Search results for: systemic lupus erythematoses

Authors: Jothilakshmy Nagammal

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This research paper deals with the different case studies, where the Form-Based Codes are adopted in general and the different implementation methods in particular are discussed to develop a method for formulating a new planning model. The organizing principle of the Form-Based Codes, the transect is used to zone the city into various context specific transects. An approach is adopted to develop the new planning model, city Specific Planning Model (CSPM), as a tool to achieve sustainability for any city in general. A case study comparison method in terms of the planning tools used, the code process adopted and the various control regulations implemented in thirty two different cities are done. The analysis shows that there are a variety of ways to implement form-based zoning concepts: Specific plans, a parallel or optional form-based code, transect-based code /smart code, required form-based standards or design guidelines. The case studies describe the positive and negative results from based zoning, Where it is implemented. From the different case studies on the method of the FBC, it is understood that the scale for formulating the Form-Based Code varies from parts of the city to the whole city. The regulating plan is prepared with the organizing principle as the transect in most of the cases. The various implementation methods adopted in these case studies for the formulation of Form-Based Codes are special districts like the Transit Oriented Development (TOD), traditional Neighbourhood Development (TND), specific plan and Street based. The implementation methods vary from mandatory, integrated and floating. To attain sustainability the research takes the approach of developing a regulating plan, using the transect as the organizing principle for the entire area of the city in general in formulating the Form-Based Codes for the selected Special Districts in the study area in specific, street based. Planning is most powerful when it is embedded in the broader context of systemic change and improvement. Systemic is best thought of as holistic, contextualized and stake holder-owned, While systematic can be thought of more as linear, generalisable, and typically top-down or expert driven. The systemic approach is a process that is based on the system theory and system design principles, which are too often ill understood by the general population and policy makers. The system theory embraces the importance of a global perspective, multiple components, interdependencies and interconnections in any system. In addition, the recognition that a change in one part of a system necessarily alters the rest of the system is a cornerstone of the system theory. The proposed regulating plan taking the transect as an organizing principle and Form-Based Codes to achieve sustainability of the city has to be a hybrid code, which is to be integrated within the existing system - A Systemic Approach with a Systematic Process. This approach of introducing a few form based zones into a conventional code could be effective in the phased replacement of an existing code. It could also be an effective way of responding to the near-term pressure of physical change in “sensitive” areas of the community. With this approach and method the new Context Specific Planning Model is created towards achieving sustainability is explained in detail this research paper.

Keywords: context based planning model, form based code, transect, systemic approach

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Authors: Ravi R. Patel, Vasudev R. Thakkar

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Use of plant growth-promoting rhizobacteria (PGPR) to increase the production and decrees disease occurrence is a recent method in agriculture. An RA2 rhizospheric culture was isolated from peanut rhizosphere from Junagadh region of Gujarat, India and showed different direct and indirect plant growth promoting activity like indole acetic acid, gibberellic acid, siderophore, hydrogen cyanide, Ammonia and (1-Aminocyclopropane-1-Carboxylate) deaminase production, N2 fixation, phosphate and potassium solubilization in vitro. RA2 was able to protect peanut germinating seedling from A. niger infection and reduce collar rot disease incidence 60-35% to 72-41% and increase germination percentage from 70-82% to 75-97% in two varieties GG20 and GG2 of peanut. RA2 was found to induce resistance in A. hypogaea L. seedlings via induction of different defense-related enzymes like phenylalanine ammonia lyase, peroxidase, polyphenol oxidase, lipoxygenase and pathogenesis related protein like chitinase, ß – 1,3- glucanase. Jasmonic acid one of the major signaling molecules of inducing systemic resistance was also found to induced due to RA2 treatments. RA2 bacterium was also promoting peanut growth and reduce A. niger infection in pot studies. 16S rDNA sequence of RA2 showed 99 % homology to Azotobacter species.

Keywords: plant growth promoting rhizobacteria, peanut, aspergillus niger, induce systemic resistance

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Authors: Mostafa A. Amer, I. A. El-Samra, I. I. Abou-ElSeoud, S. M. El-Abd, N. K. Shawertamimi

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Tomato Fusarium wilt disease caused by Fusarium oxysporum f. sp. Lycopercisi (FOL) is considered one of the most destructive diseases in Egypt. Effect of some biotic inducers such as Bacillus megaterium var. phosphaticum, Glomus intraradices and Glomus macrocarpum at seven different mixed treatments, was tested for their ability to induce resistance in tomato plants against the disease. According to pathogenicity tests, all the tested isolates of FOL showed wilt symptoms on both of the tested cultivars; however, they considerably varied in percentages of disease incidence (DI) and disease severity (DS). Castle Rock was more susceptible than Peto 86, which was relatively resistant. Pretreatment of both cultivars, under greenhouse conditions, with the tested biotic inducers alone or in combination with each other's, significantly increased the induction of chitinase, β-1,3-glucanase, peroxidase, and polyphenoloxidase and reduced disease incidence and severity, compared with untreated noninoculated (C1) and untreated inoculated (C2) controls. Application of a combination of BMP, with GI and GM was the most effective in increasing the induction rated of the tested enzymes, compared with the other treatments. Induction of enzymes in most of the tested bioinducers treatments gradually increased, attaining maximum values after 48 or/and 72 hrs after challenging with FOL, then gradually declined. GI was the least effective bioinducer.

Keywords: F. oxysporum f. sp. lycopersici, defense enzymes, induced systemic resistance, ISR, B. megaterium var. phosphaticum, G. macrocarpum, G. intraradices

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Authors: Ronal Muresano, Andrea Pagano

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Nowadays, the mathematical/statistical applications are developed with more complexity and accuracy. However, these precisions and complexities have brought as result that applications need more computational power in order to be executed faster. In this sense, the multicore environments are playing an important role to improve and to optimize the execution time of these applications. These environments allow us the inclusion of more parallelism inside the node. However, to take advantage of this parallelism is not an easy task, because we have to deal with some problems such as: cores communications, data locality, memory sizes (cache and RAM), synchronizations, data dependencies on the model, etc. These issues are becoming more important when we wish to improve the application’s performance and scalability. Hence, this paper describes an optimization method developed for Systemic Model of Banking Originated Losses (SYMBOL) tool developed by the European Commission, which is based on analyzing the application's weakness in order to exploit the advantages of the multicore. All these improvements are done in an automatic and transparent manner with the aim of improving the performance metrics of our tool. Finally, experimental evaluations show the effectiveness of our new optimized version, in which we have achieved a considerable improvement on the execution time. The time has been reduced around 96% for the best case tested, between the original serial version and the automatic parallel version.

Keywords: algorithm optimization, bank failures, OpenMP, parallel techniques, statistical tool

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Authors: Jitendra Aswani

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In the first section of this study, impact of Global Financial Crisis (GFC) on the synchronization of fourteen Asian Stock Markets (ASM’s) of countries like Hong Kong, India, Thailand, Singapore, Taiwan, Pakistan, Bangladesh, South Korea, Malaysia, Indonesia, Japan, China, Philippines and Sri Lanka, has been analysed using the network science and its metrics like degree of node, clustering coefficient and network density. Then in the second section of this study by introducing the US stock market in existing network and developing a Minimum Spanning Tree (MST) spread of crisis from the US stock market to Asian Stock Markets (ASM) has been explained. Data used for this study is adjusted the closing price of these indices from 6th January, 2000 to 15th September, 2013 which further divided into three sub-periods: Pre, during and post-crisis. Using network analysis, it is found that Asian stock markets become more interdependent during the crisis than pre and post crisis, and also Hong Kong, India, South Korea and Japan are systemic important stock markets in the Asian region. Therefore, failure or shock to any of these systemic important stock markets can cause contagion to another stock market of this region. This study is useful for global investors’ in portfolio management especially during the crisis period and also for policy makers in formulating the financial regulation norms by knowing the connections between the stock markets and how the system of these stock markets changes in crisis period and after that.

Keywords: global financial crisis, Asian stock markets, network science, Kruskal algorithm

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Authors: Ping-Lun Jiang, Hung-Jun Lin, Shen-Fu Lin, Mei-Yin Chien, Ting-Wei Li, Chun-Han Lin, Der-Zen Liu

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Mucosal vaccine induces both mucosal (secretory IgA) and systemic immune responses and it is considered an ideal vaccination strategy for prevention of infectious diseases. One important point to be considered in mucosal vaccination is effective antigen delivery system which can manage effective delivery of antigen to antigen-presenting cells (APCs) of mucosal. In the present study, cationic gelatin nanoparticles were prepared as ideal carriers for more efficient antigen delivery. The average diameter of cationic gelatin nanoparticle was approximate 190 nm, and the zeta potential was about +45 mV, then ovalbumin (OVA) was physically absorbed onto cationic gelatin nanoparticle. The OVA absorption rate was near 95% the zeta potential was about +20 mV. We show that cationic gelatin nanoparticle effectively facilitated antigen uptake by mice bone marrow-derived dendritic cells (mBMDCs) and RAW264.7 cells and induced higher levels of pro-inflammatory cytokines. C57BL/6 mice twice immunized intranasally with OVA-absorbed cationic gelatin nanoparticle induced high levels of OVA-specific IgG in the serum and IgA in their in the nasal and lung wash fluid. These results indicate that nasal administration of cationic gelatin nanoparticles induced both mucosal and systemic immune responses and cationic gelatin nanoparticles might be a potential antigen delivery carrier for further clinical applications.

Keywords: antigen delivery, antigen-presenting cells, gelatin nanoparticle, mucosal vaccine

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Authors: Christopher Leung, Guillermo Becerril-Martinez

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Amyloidosis is a rare systemic disease where abnormal proteins invade various organs and impede their function. Occasionally, they can manifest in a solidary organ such as the heart, lung, and nervous systems; rarely do they manifest in the gallbladder. Diagnosis often requires biopsy of the affected area and histopathology shows deposition of abnormally folded globular proteins called amyloid proteins. This case presents a 69-year-old male with a 3-month history of RUQ pain, diarrhea and non-specific symptoms of tiredness, etc. On imaging, both his US and CT abdomen showed gallbladder wall thickening and pericholecystic fluid, which may represent acute cholecystitis with hypodense lesions around the gallbladder, possibly representing liver abscesses. Given his symptoms of abdominal pain and imaging findings, this gentleman eventually had a laparoscopic cholecystectomy showing a gangrenous gallbladder with a mass on the liver bed. On histopathology, it showed amorphous hyaline eosinophilic material, which Congo-stained confirmed amyloidosis. Amyloidosis explained his non-specific symptoms, he avoided further biopsy, and he was commenced immediately on Lenalidomide. Involvement of the gallbladder is extremely rare, with less than 30 cases around the world. Half of the cases are reported as primary amyloidosis. This case adds to the current literature regarding primary gallbladder amyloidosis. Importantly, this case highlights how laparoscopic cholecystectomy can help with the diagnosis of gallbladder amyloidosis.

Keywords: amyloidosis, cholecystitis, gangrenous cholecystitis, gallbladder, systemic amyloidosis

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Authors: Murniwati, Nurul Khairiyah, Putri Ovieza Maizar

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The association between general and oral health is clearly important, particularly in adults with medical conditions. Many of the medical systemic conditions are either caused or aggravated by poor oral hygiene and vice versa. Hypertension is one of common medical systemic problem which has been a public health concern worldwide due to its known consequences. Those consequences must be related to oral health status as well, whether it may cause or worsen the oral health conditions. The objective of this study was to find out the association between hypertension and oral health status in adults. This study was an analytical observational study by using cross-sectional method. A total of 42 adults both male and female in Padusunan Village, Pariaman, West Sumatra, Indonesia were selected as subjects by using purposive sampling. Manual sphygmomanometer was used to measure blood pressure and dental examination was performed to calculate the decayed, missing, and filled teeth (DMFT) scores in order to represent oral health status. The data obtained was analyzed statistically using One Way ANOVA to determine the association between hypertensive adults and their oral health status. The result showed that majority age of the subjects was ranging from 51-70 years (40.5%). Based on blood pressure examination, 57.1% of subjects were classified to prehypertension. Overall, the mean of DMFT score calculated in normal, prehypertension and hypertension group was not considered statistically significant. There was no significant association (p>0.05) between hypertension and oral health status in adults.

Keywords: blood pressure, hypertension, DMFT, oral health status

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Authors: Mustafa M. Donma, Orkide Donma

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A growing list of cancers might be influenced by obesity. Obesity is associated with an increased risk for the occurrence and development of some cancers. Inflammation can lead to cancer. It is one of the characteristic features of cancer and plays a critical role in cancer development. C-reactive protein (CRP) is under evaluation related to the new and simple prognostic factors in patients with metastatic renal cell cancer. Obesity can predict and promote systemic inflammation in healthy adults. BMI is correlated with hs-CRP. In this study, SII index and CRP values were evaluated in children with normal BMI and those within the range of different obesity grades to detect the tendency towards cancer in pediatric obesity. A total of one hundred and ninety-four children; thirty-five children with normal BMI, twenty overweight (OW), forty-seven obese (OB) and ninety-two morbid obese (MO) participated in the study. Age- and sex-matched groups were constituted using BMI-for age percentiles. Informed consent was obtained. Ethical Committee approval was taken. Weight, height, waist circumference (C), hip C, head C and neck C of the children were measured. The complete blood count test was performed. C-reactive protein analysis was performed. Statistical analyses were performed using SPSS. The degree for statistical significance was p≤0.05. SII index values were progressively increasing starting from normal weight (NW) to MO children. There is a statistically significant difference between NW and OB as well as MO children. No significant difference was observed between NW and OW children, however, a correlation was observed between NW and OW children. MO constitutes the only group, which exhibited a statistically significant correlation between SII index and CRP. Obesity-related bladder, kidney, cervical, liver, colorectal, endometrial cancers are still being investigated. Obesity, characterized as a chronic low-grade inflammation, is a crucial risk factor for colon cancer. Elevated childhood BMI values may be indicative of processes leading to cancer, initiated early in life. Prevention of childhood adiposity may decrease the cancer incidence in adults. To authors’ best knowledge, this study is the first to introduce SII index values during obesity of varying degrees of severity. It is suggested that this index seems to affect all stages of obesity with an increasing tendency and may point out the concomitant status of obesity and cancer starting from very early periods of life.

Keywords: children, C-reactive protein, systemic immune-inflammation index, obesity

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Authors: Cunyu Zhang

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Through literature review about studies related to tense, it is found that there exist disagreements on the definition and existence of Chinese tense. Influenced by some researches on English language which regard tense as a grammatical category based on the verbal inflections of English, some Chinese researchers claim that there is no tense in Chinese language as there are no verbal inflections involved. Meanwhile, other Chinese researchers hold that Chinese still has tense although its verbs are non-inflectional based on the fact that Chinese lexical expressions can imply temporal meaning. We assume that the reasons for the above disagreements in terms of Chinese tense lie in the fact that all the previous studies prefer to view language “from the below” which means expressions of tense are the core part of these studies. However, there are about 6,000 languages with distinct expressions all over the world. Hence, if the language studies only concentrate on expressions, it must become more difficult to understand the nature of language. By contrast, functions of languages are similar; otherwise, the human beings could not communicate with each other. Therefore, we believe that it is necessary for us to have a theoretical study on Chinese tense within the framework of SFL which holds that language is a system where meaning is the core part while form is just the realization of meaning. In addition, SFL is a general linguistic providing a universal framework for languages all over the world. Therefore, based on Systemic Functional Linguistics, the paper firstly redefines tense as a deictic semantic category for describing the speaker’s temporal location of processes and relevant temporal relations. With reference to this definition, this study explores the meaning system of tense. It is proposed that tense expresses four kinds of meaning, namely interpersonal, experiential, logical and textual meanings. From the interpersonal angle, tense helps to exchange temporal information between the speaker and the listener, and the temporal information refers to the anchoring of a concerned process in the past, present or future by the speaker. From the experiential angle, tense plays a role in the temporal locating of material, mental, relational, existential, behavioral and verbal processes by the speaker. From the logical angle, tense denotes the temporal relations at the two levels of clause and clause complex, and such relations fall into simultaneity, anteriority and posteriority. From the textual angle, tense refers to the temporal relations at the level of text, and the temporal relations in question concern linear serial relations and synchronous serial relations.

Keywords: Chinese, meaning system, Systemic Functional Linguistics, tense

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Authors: D. M. El-Tanbouly, R. M. Abdelsalam, A. S. Attia, M. T. Abdel-Aziz

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Lipopolysaccharide (LPS) endotoxin, a component of the outer membrane of Gram-negative bacteria, is involved in the pathogenesis of sepsis. LPS administration induces systemic inflammation that mimics many of the initial clinical features of sepsis and has deleterious effects on several organs including the liver and eventually leading to septic shock and death. The present study aimed to investigate the protective effect of magnesium, a well-known cofactor in many enzymatic reactions and a critical component of the antioxidant system, on hepatic damage associated with LPS induced- endotoxima in mice. Mg (20 and 40 mg/kg, po) was administered for 7 consecutive days. Systemic inflammation was induced one hour after the last dose of Mg by a single dose of LPS (2 mg/kg, ip) and three hours thereafter plasma was separated, animals were sacrificed and their livers were isolated. LPS-treated mice suffered from hepatic dysfunction revealed by histological observation, elevation in plasma transaminases activities, C-reactive protein content and caspase-3, a critical marker of apoptosis. Liver inflammation was evident by elevation in liver cytokines contents (TNF-α and IL-10) and myeloperoxidase (MPO) activity. Additionally, oxidative stress was manifested by increased liver lipoperoxidation, glutathione depletion, elevated total nitrate/nitrite (NOx) content and glutathione peroxidase (GPx) activity. Pretreatment with Mg largely mitigated these alternations through its anti-inflammatory and antioxidant potentials. Mg, therefore, could be regarded as an effective strategy for prevention of liver damage associated with septicemia.

Keywords: LPS, liver damage, magnesium, septicemia

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Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

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Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

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Authors: Tas Yong Koh, Steve Rowlinson, Yuzhong Shen

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In construction safety management, safety climate has long been linked to workers' safety behaviors and performance. For this reason, safety climate concept and tools have been used as heuristics to diagnose a range of safety-related issues by some progressive contractors in Hong Kong and elsewhere. However, as a diagnostic tool, safety climate tends to treat the different components of the climate construct in a linear fashion. Safety management in construction projects, in reality, is a multi-faceted and multilevel phenomenon that resembles a complex system. Hence, understanding safety management in construction projects requires not only the understanding of safety climate but also the organizational-systemic nature of the phenomenon. Our involvement, diagnoses, and interpretations of a range of safety climate-related issues which culminated in the project’s sub-optimum safety performance in an infrastructure construction project have brought about such revelation. In this study, a range of data types had been collected from various hierarchies of the project site organization. These include the frontline workers and supervisors from the main and sub-contractors, and the client supervisory personnel. Data collection was performed through the administration of safety climate questionnaire, interviews, observation, and document study. The findings collectively indicate that what had emerged in parallel of the seemingly linear climate-based exploration is the exposition of the organization-systemic nature of the phenomenon. The results indicate the negative impacts of climate perceptions mismatch, insufficient work planning, and risk management, mixed safety leadership, workforce negative attributes, lapsed safety enforcement and resources shortages collectively give rise to the project sub-optimum safety performance. From the dynamic causation and multilevel perspective, the analyses show that the individual, group, and organizational levels issues are interrelated and these interrelationships are linked to negative safety climate. Hence the adoption of both perspectives has enabled a fuller understanding of the phenomenon of safety management that point to the need for an organizational-systemic intervention strategy. The core message points to the fact that intervention at an individual level will only meet with limited success if the risks embedded in the higher levels in group and project organization are not addressed. The findings can be used to guide the effective development of safety infrastructure by linking different levels of systems in a construction project organization.

Keywords: construction safety management, dynamic causation, multilevel analysis, safety climate

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Authors: Rania Al Namara

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During the Covid-19 pandemic, women disproportionately left the workforce compared to men, and many remained outside of the labor market during the Covid-19 recovery period—a phenomenon referred to as the “she-recession” or “shecession.” While the number of women returning to work has increased, long-standing systemic inequalities interfere with women's equal participation in the workforce. Previous research on media framing has explored the importance of news coverage of women’s issues in print and magazines to shaping the public’s views on an issue and the national response. This study adopts textual analysis to examine how 50 news stories published on CNN and CBS in March 2023 frame women’s employment challenges as a matter of choice or as a matter of insufficient systems and analyzes the narratives portrayed to understand how this discourse affects national policies regarding women’s equality in the workforce. Findings suggest that media coverage centers on four themes: unequal wages at work, work-life integration, experiences of minority women, and the struggle to acquire leadership positions. Media coverage gives space to women to tell personal stories about facing these four societal challenges. However, little coverage is devoted to the political figures and institutions that either reinforce gender inequalities or advance women’s rights in these areas. These findings highlight the need for media stories that discuss policies and reforms that broaden the choices available to women in the first place.

Keywords: Covid-19 recovery, media coverage, shecession, women’s employment

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

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Abstract Objectives. Rituximab (RTX) shown a positive effect in the treatment of systemic sclerosis (SSc). But there is still not enough data on comparing the effectiveness of RTX with immunosuppressants (IS). The aim of our study was to compare changes of lung function and skin score in SSc between two groups of patients (pts) - on RXT therapy (prescribed after ineffectiveness of previous therapy with IS) and on therapy with IS only. Methods. This study included 103 pts received RTX as an addition to previous therapy (group 1) and 65 pts received therapy with IS and prednisolone (group 2). The mean follow-up period was 12.6±10.7months. In group 1 the mean age was 47±12.9 years, female – 88 pts (84%), the diffuse cutaneous subset of the disease had 55 pts (53%). The mean disease duration was 6.2±5.5 years. 82% pts had interstitial lung disease (ILD) and 92% were positive for ANA, 67% of them were positive for antitopoisomerase-1. All pts received prednisolone at a dose of 11.3±4.5 mg/day, IS at inclusion received 47% of them. The cumulative mean dose of RTX was 1.7±0.6 g. In group 2 the mean age was 50.8±13.8 years, female-53 pts (82%), the diffuse cutaneous subset of the disease had 44 pts (68%). The mean disease duration was 8.8±7.7 years. 81% pts had ILD and 88% were positive for ANA, 58% of them were positive for antitopoisomerase-1. All pts received prednisolone at a dose of 8.69±4.28 mg/day, IS received 57% of them. Cyclophosphamide (CP) received 45% of pts. The cumulative mean dose of CP was 10.2±15.1g. D-penicillamine received 30% of pts. Other pts was on mycophenolate mofetil or methotrexate therapy in single cases. The pts of the compared groups did not differ in the main demographic and clinical parameters. The results are presented as delta (Δ) - difference between the baseline parameter and follow up point. Results. In group 1 there was an improvement of all outcome parameters: increased of forced vital capacity, % predicted - ΔFVC=4% (p=0.0004); Diffusing capacity for carbon monoxide, % predicted remained stable (ΔDLCO=0.1%); improvement of the Rodnan skin score-ΔmRss=3.4 (p=0.001); decrease of Activity index (EScSG-AI) - ΔActivity index=1.7 (p=0.001). In group 2 the changes was insignificant: ΔFVC=-2.3%, ΔmRss=0.87, ΔActivity index=0.3. But there was a significant decrease of DLCO: ΔDLCO=-5.1% (p=0.001). Conclusion. The results of our study confirm the data on the positive effect of RTX in complex therapy in pts with SSc (decrease of skin induration, increase of FVC, stabilization of DLCO). Meantime, pts on IS and prednisolone therapy shown the worsening of lung function and insignificant changes of other clinical parameters. RTX could be considered as a more effective option in complex treatment of SSc in comparison with IS therapy

Keywords: immunosuppressants, interstitial lung disease, systemic sclerosis, rituximab

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Authors: Elaine Y. L. Ng

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Elizabeth Gilbert’s (2006) biography Eat, Pray, Love describes her travels to Italy, India, and Indonesia after a painful divorce. The author’s experiences with love, loss, search for happiness, and meaning have resonated with a huge readership. As regards the translation of Gilbert’s (2006) Eat, Pray, Love into Chinese, it was first translated by a Taiwanese translator He Pei-Hua and published in Taiwan in 2007 by Make Boluo Wenhua Chubanshe with the fairly catching title “Enjoy! Traveling Alone.” The same translation was translocated to China, republished in simplified Chinese characters by Shanxi Shifan Daxue Chubanshe in 2008 and renamed in China, entitled “To Be a Girl for the Whole Life.” Later on, the same translation in simplified Chinese characters was reprinted by Hunan Wenyi Chubanshe in 2013. This study employs Munday’s (2002) systemic model for descriptive translation studies to investigate the translation of Gilbert’s (2006) Eat, Pray, Love into Chinese by the Taiwanese translator Hu Pei-Hua. It employs an interdisciplinary approach, combining systemic functional linguistics and corpus stylistics with sociohistorical research within a descriptive framework to study the translator’s discursive presence in the text. The research consists of three phases. The first phase is to locate the target text within its socio-cultural context. The target-text context concerning the para-texts, readers’ responses, and the publishers’ orientation will be explored. The second phase is to compare the source text and the target text for the categorization of translation shifts by using the methodological tools of systemic functional linguistics and corpus stylistics. The investigation concerns the rendering of mental clauses and speech and thought presentation. The final phase is an explanation of the causes of translation shifts. The linguistic findings are related to the extra-textual information collected in an effort to ascertain the motivations behind the translator’s choices. There exist sets of possible factors that may have contributed to shaping the textual features of the given translation within a specific socio-cultural context. The study finds that the translator generally reproduces the mental clauses and speech and thought presentation closely according to the original. Nevertheless, the language of the translation has been widely criticized to be unidiomatic and stiff, losing the elegance of the original. In addition, the several Chinese translations of the given text produced by one Taiwanese and two Chinese publishers are basically the same. They are repackaged slightly differently, mainly with the change of the book cover and its captions for each version. By relating the textual findings to the extra-textual data of the study, it is argued that the popularity of the Chinese translation of Gilbert’s (2006) Eat, Pray, Love may not be attributed to the quality of the translation. Instead, it may have to do with the way the work is promoted strategically by the social media manipulated by the four e-bookstores promoting and selling the book online in China.

Keywords: chinese translation of eat pray love, corpus stylistics, motivations for translation shifts, systemic approach to translation studies

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Authors: Leonardo C. Pacheco-Londoño, Nataly J. Galan-Freyle, Lisandro Pacheco-Lugo, Antonio Acosta, Elkin Navarro, Gustavo Aroca-Martínez, Karin Rondón-Payares, Samuel P. Hernández-Rivera

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In our Life Science Research Center of the University Simon Bolivar (LSRC), one of the focuses is the diagnosis and prognosis of different diseases; we have been implementing the use of gold nanoparticles (Au-NPs) for various biomedical applications. In this case, Au-NPs were used for Surface-Enhanced Raman Spectroscopy (SERS) in different diseases' diagnostics, such as Lupus Nephritis (LN), hypertension (H), preeclampsia (PC), and others. This methodology is proposed for the diagnosis of each disease. First, good signals of the different metabolites by SERS were obtained through a mixture of urine samples and Au-NPs. Second, PLS-DA models based on SERS spectra to discriminate each disease were able to differentiate between sick and healthy patients with different diseases. Finally, the sensibility and specificity for the different models were determined in the order of 0.9. On the other hand, a second methodology was developed using machine learning models from all data of the different diseases, and, as a result, a discriminant spectral map of the diseases was generated. These studies were possible thanks to joint research between two university research centers and two health sector entities, and the patient samples were treated with ethical rigor and their consent.

Keywords: SERS, Raman, PLS-DA, diseases

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Authors: Venkatalakshmi Ranganathan, Ong Hsin Ju, Tan Yinn Ming, Lim Kien Sin, Wong Man Ting, Venkata Srikanth Meka

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The mucoadhesive buccal tablet is an oral drug delivery system which attached to the buccal surface for direct drug absorption into the systemic circulation and the unidirectional drug release is ensured by formulating a hydrophobic backing layer. The objective of present study was to formulate mucoadhesive atenolol bilayer buccal tablets by using sodium alginate, hydroxyethyl cellulose, and xanthan gum as mucoadhesive polymer and the technique applied was direct compression method. Ethyl cellulose was used as backing layer of the tablet. FTIR and DSC analysis were carried out to identify the drug polymer interactions. The prepared tablets were evaluated for physicochemical parameters, ex vivo mucoadhesion time and in-vitro drug release. The formulated tablets showed the average surface pH 6-7 which is favourable for oral mucosa. The formulation containing sodium alginate showed more than 90 % of drug release at the end of the 7 hours in vitro dissolution studies. The formulation containing xanthan gum showed more than 8 hours of mucoadhesion time and all formulation exhibited non fickian release kinetics. The present study indicates enormous potential of erodible mucoadhesive buccal tablet containing atenolol for systemic delivery with an added advantage of circumventing the hepatic first pass metabolism.

Keywords: atenolol, mucoadhesion, in vitro drug release, direct compression, ethyl cellulose

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Authors: P. Pötters, A. Marquet, B. Leyendecker

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The objective of this paper is to investigate different implementation approaches for the implementation of Lean production in companies. Furthermore, a structured overview of those different approaches is to be made. Therefore, the present work is intended to answer the following research question: What differences and similarities exist between the various systematic approaches and phase models for the implementation of Lean Production? To present various approaches for the implementation of Lean Production discussed in the literature, a qualitative content analysis was conducted. Within the framework of a qualitative survey, a selection of texts dealing with lean production and its introduction was examined. The analysis presents different implementation approaches from the literature, covering the descriptive aspect of the study. The study also provides insights into similarities and differences among the implementation approaches, which are drawn from the analysis of latent text contents and author interpretations. In this study, the focus is on identifying differences and similarities among systemic approaches for implementing Lean Production. The research question takes into account the main object of consideration, objectives pursued, starting point, procedure, and endpoint of the implementation approach. The study defines the concept of Lean Production and presents various approaches described in literature that companies can use to implement Lean Production successfully. The study distinguishes between five systemic implementation approaches and seven phase models to help companies choose the most suitable approach for their implementation project. The findings of this study can contribute to enhancing transparency regarding the existing approaches for implementing Lean Production. This can enable companies to compare and contrast the available implementation approaches and choose the most suitable one for their specific project.

Keywords: implementation, lean production, phase models, systematic approaches

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Authors: Ulisses Tadeu Vaz de Oliveira

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The development of multifunctional studies in the theoretical-methodological perspective of the Systemic-Functional Grammar (SFG) and the increasing number of critical literary studies have introduced new opportunities for the study of ideologies and societies, but also brought up new challenges across and within many areas. In this regard, the Critical Linguistics researches allow a form of pairing a textual linguistic analysis method (micro level) with a social language theory in political and ideological processes (macro level), presented in the literature. This presentation will report on strategies to criticize power holders in literary productions from three distinct eras, namely: (a) Satirical Galego-Portuguese chants of Gil Pérez Conde (thirteenth century), (b) Poems of Gregorio de Matos Guerra (seventeenth century), and (c) Songs of Chico Buarque de Holanda (twentieth century). The analysis of these productions is based on the SFG proposals, which considers the clause as a social event. Therefore, the structure serves to realize three concurrent meanings (metafunctions): Ideational, Interpersonal and Textual. The presenter aims to shed light on the core issues relevant to the successes of the authors to criticize authorities in repressive times while caring about face-threatening and politeness. The effective and meaningful critical discourse was a way of moving the society`s chains towards new ideologies reflected in the lexicogrammatical choices made and the rhetorical functions of the persuasive structures used by the authors.

Keywords: ideology, literature, persuasion, systemic-functional grammar

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Authors: Mahboobe Daneshvar

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Introduction: Clinical studies on the effect of systemic conditions on periodontal diseases have shown that some systemic deficiencies may provide grounds for the onset of periodontal diseases. One of these systemic problems is osteoporosis, which may be a risk factor for the onset and exacerbation of periodontitis. This study tends to evaluate periodontal indices in osteoporotic menopausal women and compare them with healthy controls. Materials and Methods: In this case-control study, participants included 45-75-year-old menopausal women referred to rheumatology wards of the Khatamolanbia Clinic and Shahid Sadoughi Hospital in Yazd; Their bone density was determined by DEXA-scan and by imaging the femoral-lumbar bone. Thirty patients with osteoporosis and 30 subjects with normal BMD were selected. Then, informed consent was obtained for participation in the study. During the clinical examinations, tooth loss (TL), plaque index (PI), gingival recession, pocket probing depth (PPD), clinical attachment loss (CAL), and tooth mobility (TM) were measured to evaluate the periodontal status. These clinical examinations were performed to determine the periodontal status by catheter, mirror and probe. Results: During the evaluation, there was no significant difference in PPD, PI, TM, gingival recession, and CAL between case and control groups (P-value>0.05); that is, osteoporosis has no effect on the above factors. These periodontal factors are almost the same in both healthy and patient groups. In the case of missing teeth, the following results were obtained: the mean of missing teeth was 22.173% of the total teeth in the case group and 18.583% of the total teeth in the control group. In the study of the missing teeth in the case and control groups, there was a significant relationship between case and control groups (P-value = 0.025). Conclusion: In fact, since periodontal disease is multifactorial and microbial plaque is the main cause, osteoporosis is considered a predisposing factor in exacerbation or persistence of periodontal disease. In patients with osteoporosis, usually pathological fractures, hormonal changes, and aging lead to reduced physical activity and affect oral health, which leads to the manifestation of periodontal disease. But this disease increases tooth loss by changing the shape and structure of bone trabeculae and weakening them. Osteoporosis does not seem to be a deterministic factor in the incidence of periodontal disease, since it affects bone quality rather than bone quantity.

Keywords: plaque index, Osteoporosis, tooth mobility, periodontal packet

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Authors: Vangelis Papadimitropoulos

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This paper is part of the research program “Techno-Social Innovation in the Collaborative Economy”, funded by the Hellenic Foundation for Research and Innovation (H.F.R.I.) for the years 2022-2024. The paper showcases the Open Food Network (OFN) as an open-sourced digital platform supporting short food supply chains in local agricultural production and consumption. The paper outlines the research hypothesis, the theoretical framework, and the methodology of research as well as the findings and conclusions. Research hypothesis: The model of open cooperativism as a vehicle for systemic change in the agricultural sector. Theoretical framework: The research reviews the OFN as an illustrative case study of the three-zoned model of open cooperativism. The OFN is considered a paradigmatic case of the model of open cooperativism inasmuch as it produces commons, it consists of multiple stakeholders including ethical market entities, and it is variously supported by local authorities across the globe, the latter prefiguring the mini role of a partner state. Methodology: Research employs Ernesto Laclau and Chantal Mouffe’s discourse analysis -elements, floating signifiers, nodal points, discourses, logics of equivalence and difference- to analyse the breadth of empirical data gathered through literature review, digital ethnography, a survey, and in-depth interviews with core OFN members. Discourse analysis classifies OFN floating signifiers, nodal points, and discourses into four themes: value proposition, governance, economic policy, and legal policy. Findings: OFN floating signifiers align around the following nodal points and discourses: “digital commons”, “short food supply chains”, “sustainability”, “local”, “the elimination of intermediaries” and “systemic change”. The current research identifies a lack of common ground of what the discourse of “systemic change” signifies on the premises of the OFN’s value proposition. The lack of a common mission may be detrimental to the formation of a common strategy that would be perhaps deemed necessary to bring about systemic change in agriculture. Conclusions: Drawing on Laclau and Mouffe’s discourse theory of hegemony, research introduces a chain of equivalence by aligning discourses such as “agro-ecology”, “commons-based peer production”, “partner state” and “ethical market entities” under the model of open cooperativism, juxtaposed against the current hegemony of neoliberalism, which articulates discourses such as “market fundamentalism”, “privatization”, “green growth” and “the capitalist state” to promote corporatism and entrepreneurship. Research makes the case that for OFN to further agroecology and challenge the current hegemony of industrial agriculture, it is vital that it opens up its supply chains into equivalent sectors of the economy, civil society, and politics to form a chain of equivalence linking together ethical market entities, the commons and a partner state around the model of open cooperativism.

Keywords: sustainability, the digital commons, open cooperativism, innovation

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Authors: Sydney Burnett

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The history of the relationship between elder abuse and its tendency to go underreported is rooted in the oppressive nature of ageism and victimization. Approximately 8% of the world's population was aged sixty or over in 1950, whereas, in 2020, the number more than doubled to 16.9%. By 2050, that number is expected to reach 22%. Although difficult for individuals of any age to feel completely supported in society, this task proves especially difficult for the elderly demographic. And as the elderly population continues to grow, the systemic abuse and neglect that this group encounters, and thus its underreported nature, multiply at a similar rate. Although a recent increase in awareness has initiated stronger efforts towards addressing the meager resources, processes, and personnel present to manage elder abuse, both reported and unreported, the destructive complexities of ageism and victimization persist. Examining the byproducts of the rapidly growing elderly demographic in China, the United States, and Israel, in cohesion with the inherent challenges in the context of terminology, definition, and typologies of elder abuse should provide insight into the pernicious influences of elder abuse that contribute to the non-identification and non-recognition of elder maltreatment present in these three countries in different stages of development. This investigation aims to understand the intricacy of elder abuse and its correlation to a lack of acknowledgment as well as its consequences in society by exploring the variation between China, the United States, and Israel's attitudes surrounding the subject. Furthermore, the systemic abuse and neglect embedded in global ageism can be revealed by the differences between the three countries' approaches to reporting elder abuse.

Keywords: elder abuse, ageism, mistreatment, underreported

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Authors: David A. Scott, Michelle G. Scott

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The problem of juvenile crime, school suspensions and oppositional behaviors indicates a need for a wide range of intervention programs for at-risk youth. Juvenile court systems and mental health agencies are examining alternative ways to deal with at-risk youth that will allow the adolescent to live within their home community. The previous trend that treatment away from home is more effective than treatment near one's community has shifted. Research now suggests that treatment be close to home for several reasons, such as increased treatment success, parental involvement, and reduced costs. Treatment options consist of a wide range of interventions, including outpatient, inpatient, and community-based services (therapeutic group homes, foster care and in-home preservation services). The juvenile justice system, families and other mental health agencies continue to seek the most effective treatment for at-risk youth in their communities. This research examines two possible treatment modalities, a multi-systemic outpatient program and a residential program. Research examining effective, evidence- based counseling will be discussed during this presentation. The presenter recently completed a three-year research grant examining effective treatment modalities for at-risk youth participating in a multi-systemic program. The presenter has also been involved in several research activities gathering data on effective techniques used in residential programs. The data and discussion will be broken down into two parts, each discussing one of the treatment modalities mentioned above. Data on the residential programs was collected on both a sample of 740 at- risk youth over a five-year period and also a sample of 63 participants during a one-year period residing in a residential programs. The effectiveness of these residential services was measured in three ways: services are evaluated by primary referral sources; follow-up data is obtained at various intervals after program participation to measure recidivism (what percentage got back into trouble with the Department of Juvenile Justice); and a more sensitive, "Offense Seriousness Score", has been computed and analyzed prior to, during and after treatment in the residential program. Data on the multi-systemic program was gathered over the past three years on 190 participants. Research will discuss pre and post test results, recidivism rates, academic performance, parental involvement, and effective counseling treatment modalities.

Keywords: at-risk youth, group homes, therapeutic group homes, recidivism rates

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Authors: Rachna Agarwal, R. Naveen, Darpan Thakre, Rohit Shahi, Maryam Abbasi, Upendra Rathore, Latika Gupta

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Aim: Retinal changes are the window to systemic vasculature. Therefore, we explored retinal changes in patients with idiopathic inflammatory myopathies (IIM) as a surrogate for vascular health. Methods: Adult and juvenile IIM patients visiting a tertiary care centre in 2021 satisfying the International Myositis Classification Criteria were enrolled for detailed ophthalmic examination in comparison with healthy controls (HC). Patients with conditions that precluded thorough posterior chamber examination were excluded. Scale variables are expressed as median (IQR). Multivariate analysis (binary logistic regression-BLR) was conducted, adjusting for age, gender, and comorbidities besides factors significant in univariate analysis. Results: 43 patients with IIM [31 females; age 36 (23-45) years; disease duration 5.5 (2-12) months] were enrolled for participation. DM (44%) was the most common diagnosis. IIM patients exhibited frequent attenuation of retinal vessels (32.6% vs. 4.3%, p <0.001), AV nicking (14% vs. 2.2%, p=0.053), and vascular tortuosity (18.6% vs. 2.2%, p=0.012), besides decreased visual acuity (53.5% vs. 10.9%, p<0.001) and immature cataracts (34.9% vs. 2.2%, p<0.001). Attenuation of vessels [OR 10.9 (1.7-71), p=0.004] emerged as significantly different from HC after adjusting for covariates in BLR. Notably, adults with IIM were more predisposed to retinal abnormalities [21 (57%) vs. 1 (16%), p=0.068], especially attenuation of vessels [14(38%) vs. 0(0), p=0.067] than jIIM. However, no difference was found in retinal features amongst the subtypes of adult IIM, nor did they correlate with MDAAT, MDI, or HAQ-DI. Conclusion: Retinal microvasculopathy and diminution of vision occur in nearly one-third to half of the patients with IIM. Microvasculopathy occurs across subtypes of IIM, and more so in adults, calling for further investigation as a surrogate for damage assessment and potentially even systemic vascular health.

Keywords: idiopathic inflammatory myopathies, vascular health, retinal microvasculopathy, arterial attenuation

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Authors: Mahdi Bastan, Ali Mohammad Ahmadvand, Fatemeh Soltani Khamsehpour

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Health organizations’ sustainable development has nowadays become highly affected by customers’ satisfaction due to significant changes made in the business environment of the healthcare system and emerging of Competitiveness paradigm. In case we look at the hospitals and other health organizations as service providers concerning profit issues, the satisfaction of employees as interior customers, and patients as exterior customers would be of significant importance in health business success. Furthermore, satisfaction rate could be considered in performance assessment of healthcare organizations as a perceived quality measure. Several researches have been carried out in identification of effective factors on patients’ satisfaction in health organizations. However, considering a systemic view, the complex causal relations among many components of healthcare system would be an issue that its acquisition and sustainability requires an understanding of the dynamic complexity, an appropriate cognition of different components, and effective relationships among them resulting ultimately in identifying the generative structure of patients’ satisfaction. Hence, the presenting paper applies system dynamics approaches coherently and methodologically to represent the systemic structure of customers’ satisfaction of a health system involving the constituent components and interactions among them. Then, the results of different policies taken on the system are simulated via developing mathematical models, identifying leverage points, and using scenario making technique and then, the best solutions are presented to improve customers’ satisfaction of the services. The presenting approach supports taking advantage of decision support systems. Additionally, relying on understanding of system behavior Dynamics, the effective policies for improving the health system would be recognized.

Keywords: customer satisfaction, healthcare, scenario, simulation, system dynamics

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Authors: Massimo Tadi, M. Hadi Mohammad Zadeh, Ozge Ogut

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Although how cities’ forms are structured is studied, more efforts are needed on systemic comprehensions and evaluations of the urban morphology through quantitative metrics that are able to describe the performance of a city in relation to its formal properties. More research is required in this direction in order to better describe the urban form characteristics and their impact on the environmental performance of cities and to increase their sustainability stewardship. With the aim of developing a better understanding of the built environment’s systemic structure, the intention of this paper is to present a holistic methodology for studying the behavior of the built environment and investigate the methods for measuring the effect of urban structure to the environmental performance. This goal will be pursued through an inquiry into the morphological components of the urban systems and the complex relationships between them. Particularly, this paper focuses on proximity, referring to the proximity of different land-uses, is a concept with which Integrated Modification Methodology (IMM) explains how land-use allocation might affect the choice of mobility in neighborhoods, and especially, encourage or discourage non-motived mobility. This paper uses proximity to demonstrate that the structure attributes can quantifiably relate to the performing behavior in the city. The target is to devise a mathematical pattern from the structural elements and correlate it directly with urban performance indicators concerned with environmental sustainability. The paper presents some results of this rigorous investigation of urban proximity and its correlation with performance indicators in four different areas in the city of Milan, each of them characterized by different morphological features.

Keywords: built environment, ecology, sustainable indicators, sustainability, urban morphology

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Authors: Anagha Pavithran Vattamparambil, Niranjana Regimon

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Dalit and tribal communities in India have the largest suicide rate; however, the current literature does not reflect this reality. While existing research acknowledges socio-cultural risk factors, it fails to discuss structural issues pertaining to marginalized communities in India. Furthermore, the language is framed in an individualistic manner which denies room for recognizing systemic violence and injustice among causative agents of suicide. We aim to examine the representation of Dalit and tribal identities and their experiences of marginalisation as a contributive factor of suicide, as well as discuss the epistemic injustice involved in its exclusion. Electronic searches of PubMed, PsychInfo, and Web of Science databases will be carried out from inception till January 2023 to conduct a systematic scoping review of peer-reviewed articles; it will include all studies involving psychological autopsy in India. A narrative synthesis will be performed to gain insight into the inclusion of the experiences of Dalits and Tribals, the absence of which indicates a lacking understanding of suicide in India. It is also expected to highlight the alienation of lived experiences and narratives of marginalisation from mainstream discourse on suicide that constitutes epistemic injustice. There is a complex interplay of psychological, socio-cultural, economic, and political factors for suicide in the Indian setting. But, political and systemic issues are often downplayed in suicide etiology, including casteist assault, rape, violence, public humiliation, and discrimination which deserves more research attention.

Keywords: dalits, marginalisation, psychological autopsy, suicide, tribals

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Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

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The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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Authors: Luís Marques, João Rocha, Andreia Fernandes, Maria Moura, Cláudia Caseiro, Filipa Figueiredo, João Nunes

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The implementation of circularity strategies other than recycling, such as reducing the amount of raw material, as well as reusing or sharing existing products, remains marginal. The European Commission announced that the transition towards a more circular economy could lead to the net creation of about 700,000 jobs in Europe by 2030, through additional labour demand from recycling plants, repair services and other circular activities. Efforts to create new circular business models in accordance with completely circular processes, as opposed to linear ones, have increased considerably in recent years. In order to create a societal Circular Economy transition model, it is necessary to include innovative solutions, where startups play a key role. Early-stage startups based on new business models according to circular processes often face difficulties in creating enough impact. The StartUp Zero Program designs a model and approach to increase the flow of startups in the Circular Economy field, focusing on a systemic decision analysis and multi-generational approach, considering Multi-Criteria Decision Analysis to support a decision-making tool, which is also supported by the use of a combination of an Analytical Hierarchy Process and Multi-Attribute Value Theory methods. We define principles, criteria and indicators for evaluating startup prerogatives, quantifying the evaluation process in a unique result. Additionally, this entrepreneurship program spanning 16 months involved more than 2400 young people, from ages 14 to 23, in more than 200 interaction activities.

Keywords: circular economy, entrepreneurship, startups;, multi-criteria decision analysis

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