retrospective case series was conducted at a single tertiary endoscopy unit, analysing patient data over a 5-year period. Inclusion criteria outlined patients age 5 to 80-years-old, traumatic pancreatic injury of at least Grade IV and haemodynamic stability. Exclusion criteria involved previous episodes of pancreatitis or abdominal trauma. Patient demographics and clinicopathological characteristics were retrospectively collected. Results: The study identified 7 patients with traumatic pancreatic injuries that were managed from 2018-2022; age ranging from 5 to 34 years old, with majority being female (n=5). Majority of the mechanisms of trauma were a handlebar injury (n=4). Diagnosis was confirmed with an elevated lipase and computerized tomotography (CT) confirmation of proximal pancreatic transection with MPD disruption. All patients sustained an isolated single organ grade IV pancreatic injury, except case 4 and 5 with other intra-abdominal visceral Grade 1 injuries. 6 patients underwent early ERCP-guided transpapillary drainage with 1 being unsuccessful for pancreatic duct stent insertion (case 1) and 1 complication of stent migration (case 2). Surveillance imaging post ERCP showed the stents were unable to bridge the disrupted duct and development of symptomatic collections with an average size of 9.9cm. Hence, all patients proceeded to EUS-guided transmural drainage, with 2/7 patients requiring repeat drainages (case 6 and 7). Majority (n=6) had a cystogastrostomy, whilst 1 (case 6) had a cystoenterostomy due to feasibility of the peripancreatic collection being adjacent to duodenum rather than stomach. However, case 6 subsequently required repeat EUS-guided drainage with cystogastrostomy for ongoing collections. Hence all patients avoided initial laparotomy with an average index length of stay of 11.7 days. Successful transmural drainage was demonstrated, with no long-term complications of pancreatic insufficiency; except for 1 patient requiring a distal pancreatectomy at 2 year follow-up due to chronic pain. Conclusion: The early results of this series support EUS-guided transmural drainage as a viable management option for traumatic peripancreatic collections, showcasing successful outcomes, minimal complications, and long-term efficacy in avoiding surgical interventions. More studies are required before the adoption of this procedure as a less invasive and complication-prone management approach for traumatic peripancreatic collections.

Keywords: endoscopic ultrasound, cystogastrostomy, pancreatic trauma, traumatic peripancreatic collection, transmural drainage

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Authors: Fabio Rodriguez Sanchez, Josef Bruers, Iciar Arteagoitia, Carlos Rodriguez Andres

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Background: Oral implants are a routine treatment to replace lost teeth. Although they have a high rate of success, implant failures do occur. Perioperative antibiotics have been suggested to prevent postoperative infections and dental implant failures, but they remain a controversial treatment among healthy patients. The objective of this study was to determine whether antibiotic prophylaxis is a common treatment in the Netherlands among general dentists, maxillofacial-surgeons, periodontists and implantologists in conjunction with oral implant surgery among healthy patients and to assess the nature of antibiotics prescriptions in order to evaluate whether any consensus has been reached and the current recommendations are being followed. Methodology: Observational cross-sectional study based on a web-survey reported according to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines. A validated questionnaire, developed by Deeb et al. (2015), was translated and slightly adjusted to circumstances in the Netherlands. It was used with the explicit permission of the authors. This questionnaire contained both close-ended and some open-ended questions in relation to the following topics: demographics, qualification, antibiotic type, prescription-duration and dosage. An email was sent February 2018 to a sample of 600 general dentists and all 302 oral implantologists, periodontists and maxillofacial surgeons who were recognized by the Dutch Association of Oral Implantology (NVOI) as oral health care providers placing oral implants. The email included a brief introduction about the study objectives and a link to the web questionnaire, which could be filled in anonymously. Overall, 902 questionnaires were sent. However, 29 questionnaires were not correctly received due to an incorrect email address. So a total number of 873 professionals were reached. Collected data were analyzed using SPSS (IBM Corp., released 2012, Armonk, NY). Results: The questionnaire was sent back by a total number of 218 participants (response rate=24.2%), 45 female (20.8%) and 171 male (79.2%). Two respondents were excluded from the study group because they were not currently working as oral health providers. Overall 151 (69.9%) placed oral implants on regular basis. Approximately 79 (52.7%) of these participants prescribed antibiotics only in determined situations, 66 (44.0%) prescribed antibiotics always and 5 dentists (3.3%) did not prescribe antibiotics at all when placing oral implants. Overall, 83 participants who prescribed antibiotics, did so both pre- and postoperatively (58.5%), 12 exclusively postoperative (8.5%), and 47 followed an exclusive preoperative regime (33.1%). A single dose of 2,000 mg amoxicillin orally 1-hour prior treatment was the most prescribed preoperative regimen. The most frequent prescribed postoperative regimen was 500 mg amoxicillin three times daily for 7 days after surgery. On average, oral health professionals prescribed 6,923 mg antibiotics in conjunction with oral implant surgery, varying from 500 to 14,600 mg. Conclusions: Antibiotic prophylaxis in conjunction with oral implant surgery is prescribed in the Netherlands on a rather large scale. Dutch professionals might prescribe antibiotics more cautiously than in other countries and there seems to be a lower range on the different antibiotic types and regimens being prescribed. Anyway, recommendations based on last-published evidence are frequently not being followed.

Keywords: clinical decision making, infection control, antibiotic prophylaxis, dental implants

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

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

Keywords: emergency medicine, medical scribe, scribe, documentation

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