Search results for: patients rights
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 6980

Search results for: patients rights

2090 Work Life Balance Strategies and Retention of Medical Professionals

Authors: Naseem M. Twaissi

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Medical professionals play an important role in society, and in general, they care more about their patients than about their personal well-being. They need to take a professional approach to maintain a work-life balance. Through a collection of primary data from 1020 medical professionals and the application of relevant statistical tools, this paper explores the pressures on medical professionals with reference to their work-life balance. This study highlights how hospital management, in addition to economic reasons, needs to identify variables to enhance the work-life balance of medical professionals so that quality healthcare facilities may be provided to the citizens of Jordan. Results indicate that formulation and implementation of policies for enhancing work-life balance together with career and retention plans for medical professionals would enhance the performance of hospitals and the quality of health care in Jordan, leading to greater societal well-being.

Keywords: work life balance, job environment, job satisfaction, employee well-being, stress, hospital industry

Procedia PDF Downloads 141
2089 U-Net Based Multi-Output Network for Lung Disease Segmentation and Classification Using Chest X-Ray Dataset

Authors: Jaiden X. Schraut

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Medical Imaging Segmentation of Chest X-rays is used for the purpose of identification and differentiation of lung cancer, pneumonia, COVID-19, and similar respiratory diseases. Widespread application of computer-supported perception methods into the diagnostic pipeline has been demonstrated to increase prognostic accuracy and aid doctors in efficiently treating patients. Modern models attempt the task of segmentation and classification separately and improve diagnostic efficiency; however, to further enhance this process, this paper proposes a multi-output network that follows a U-Net architecture for image segmentation output and features an additional CNN module for auxiliary classification output. The proposed model achieves a final Jaccard Index of .9634 for image segmentation and a final accuracy of .9600 for classification on the COVID-19 radiography database.

Keywords: chest X-ray, deep learning, image segmentation, image classification

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2088 Operative Technique of Glenoid Anteversion Osteotomy and Soft Tissue Rebalancing for Brachial Plexus Birth Palsy

Authors: Michael Zaidman, Naum Simanovsky

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The most of brachial birth palsies are transient. Children with incomplete recovery almost always develop an internal rotation and adduction contracture. The muscle imbalance around the shoulder results in glenohumeral joint deformity and functional limitations. Natural history of glenohumeral deformity is it’s progression with worsening of function. Anteversion glenoid osteotomy with latissimus dorsi and teres major tendon transfers could be an alternative procedure of proximal humeral external rotation osteotomy for patients with severe glenohumeral dysplasia secondary to brachial plexus birth palsy. We will discuss pre-operative planning and stepped operative technique of the procedure on clinical example.

Keywords: obstetric brachial plexus palsy, glenoid anteversion osteotomy, tendon transfer, operative technique

Procedia PDF Downloads 74
2087 Efficacy of CAM Methods for Pain Reduction in Acute Non-specific Lower Back Pain

Authors: John Gaber

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Objectives: Complementary and alternative medicine (CAM) is a medicine or health practice that is used alongside conventional practice. Nowadays, CAM is commonly used in North America and other countries, and there is a need for more scientific study to understand its efficacy in different clinical cases. This retrospective study explores the effectiveness and recovery time of CAMs such as cupping, acupuncture, and sotai to treat cases of non-specific low back pain (ANLBP). Methods: We assessed the effectiveness of acupuncture, cupping, and sotai methods on pain and for the treatment of ANLBP. We have compared the magnitude of pain relief using a pain scale assessment method to compare the efficacy of each treatment. The Face Pain Scale assessment was conducted before and 24 hours post-treatment. This retrospective study analyzed 40 patients and categorized them according to the treatment they received. The study included the control group, and the three intervention groups, each with ten patients. Each of the three intervention groups received one of the intervention methods. The first group received the cupping treatment, where cups were placed on the lower back of both sides on points: BL23, BL25, BL26, BL54, BL37, BL40, and BL57. After vacuuming, the cups will stay for 10-15 minutes under infrared light (IR) heating. IR heating is applied by an infrared heat lamp. The second group received the acupuncture treatment, placing needles on points: BL23, BL25, BL26, BL52BL54, GB30, BL37, BL40, BL57, BL59, BL60, and KI3. The needles will be simulated with IR light. The final group received the sotai treatment, a Japanese form of structural realignment that relieves pain, balance, and mobility -moving the body naturally and spontaneously towards a comfortable direction by focusing on the inner feeling and synchronizing with the patient’s breathing. The SPSS statistical software was used to analyze the data using repeated-measures ANOVA. The data collected demonstrates the change in the FPS assessment method value over the course of treatment. p<0.05 was considered statistically significant. Results: In the cupping, acupuncture, and sotai therapy groups, the mean of the FPS value reduced from 8.7±1.2, 8.8±1.2, 9.0±0.8 before the intervention to 3.5±1.4, 4.3±1.4, 3.3±1.3, 24 hours after the intervention, respectively. The data collected shows that the CAM methods included in this study all show improvements in pain relief 24 hours after treatment. Conclusion: Complementary and alternative medicine were developed to treat injuries and illnesses with the whole body in mind, designed to be used in addition to standard treatments. The data above shows that the use of these treatments can have a pain-relieving effect, but more research should be done on the matter, as finding CAM methods that are efficacious is crucial in the landscape of health sciences.

Keywords: acupuncture, cupping, alternative medicine, rehabilitation, acute injury

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2086 The Minimum Age of Criminal Responsibility in the Philippines: Balancing International Standards and Domestic Concerns

Authors: Harold P. Pareja

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This paper answers the question whether the minimum age of criminal responsibility under the Republic Act No. 9344 (Juvenile Justice Act) as amended by Republic Act No. 10630 should be lowered to 15 years of age or not in the light of international standards and domestic concerns both of which will definitely elicit strong views. It also explores the specific provision on the minimum age of criminal responsibility under the Republic Act No. 9344 (Juvenile Justice Act) and traces the bases of such law by discussing its presented evidences and justifications as reflected in the records of proceedings in the law-making phase. On one hand, the paper discusses the impact of lowering the minimum age to the state of juvenile delinquencies and to the rate of rehabilitation for those CICL who have undergone the DSWD-supervised recovery programs. On the other hand, it presents its impact to the international community specifically to the Committee of the Rights of the Child and the UNICEF considering that the even the current minimum age set in RA 9344 is lower than the international standards. Document review and content analysis are the major research tools. Primary and secondary sources were used as references such as Philippine laws on juvenile justice and from the different states international think-tanks. The absence of reliable evidences on criminal capacity made the arguments in increasing the MACR in the harder position. Studies on criminal capacity vary from different countries and from practitioners in in the fields of psychology, psychiatry and forensics. Juvenile delinquency is mainly contributed by poverty and dysfunctional families. On the other hand, the science of the criminal mind specifically among children has not been established yet. Philippines have the legal obligations to be faithful to the CRC and other related international instruments for the juvenile justice and welfare system. Decreasing MACR does not only send wrong message to the international community but the Philippines is violating its own laws.

Keywords: juvenile justice, minimum age of responsibility (MAR), juvenile justice act of the Philippines, children in conflict with the law, international standards on juvenile justice

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2085 Tuberculosis (TB) and Lung Cancer

Authors: Asghar Arif

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Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

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2084 ‘Green Gait’ – The Growing Relevance of Podiatric Medicine amid Climate Change

Authors: Angela Evans, Gabriel Gijon-Nogueron, Alfonso Martinez-Nova

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Background The health sector, whose mission is protecting health, also contributes to the climate crisis, the greatest health threat of the 21st century. The carbon footprint from healthcare exceeds 5% of emissions globally, surpassing 7% in the USA and Australia. Global recognition has led to the Paris Agreement, the United Nations Sustainable Development Goals, and the World Health Organization's Climate Change Action Plan. It is agreed that the majority of health impacts stem from energy and resource consumption, as well as the production of greenhouse gases in the environment and deforestation. Many professional medical associations and healthcare providers advocate for their members to take the lead in environmental sustainability. Objectives To avail and expand ‘Green Podiatry’ via the three pillars of: Exercise ; Evidence ; Everyday changes; to highlight the benefits of physical activity and exercise for both human health and planet health. Walking and running are beneficial for health, provide low carbon transport, and have evidence-based health benefits. Podiatrists are key healthcare professionals in the physical activity space and can influence and guide their patients to increase physical activity and avert the many non-communicable diseases that are decimating public health, eg diabetes, arthritis, depression, cancer, obesity. Methods Publications, conference presentations, and pilot projects pertinent to ‘Green Podiatry’ have been activated since 2021, and a survey of podiatrist’s knowledge and awareness has been undertaken.The survey assessed attitudes towards environmental sustainability in work environment. The questions addressed commuting habits, hours of physical exercise per week, and attitudes in the clinic, such as prescribing unnecessary treatments or emphasizing sports as primary treatment. Results Teaching and Learning modules have been developed for podiatric medicine students and graduates globally. These will be availed. A pilot foot orthoses recycling project has been undertaken and will be reported, in addition to established footwear recycling. The preliminary survey found almost 90% of respondents had no knowledge of green podiatry or footwear recycling. Only 30% prescribe sports/exercise as the primary treatment for patients, and 45% do not to prescribe unnecessary treatments. Conclusions Podiatrists are in a good position to lead in the crucial area of healthcare and climate change implications. Sufficient education of podiatrists is essential for the profession to beneficially promote health and physical activity, which is beneficial for the health of all peoples and all communities.

Keywords: climate change, gait, green, healthcare, sustainability

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2083 An Analysis of the Affect of Climate Change on Humanitarian Law: The Way Forward

Authors: Anjali Kanagali, Astha Sinha

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Climate change is the greatest threat being faced by mankind in the 21st century. It no longer is merely an environmental, scientific or economic issue but is a humanitarian issue as well. Paris Agreement put great pressure on the businesses to reduce carbon emissions and mitigate the impact of climate change. However, the already increased climate variability and extreme weather are aggravating emergency humanitarian needs. According to the Intergovernmental Panel on Climate Change (IPCC), if efficient policy changes are not made in time to combat the climate change issues, the situation will deteriorate with an estimated global temperature rise of 4 degrees. The existing international network of Humanitarian system is not adequately structured to handle the projected natural disasters and climate change crisis. The 2030 Agenda which embraces the 17 Sustainable Development Goals (SGDs) discussed the relationship between the climate change and humanitarian assistance. The Humanitarian law aims to protect, amongst other things, ‘internally displaced persons’ which includes people displaced due to natural hazard related disasters engulfing the hazards of climate change. ‘Legal protection’ of displaced people to protect their rights is becoming a pressing need in such times. In this paper, attempts will be made to analyze the causes of the displacement, identify areas where the effect of the climate change is most likely to occur and to examine the character of forced displacement triggering population movement. We shall discuss the pressure on the Humanitarian system and assistance due to climate change issues and the need for vesting powers to the local communities or local government players to deal with the climate changes. We shall also discuss the possibility of setting up a new framework where non-state actors could be set up for climate change impact and its governance.

Keywords: humanitarian assistance to climate change, humanitarian crisis, internally displaced person, legal framework for climate migrants, non-state actors

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2082 Role of Lipid-Lowering Treatment in the Monocyte Phenotype and Chemokine Receptor Levels after Acute Myocardial Infarction

Authors: Carolina N. França, Jônatas B. do Amaral, Maria C.O. Izar, Ighor L. Teixeira, Francisco A. Fonseca

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Introduction: Atherosclerosis is a progressive disease, characterized by lipid and fibrotic element deposition in large-caliber arteries. Conditions related to the development of atherosclerosis, as dyslipidemia, hypertension, diabetes, and smoking are associated with endothelial dysfunction. There is a frequent recurrence of cardiovascular outcomes after acute myocardial infarction and, at this sense, cycles of mobilization of monocyte subtypes (classical, intermediate and nonclassical) secondary to myocardial infarction may determine the colonization of atherosclerotic plaques in different stages of the development, contributing to early recurrence of ischemic events. The recruitment of different monocyte subsets during inflammatory process requires the expression of chemokine receptors CCR2, CCR5, and CX3CR1, to promote the migration of monocytes to the inflammatory site. The aim of this study was to evaluate the effect of lipid-lowering treatment by six months in the monocyte phenotype and chemokine receptor levels of patients after Acute Myocardial Infarction (AMI). Methods: This is a PROBE (prospective, randomized, open-label trial with blinded endpoints) study (ClinicalTrials.gov Identifier: NCT02428374). Adult patients (n=147) of both genders, ageing 18-75 years, were randomized in a 2x2 factorial design for treatment with rosuvastatin 20 mg/day or simvastatin 40 mg/day plus ezetimibe 10 mg/day as well as ticagrelor 90 mg 2x/day and clopidogrel 75 mg, in addition to conventional AMI therapy. Blood samples were collected at baseline, after one month and six months of treatment. Monocyte subtypes (classical - inflammatory, intermediate - phagocytic and nonclassical – anti-inflammatory) were identified, quantified and characterized by flow cytometry, as well as the expressions of the chemokine receptors (CCR2, CCR5 and CX3CR1) were also evaluated in the mononuclear cells. Results: After six months of treatment, there was an increase in the percentage of classical monocytes and reduction in the nonclassical monocytes (p=0.038 and p < 0.0001 Friedman Test), without differences for intermediate monocytes. Besides, classical monocytes had higher expressions of CCR5 and CX3CR1 after treatment, without differences related to CCR2 (p < 0.0001 for CCR5 and CX3CR1; p=0.175 for CCR2). Intermediate monocytes had higher expressions of CCR5 and CX3CR1 and lower expression of CCR2 (p = 0.003; p < 0.0001 and p = 0.011, respectively). Nonclassical monocytes had lower expressions of CCR2 and CCR5, without differences for CX3CR1 (p < 0.0001; p = 0.009 and p = 0.138, respectively). There were no differences after the comparison between the four treatment arms. Conclusion: The data suggest a time-dependent modulation of classical and nonclassical monocytes and chemokine receptor levels. The higher percentage of classical monocytes (inflammatory cells) suggest a residual inflammatory risk, even under preconized treatments to AMI. Indeed, these changes do not seem to be affected by choice of the lipid-lowering strategy.

Keywords: acute myocardial infarction, chemokine receptors, lipid-lowering treatment, monocyte subtypes

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2081 The Effects of an Immigration Policy on the Economic Integration of Migrants and on Natives’ Attitudes: The Case of Syrian Refugees in Turkey

Authors: S. Zeynep Siretioglu Girgin, Gizem Turna Cebeci

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Turkey’s immigration policy is a controversial issue considering its legal, economic, social, and political and human rights dimensions. Formulation of an immigration policy goes hand in hand with political processes, where natives’ attitudes play a significant role. On the other hand, as was the case in Turkey, radical changes made in immigration policy or policies lacking transparency may cause severe reactions by the host society. The underlying discussion paper aims to analyze quantitatively the effects of the existing ‘open door’ immigration policy on the economic integration of Syrian refugees in Turkey, and on the perception of the native population of refugees. For the analysis, semi-structured in-depth interviews and focus group interviews have been conducted. After the introduction, a literature review is provided, followed by theoretical background on the explanation of natives’ attitudes towards immigrants. In the next section, a qualitative analysis of natives’ attitudes towards Syrian refugees is presented with the subtopics of (i) awareness, general opinions and expectations, (ii) open-door policy and management of the migration process, (iii) perception of positive and negative impacts of immigration, (iv) economic integration, and (v) cultural similarity. Results indicate that, natives concurrently have social, economic and security concerns regarding refugees, while difficulties regarding security and economic integration of refugees stand out. Socio-economic characteristics of the respondents, such as the educational level and employment status, are not sufficient to explain the overall attitudes towards refugees, while they can be used to explain the awareness of the respondents and the priority of the concerns felt.

Keywords: economic integration, immigration policy, integration policies, migrants, natives’ sentiments, perception, Syrian refugees, Turkey

Procedia PDF Downloads 355
2080 Context, Challenges, Constraints and Strategies of Non-Profit Organisations in Responding to the Needs of Asylum Seekers and Refugees in Cape Town, South Africa

Authors: C. O’Brien, Chloe Reiss

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While South Africa has been the chosen host country for over 1,2 million asylum seekers/refugees it has at the same time, been struggling to address the needs of its own people who are still trapped in poverty with little prospects of employment. This limited exploratory, qualitative study was undertaken in Cape Town with a purposive sample of 21 key personnel from various NPOs providing a service to asylum seekers/refugees. Individual in-depth face to face interviews were carried out and the main findings were: Some of the officials at the Department of Home Affairs, health personnel, landlords, school principals, employers, bank officials and police officers were prejudicial in their practices towards asylum seekers/ refugees. The major constraints experienced by NPOs in this study were linked to a lack of funding and minimal government support, strained relationship with the Department of Home Affairs and difficulties in accessing refugees. And finally, the strategies adopted by these NPOs included networking with other service providers, engaging in advocacy, raising community awareness and liaising with government. Thus, more focused intervention strategies are needed to build social cohesion, address prejudices which fuels xenophobic attacks and raise awareness/educate various sectors about refugee rights. Given this burgeoning global problem, social work education and training should include curriculum content on migrant issues. Furthermore, larger studies using mixed methodology approaches would yield more nuanced data and provide for more strategic interventions.

Keywords: refugees and asylum seekers, constraints of service delivery, non-profit organisations, refugee challenges

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2079 Association of Selected Biochemical Markers and Body Mass Index in Women with Endocrine Disorders

Authors: M. Mydlárová Blaščáková, J. Bernasovská, J. Poráčová, I. Boroňová

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Obesity is frequent attendant phenomenon of patients with endocrinological disease. Between BMI and endocrinological diseases is close correlation. In thesis we focused on the allocation of hormone concentration – PTH and TSH, CHOL a mineral element Ca in a blood serum. The examined group was formed by 100 respondents (women) aged 36 – 83 years, who were divided into two groups – control group (CG), group with diagnosed endocrine disease (DED). The concentration of PTH and TSH, Ca and CHOL was measured through the medium of analyzers Cobas e411 (Japan); Cobas Integra 400 (Switzerland). At individuals was measured body weight as well as stature and thereupon from those data we enumerated BMI. On the basis of Student T-test in biochemical parameter of PTH and Ca we found out significantly meaningful difference (p<0,05) between CG and DED. In CG we made a founding the association between BMI and PTH by means of correlation analysis.

Keywords: biochemical markers, hormones, obesity, women

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2078 Effect of Nigella Sativa Seeds and Ajwa Date on Blood Glucose Level in Saudi Patients with Type 2 Diabetes Mellitus

Authors: Reham Algheshairy, Khaled Tayeb, Christopher Smith, Rebecca Gregg, Haruna Musa

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Background: Diabetes is a medical condition that refers to the pancreas’ inability to secrete sufficient insulin levels, a hormone responsible for controlling glucose levels in the body. Any surplus glucose in the blood stream is excreted through the urinary system. Insulin resistance in blood cells can also cause this condition despite the fact that the pancreas is producing the required amount of insulin A number of researchers claim that the prevalence of diabetes in Saudi Arabia has reached epidemic proportions, although one study did observe one positive in the rise in the awareness of diabetes, possibly indicative of Saudi Arabia’s improving healthcare system. While a number of factors can cause diabetes, the ever-increasing incidence of the disease in Saudi Arabia has been blamed primarily on low levels of physical activity and high levels of obesity. Objectives: The project has two aims. The first aim of the project is to investigate the regulatory effects of consumption of Nigella seeds and Ajwah dates on blood glucose levels in diabetic patients with type 2 diabetes. The second aim of the project is to investigate whether these dietary factors may have potentially beneficial effects in controlling the complications that associated with type 2 diabetes. Methods: This use a random-cross intervention trail of 75 Saudi male and female with type 2 diabetes in Al-Noor hospital in Makkah ( KSA) aged between 18 and 70 years were divided into 3 groups. Group 1 will consume 2g of Nigella Sativa seeds daily along with a modified diet for 12 weeks, group 2 will be given Ajwah dates daily with a modified diet for 12 weeks and group 3 will follow a modified diet for 12 weeks. Anthropometric measurements were taken at baseline, along with bloods for HbA1c, fasting blood sugar and at the end of 12 weeks. Results: This study found significant decrease in blood level (FBG & 2PPBG) and HbA1c in the groups with diet and Nigella seeds) compared to Ajwa date. However, there is no significant change were found in HbA1c, FBG and 2hrpp regarding Ajwa group. Conclusion: This study illustrated a significant improvement in some markers of glycaemia following 2 g of Ns and diet for 12 weeks. The dose of 2g/day of consumed Nigella seeds was found to be more effective in controlling BGL and HbA1c than control and Ajwa groups. This suggests that Nigella seeds and following a diet may have a potential effect (a role in controlling outcomes for type 2 diabetes and controlling the disease). Further research is needed on a large scale to determine the optimum dose and duration of Nigella and Ajwa in order to achieve the desired results.

Keywords: type 2 diabetes, Nigella seeds, Ajwa dates, fasting blood glucose, control

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2077 Impact of Development Induced Displaced on Tribal Indigenous Women of North East India

Authors: Bitopi Dutta

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Forced Displacement of marginalised groups has been widely debated whole across the world, including India. This paper will do a gender analysis of Development Induced Displacement(DID) in tribal indigenous societies of North East India (NEI), a region that is frequently quoted as a relatively gender equal society as compared to the other parts of India. The central argument of the paper concerns how patriarchies in the discourses of the state and societies work together in shaping a particular gendered experience for women (and men) - in this context a violent gendered transformation in displaced indigenous communities. The primary analysis of the paper will be centered on the acquisition of Common Property Resources (CPRs) under the Land Law of India which has devastating consequences for the tribal women since CPRs forms the basis of their high status, identity and autonomy. Tracing the trajectory of DID in the NEI since 1947 to 2010, this paper will locate the violent gendered transition that these tribal societies have undergone during this period vis.a.vis their tradition which was grounded on a far more gender equal worldview. The paper will place this argument in terms of the lost status and impoverishment of tribal women in the social and economic domain reflected in terms of loss of property and land ownership rights, monetisation of the tribal economy under the sole custody of the men, forced internalisation of this reduced status by the women themselves and so on. DID in this sense will not only be understood as only physical displacement, but also as social and cultural displacement. Interviews of people displaced/affected by the development projects will be the primary mode of data collection which will be supplemented with documentary research using Government Data, and local archives of the region.

Keywords: common property resources, displacement, north east India, tribal, women

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2076 The Right to Family Reunification of Immigrants in Spain

Authors: María José Benitez Jimenez

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This study seeks to make clear the importance of family reunification in order to establish consolidated habits of coexistence of immigrants, directly favoring the relationship of the family nucleus and indirectly the social integration of foreigners. In addition to the theoretical analysis of the subject, information has been reviewed by the National Institute of Statistics and Reports of Spanish organizations that compile data on immigrants and specifically on family reunification. The Spanish regulations on foreigners include the right of foreigners legally residing in Spain to regroup their families. The general conditions required to exercise this right are having legally resided in Spain for one year and having obtained authorization to reside for one more year. There are exceptions to the requirement of having resided for one year in our country. Article 39 of the Spanish Constitution, although it does not express what is to be understood as a family, does refer to the fact that ‘the public authorities ensure the social, economic and legal protection of the family’. Therefore for the Spanish State, the family institution, in a broad sense, enjoys a privileged treatment that is revealed in the Supreme Norm and that reflects the interest of our society to address the relationships that subjects have in their immediate environment. Although we are aware of the reluctant position of the Spanish Constitutional Court to consider as a fundamental right the right to family life despite being enshrined in Article 8 of the European Convention on Human Rights, it is questionable whether access to authorization for family reunification should be more uniform in terms of requirements related to nationality, employment or training of applicants in order to have an egalitarian character. The requirement of having resided one year in Spain to be able to request successful family reunification seems dispensable because if foreigners can obviate this requirement by having a certain status, its abolition would be feasible by equating all situations and benefiting foreigners in general. The achievement of this proposal would help to strengthen the family life of immigrants from the beginning of their life in Spain.

Keywords: family, immigrants, social integration, reunification

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2075 'Explainable Artificial Intelligence' and Reasons for Judicial Decisions: Why Justifications and Not Just Explanations May Be Required

Authors: Jacquelyn Burkell, Jane Bailey

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Artificial intelligence (AI) solutions deployed within the justice system face the critical task of providing acceptable explanations for decisions or actions. These explanations must satisfy the joint criteria of public and professional accountability, taking into account the perspectives and requirements of multiple stakeholders, including judges, lawyers, parties, witnesses, and the general public. This research project analyzes and integrates two existing literature on explanations in order to propose guidelines for explainable AI in the justice system. Specifically, we review three bodies of literature: (i) explanations of the purpose and function of 'explainable AI'; (ii) the relevant case law, judicial commentary and legal literature focused on the form and function of reasons for judicial decisions; and (iii) the literature focused on the psychological and sociological functions of these reasons for judicial decisions from the perspective of the public. Our research suggests that while judicial ‘reasons’ (arguably accurate descriptions of the decision-making process and factors) do serve similar explanatory functions as those identified in the literature on 'explainable AI', they also serve an important ‘justification’ function (post hoc constructions that justify the decision that was reached). Further, members of the public are also looking for both justification and explanation in reasons for judicial decisions, and that the absence of either feature is likely to contribute to diminished public confidence in the legal system. Therefore, artificially automated judicial decision-making systems that simply attempt to document the process of decision-making are unlikely in many cases to be useful to and accepted within the justice system. Instead, these systems should focus on the post-hoc articulation of principles and precedents that support the decision or action, especially in cases where legal subjects’ fundamental rights and liberties are at stake.

Keywords: explainable AI, judicial reasons, public accountability, explanation, justification

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2074 An Android Application for ECG Monitoring and Evaluation Using Pan-Tompkins Algorithm

Authors: Cebrail Çiflikli, Emre Öner Tartan

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Parallel to the fast worldwide increase of elderly population and spreading unhealthy life habits, there is a significant rise in the number of patients and health problems. The supervision of people who have health problems and oversight in detection of people who have potential risks, bring a considerable cost to health system and increase workload of physician. To provide an efficient solution to this problem, in the recent years mobile applications have shown their potential for wide usage in health monitoring. In this paper we present an Android mobile application that records and evaluates ECG signal using Pan-Tompkins algorithm for QRS detection. The application model includes an alarm mechanism that is proposed to be used for sending message including abnormality information and location information to health supervisor.

Keywords: Android mobile application, ECG monitoring, QRS detection, Pan-Tompkins Algorithm

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2073 Association of Xeroderma pigmentosum Group D Gene Polymorphism with Colorectal Cancer Risk in Kashmiri Population

Authors: Syed Sameer Aga, Saniya Nissar

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The Xeroderma pigmentosum group D gene (XPD) plays a key role in nucleotide excision repair (NER) pathway of the damaged DNA. Genetic polymorphisms in the coding region of the XPD gene may alter DNA repair capacity of the protein and hence can modulate the risk of colorectal cancer (CRC) risk. The aim of the study was to determine the genetic association of XPD Lys751Gln polymorphism with the risk of colorectal cancer (CRC) development. 120 CRC patients and 160 normal controls were assessed for genotype frequencies of XPD Lys751Gln polymorphism using PCR-RFLP technique. We observed a significant association (p < 0.05) between the XPD Lys751Gln polymorphism and the risk of developing CRC (p < 0.05). Additionally, Gln/Gln genotype of the XPD gene doubled the risk for the development of CRC [p < 0.05; OR=2.25 95% CI (1.07-4.7)]. Our results suggest that there is a significant association between the XPD Lys751Gln polymorphism and the risk of CRC.

Keywords: colorectal cancer, polymorphism, RFLP, DNA Repair, NER, XPD

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2072 The Possible Application of Artificial Intelligence in Hungarian Court Practice

Authors: László Schmidt

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In the context of artificial intelligence, we need to pay primary and particular attention to ethical principles not only in the design process but also during the application process. According to the European Commission's Ethical Guidelines, AI must have three main characteristics: it must be legal, ethical and stabil. We must never lose sight of the ethical principles because we risk that this new technology will not help democratic decision-making under the rule of law, but will, on the contrary, destroy it. The rapid spread and use of artificial intelligence poses an enormous challenge to both lawmaking and law enforcement. On legislation because AI permeates many areas of our daily lives that the legislator must regulate. We can see how challenging it is to regulate e.g., selfdriving cars/taxis/vans etc. Not to mention, more recently, cryptocurrencies and Chat GPT, the use of which also requires legislative intervention, from copyright to scientific use and even law of succession. Artificial intelligence also poses an extraordinary challenge to law enforcement. In criminal cases, police and prosecutors can make great use of AI in investigations, e.g. in forensics, DNA samples, reconstruction, identification, etc. But it can also be of great help in the detection of crimes committed in cyberspace. In criminal or civil court proceedings, AI can also play a major role in the evaluation of evidence and proof. For example, a photo or video or audio recording could be immediately revealed as genuine or fake. Likewise, the authenticity or falsification of a document could be determined much more quickly and cheaply than with current procedure (expert witnesses). Neither the current Hungarian Civil Procedure Act nor the Criminal Procedure Act allows the use of artificial intelligence in the evidentiary process. However, this should be changed. To use this technology in court proceedings would be very useful. The procedures would be faster, simpler, and therefore cheaper. Artificial intelligence could also replace much of the work of expert witnesses. Its introduction into judicial procedures would certainly be justified, but with due respect for human rights, the right to a fair trial and other democratic and rule of law guarantees.

Keywords: artificial intelligence, judiciary, Hungarian, court practice

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2071 Hypersensitivity Reactions Following Intravenous Administration of Contrast Medium

Authors: Joanna Cydejko, Paulina Mika

Abstract:

Hypersensitivity reactions are side effects of medications that resemble an allergic reaction. Anaphylaxis is a generalized, severe allergic reaction of the body caused by exposure to a specific agent at a dose tolerated by a healthy body. The most common causes of anaphylaxis are food (about 70%), Hymenoptera venoms (22%), and medications (7%), despite detailed diagnostics in 1% of people, the cause of the anaphylactic reaction was not indicated. Contrast media are anaphylactic agents of unknown mechanism. Hypersensitivity reactions can occur with both immunological and non-immunological mechanisms. Symptoms of anaphylaxis occur within a few seconds to several minutes after exposure to the allergen. Contrast agents are chemical compounds that make it possible to visualize or improve the visibility of anatomical structures. In the diagnosis of computed tomography, the preparations currently used are derivatives of the triiodide benzene ring. Pharmacokinetic and pharmacodynamic properties, i.e., their osmolality, viscosity, low chemotoxicity and high hydrophilicity, have an impact on better tolerance of the substance by the patient's body. In MRI diagnostics, macrocyclic gadolinium contrast agents are administered during examinations. The aim of this study is to present the results of the number and severity of anaphylactic reactions that occurred in patients in all age groups undergoing diagnostic imaging with intravenous administration of contrast agents. In non-ionic iodine CT and in macrocyclic gadolinium MRI. A retrospective assessment of the number of adverse reactions after contrast administration was carried out on the basis of data from the Department of Radiology of the University Clinical Center in Gdańsk, and it was assessed whether their different physicochemical properties had an impact on the incidence of acute complications. Adverse reactions are divided according to the severity of the patient's condition and the diagnostic method used in a given patient. Complications following the administration of a contrast medium in the form of acute anaphylaxis accounted for less than 0.5% of all diagnostic procedures performed with the use of a contrast agent. In the analysis period from January to December 2022, 34,053 CT scans and 15,279 MRI examinations with the use of contrast medium were performed. The total number of acute complications was 21, of which 17 were complications of iodine-based contrast agents and 5 of gadolinium preparations. The introduction of state-of-the-art contrast formulations was an important step toward improving the safety and tolerability of contrast agents used in imaging. Currently, contrast agents administered to patients are considered to be one of the best-tolerated preparations used in medicine. However, like any drug, they can be responsible for the occurrence of adverse reactions resulting from their toxic effects. The increase in the number of imaging tests performed with the use of contrast agents has a direct impact on the number of adverse events associated with their administration. However, despite the low risk of anaphylaxis, this risk should not be marginalized. The growing threat associated with the mass performance of radiological procedures with the use of contrast agents forces the knowledge of the rules of conduct in the event of symptoms of hypersensitivity to these preparations.

Keywords: anaphylactic, contrast medium, diagnostic, medical imagine

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2070 Experiences of Homophobia, Machismo and Misogyny in Tourist Destinations: A Netnography in a Facebook Community of LGBT Backpackers

Authors: Renan De Caldas Honorato, Ana Augusta Ferreira De Freitas

Abstract:

Homosexuality is still criminalized in a large number of countries. In some of them, being gay or lesbian can even be punished by death. Added to this context, the experiences of social discrimination faced by the LGBT population, including homophobia, machismo and misogyny, cause numerous restrictions throughout their lives. The possibility of confronting these challenges in moments that should be pleasant, such as on a trip or on vacation, is unpleasant, to say the least. In the current scenario of intensifying the use of Social network sites (SNSs) to search for information, including in the tourist area, this work aims to analyze the sharing of tourist experiences with situations of confrontation and perceptions of homophobia, machismo and misogyny, and restrictions suffered in tourist destinations. The fieldwork is a community of LGBT backpackers based on Facebook. Netnography was the core method adopted. A qualitative approach was conducted and 463 publications posted from January to December 2020 were assessed through the computer-mediated discourse analysis (CMDA). The results suggest that these publications exist to identify the potential exposure to these offensive behaviors while traveling. Individuals affirm that the laws, positive or not, in relation to the LGBT public are not the only factors for a place to be defined as safe or not for gay travelers. The social situation of a country and its laws are quite different and this is the main target of these publications. The perception of others about the chosen destination is more important than knowing your rights and the legal status of each country and it also lessens uncertainty, even when they are never totally confident when choosing a travel destination. In certain circumstances, sexual orientation also needs to be protected from the judgment of hosts and residents. The systemic treatment of homophobic behavior and the construction of a more inclusive society are urgent.

Keywords: homophobia, hospitality, machismo, misogyny

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2069 Co-Existence of Central Serous Retinopathy and Diabetic Retinopathy: A Diagnostic Dilemma

Authors: Avantika Verma

Abstract:

Diabetic retinopathy (DR) and Central serous retinopathy (CSR) are 2 distinct entities, with difference in age of presentation, eitiopathogenesis and clinical features, but when occurring together, can be a diagnostic dilemma and requires careful evaluation. Case study of 3 patients with long standing diabetes (>15yrs) and features of Central serous retinopathy was done at Bangalore West Lions Superspeciality Eye Hospital, Bangalore, India in 2013. Even though diabetic retinopathy and CSR have different pathologies, they can coexist. The reason for coexistence could be the following: A patient with CSR as a young adult could develop DR in later years. Stress could be the contributing factor in older patient with diabetes.Stress could be a common factor for both, as it is one of the important factors in the pathogenesis of Maturity Onset Diabetes Miletus (MODY). In any situation, a careful evaluation is necessary to differentiate the cause of fundus picture, as treatment differs for the two diseases.

Keywords: central serous retinopathy, diabetic retinopathy, existence, stress

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2068 Traditional Phytotherapy among Tribes of Madhya Pradesh, India Used in the Treatment of Ear, Nose and Throat Disorders

Authors: Sumeet Dwivedi, Shweta Shriwas, Raghvendra Dubey

Abstract:

Madhya Pradesh, a Central State of India is rich in natural heritage due to tribal impact. Herbal harmony present either cultivated or by naturally being used by the tribes of the state in the treatment of several human and animal disorders. Diseases of ear, nose and throat (ENT) often have serious consequences including hearing impairment, and emotional strain that lower the quality of life of patients. Traditional phytotherapy have now been found to be instrumental in improving chances of discovering plants with antimicrobial activity in new drug development. The present paper enumerates the uses of ten herbs viz., garlic, eucalyptus, marigold, tulsi, euphorbia, lemon grass, haldi, bhringraj, ginger and ajwain. An attempt has also been made to reveal the method of preparation, dose, duration possible MOA of these herbs used for ENT disorders.

Keywords: ENT, traditional phytotherapy, herbs, Madhya Pradesh

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2067 Recent Developments and Expectations in the Legal Expenses Insurance in Turkey

Authors: İbrahim Arslan, Mücahit Ünal

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An important issue to ensure justice is to simplify the right to seek justice. But there is a cost of seeking justice in civil law. It costs at least, attorneys' fees and judicial expenses during the beginning and in case of losing a trial. Indeed, most of the people refrain from seeking justice because of these expenses. Therefore, it is not inappropriate to say that the removal of obstacles staying on the way of seeking justice will increase the belief in justice. Legal expenses insurance is a private law contract of insurance in which the insurer is obliged to pay premiums of the insured, to provide the necessary services for the protection of legal interests of the insured person within the agreed scope. This type of insurance is being practiced in the Western world for a long time. The special rights, duties and obligations of the parties to a legal expenses insurance contract shall be governed by the Turkish Commercial Code (TCC) and the contractual agreements which are regularly closed in the form of general terms and conditions. If the number of the legal expenses insurance contracts concluded increase this will definitely improve the percentage of seeking justice before the courts. The general terms and conditions applicable in Turkey generally include litigation costs, referee fees, guarantee fund , enforcement costs , appeal costs borne decision corrections costs. In addition, besides the insured, other family members or the people specified in the policy are protected in the scope of personal/family legal expenses insurance. The commercial law disputes fall outside the scope of coverage in this insurance branch. The insured person chooses his own lawyer and the insurer is not allowed to give advice during the selection of a lawyer. In April 2015, the Prime Minister announced of a new era in the field of legal expenses insurance in Turkey and this announcement excited the insurance industry and legal community.

Keywords: insurance, in the Turkish law on legal protection insurance, legal protection insurance, legal protection

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2066 Cranioplasty With Custom Implant Realized Using 3D Printing Technology

Authors: R. Trad Khodja, A. Guessmi, R. Ghoul, A. Mahtout, S. A. Benbouali, M. A. Boulahlib

Abstract:

Cranioplasty is a surgical act that aims to restore cranial bone losses in order to protect the brain from external aggressions and to improve the patient's aesthetic appearance. This objective can be achieved by taking advantage of the current technological development in computer science and biomechanics. The objective of this paper is to present an approach for the realization of high-precision biocompatible cranial implants using new 3D printing technologies at the lowest cost. The proposed method is to reproduce the missing part of the skull by referring to its healthy contralateral part. Once the model is validated by the neurosurgeons, a mold is 3D printed for the production of a biocompatible implant in Poly-Methyl-Methacrylate (PMMA) acrylic cement. Using this procedure, ten patients underwent this procedure with excellent aesthetic results.

Keywords: cranioplasty, cranial defect, PMMA, 3d printing, custom made implants

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2065 A Survey of Digital Health Companies: Opportunities and Business Model Challenges

Authors: Iris Xiaohong Quan

Abstract:

The global digital health market reached 175 billion U.S. dollars in 2019, and is expected to grow at about 25% CAGR to over 650 billion USD by 2025. Different terms such as digital health, e-health, mHealth, telehealth have been used in the field, which can sometimes cause confusion. The term digital health was originally introduced to refer specifically to the use of interactive media, tools, platforms, applications, and solutions that are connected to the Internet to address health concerns of providers as well as consumers. While mHealth emphasizes the use of mobile phones in healthcare, telehealth means using technology to remotely deliver clinical health services to patients. According to FDA, “the broad scope of digital health includes categories such as mobile health (mHealth), health information technology (IT), wearable devices, telehealth and telemedicine, and personalized medicine.” Some researchers believe that digital health is nothing else but the cultural transformation healthcare has been going through in the 21st century because of digital health technologies that provide data to both patients and medical professionals. As digital health is burgeoning, but research in the area is still inadequate, our paper aims to clear the definition confusion and provide an overall picture of digital health companies. We further investigate how business models are designed and differentiated in the emerging digital health sector. Both quantitative and qualitative methods are adopted in the research. For the quantitative analysis, our research data came from two databases Crunchbase and CBInsights, which are well-recognized information sources for researchers, entrepreneurs, managers, and investors. We searched a few keywords in the Crunchbase database based on companies’ self-description: digital health, e-health, and telehealth. A search of “digital health” returned 941 unique results, “e-health” returned 167 companies, while “telehealth” 427. We also searched the CBInsights database for similar information. After merging and removing duplicate ones and cleaning up the database, we came up with a list of 1464 companies as digital health companies. A qualitative method will be used to complement the quantitative analysis. We will do an in-depth case analysis of three successful unicorn digital health companies to understand how business models evolve and discuss the challenges faced in this sector. Our research returned some interesting findings. For instance, we found that 86% of the digital health startups were founded in the recent decade since 2010. 75% of the digital health companies have less than 50 employees, and almost 50% with less than 10 employees. This shows that digital health companies are relatively young and small in scale. On the business model analysis, while traditional healthcare businesses emphasize the so-called “3P”—patient, physicians, and payer, digital health companies extend to “5p” by adding patents, which is the result of technology requirements (such as the development of artificial intelligence models), and platform, which is an effective value creation approach to bring the stakeholders together. Our case analysis will detail the 5p framework and contribute to the extant knowledge on business models in the healthcare industry.

Keywords: digital health, business models, entrepreneurship opportunities, healthcare

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2064 Changing Pedagogy from Segregation to Inclusion: A Phenomenological Case Study of Ten Special Educators

Authors: Monique Somma

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As special education service delivery models are shifting in order to better meet the academic and social rights of students with exceptionalities, teaching practices must also align with these goals. This phenomenological case study explored the change experiences of special education teachers who have transitioned from teaching in a self-contained special education class to an inclusive class setting. Ten special educators who had recently changed their teaching roles to inclusive classrooms, completed surveys and participated in a focus group. Of the original ten educators, five chose to participate further in individual interviews. Data collected from the three methods was examined and compared for common themes. Emergent themes included, support and training, attitudes and perceptions, inclusive practice, growth and change, and teaching practice. The overall findings indicated that despite their special education training, these educators were challenged by their own beliefs and expectations, the attitudes of others and systematic barriers in the education system. They were equally surprised by the overall social and academic performance of students with exceptionalities in inclusive classes, as well as, the social and academic growth and development of the other students in the class. Over the course of their careers, they all identified an overall personal pedagogical shift, to some degree or another, which they contributed to the successful experiences of inclusion they had. They also recognized that collaborating with others was essential for inclusion to be successful. The findings from this study suggest several implications for professional development and training needs specific to special education teachers moving into inclusive settings. Maximizing the skills of teachers with special education experience in a Professional Learning Community (PLC) and mentorship opportunities would be beneficial to all staffs working toward creating inclusive classrooms and schools.

Keywords: attitudes and perceptions, inclusion of students with exceptionalities, special education teachers, teacher change

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2063 Saudi Women Facing Challenges in a Mixed-Gender Work Environment

Authors: A. Aldawsari

Abstract:

The complex issue of women working in a mixed-gender work environment has its roots in social and cultural factors. This research was done to identify and explore the social and cultural challenges Saudi women face in a mixed-gender work environment in Saudi Arabia. Over the years, Saudi women in mixed-gender work environments in Saudi Arabia have been of interest in various research areas, especially within the context of a hospital work environment. This research, which involves a female researcher interacting one-on-one with Saudi women, will address this issue as well as the effect of the 2030 Vision in Saudi Arabia, and it will aim to include several new fields of work environments for women in Saudi Arabia. The aim of this research is to examine the perceptions of Saudi women who work in a mixed gender environment regarding the general empowerment of women in these settings. The objective of this research is to explore the cultural and social challenges that influence Saudi women's rights to work in a mixed-gender environment in Saudi Arabia. The significance of this research lies in the fact that there is an urgency to resolve issue of female employment in Saudi Arabia, where Saudi women still suffer from inequality in employment opportunity. Although the Saudi government is seeking to empower women by integrating them into a mixed-gender work environment, which is a key goal and prominent social change advocated for in the 2030 Vision, this same goal is one of the main challenges in the face of achieving female empowerment. The methodology section focuses on appropriate methods that can be used to study the effect of social and cultural challenges on the employment of women. It then determines the conditions and limitations of the research by applying a qualitative research approach to the investigation and analysing the data collected from the interviews. A statistical analysis tool, such as NVivo, will be used for the qualitative analysis of the interviews. The study found that the factor most responsible for creating social and cultural challenges is family—whether close family or distant family—more so than tribe or community.

Keywords: women, work, mixed-gender, environment

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2062 Intensive Care Nursing Experience of a Lung Cancer Patient Receiving Palliative

Authors: Huang Wei-Yi

Abstract:

Objective: This article explores the intensive care nursing experience of a terminal lung cancer patient who received palliative care after tracheal intubation. The patient was nearing death, and the family experienced sadness and grief as they faced the patient’s deteriorating condition and impending death. Methods: The patient was diagnosed with lung cancer in 2018 and received chemotherapy and radiation therapy with regular outpatient follow-ups. Due to brain metastasis and recent poor pain control and treatment outcomes, the patient was admitted to the intensive care unit (ICU), where the tracheal tube was removed, and palliative care was initiated. During the care period, a holistic assessment was conducted, addressing the physical, psychological, social, and spiritual aspects of care. Medical records were reviewed, interviews and family meetings were held, and a comprehensive assessment was carried out by the critical care team in collaboration with the palliative care team. The primary nursing issues identified included pain, ineffective breathing patterns, fear of death, and altered tissue perfusion. Results: Throughout the care process, the palliative care nurse, along with the family, utilized listening, caring, companionship, pain management, essential oil massage, distraction, and comfortable positioning to alleviate the patient’s pain and breathing difficulties. The use of Morphine 6mg in 0.9% N/S 50ml IV drip q6h reduced the FLACC pain score from 6 to 3. The patient’s respiratory rate improved from 28 breaths/min to 18-22 breaths/min, and sleep duration increased from 4 to 7 uninterrupted hours. The holistic palliative care approach, coupled with the involvement of the palliative care team, facilitated expressions of gratitude, apologies, and love between the patient and family. Visiting hours were extended, and with the nurse’s assistance, these moments were recorded and shared with the patient’s consent, providing cherished memories for the family. The patient’s end-of-life experience was thus improved, and the family was able to find peace. This case also served to promote the concept of palliative care, ensuring that more patients and families receive high-quality nursing care. Conclusion: When caring for terminal patients, collaboration with the palliative care team, including social workers, clergy, psychologists, and nutritionists, is essential. Involving the family in decision-making and providing opportunities for closeness and expressions of gratitude improve personalized care and enhance the patient's quality of life. Upon transferring to the ward, the patient’s hemodynamic stability was maintained, including SBP 110-130 mmHg, respiratory rate 20-22 breaths/min, and pain score <3. The patient was later discharged and transitioned to home hospice care for ongoing support.

Keywords: intensive care, lung cancer, palliative care, ICU

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2061 Human 3D Metastatic Melanoma Models for in vitro Evaluation of Targeted Therapy Efficiency

Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

Abstract:

Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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