Search results for: failed trabeculectomy
Commenced in January 2007
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Edition: International
Paper Count: 536

Search results for: failed trabeculectomy

56 Fuzzy Availability Analysis of a Battery Production System

Authors: Merve Uzuner Sahin, Kumru D. Atalay, Berna Dengiz

Abstract:

In today’s competitive market, there are many alternative products that can be used in similar manner and purpose. Therefore, the utility of the product is an important issue for the preferability of the brand. This utility could be measured in terms of its functionality, durability, reliability. These all are affected by the system capabilities. Reliability is an important system design criteria for the manufacturers to be able to have high availability. Availability is the probability that a system (or a component) is operating properly to its function at a specific point in time or a specific period of times. System availability provides valuable input to estimate the production rate for the company to realize the production plan. When considering only the corrective maintenance downtime of the system, mean time between failure (MTBF) and mean time to repair (MTTR) are used to obtain system availability. Also, the MTBF and MTTR values are important measures to improve system performance by adopting suitable maintenance strategies for reliability engineers and practitioners working in a system. Failure and repair time probability distributions of each component in the system should be known for the conventional availability analysis. However, generally, companies do not have statistics or quality control departments to store such a large amount of data. Real events or situations are defined deterministically instead of using stochastic data for the complete description of real systems. A fuzzy set is an alternative theory which is used to analyze the uncertainty and vagueness in real systems. The aim of this study is to present a novel approach to compute system availability using representation of MTBF and MTTR in fuzzy numbers. Based on the experience in the system, it is decided to choose 3 different spread of MTBF and MTTR such as 15%, 20% and 25% to obtain lower and upper limits of the fuzzy numbers. To the best of our knowledge, the proposed method is the first application that is used fuzzy MTBF and fuzzy MTTR for fuzzy system availability estimation. This method is easy to apply in any repairable production system by practitioners working in industry. It is provided that the reliability engineers/managers/practitioners could analyze the system performance in a more consistent and logical manner based on fuzzy availability. This paper presents a real case study of a repairable multi-stage production line in lead-acid battery production factory in Turkey. The following is focusing on the considered wet-charging battery process which has a higher production level than the other types of battery. In this system, system components could exist only in two states, working or failed, and it is assumed that when a component in the system fails, it becomes as good as new after repair. Instead of classical methods, using fuzzy set theory and obtaining intervals for these measures would be very useful for system managers, practitioners to analyze system qualifications to find better results for their working conditions. Thus, much more detailed information about system characteristics is obtained.

Keywords: availability analysis, battery production system, fuzzy sets, triangular fuzzy numbers (TFNs)

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55 Income Inequality and Its Effects on Household Livelihoods in Parker Paint Community, Liberia

Authors: Robertson Freeman

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The prime objective of this research is to examine income inequality and its effects on household livelihoods in Parker Paint. Many researchers failed to address the potential threat of income inequality on diverse household livelihood indicators, including health, food, housing, transport and many others. They examine and generalize the effects of income differentials on household livelihoods by addressing one indicator of livelihood security. This research fills the loopholes of previous research by examining the effects of income inequality and how it affects the livelihoods of households, taking into consideration livelihood indicators including health, food security, and transport. The researcher employed the mixed research method to analyze the distribution of income and solicit opinions of household heads on the effects of their monthly income on their livelihoods. Age and sex structure, household composition, type of employment and educational status influence income inequality. The level of income, Lorenz curve and the Gini coefficient was mutually employed to calculate and determine the level of income inequality. One hundred eighty-two representing 96% of household heads are employed while 8, representing 4%, are unemployed. However, out of a total number of 182 employed, representing 96%, 27 people representing 14%, are employed in the formal private sector, while 110, representing 58%, are employed in the private informal sector. Monthly average income, savings, investments and unexpected circumstances affect the livelihood of households. Infrastructural development and wellbeing should be pursued by reducing expenditure earmarked in other sectors and channeling the funds towards the provision of household needs. One of the potent tools for consolidating household livelihoods is to initiate livelihood empowerment programs. Government and private sector agencies should establish more health insurance schemes, providing mosquito nets, immunization services, public transport, as well as embarking on feeding programs, especially in the remote areas of Parker paint. To climax the research findings, self-employment, entrepreneurship and the general private sector employment is a transparent double-edged sword. If employed in the private sector, there is the likelihood to increase one’s income. However, this also induces the income gap between the rich and poor since many people are exploited by affluence, thereby relegating the poor from the wealth hierarchy. Age and sex structure, as well as type of employment, should not be overlooked since they all play fundamental roles in influencing income inequality. Savings and investments seem to play a positive role in reducing income inequality. However, savings and investment in this research affect livelihoods negatively. It behooves mankind to strive and work hard to the best of ability in earning sufficient income and embracing measures to retain his financial strength. In so doing, people will be able to provide basic household needs, celebrate the reduction in unemployment and dependence and finally ensure sustainable livelihoods.

Keywords: income, inequality, livelihood, pakerpaint

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54 The History and Pattern of Migration from Punjab to West: Colonial to Global Punjab

Authors: Malkit Singh

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This paper presents an in-depth analysis of the problem of migration from Punjab to the West while analyzing the history and patterns of generations of migration of Punjabis to the West. A special emphasis is given to link the present socio-economic and political crisis with the historical pattern of Punjabis’ migration to the West from colonial India to Independent Bharat, along with the stories of the success and failures of Western aspirants’ youth from Punjab. The roots of the migration from Punjab to the West have been traced from the invasion of the British in Punjab, resulting in the socio-economic and political dismantling of the Punjabi society, which resulted in the migration of the Punjabis to the other colonies of the British Empire. The grim position at home despite of all the efforts and hard work by the majority of the Punjabis, particularly from the farmer community and the shining lifestyle of some families of the village or vicinity who have some relatives in the West have encouraged the large number of Punjabis to change their fortune by working in West. However, the Visa and Work Permit regime has closed the doors of the West for those who are unskilled, semi-skilled and not qualified for the visa and work permit norms, but their inspiration to change their fortune by working abroad at any cost has resulted into the development of big business fraud of immigration agent and firms in Punjab that resulted into the loss of the thousands lives, imprisonment in the foreign and selling of the properties of the Punjabis. The greed for the greener pastures in the West and, the plight of the deserted wives of NRIs and the illegal routes adopted by the Punjabi youth due to the non-availability of visas and work permits are dealt in a comprehensive method. The rise and fall of Punjab as a land of the breadbasket of Bharat and the marginalization of the farmers with middle and small holdings due to the capital-intensive techniques are linked with the forced migration of the Punjabis. The failure of the government to address and respond to the rampant corruption, agriculture failure and the resulting problems of law and order before and after the troubled period of militancy in Punjab and the resulting migration to the West are comprehensively covered. The new trend of the Student Visa and Study abroad, particularly in Canada, Australia, and New Zealand, despite of the availability of quality education at very low cost in India. The early success of some students in getting study visas from Australia, Canada, New Zealand etc. and getting permanent immigration to these countries have encouraged the majority of Punjabi youth to leave their motherland for better opportunities in the prosperous lands, that is, again, failed as these countries are flooded with the Punjabi students. Moreover, the total failure of the political leadership of Punjab to address the basic needs of society, like law and order and stop the drug menace issues in the post-militancy Punjab is also done to understand the problem.

Keywords: Punjab, migration, West, agriculture

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53 How Restorative Justice Can Inform and Assist the Provision of Effective Remedies to Hate Crime, Case Study: The Christchurch Terrorist Attack

Authors: Daniel O. Kleinsman

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The 2019 terrorist attack on two masjidain in Christchurch, New Zealand, was a shocking demonstration of the harm that can be caused by hate crime. As legal and governmental responses to the attack struggle to provide effective remedies to its victims, restorative justice has emerged as a tool that can assist, in terms of both meeting victims’ needs and discharging the obligations of the state under the International Covenant on Civil and Political Rights (ICCPR), arts 2(3), 26, 27. Restorative justice is a model that emphasizes the repair of harm caused or revealed by unjust behavior. It also prioritises the facilitation of dialogue, the restoration of equitable relationships, and the prevention of future harm. Returning to the case study, in the remarks of the sentencing judge, the terrorist’s actions were described as a hate crime of vicious malevolence that the Court was required to decisively reject, as anathema to the values of acceptance, tolerance and mutual respect upon which New Zealand’s inclusive society is based and which the country strives to maintain. This was one of the reasons for which the terrorist received a life sentence with no possibility of parole. However, in the report of the Royal Commission of Inquiry into the Attack, it was found that victims felt the attack occurred within the context of widespread racism, discrimination and Islamophobia, where hostile behaviors, including hate-based threats and attacks, were rarely recorded, analysed or acted on. It was also found that the Government had inappropriately concentrated intelligence resources on the risk of ‘Islamist’ terrorism and had failed to adequately respond to concerns raised about threats against the Muslim community. In this light, the remarks of the sentencing judge can be seen to reflect a criminal justice system that, in the absence of other remedies, denies systemic accountability and renders hate crime an isolated incident rather than an expression of more widespread discrimination and hate to be holistically addressed. One of the recommendations of the Royal Commission was to explore with victims the desirability and design of restorative justice processes. This presents an opportunity for victims to meet with state representatives and pursue effective remedies (ICCPR art 2(3)) not only for the harm caused by the terrorist but the harm revealed by a system that has exposed the minority Muslim community in New Zealand to hate in all forms, including but not limited to violent extremism. In this sense, restorative justice can also assist the state in discharging its wider obligations to protect all persons from discrimination (art 26) and allow ethnic and religious minorities to enjoy their own culture and profess and practice their own religion (art 27). It can also help give effect to the law and its purpose as a remedy to hate crime, as expressed in this case study by the sentencing judge.

Keywords: hate crime, restorative justice, minorities, victims' rights

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52 Good Governance Complementary to Corruption Abatement: A Cross-Country Analysis

Authors: Kamal Ray, Tapati Bhattacharya

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Private use of public office for private gain could be a tentative definition of corruption and most distasteful event of corruption is that it is not there, nor that it is pervasive, but it is socially acknowledged in the global economy, especially in the developing nations. We attempted to assess the interrelationship between the Corruption perception index (CPI) and the principal components of governance indicators as per World Bank like Control of Corruption (CC), rule of law (RL), regulatory quality (RQ) and government effectiveness (GE). Our empirical investigation concentrates upon the degree of reflection of governance indicators upon the CPI in order to single out the most powerful corruption-generating indicator in the selected countries. We have collected time series data on above governance indicators such as CC, RL, RQ and GE of the selected eleven countries from the year of 1996 to 2012 from World Bank data set. The countries are USA, UK, France, Germany, Greece, China, India, Japan, Thailand, Brazil, and South Africa. Corruption Perception Index (CPI) of the countries mentioned above for the period of 1996 to 2012is also collected. Graphical method of simple line diagram against the time series data on CPI is applied for quick view for the relative positions of different trend lines of different nations. The correlation coefficient is enough to assess primarily the degree and direction of association between the variables as we get the numerical data on governance indicators of the selected countries. The tool of Granger Causality Test (1969) is taken into account for investigating causal relationships between the variables, cause and effect to speak of. We do not need to verify stationary test as length of time series is short. Linear regression is taken as a tool for quantification of a change in explained variables due to change in explanatory variable in respect of governance vis a vis corruption. A bilateral positive causal link between CPI and CC is noticed in UK, index-value of CC increases by 1.59 units as CPI increases by one unit and CPI rises by 0.39 units as CC rises by one unit, and hence it has a multiplier effect so far as reduction in corruption is concerned in UK. GE causes strongly to the reduction of corruption in UK. In France, RQ is observed to be a most powerful indicator in reducing corruption whereas it is second most powerful indicator after GE in reducing of corruption in Japan. Governance-indicator like GE plays an important role to push down the corruption in Japan. In China and India, GE is proactive as well as influencing indicator to curb corruption. The inverse relationship between RL and CPI in Thailand indicates that ongoing machineries related to RL is not complementary to the reduction of corruption. The state machineries of CC in S. Africa are highly relevant to reduce the volume of corruption. In Greece, the variations of CPI positively influence the variations of CC and the indicator like GE is effective in controlling corruption as reflected by CPI. All the governance-indicators selected so far have failed to arrest their state level corruptions in USA, Germany and Brazil.

Keywords: corruption perception index, governance indicators, granger causality test, regression

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51 Evaluation of Trabectedin Safety and Effectiveness at a Tertiary Cancer Center at Qatar: A Retrospective Analysis

Authors: Nabil Omar, Farah Jibril, Oraib Amjad

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Purpose: Trabecatine is a is a potent marine-derived antineoplastic drug which binds to the minor groove of the DNA, bending DNA towards the major groove resulting in a changed conformation that interferes with several DNA transcription factors, repair pathways and cell proliferation. Trabectedin was approved by the European Medicines Agency (EMA; London, UK) for the treatment of adult patients with advanced stage soft tissue sarcomas in whom treatment with anthracyclines and ifosfamide has failed, or for those who are not candidates for these therapies. The recommended dosing regimen is 1.5 mg/m2 IV over 24 hours every 3 weeks. The purpose of this study was to comprehensively review available data on the safety and efficacy of trabectedin used as indicated for patients at a Tertiary Cancer Center at Qatar. Methods: A medication administration report generated in the electronic health record identified all patients who received trabectedin between November 1, 2015 and November 1, 2017. This retrospective chart review evaluated the indication of trabectedin use, compliance to administration protocol and the recommended monitoring parameters, number of patients improved on the drug and continued treatment, number of patients discontinued treatment due to side-effects and the reported side effects. Progress and discharged notes were utilized to report experienced side effects during trabectedin therapy. A total of 3 patients were reviewed. Results: Total of 2 out of 3 patients who received trabectedin were receiving it for non-FDA and non-EMA, approved indications; metastatic rhabdomyosarcoma and ovarian cancer stage IV with poor prognosis. And only one patient received it as indicated for leiomyosarcoma of left ureter with metastases to liver, lungs and bone. None of the patients has continued the therapy due to development of serious side effects. One patient had stopped the medication after one cycle due to disease progression and transient hepatic toxicity, the other one had disease progression and developed 12 % reduction in LVEF after 12 cycles of trabectedin, and the third patient deceased, had disease progression on trabectedin after the 10th cycle that was received through peripheral line which resulted in developing extravasation and left arm cellulitis requiring debridement. Regarding monitoring parameters, at baseline the three patients had ECHO, and Creatine Phosphokinase (CPK) but it was not monitored during treatment as recommended. Conclusion: Utilizing this medication as indicated with performing the appropriate monitoring parameters as recommended can benefit patients who are receiving it. It is important to reinforce the intravenous administration via central intravenous line, the re-assessment of left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan at 2- to 3-month intervals thereafter until therapy is discontinued, and CPK and LFTs levels prior to each administration of trabectedin.

Keywords: trabectedin, drug-use evaluation, safety, effectiveness, adverse drug reaction, monitoring

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50 Role of Empirical Evidence in Law-Making: Case Study from India

Authors: Kaushiki Sanyal, Rajesh Chakrabarti

Abstract:

In India, on average, about 60 Bills are passed every year in both Houses of Parliament – Lok Sabha and Rajya Sabha (calculated from information on websites of both Houses). These are debated in both Lok Sabha (House of Commons) and Rajya Sabha (Council of States) before they are passed. However, lawmakers rarely use empirical evidence to make a case for a law. Most of the time, they support a law on the basis of anecdote, intuition, and common sense. While these do play a role in law-making, without the necessary empirical evidence, laws often fail to achieve their desired results. The quality of legislative debates is an indicator of the efficacy of the legislative process through which a Bill is enacted. However, the study of legislative debates has not received much attention either in India or worldwide due to the difficulty of objectively measuring the quality of a debate. Broadly, three approaches have emerged in the study of legislative debates. The rational-choice or formal approach shows that speeches vary based on different institutional arrangements, intra-party politics, and the political culture of a country. The discourse approach focuses on the underlying rules and conventions and how they impact the content of the debates. The deliberative approach posits that legislative speech can be reasoned, respectful, and informed. This paper aims to (a) develop a framework to judge the quality of debates by using the deliberative approach; (b) examine the legislative debates of three Bills passed in different periods as a demonstration of the framework, and (c) examine the broader structural issues that disincentive MPs from scrutinizing Bills. The framework would include qualitative and quantitative indicators to judge a debate. The idea is that the framework would provide useful insights into the legislators’ knowledge of the subject, the depth of their scrutiny of Bills, and their inclination toward evidence-based research. The three Bills that the paper plans to examine are as follows: 1. The Narcotics Drugs and Psychotropic Substances Act, 1985: This act was passed to curb drug trafficking and abuse. However, it mostly failed to fulfill its purpose. Consequently, it was amended thrice but without much impact on the ground. 2. The Criminal Laws (Amendment) Act, 2013: This act amended the Indian Penal Code to add a section on human trafficking. The purpose was to curb trafficking and penalise traffickers, pimps, and middlemen. However, the crime rate remains high while the conviction rate is low. 3. The Surrogacy (Regulation) Act, 2021: This act bans commercial surrogacy allowing only relatives to act as surrogates as long as there is no monetary payment. Experts fear that instead of preventing commercial surrogacy, it would drive the activity underground. The consequences would be borne by the surrogate, who would not be protected by law. The purpose of the paper is to objectively analyse the quality of parliamentary debates, get insights into how MPs understand the evidence and deliberate on steps to incentivise them to use empirical evidence.

Keywords: legislature, debates, empirical, India

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49 Therapeutic Potential of GSTM2-2 C-Terminal Domain and Its Mutants, F157A and Y160A on the Treatment of Cardiac Arrhythmias: Effect on Ca2+ Transients in Neonatal Ventricular Cardiomyocytes

Authors: R. P. Hewawasam, A. F. Dulhunty

Abstract:

The ryanodine receptor (RyR) is an intracellular ion channel that releases Ca2+ from the sarcoplasmic reticulum and is essential for the excitation-contraction coupling and contraction in striated muscle. Human muscle specific glutathione transferase M2-2 (GSTM2-2) is a highly specific inhibitor of cardiac ryanodine receptor (RyR2) activity. Single channel-lipid bilayer studies and Ca2+ release assays performed using the C-terminal half of the GSTM2-2 and its mutants F157A and Y160A confirmed the ability of the C terminal domain of GSTM2-2 to specifically inhibit the cardiac ryanodine receptor activity. Objective of the present study is to determine the effect of C terminal domain of GSTM2-2 (GSTM2-2C) and the mutants, F157A and Y160A on the Ca2+ transients of neonatal ventricular cardiomyocytes. Primary cardiomyocytes were cultured from neonatal rats. They were treated with GSTM2-2C and the two mutants F157A and Y160A at 15µM and incubated for 2 hours. Then the cells were led with Fluo-4AM, fluorescent Ca2+ indicator, and the field stimulated (1 Hz, 3V and 2ms) cells were excited using the 488 nm argon laser. Contractility of the cells were measured and the Ca2+ transients in the stained cells were imaged using Leica SP5 confocal microscope. Peak amplitude of the Ca2+ transient, rise time and decay time from the peak were measured for each transient. In contrast to GSTM2C which significantly reduced the % shortening (42.8%) in the field stimulated cells, F157A and Y160A failed to reduce the % shortening.Analysis revealed that the average amplitude of the Ca2+ transient was significantly reduced (P<0.001) in cells treated with the wild type GSTM2-2C compared to that of untreated cells. Cells treated with the mutants F157A and Y160A didn’t change the Ca2+ transient significantly compared to the control. A significant increase in the rise time (P< 0.001) and a significant reduction in the decay time (P< 0.001) were observed in cardiomyocytes treated with GSTM2-2C compared to the control but not with F157A and Y160A. These results are consistent with the observation that GSTM2-2C reduced the Ca2+ release from the cardiac SR significantly whereas the mutants, F157A and Y160A didn’t show any effect compared to the control. GSTM2-2C has an isoform-specific effect on the cardiac ryanodine receptor activity and also it inhibits RyR2 channel activity only during diastole. Selective inhibition of RyR2 by GSTM2-2C has significant clinical potential in the treatment of cardiac arrhythmias and heart failure. Since GSTM2-2C-terminal construct has no GST enzyme activity, its introduction to the cardiomyocyte would not exert any unwanted side effects that may alter its enzymatic action. The present study further confirms that GSTM2-2C is capable of decreasing the Ca2+ release from the cardiac SR during diastole. These results raise the future possibility of using GSTM2-2C as a template for therapeutics that can depress RyR2 function when the channel is hyperactive in cardiac arrhythmias and heart failure.

Keywords: arrhythmia, cardiac muscle, cardiac ryanodine receptor, GSTM2-2

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48 The Link between Strategic Sense-Making and Performance in Dubai Public Sector

Authors: Mohammad Rahman, Guy Burton, Megan Mathias

Abstract:

Strategic management as an organizational practice was adopted by the public sector in the New Public Management (NPM) era that began in most parts of the world in the 1980s. Strategy as a new public management concept was subscribed by governments in both developed and developing world, as they were persuaded that clearly defined vision, mission and goals, as well as programs and projects - aligned with the goals - could potentially help achieve government vision at the national level and organizational goals at the service-delivery level. The advocates for strategic management in the public sector saw an inherent link between strategy and performance, claiming that the implementation of organizational strategy has an effect on the overall performance of an organization. Arguably, many government entities that have failed in enhancing team and individual performance had poorly-designed strategy or weak strategy implementation. Another key argument about low-level performance is linked with lack of strategic sense-making and orientation by middle managers in particular. Scholars maintain that employees at all levels need to understand strategic management plan in order to facilitate its implementation. Therefore, involving employees (particularly the middle managers) from the beginning potentially helps an organization avoid the drop in performance, and on the contrary would increase their commitment. The United Arab Emirates (UAE) is well known for adopting public sector reform strategies and tools since the 1990s. This observation is contextually pertinent in the case of the Government of Dubai, which has provided a Strategy Execution Guide to all of its entities to achieve high level strategic success in service delivery. The Dubai public sector also adopts road maps for e-Government, Smart Dubai, Expo 2020, investment, environment, education, health and other sectors. Evidently, some of these strategies are bringing tangible (e.g. Smart Dubai transformation) results in a transformational manner. However, the amount of academic research and literature on the strategy process vis-à-vis staff performance in the Government of Dubai is limited. In this backdrop, this study examines how individual performance of public sector employees in Dubai is linked with their sense-making, engagement and orientation with strategy development and implementation processes. Based on a theoretical framework, this study will undertake a sample-based questionnaire survey amongst middle managers in Dubai public sector to (a) measure the level of engagement of middle managers in strategy development and implementation processes as perceived by them; (b) observe the organizational landscape in which role expectations are placed on middle managers; and (c) examine the impact of employee engagement in strategy development process and the conditions for role expectations on individual performance. The paper is expected to provide new insights on the interface between strategic sense-making and performance in order to contribute a better understanding of the current culture/practices of staff engagement in strategic management in the public sector of Dubai.

Keywords: employee performance, government of Dubai, middle managers, strategic sense-making

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47 Multilevel Regression Model - Evaluate Relationship Between Early Years’ Activities of Daily Living and Alzheimer’s Disease Onset Accounting for Influence of Key Sociodemographic Factors Using a Longitudinal Household Survey Data

Authors: Linyi Fan, C.J. Schumaker

Abstract:

Background: Biomedical efforts to treat Alzheimer’s disease (AD) have typically produced mixed to poor results, while more lifestyle-focused treatments such as exercise may fare better than existing biomedical treatments. A few promising studies have indicated that activities of daily life (ADL) may be a useful way of predicting AD. However, the existing cross-sectional studies fail to show how functional-related issues such as ADL in early years predict AD and how social factors influence health either in addition to or in interaction with individual risk factors. This study would helpbetterscreening and early treatments for the elderly population and healthcare practice. The findings have significance academically and practically in terms of creating positive social change. Methodology: The purpose of this quantitative historical, correlational study was to examine the relationship between early years’ ADL and the development of AD in later years. The studyincluded 4,526participantsderived fromRAND HRS dataset. The Health and Retirement Study (HRS) is a longitudinal household survey data set that is available forresearchof retirement and health among the elderly in the United States. The sample was selected by the completion of survey questionnaire about AD and dementia. The variablethat indicates whether the participant has been diagnosed with AD was the dependent variable. The ADL indices and changes in ADL were the independent variables. A four-step multilevel regression model approach was utilized to address the research questions. Results: Amongst 4,526 patients who completed the AD and dementia questionnaire, 144 (3.1%) were diagnosed with AD. Of the 4,526 participants, 3,465 (76.6%) have high school and upper education degrees,4,074 (90.0%) were above poverty threshold. The model evaluatedthe effect of ADL and change in ADL on onset of AD in late years while allowing the intercept of the model to vary by level of education. The results suggested that the only significant predictor of the onset of AD was changes in early years’ ADL (b = 20.253, z = 2.761, p < .05). However, the result of the sensitivity analysis (b = 7.562, z = 1.900, p =.058), which included more control variables and increased the observation period of ADL, are not supported this finding. The model also estimated whether the variances of random effect vary by Level-2 variables. The results suggested that the variances associated with random slopes were approximately zero, suggesting that the relationship between early years’ ADL were not influenced bysociodemographic factors. Conclusion: The finding indicated that an increase in changes in ADL leads to an increase in the probability of onset AD in the future. However, this finding is not support in a broad observation period model. The study also failed to reject the hypothesis that the sociodemographic factors explained significant amounts of variance in random effect. Recommendations were then made for future research and practice based on these limitations and the significance of the findings.

Keywords: alzheimer’s disease, epidemiology, moderation, multilevel modeling

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46 The Last National Anthem of the Ottoman Empire: Musical Code, Sociopolitical Control and Historical Realities

Authors: Nuray Ocakli

Abstract:

19th century was the era of changes and transformations for the Ottoman Empire. The first sultan of this century, Mahmud II (1808-1839), was the architect of Ottoman modernization and fundamental changes. The most radical of these was abolishing the Janissary corps and the traditional Ottoman military band, Mehteran. Mahmud II introduced modernized military corps as well as western style royal and military music. Mahmut II invited the Italian composer Giuseppe Donizetti to establish a modern military band for the new army and to compose the Sultan’s royal anthem. In 1828, Donizetti composed the first western-style Ottoman anthem, Mahmudiyye anthem. During the 19th and early 20th century, four other western style Ottoman anthems (Aziziyye, Mecidiyye, Hamidiyye, and Resadiyye) were composed but the last anthem adopted in the reign of Mehmet VI (r. 1918-1922) was again Mahmudiyye anthem. This paper aims to analyze the Mahmudiyye anthem composed as royal anthem in 1828 but adopted as national anthem in 1918. Research questions of this paper are as follows: What were the characteristics of the Mahmudiyye anthem making it the best choice of the last sultan for the last national anthem? Are there specific reasons of the last sultan to adopt Mahmudiyye anthem or not to adopt any of the other four anthems? The musical characteristics of the anthem are analyzed based on the Cerulo’s empirical research. Cerulo examined the musical structures of 124 western style anthems from 150 countries in the 1580-1976 period. Cerulo’s research categorizes musical codes of the anthems as basic and embellished related with the level of sociopolitical control. Musical analysis of the anthem indicates that the basic musical code of the anthem implies a high level of socio-political control during the reign of both Mahmut II and Mehmet VI. Historical analysis of each sultans’ reign shows that both sultans were autocratic. Mahmut II designed authoritarian government policies to suppress possible reactions against his reforms. On the other hand, authoritarian policies of Mehmet VI are related with the domestic and international political conditions following the World War I. Historical analysis of the research questions show that compared to the other western style Ottoman anthems, Mahmudiyye anthem remained the only neutral anthem symbolizing modernization and westernization of the empire. Other anthems were all the symbols of failed ideologies such as Ottomanism, pan-Islamism, and pan-Turkism. In the early 20th century, there were a few common things remained among the diverse communities of the Ottoman Empire: The land they shared as homeland and the idea of modernization to save the homeland. For this reason, the last sultan Mehmet VI adopted Mahmudiyye anthem as the memory of a unified empire under the rule of a powerful and modernist sultan. The last sultan’s reign lasted just for four years, and the Ottoman Empire disintegrated in 1922, but his adaptation of the Mahmudiyye anthem indicates his unifying policies, his attitudes to save the empire and the caliphate.

Keywords: Mahmudiyye anthem, musical code, national anthem, Ottoman Empire, royal anthem

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45 Patterns of Libido, Sexual Activity and Sexual Performance in Female Migraineurs

Authors: John Farr Rothrock

Abstract:

Although migraine traditionally has been assumed to convey a relative decrease in libido, sexual activity and sexual performance, recent data have suggested that the female migraine population is far from homogenous in this regard. We sought to determine the levels of libido, sexual activity and sexual performance in the female migraine patient population both generally and according to clinical phenotype. In this single-blind study, a consecutive series of sexually active new female patients ages 25-55 initially presenting to a university-based headache clinic and having a >1 year history of migraine were asked to complete anonymously a survey assessing their sexual histories generally and as they related to their headache disorder and the 19-item Female Sexual Function Index (FSFI). To serve as 2 separate control groups, 100 sexually active females with no history of migraine and 100 female migraineurs from the general (non-clinic) population but matched for age, marital status, educational background and socioeconomic status completed a similar survey. Over a period of 3 months, 188 consecutive migraine patients were invited to participate. Twenty declined, and 28 of the remaining 160 potential subjects failed to meet the inclusion criterion utilized for “sexually active” (ie, heterosexual intercourse at a frequency of > once per month in each of the preceding 6 months). In all groups younger age (p<.005), higher educational level attained (p<.05) and higher socioeconomic status (p<.025) correlated with a higher monthly frequency of intercourse and a higher likelihood of intercourse resulting in orgasm. Relative to the 100 control subjects with no history of migraine, the two migraine groups (total n=232) reported a lower monthly frequency of intercourse and recorded a lower FSFI score (both p<.025), but the contribution to this difference came primarily from the chronic migraine (CM) subgroup (n=92). Patients with low frequency episodic migraine (LFEM) and mid frequency episodic migraine (MFEM) reported a higher FSFI score, higher monthly frequency of intercourse, higher likelihood of intercourse resulting in orgasm and higher likelihood of multiple active sex partners than controls. All migraine subgroups reported a decreased likelihood of engaging in intercourse during an active migraine attack, but relative to the CM subgroup (8/92=9%), a higher proportion of patients in the LFEM (12/49=25%), MFEM (14/67=21%) and high frequency episodic migraine (HFEM: 6/14=43%) subgroups reported utilizing intercourse - and orgasm specifically - as a means of potentially terminating a migraine attack. In the clinic vs no-clinic groups there were no significant differences in the dependent variables assessed. Research subjects with LFEM and MFEM may report a level of libido, frequency of intercourse and likelihood of orgasm-associated intercourse that exceeds what is reported by age-matched controls free of migraine. Many patients with LFEM, MFEM and HFEM appear to utilize intercourse/orgasm as a means to potentially terminate an acute migraine attack.

Keywords: migraine, female, libido, sexual activity, phenotype

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44 Common Misconceptions around Human Immunodeficiency Virus in Rural Uganda: Establishing the Role for Patient Education Leaflets Using Patient and Staff Surveys

Authors: Sara Qandil, Harriet Bothwell, Lowri Evans, Kevin Jones, Simon Collin

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Background: Uganda suffers from high rates of HIV. Misconceptions around HIV are known to be prevalent in Sub-Saharan Africa (SSA). Two of the most common misconceptions in Uganda are that HIV can be transmitted by mosquito bites or from sharing food. The aim of this project was to establish the local misconceptions around HIV in a Central Ugandan population, and identify if there is a role for patient education leaflets. This project was undertaken as a student selected component (SSC) offered by Swindon Academy, based at the Great Western Hospital, to medical students in their fourth year of the undergraduate programme. Methods: The study was conducted at Villa Maria Hospital; a private, rural hospital in Kalungu District, Central Uganda. 36 patients, 23 from the hospital clinic and 13 from the community were interviewed regarding their understanding of HIV and by what channels they had obtained this understanding. Interviews were conducted using local student nurses as translators. Verbal responses were translated and then transcribed by the researcher. The same 36 patients then undertook a 'misconception' test consisting of 35 questions. Quantitative data was analysed using descriptive statistics and results were scored based on three components of 'transmission knowledge', 'prevention knowledge' and 'misconception rejection'. Each correct response to a question was scored one point, otherwise zero e.g. correctly rejecting a misconception scored one point, but answering ‘yes’ or ‘don’t know’ scored zero. Scores ≤ 27 (the average score) were classified as having ‘poor understanding’. Mean scores were compared between participants seen at the HIV clinic and in the community, and p-values (including Fisher’s exact test) were calculated using Stata 2015. Level of significance was set at 0.05. Interviews with 7 members of staff working in the HIV clinic were undertaken to establish what methods of communication are used to educate patients. Interviews were transcribed and thematic analysis undertaken. Results: The commonest misconceptions which failed to be rejected included transmission of HIV by kissing (78%), mosquitoes (69%) and touching (36%). 33% believed HIV may be prevented by praying. The overall mean scores for transmission knowledge (87.5%) and prevention knowledge (81.1%) were better than misconception rejection scores (69.3%). HIV clinic respondents did tend to have higher scores, i.e. fewer misconceptions, although there was statistical evidence of a significant difference only for prevention knowledge (p=0.03). Analysis of the qualitative data is ongoing but several patients expressed concerns about not being able to read and therefore leaflets not having a helpful role. Conclusions: Results from this paper identified that a high proportion of the population studied held misconceptions about HIV. Qualitative data suggests that there may be a role for patient education leaflets, if pictorial-based and suitable for those with low literacy skill.

Keywords: HIV, human immunodeficiency virus, misconceptions, patient education, Sub-Saharan Africa, Uganda

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43 Analysis of Tilting Cause of a Residential Building in Durres by the Use of Cptu Test

Authors: Neritan Shkodrani

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On November 26, 2019, an earthquake hit the central western part of Albania. It was assessed as Mw 6.4. Its epicenter was located offshore north western Durrës, about 7 km north of the city. In this paper, the consequences of settlements of very soft soils have been discussed for the case of a residential building, mentioned as “K Building”, which was suffering a significant tilting after the earthquake. “KBuilding” is an RC framed building having 12+1 (basement) storiesand a floor area of 21000 m2. The construction of the building was completed in 2012. “KBuilding”, located in Durres city, suffered severe non-structural damage during November 26, 2019, Durrës Earthquake sequences. During the in-site inspections immediately after the earthquake, the general condition of the buildings, the presence of observable settlements on the ground, and the crack situation in the structure were determined, and damage inspection were performed. It was significant to note that the “K Building” presented tilting that might be attributed, as it was believed at the beginning, partially to the failure of the columns of the ground floor and partially to liquefaction phenomena, but it did not collapse. At the first moment was not clear if the foundation had a bearing capacity failure or the foundation failed because of the soil liquefaction. Geotechnical soil investigations by using CPTU test were executed, and their data are usedto evaluatebearing capacity, consolidation settlement of the mat foundation, and soil liquefaction since they were believed to be the main reasons of this building tilting.Geotechnical soil investigation consist in 5 (five) Static Cone Penetration tests with pore pressure measurement (piezocone test). They reached a penetration depth of 20.0 m to 30.0 mand, clearly shown the presence of very soft and organic soils in the soil profile of the site. Geotechnical CPT based analysis of bearing capacity, consolidation, and secondary settlement are applied, and results are reported for each test. These results shown very small values of allowable bearing capacity and very high values of consolidation and secondary settlements. Liquefaction analysis based on the data of CPTU tests and the characteristics of ground shaking of the mentioned earthquake has shown the possibility of liquefaction for some layers of the considered soil profile, but the estimated vertical settlements are at a small range and clearly shown that the main reason of the building tilting was not related to the consequences of liquefaction, but was an existing settlement caused from the applied bearing pressure of this building. All the CPTU tests were carried out on August 2021, almost two years after the November 26, 2019, Durrës Earthquake and when the building itself was demolished. After removing the mat foundation on September 2021, it was possible to carry out CPTU tests even on the footprint of the existing building, which made possible to observe the effects of long time applied of foundation bearing pressure to the consolidation on the considered soil profile.

Keywords: bearing capacity, cone penetration test, consolidation settlement, secondary settlement, soil liquefaction, etc

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42 Evaluation of Kabul BRT Route Network with Application of Integrated Land-use and Transportation Model

Authors: Mustafa Mutahari, Nao Sugiki, Kojiro Matsuo

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The four decades of war, lack of job opportunities, poverty, lack of services, and natural disasters in different provinces of Afghanistan have contributed to a rapid increase in the population of Kabul, the capital city of Afghanistan. Population census has not been conducted since 1979, the first and last population census in Afghanistan. However, according to population estimations by Afghan authorities, the population of Kabul has been estimated at more than 4 million people, whereas the city was designed for two million people. Although the major transport mode of Kabul residents is public transport, responsible authorities within the country failed to supply the required means of transportation systems for the city. Besides, informal resettlement, lack of intersection control devices, presence of illegal vendors on streets, presence of illegal and unstandardized on-street parking and bus stops, driver`s unprofessional behavior, weak traffic law enforcement, and blocked roads and sidewalks have contributed to the extreme traffic congestion of Kabul. In 2018, the government of Afghanistan approved the Kabul city Urban Design Framework (KUDF), a vision towards the future of Kabul, which provides strategies and design guidance at different scales to direct urban development. Considering traffic congestion of the city and its budget limitations, the KUDF proposes a BRT route network with seven lines to reduce the traffic congestion, and it is said to facilitate more than 50% of Kabul population to benefit from this service. Based on the KUDF, it is planned to increase the BRT mode share from 0% to 17% and later to 30% in medium and long-term planning scenarios, respectively. Therefore, a detailed research study is needed to evaluate the proposed system before the implementation stage starts. The integrated land-use transport model is an effective tool to evaluate the Kabul BRT because of its future assessment capabilities that take into account the interaction between land use and transportation. This research aims to analyze and evaluate the proposed BRT route network with the application of an integrated land-use and transportation model. The research estimates the population distribution and travel behavior of Kabul within small boundary scales. The actual road network and land-use detailed data of the city are used to perform the analysis. The BRT corridors are evaluated not only considering its impacts on the spatial interactions in the city`s transportation system but also on the spatial developments. Therefore, the BRT are evaluated with the scenarios of improving the Kabul transportation system based on the distribution of land-use or spatial developments, planned development typology and population distribution of the city. The impacts of the new improved transport system on the BRT network are analyzed and the BRT network is evaluated accordingly. In addition, the research also focuses on the spatial accessibility of BRT stops, corridors, and BRT line beneficiaries, and each BRT stop and corridor are evaluated in terms of both access and geographic coverage, as well.

Keywords: accessibility, BRT, integrated land-use and transport model, travel behavior, spatial development

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41 An Integrative Review on Effects of Educational Interventions for Children with Eczema

Authors: Nam Sze Cheng, P. C. Janita Chau

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Background: Eczema is a chronic inflammatory disease with high global prevalence rates in many childhood populations. It is also the most common paediatric skin problem. Although eczema education and proper skin care were effective in controlling eczema symptoms, the lack of both sufficient time for patient consultation and structured eczema education programme hindered the transferability of knowledge to patients and their parents. As a result, these young patients and their families suffer from a significant physical disability and psychological distress, which can substantially impair their quality of life. Objectives: This integrative review is to examine the effects of educational interventions for children with eczema and identify the core elements associated with an effective intervention. Methods: This integrative review targeted all articles published in 10 databases between May 2016 and February 2017 that reported the outcomes of disease interventions of any format for children and adolescents with the clinical diagnosis of eczema who were under 18 years of age. Five randomized controlled trials (RCT) and one systematic review of 10 RCTs were identified for review. All these publications had high methodological quality, except one study of web-based eczema education that was limited by selection bias and poor subject blinding. Findings: This review found that most studies adopted nurse-led or multi-disciplinary parental eczema education programme at the outpatient clinic setting. The format of these programmes included individual lectures, demonstration and group sharing, and the educational materials covered basic eczema knowledge and management as well as methods to interrupt itch-scratch cycle. The main outcome measures of these studies included severity of eczema symptoms, treatment adherence and quality of life of both patients and their families. Nine included studies reported statistically significant improvement in the primary outcome of symptom severity of these eczematous children. On the other hand, all these reviews failed to identify an effective dosage of intervention under these educational programmes that was attributed to the heterogeneity of the interventions. One study that was designed based on the social cognitive theory to guide the interventional content yielded statistically significant results. The systematic review recommended the importance of measuring parental self-efficacy. Implication: This integrative review concludes that structured educational programme can help nurses understand the theories behind different health interventions. They can then deliver eczema education to their patients in a consistent manner. These interventions also result in behavioral changes through patient education. Due to the lack of validated educational programmes in Chinese, it is imperative to conduct an RCT of eczema educational programme to investigate its effects on eczema severity, quality of life and treatment adherence in Hong Kong children as well as to promote the importance of parental self-efficacy.

Keywords: children, eczema, education, intervention

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40 Disrupting Traditional Industries: A Scenario-Based Experiment on How Blockchain-Enabled Trust and Transparency Transform Nonprofit Organizations

Authors: Michael Mertel, Lars Friedrich, Kai-Ingo Voigt

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Based on principle-agent theory, an information asymmetry exists in the traditional donation process. Consumers cannot comprehend whether nonprofit organizations (NPOs) use raised funds according to the designated cause after the transaction took place (hidden action). Therefore, charity organizations have tried to appear transparent and gain trust by using the same marketing instruments for decades (e.g., releasing project success reports). However, none of these measures can guarantee consumers that charities will use their donations for the purpose. With awareness of misuse of donations rising due to the Ukraine conflict (e.g., funding crime), consumers are increasingly concerned about the destination of their charitable purposes. Therefore, innovative charities like the Human Rights Foundation have started to offer donations via blockchain. Blockchain technology has the potential to establish profound trust and transparency in the donation process: Consumers can publicly track the progress of their donation at any time after deciding to donate. This ensures that the charity is not using donations against its original intent. Hence, the aim is to investigate the effect of blockchain-enabled transactions on the willingness to donate. Sample and Design: To investigate consumers' behavior, we use a scenario-based experiment. After removing participants (e.g., due to failed attention checks), 3192 potential donors participated (47.9% female, 62.4% bachelor or above). Procedure: We randomly assigned the participants to one of two scenarios. In all conditions, the participants read a scenario about a fictive charity organization called "Helper NPO." Afterward, the participants answered questions regarding their perception of the charity. Manipulation: The first scenario (n = 1405) represents a typical donation process, where consumers donate money without any option to track and trace. The second scenario (n = 1787) represents a donation process via blockchain, where consumers can track and trace their donations respectively. Using t-statistics, the findings demonstrate a positive effect of donating via blockchain on participants’ willingness to donate (mean difference = 0.667, p < .001, Cohen’s d effect size = 0.482). A mediation analysis shows significant effects for the mediation of transparency (Estimate = 0.199, p < .001), trust (Estimate = 0.144, p < .001), and transparency and trust (Estimate = 0.158, p < .001). The total effect of blockchain usage on participants’ willingness to donate (Estimate = 0.690, p < .001) consists of the direct effect (Estimate = 0.189, p < .001) and the indirect effects of transparency and trust (Estimate = 0.501, p < .001). Furthermore, consumers' affinity for technology moderates the direct effect of blockchain usage on participants' willingness to donate (Estimate = 0.150, p < .001). Donating via blockchain is a promising way for charities to engage consumers for several reasons: (1) Charities can emphasize trust and transparency in their advertising campaigns. (2) Established charities can target new customer segments by specifically engaging technology-affine consumers in the future. (3) Charities can raise international funds without previous barriers (e.g., setting up bank accounts). Nevertheless, increased transparency can also backfire (e.g., disclosure of costs). Such cases require further research.

Keywords: blockchain, social sector, transparency, trust

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39 Blending Synchronous with Asynchronous Learning Tools: Students’ Experiences and Preferences for Online Learning Environment in a Resource-Constrained Higher Education Situations in Uganda

Authors: Stephen Kyakulumbye, Vivian Kobusingye

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Generally, World over, COVID-19 has had adverse effects on all sectors but with more debilitating effects on the education sector. After reactive lockdowns, education institutions that could continue teaching and learning had to go a distance mediated by digital technological tools. In Uganda, the Ministry of Education thereby issued COVID-19 Online Distance E-learning (ODeL) emergent guidelines. Despite such guidelines, academic institutions in Uganda and similar developing contexts with academically constrained resource environments were caught off-guard and ill-prepared to transform from face-to-face learning to online distance learning mode. Most academic institutions that migrated spontaneously did so with no deliberate tools, systems, strategies, or software to cause active, meaningful, and engaging learning for students. By experience, most of these academic institutions shifted to Zoom and WhatsApp and instead conducted online teaching in real-time than blended synchronous and asynchronous tools. This paper provides students’ experiences while blending synchronous and asynchronous content-creating and learning tools within a technological resource-constrained environment to navigate in such a challenging Uganda context. These conceptual case-based findings, using experience from Uganda Christian University (UCU), point at the design of learning activities with two certain characteristics, the enhancement of synchronous learning technologies with asynchronous ones to mitigate the challenge of system breakdown, passive learning to active learning, and enhances the types of presence (social, cognitive and facilitatory). The paper, both empirical and experiential in nature, uses online experiences from third-year students in Bachelor of Business Administration student lectured using asynchronous text, audio, and video created with Open Broadcaster Studio software and compressed with Handbrake, all open-source software to mitigate disk space and bandwidth usage challenges. The synchronous online engagements with students were a blend of zoom or BigBlueButton, to ensure that students had an alternative just in case one failed due to excessive real-time traffic. Generally, students report that compared to their previous face-to-face lectures, the pre-recorded lectures via Youtube provided them an opportunity to reflect on content in a self-paced manner, which later on enabled them to engage actively during the live zoom and/or BigBlueButton real-time discussions and presentations. The major recommendation is that lecturers and teachers in a resource-constrained environment with limited digital resources like the internet and digital devices should harness this approach to offer students access to learning content in a self-paced manner and thereby enabling reflective active learning through reflective and high-order thinking.

Keywords: synchronous learning, asynchronous learning, active learning, reflective learning, resource-constrained environment

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38 Exploring the Role of Private Commercial Banks in Increasing Small and Medium Size Enterprises’ Financial Accessibility in Developing Countries: A Study in Bangladesh

Authors: Khondokar Farid Ahmmed, Robin Bown

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It is widely recognized that the formal financing of Small and Medium Size Enterprises (SMEs) by Private Commercial Banks (PCBs) is restricted. Due to changing financial market competition, SMEs are now important customers to PCBs in the member countries of the Asian Development Bank (ADB). Various initiatives in enhancing the efficiency of risk assessment of PCBs have failed in increasing financing accessibility in the traditional financing system where information asymmetry is a key constraint. In this circumstance, PCBs need to undertake a holistic approach. Holistic approach refers to methods that attempt to fundamentally change established traditions. To undertake holistic approach, this study intends to find the entire established financing culture between PCBs and SMEs in a new lens beyond the tradition on the basis of two basic questions: “What is the traditional lending culture between PCBs and SMEs” and “What could be potential role of PCBs to develop that culture where focusing on SME financing to PCBs". This study considered formal SME financing in Bangladesh by focusing on SMEs applying for their first loan. Bangladesh is a member country of ADB. The data collection method is semi-structured and we utilized face-to-face interviews with in-depth branch managers, higher officials and owner-managers of SME customers of PCBs and higher officials of SME Foundation and the Bangladesh central bank. Discourse analysis method was used for data analysis on the frame of thematic discussion fully based on participants’ views. The research found that branch managers and loan officers have a high level of power in assessing and financing decision-making. There is a changing attitude in PCB sector in requiring flexible collateral assets. Branch managers (Loan Officers) consider value of business prospect of owner-mangers as complementary of collateral assets. However, the study found the assessment process of business prospect is entirely unstructured and linked with socio-cultural settings that does not support PCBs’ changing manner in terms of collateral requirement. The study redefined and classified collateral assets to include all financing constructs in a structure. The degree of value of the collateral assets determines the degree of business prospects. This study suggested applying an outside classroom-learning paradigm such as “knowledge tour” to enhance the value of the kinds of collateral assets. This is the scope of PCBs in increasing SMEs’ financing eligibility in win-win basis. The findings and proposition could be effective in other ADB member countries and audiences in the field.

Keywords: CCA, financing, information asymmetry, PCA, PCB, financing

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37 Communicating Safety: A Digital Ethnography Investigating Social Media Use for Workplace Safety

Authors: Kelly Jaunzems

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Social media is a powerful instrument of communication, enabling the presentation of information in multiple forms and modes, amplifying the interactions between people, organisations, and stakeholders, and increasing the range of communication channels available. Younger generations are highly engaged with social media and more likely to use this channel than any other to seek information. Given this, it may appear extraordinary that occupational safety and health professionals have yet to seriously engage with social media for communicating safety messages to younger audiences who, in many industries, might be statistically more likely to encounter more workplace harm or injury. Millennials, defined as those born between 1981-2000, have distinctive characteristics that also impact their interaction patterns rendering many traditional occupational safety and health communication channels sub-optimal or near obsolete. Used to immediate responses, 280-character communication, shares, likes, and visual imagery, millennials struggle to take seriously the low-tech, top-down communication channels such as safety noticeboards, toolbox meetings, and passive tick-box online inductions favoured by traditional OSH professionals. This paper draws upon well-established communication findings, which argue that it is important to know a target audience and reach them using their preferred communication pathways, particularly if the aim is to impact attitudes and behaviours. Health practitioners have adopted social media as a communication channel with great success, yet safety practitioners have failed to follow this lead. Using a digital ethnography approach, this paper examines seven organisations’ Facebook posts from two one-month periods one year apart, one in 2018 and one in 2019. Each of the years informs organisation-based case studies. Comparing, contrasting, and drawing upon these case studies, the paper discusses and evaluates the (non) use of social media communication of safety information in terms of user engagement, shareability, and overall appeal. The success of health practitioners’ use of social media provides a compelling template for the implementation of social media into organisations’ safety communication strategies. Highly visible content such as that found on social media allows an organization to become more responsive and engage in two-way conversations with their audience, creating more engaged and participatory conversations around safety. Further, using social media to address younger audiences with a range of tonal qualities (for example, the use of humour) can achieve cut through in a way that grim statistics fail to do. On the basis of 18 months of interviews, filed work, and data analysis, the paper concludes with recommendations for communicating safety information via social media. It proposes exploration of the social media communication formula that, when utilised by safety practitioners, may create an effective social media presence. It is anticipated that such social media use will increase engagement, expand the number of followers and reduce the likelihood and severity of safety-related incidents. The tools offered may provide a path for safety practitioners to reach a disengaged generation of workers to build a cohesive and inclusive conversation around ways to keep people safe at work.

Keywords: social media, workplace safety, communication strategies, young workers

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36 Multiscale Modelization of Multilayered Bi-Dimensional Soils

Authors: I. Hosni, L. Bennaceur Farah, N. Saber, R Bennaceur

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Soil moisture content is a key variable in many environmental sciences. Even though it represents a small proportion of the liquid freshwater on Earth, it modulates interactions between the land surface and the atmosphere, thereby influencing climate and weather. Accurate modeling of the above processes depends on the ability to provide a proper spatial characterization of soil moisture. The measurement of soil moisture content allows assessment of soil water resources in the field of hydrology and agronomy. The second parameter in interaction with the radar signal is the geometric structure of the soil. Most traditional electromagnetic models consider natural surfaces as single scale zero mean stationary Gaussian random processes. Roughness behavior is characterized by statistical parameters like the Root Mean Square (RMS) height and the correlation length. Then, the main problem is that the agreement between experimental measurements and theoretical values is usually poor due to the large variability of the correlation function, and as a consequence, backscattering models have often failed to predict correctly backscattering. In this study, surfaces are considered as band-limited fractal random processes corresponding to a superposition of a finite number of one-dimensional Gaussian process each one having a spatial scale. Multiscale roughness is characterized by two parameters, the first one is proportional to the RMS height, and the other one is related to the fractal dimension. Soil moisture is related to the complex dielectric constant. This multiscale description has been adapted to two-dimensional profiles using the bi-dimensional wavelet transform and the Mallat algorithm to describe more correctly natural surfaces. We characterize the soil surfaces and sub-surfaces by a three layers geo-electrical model. The upper layer is described by its dielectric constant, thickness, a multiscale bi-dimensional surface roughness model by using the wavelet transform and the Mallat algorithm, and volume scattering parameters. The lower layer is divided into three fictive layers separated by an assumed plane interface. These three layers were modeled by an effective medium characterized by an apparent effective dielectric constant taking into account the presence of air pockets in the soil. We have adopted the 2D multiscale three layers small perturbations model including, firstly air pockets in the soil sub-structure, and then a vegetable canopy in the soil surface structure, that is to simulate the radar backscattering. A sensitivity analysis of backscattering coefficient dependence on multiscale roughness and new soil moisture has been performed. Later, we proposed to change the dielectric constant of the multilayer medium because it takes into account the different moisture values of each layer in the soil. A sensitivity analysis of the backscattering coefficient, including the air pockets in the volume structure with respect to the multiscale roughness parameters and the apparent dielectric constant, was carried out. Finally, we proposed to study the behavior of the backscattering coefficient of the radar on a soil having a vegetable layer in its surface structure.

Keywords: multiscale, bidimensional, wavelets, backscattering, multilayer, SPM, air pockets

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35 Safety of Mesenchymal Stem Cells Therapy: Potential Risk of Spontaneous Transformations

Authors: Katarzyna Drela, Miroslaw Wielgos, Mikolaj Wrobel, Barbara Lukomska

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Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine. Since the initial number of isolated MSCs is limited, in vitro propagation is often required to reach sufficient numbers of cells for therapeutic applications. During long-term culture MSCs may undergo genetic or epigenetic alterations that subsequently increase the probability of spontaneous malignant transformation. Thus, factors that influence genomic stability of MSCs following long-term expansions need to be clarified before cultured MSCs are employed for clinical application. The aim of our study was to investigate the potential for spontaneous transformation of human neonatal cord blood (HUCB-MSCs) and adult bone marrow (BM-MSCs) derived MSCs. Materials and Methods: HUCB-MSCs and BM-MSCs were isolated by standard Ficoll gradient centrifugations method. Isolated cells were initially plated in high density 106 cells per cm2. After 48 h medium were changed and non-adherent cells were removed. The malignant transformation of MSCs in vitro was evaluated by morphological changes, proliferation rate, ability to enter cell senescence, the telomerase expression and chromosomal abnormality. Proliferation of MSCs was analyzed with WST-1 reduction method and population doubling time (PDT) was calculated at different culture stages. Then the expression pattern of genes characteristic for mesenchymal or epithelial cells, as well as transcriptions factors were examined by RT-PCR. Concomitantly, immunocytochemical analysis of gene-related proteins was employed. Results: Our studies showed that MSCs from all bone marrow isolations ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUCB-MSCs from one of the 15 donors displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. In this sample we observed two different cell phenotypes: one mesenchymal-like exhibited spindle shaped morphology and express specific mesenchymal surface markers (CD73, CD90, CD105, CD166) with low proliferation rate, and the second one with round, densely package epithelial-like cells with significantly increased proliferation rate. The PDT of epithelial-like populations was around 1day and 100% of cells were positive for proliferation marker Ki-67. Moreover, HUCB-MSCs showed a positive expression of human telomerase reverse transcriptase (hTERT), cMYC and exhibit increased number of CFU during the long-term culture in vitro. Furthermore, karyotype analysis revealed chromosomal abnormalities including duplications. Conclusions: Our studies demonstrate that HUCB-MSCs are susceptible to spontaneous malignant transformation during long-term culture. Spontaneous malignant transformation process following in vitro culture has enormous effect on the biosafety issues of future cell-based therapies and regenerative medicine regimens.

Keywords: mesenchymal stem cells, spontaneous, transformation, long-term culture

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34 Computational and Experimental Study of the Mechanics of Heart Tube Formation in the Chick Embryo

Authors: Hadi S. Hosseini, Larry A. Taber

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In the embryo, heart is initially a simple tubular structure that undergoes complex morphological changes as it transforms into a four-chambered pump. This work focuses on mechanisms that create heart tube (HT). The early embryo is composed of three relatively flat primary germ layers called endoderm, mesoderm, and ectoderm. Precardiac cells located within bilateral regions of the mesoderm called heart fields (HFs) fold and fuse along the embryonic midline to create the HT. The right and left halves of this plate fold symmetrically to bring their upper edges into contact along the midline, where they fuse. In a region near the fusion line, these layers then separate to generate the primitive HT and foregut, which then extend vertically. The anterior intestinal portal (AIP) is the opening at the caudal end of the foregut, which descends as the HT lengthens. The biomechanical mechanisms that drive this folding are poorly understood. Our central hypothesis is that folding is caused by differences in growth between the endoderm and mesoderm while subsequent extension is driven by contraction along the AIP. The feasibility of this hypothesis is examined using experiments with chick embryos and finite-element modeling (FEM). Fertilized white Leghorn chicken eggs were incubated for approximately 22-33 hours until appropriate Hamburger and Hamilton stage (HH5 to HH9) was reached. To inhibit contraction, embryos were cultured in media containing blebbistatin (myosin II inhibitor) for 18h. Three-dimensional models were created using ABAQUS (D. S. Simulia). The initial geometry consists of a flat plate including two layers representing the mesoderm and endoderm. Tissue was considered as a nonlinear elastic material with growth and contraction (negative growth) simulated using a theory, in which the total deformation gradient is given by F=F^*.G, where G is growth tensor and F* is the elastic deformation gradient tensor. In embryos exposed to blebbistatin, initial folding and AIP descension occurred normally. However, after HFs partially fused to create the upper part of the HT, fusion, and AIP descension stopped, and the HT failed to grow longer. These results suggest that cytoskeletal contraction is required only for the later stages of HT formation. In the model, a larger biaxial growth rate in the mesoderm compared to the endoderm causes the bilayered plate to bend ventrally, as the upper edge moves toward the midline, where it 'fuses' with the other half . This folding creates the upper section of the HT, as well as the foregut pocket bordered by the AIP. After this phase completes by stage HH7, contraction along the arch-shaped AIP pulls the lower edge of the plate downward, stretching the two layers. Results given by model are in reasonable agreement with experimental data for the shape of HT, as well as patterns of stress and strain. In conclusion, results of our study support our hypothesis for the creation of the heart tube.

Keywords: heart tube formation, FEM, chick embryo, biomechanics

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33 A Foucauldian Analysis of Child Play: Case Study of a Preschool in the United States

Authors: Meng Wang

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Historically, young members (children) in the society have been oppressed by adults through direct violent acts. Direct violence was evident in rampant child labor and child maltreatment cases. After acknowledging the rights of children from the United Nations, it is believed in public that children have been protected against direct physical violence. Nevertheless, at present, this paper argues from Foucauldian and disability study standpoints that similar to the old times, children are oppressed objects in the context of child play, which is constructed by adults to substitute direct violence in regulating children. Particularly, this paper suggests that on the one hand, preschool play is a new way that adults adopt to oppress preschoolers and regulate the society as a whole; on the other hand, preschoolers are taught how to play as an acquired skill and master self-regulation through play. There is a line of contemporary research that centers on child play from social constructivism perspective. Yet, current teaching practices pertaining to child play including guided child play and free play, in fact, serve the interest of adults and society at large. By acknowledging and deconstructing the prevalence of 'evidence-based best practice' in early childhood education field within western society, reconstruction of child-adult power relation could be achieved and alternative truth could be found in early childhood education. To support the argument of this paper, an on-going observational case study is conducted in a preschool setting in the United States. Age range of children is 2.5 to 4 years old. Approximately 10 children (5 boys) are participating in this case study. Observation is conducted throughout the weekdays as children follow through the classroom routine with a lead and an assistant teacher. Classroom teachers are interviewed pertaining to their classroom management strategies. Preliminary research finding of this case study suggested that preschool teachers tended to utilize scenarios from preschoolers’ dramatic play to impart core cultural values to young children. These values were pre-determined by adults. In addition, if young children have failed to follow teachers' guidance in terms of playing in a correct way, children ran the risk of being excluded from the play scenario by peers and adults. Furthermore, this study tended to indicate that through child play, preschoolers are obliged to develop an internal violence system, that is self-regulation skill to regulate their own behavior; and if this internal system is unestablished based on various assessments by adults, then potentially there will be consequences of negative labeling and disabling toward young children intended by adults. In conclusion, this paper applies Foucauldian analysis into the context of child play. At present, within preschool, child play is not free as it seems to be. Young children are expected to perform cultural tasks through their play activities designed by adults. Adults utilize child play as technologies of governmentality to further predict and regulate future society at large.

Keywords: child play, developmentally appropriate practice, DAP, poststructuralism, technologies of governmentality

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32 4D Monitoring of Subsurface Conditions in Concrete Infrastructure Prior to Failure Using Ground Penetrating Radar

Authors: Lee Tasker, Ali Karrech, Jeffrey Shragge, Matthew Josh

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Monitoring for the deterioration of concrete infrastructure is an important assessment tool for an engineer and difficulties can be experienced with monitoring for deterioration within an infrastructure. If a failure crack, or fluid seepage through such a crack, is observed from the surface often the source location of the deterioration is not known. Geophysical methods are used to assist engineers with assessing the subsurface conditions of materials. Techniques such as Ground Penetrating Radar (GPR) provide information on the location of buried infrastructure such as pipes and conduits, positions of reinforcements within concrete blocks, and regions of voids/cavities behind tunnel lining. This experiment underlines the application of GPR as an infrastructure-monitoring tool to highlight and monitor regions of possible deterioration within a concrete test wall due to an increase in the generation of fractures; in particular, during a time period of applied load to a concrete wall up to and including structural failure. A three-point load was applied to a concrete test wall of dimensions 1700 x 600 x 300 mm³ in increments of 10 kN, until the wall structurally failed at 107.6 kN. At each increment of applied load, the load was kept constant and the wall was scanned using GPR along profile lines across the wall surface. The measured radar amplitude responses of the GPR profiles, at each applied load interval, were reconstructed into depth-slice grids and presented at fixed depth-slice intervals. The corresponding depth-slices were subtracted from each data set to compare the radar amplitude response between datasets and monitor for changes in the radar amplitude response. At lower values of applied load (i.e., 0-60 kN), few changes were observed in the difference of radar amplitude responses between data sets. At higher values of applied load (i.e., 100 kN), closer to structural failure, larger differences in radar amplitude response between data sets were highlighted in the GPR data; up to 300% increase in radar amplitude response at some locations between the 0 kN and 100 kN radar datasets. Distinct regions were observed in the 100 kN difference dataset (i.e., 100 kN-0 kN) close to the location of the final failure crack. The key regions observed were a conical feature located between approximately 3.0-12.0 cm depth from surface and a vertical linear feature located approximately 12.1-21.0 cm depth from surface. These key regions have been interpreted as locations exhibiting an increased change in pore-space due to increased mechanical loading, or locations displaying an increase in volume of micro-cracks, or locations showing the development of a larger macro-crack. The experiment showed that GPR is a useful geophysical monitoring tool to assist engineers with highlighting and monitoring regions of large changes of radar amplitude response that may be associated with locations of significant internal structural change (e.g. crack development). GPR is a non-destructive technique that is fast to deploy in a production setting. GPR can assist with reducing risk and costs in future infrastructure maintenance programs by highlighting and monitoring locations within the structure exhibiting large changes in radar amplitude over calendar-time.

Keywords: 4D GPR, engineering geophysics, ground penetrating radar, infrastructure monitoring

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31 Modern Architecture and the Scientific World Conception

Authors: Sean Griffiths

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Introduction: This paper examines the expression of ‘objectivity’ in architecture in the context of the post-war rejection of this concept. It aims to re-examine the question in light of the assault on truth characterizing contemporary culture and of the unassailable truth of the climate emergency. The paper analyses the search for objective truth as it was prosecuted in the Modern Movement in the early 20th century, looking at the extent to which this quest was successful in contributing to the development of a radically new, politically-informed architecture and the extent to which its particular interpretation of objectivity, limited that development. The paper studies the influence of the Vienna Circle philosophers Rudolph Carnap and Otto Neurath on the pedagogy of the Bauhaus and the architecture of the Neue Sachlichkeit in Germany. Their logical positivism sought to determine objective truths through empirical analysis, expressed in an austere formal language as part of a ‘scientific world conception’ which would overcome metaphysics and unverifiable mystification. These ideas, and the concurrent prioritizing of measurement as the determinant of environmental quality, became key influences in the socially-driven architecture constructed in the 1920s and 30s by Bauhaus architects in numerous German Cities. Methodology: The paper reviews the history of the early Modern Movement and summarizes accounts of the relationship between the Vienna Circle and the Bauhaus. It looks at key differences in the approaches Neurath and Carnap took to the achievement of their shared philosophical and political aims. It analyses how the adoption of Carnap’s foundationalism influenced the architectural language of modern architecture and compares, through a close reading of the structure of Neurath’s ‘protocol sentences,’ the latter’s alternative approach, speculating on the possibility that its adoption offered a different direction of travel for Modern Architecture. Findings: The paper finds that the adoption of Carnap’s foundationalism, while helping Modern Architecture forge a new visual language, ultimately limited its development and is implicated in its failure to escape the very metaphysics against which it had set itself. It speculates that Neurath’s relational language-based approach to the issue of establishing objectivity has its architectural corollary in the process of revision and renovation that offers new ways an ‘objective’ language of architecture might be developed in a manner that is more responsive to our present-day crisis. Conclusion: The philosophical principles of the Vienna Circle and the architects of the Modern Movement had much in common. Both contributed to radical historical departures which sought to instantiate a world scientific conception in their respective fields, which would attempt to banish mystification and metaphysics and would align itself with socialism. However, in adopting Carnap’s foundationalism as the theoretical basis for the new architecture, Modern Architecture not only failed to escape metaphysics but arguably closed off new avenues of development to itself. The adoption of Neurath’s more open-ended and interactive approach to objectivity offers possibilities for new conceptions of the expression of objectivity in architecture that might be more tailored to the multiple crises we face today.

Keywords: Bauhaus, logical positivism, Neue Sachlichkeit, rationalism, Vienna Circle

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30 Conditionality of Aid as a Counterproductive Factor in Peacebuilding in the Afghan Context

Authors: Karimova Sitora Yuldashevna

Abstract:

The August 2021 resurgence of Taliban as a ruling force in Afghanistan once again challenged the global community into dealing with an unprecedentedly unlike-minded government. To express their disapproval of the new regime, Western governments and intergovernmental institutions have suspended their infrastructural projects and other forms of support. Moreover, the Afghan offshore reserves were frozen, and Afghanistan was disconnected from the international financial system, which impeded even independent aid agencies’ work. The already poor provision of aid was then further complicated with political conditionality. The purpose of this paper is to investigate the efficacy of conditional aid policy in the Afghan peacebuilding under Taliban rule and provide recommendations to international donors on further course of action. Arguing that conditionality of aid is a counterproductive factor in the peacebuilding process, this paper employs scholarly literature on peacebuilding alongside reports from International non-governmental organizations INGOs who operate directly in Afghanistan. The existing debate on peacebuilding in Afghanistan revolves around aid as a means of building democratic foundation for achieving peace on communal and national levels and why the previous attempts to do so were unsuccessful. This paper focuses on how to recalibrate the approach to aid provision and peacebuilding in the new reality. In the early 2000s, amid the weak Post-Cold War international will for a profound engagement in the conflict, humanitarian and development aid became the new means of achieving peace. Aid agencies provided resources directly to communities, minimizing the risk of local disputes. Through subsidizing education, governance reforms, and infrastructural projects, international aid accelerated school enrollment, introduced peace education, funded provincial council and parliamentary elections, and helped rebuild a conflict-torn country.When the Taliban seized power, the international community called on them to build an inclusive government based on respect for human rights, particularly girls’ and women’s schooling and work, as a condition to retain the aid flow. As the Taliban clearly failed to meet the demands, development aid was withdrawn. Some key United Nation agencies also refrained from collaborating with the de-facto authorities. However, contrary to the intended change in Talibs’ behavior, such a move has only led to further deprivation of those whom the donors strived to protect. This is because concern for civilians has always been the second priority for the warring parties. This paper consists of four parts. First, it describes the scope of the humanitarian crisis that began in Afghanistan in 2001. Second, it examines the previous peacebuilding attempts undertaken by the international community and the contribution that the international aid had in the peacebuilding process. Third, the paper describes the current regime and its relationships with the international donors. Finally, the paper concludes with recommendations for donors who would have to be more realistic and reconsider their priorities. While it is certainly not suggested that the Taliban regime is legitimized internationally, the crisis calls upon donors to be more flexible in collaborating with the de-facto authorities for the sake of the civilians.

Keywords: Afghanistan, international aid, donors, peacebuilding

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29 The Role of Uterine Artery Embolization in the Management of Postpartum Hemorrhage

Authors: Chee Wai Ku, Pui See Chin

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As an emerging alternative to hysterectomy, uterine artery embolization (UAE) has been widely used in the management of fibroids and in controlling postpartum hemorrhage (PPH) unresponsive to other therapies. Research has shown UAE to be a safe, minimally invasive procedure with few complications and minimal effects on future fertility. We present two cases highlighting the use of UAE in preventing PPH in a patient with a large fibroid at the time of cesarean section and in the treatment of secondary PPH refractory to other therapies in another patient. We present a 36-year primiparous woman who booked at 18+6 weeks gestation with a 13.7 cm subserosal fibroid at the lower anterior wall of the uterus near the cervix and a 10.8 cm subserosal fibroid in the left wall. Prophylactic internal iliac artery occlusion balloons were placed prior to the planned classical midline cesarean section. The balloons were inflated once the baby was delivered. Bilateral uterine arteries were embolized subsequently. The estimated blood loss (EBL) was 400 mls and hemoglobin (Hb) remained stable at 10 g/DL. Ultrasound scan 2 years postnatally showed stable uterine fibroids 10.4 and 7.1 cm, which was significantly smaller than before. We present the second case of a 40-year-old G2P1 with a previous cesarean section for failure to progress. There were no antenatal problems, and the placenta was not previa. She presented with term labour and underwent an emergency cesarean section for failed vaginal birth after cesarean. Intraoperatively extensive adhesions were noted with bladder drawn high, and EBL was 300 mls. Postpartum recovery was uneventful. She presented with secondary PPH 3 weeks later complicated by hypovolemic shock. She underwent an emergency examination under anesthesia and evacuation of the uterus, with EBL 2500mls. Histology showed decidua with chronic inflammation. She was discharged well with no further PPH. She subsequently returned one week later for secondary PPH. Bedside ultrasound showed that the endometrium was thin with no evidence of retained products of conception. Uterotonics were administered, and examination under anesthesia was performed, with uterine Bakri balloon and vaginal pack insertion after. EBL was 1000 mls. There was no definite cause of PPH with no uterine atony or products of conception. To evaluate a potential cause, pelvic angiogram and super selective left uterine arteriogram was performed which showed profuse contrast extravasation and acute bleeding from the left uterine artery. Superselective embolization of the left uterine artery was performed. No gross contrast extravasation from the right uterine artery was seen. These two cases demonstrated the superior efficacy of UAE. Firstly, the prophylactic use of intra-arterial balloon catheters in pregnant patients with large fibroids, and secondly, in the diagnosis and management of secondary PPH refractory to uterotonics and uterine tamponade. In both cases, the need for laparotomy hysterectomy was avoided, resulting in the preservation of future fertility. UAE should be a consideration for hemodynamically stable patients in centres with access to interventional radiology.

Keywords: fertility preservation, secondary postpartum hemorrhage, uterine embolization, uterine fibroids

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28 Interactively Developed Capabilities for Environmental Management Systems: An Exploratory Investigation of SMEs

Authors: Zhuang Ma, Zihan Zhang, Yu Li

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Environmental concerns from stakeholders (e.g., governments & customers) have pushed firms to integrate environmental management systems into business processes such as R&D, manufacturing, and marketing. Environmental systems include managing environmental risks and pollution control (e.g., air pollution control, waste-water treatment, noise control, energy recycling & solid waste treatment) through raw material management, the elimination and reduction of contaminants, recycling, and reuse in firms' operational processes. Despite increasing studies on firms' proactive adoption of environmental management, their focus is primarily on large corporations operating in developed economies. Investigations in the environmental management efforts of small and medium-sized enterprises (SMEs) are scarce. This is problematic for SMEs because, unlike large corporations, SMEs have limited awareness, resources, capabilities to adapt their operational routines to address environmental impacts. The purpose of this study is to explore how SMEs develop organizational capabilities through interactions with business partners (e.g., environmental management specialists & customers). Drawing on the resource-based view (RBV) and an organizational capabilities perspective, this study investigates the interactively developed capabilities that allow SMEs to adopt environmental management systems. Using an exploratory approach, the study includes 12 semi-structured interviews with senior managers from four SMEs, two environmental management specialists, and two customers in the pharmaceutical sector in Chongqing, China. Findings of this study include four key organizational capabilities: 1) ‘dynamic marketing’ capability, which allows SMEs to recoup the investments in environmental management systems by developing environmentally friendly products to address customers' ever-changing needs; 2) ‘process improvement’ capability, which allows SMEs to select and adopt the latest technologies from biology, chemistry, new material, and new energy sectors into the production system for improved environmental performance and cost-reductions; and 3) ‘relationship management’ capability which allows SMEs to improve corporate image among the public, social media, government agencies, and customers, who in turn help SMEs to overcome their competitive disadvantages. These interactively developed capabilities help SMEs to address larger competitors' foothold in the local market, reduce market constraints, and exploit competitive advantages in other regions (e.g., Guangdong & Jiangsu) of China. These findings extend the RBV and organizational capabilities perspective; that is, SMEs can develop the essential resources and capabilities required for environmental management through interactions with upstream and downstream business partners. While a limited number of studies did highlight the importance of interactions among SMEs, customers, suppliers, NGOs, industrial associations, and consulting firms, they failed to explore the specific capabilities developed through these interactions. Additionally, the findings can explain how a proactive adoption of environmental management systems could help some SMEs to overcome the institutional and market restraints on their products, thereby springboarding into larger, more environmentally demanding, yet more profitable markets compared with their existing market.

Keywords: capabilities, environmental management systems, interactions, SMEs

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27 Capability of a Single Antigen to Induce Both Protective and Disease Enhancing Antibody: An Obstacle in the Creation of Vaccines and Passive Immunotherapies

Authors: Parul Kulshreshtha, Subrata Sinha, Rakesh Bhatnagar

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This study was conducted by taking B. anthracis as a model pathogen. On infecting a host, B. anthracis secretes three proteins, namely, protective antigen (PA, 83kDa), edema factor (EF, 89 kDa) and lethal factor (LF, 90 kDa). These three proteins are the components of two anthrax toxins. PA binds to the cell surface receptors, namely, tumor endothelial marker (TEM) 8 and capillary morphogenesis protein (CMG) 2. TEM8 and CMG2 interact with LDL-receptor related protein (LRP) 6 for endocytosis of EF and LF. On entering the cell, EF acts as a calmodulin-dependent adenylate cyclase that causes a prolonged increase of cytosolic cyclic adenosine monophosphate (cAMP). LF is a metalloprotease that cleaves most isoforms of mitogen-activated protein kinase kinases (MAPKK/MEK) close to their N-terminus. By secreting these two toxins, B.anthracis ascertains death of the host. Once the systemic levels of the toxins rise, antibiotics alone cannot save the host. Therefore, toxin-specific inhibitors have to be developed. In this wake, monoclonal antibodies have been developed for the neutralization of toxic effects of anthrax toxins. We created hybridomas by using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor of B. anthracis) to obtain anti-toxin antibodies. Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immunized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies from all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H8 and H10) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). The protective efficacy of H7, H8, H10 and H11 was investigated. H7, H8 and H10 were found to be protective. H11 was found to have disease enhancing characteristics in-vitro and in mouse model of challenge with B. anthracis. In this study the disease enhancing character of H11 monoclonal antibody and anti-rLFn polyclonal sera was investigated. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature both in-vitro and in-vivo. But combination of H11 with LETscFv (an scFv with VH and VL identical to H10 but lacking Fc region) could not abrogate the disease-enhancing character of H11 mAb. Therefore it was concluded that for suppression of disease enhancement, Fc portion was absolutely essential for interaction of H10 with H11. Our study indicates that the protective potential of an antibody depends equally on its idiotype/ antigen specificity and its isotype. A number of monoclonal and engineered antibodies are being explored as immunotherapeutics but it is absolutely essential to characterize each one for their individual and combined protective potential. Although new in the sphere of toxin-based diseases, it is extremely important to characterize the disease-enhancing nature of polyclonal as well as monoclonal antibodies. This is because several anti-viral therapeutics and vaccines have failed in the face of this phenomenon. The passive –immunotherapy thus needs to be well formulated to avoid any contraindications.

Keywords: immunotherapy, polyclonal, monoclonal, antibody-dependent disease enhancement

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