Search results for: systemic lupus Erythemotosus

Authors: Leila Asadollahi

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Dry powder inhalers (DPIs) have come a long way since their creation, starting with the Spinhaler Fisons in 1967. For optimal performance, it is important to consider the interplay between formulation, device, and patient. DPIs have shown great potential in treating systemic disorders, as evidenced by their success in clinical practices. Ongoing clinical trials and market availability of DPI products for systemic disease treatment are also examined. Furthermore, the current COVID-19 pandemic has sparked increased interest in dry powder inhalation as a potential avenue for vaccines and antiviral drugs, prompting further exploration of its applications. To achieve optimal treatment outcomes for respiratory diseases, a thorough understanding of the various types of DPIs currently available is crucial. These include single-dose, multiple-unit dose, and multi-dose DPIs. This informative article delves into the administration of drugs via inhalation, examining its diverse routes of administration. Additionally, it illuminates the exciting advancements in inhalation delivery systems and investigates the latest therapeutic approaches for the treatment of respiratory ailments. Additionally, the article discusses the historical development of DPIs and the need for improved designs to enhance efficacy and patient adherence. The potential of DPIs in treating systemic diseases is also examined. Overall, this review provides valuable insights into the advancements, challenges, and future prospects of inhalation drug delivery systems, highlighting the potential they hold for respiratory and systemic disorders. The review aims to provide valuable insights into the advancements, challenges, and future prospects of inhalation drug delivery systems, highlighting the potential they hold for respiratory and systemic disorders.

Keywords: dry powder inhalers (DPIs), respiratory diseases, systemic disorders, pulmonary drug delivery

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Authors: Laura Gleason, Sahithi Talasila, Lauren Banner, Ladan Afifi, Neda Nikbakht

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Primary cutaneous anaplastic large cell lymphoma (pcALCL) accounts for 9% of all cutaneous T-cell lymphomas. pcALCL is classically characterized as a solitary papulonodule that often enlarges, ulcerates, and can be locally destructive, but overall exhibits an indolent course with overall 5-year survival estimated to be 90%. Distinguishing pcALCL from systemic ALCL (sALCL) is essential as sALCL confers a poorer prognosis with average 5-year survival being 40-50%. Although extremely rare, there have been several cases of ALK-positive ALCL diagnosed on skin biopsy without evidence of systemic involvement, which poses several challenges in the classification, prognostication, treatment, and follow-up of these patients. Objectives: We present a case of cutaneous ALK-positive ALCL without evidence of systemic involvement, and a narrative review of the literature to further characterize that ALK-positive ALCL limited to the skin is a distinct variant with a unique presentation, history, and prognosis. A 30-year-old woman presented for evaluation of an erythematous-violaceous papule present on her right chest for two months. With the development of multifocal disease and persistent lymphadenopathy, a bone marrow biopsy and lymph node excisional biopsy were performed to assess for systemic disease. Both biopsies were unrevealing. The patient was counseled on pursuing systemic therapy consisting of Brentuximab, Cyclophosphamide, Doxorubicin, and Prednisone given the concern for sALCL. Apropos of the patient we searched for clinically evident, cutaneous ALK-positive ALCL cases, with and without systemic involvement, in the English literature. Risk factors, such as tumor location, number, size, ALK localization, ALK translocations, and recurrence, were evaluated in cases of cutaneous ALK-positive ALCL. The majority of patients with cutaneous ALK-positive ALCL did not progress to systemic disease. The majority of cases that progressed to systemic disease in adults had recurring skin lesions and cytoplasmic localization of ALK. ALK translocations did not influence disease progression. Mean time to disease progression was 16.7 months, and significant mortality (50%) was observed in those cases that progressed to systemic disease. Pediatric cases did not exhibit a trend similar to adult cases. In both the adult and pediatric cases, a subset of cutaneous-limited ALK-positive ALCL were treated with chemotherapy. All cases treated with chemotherapy did not progress to systemic disease. Apropos of an ALK-positive ALCL patient with clinical cutaneous limited disease in the histologic presence of systemic markers, we discussed the literature data, highlighting the crucial issues related to developing a clinical strategy to approach this rare subtype of ALCL. Physicians need to be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK and EMA positivity, and disease with skin recurrence.

Keywords: anaplastic large cell lymphoma, systemic, cutaneous, anaplastic lymphoma kinase, ALK, ALCL, sALCL, pcALCL, cALCL

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Authors: Carl Eiselen, Stephen O’Hagan

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Background: Q fever, caused by the obligate intracellular bacterium Coxiella burnetii, is an infectious disease with variable systemic manifestations. Its potential to cause ocular complications has not been reported before in Australia. This case study explores the unusual presentation of asymptomatic acute multifocal retinitis (AMR) in a patient with acute Q fever endocarditis and hepatitis in rural Queensland, Australia. Case Presentation: A 48-year-old male gardener presented with flu-like symptoms, weight loss, and encephalopathy. Despite systemic malaise, he had no ocular symptoms. Laboratory investigations confirmed acute Q fever, and imaging studies identified hepatic involvement and endocarditis. The retinal screening revealed asymptomatic AMR, corroborated by fundus examination and SD-OCT. Following treatment with Doxycycline and hydroxychloroquine, both systemic and ocular manifestations improved. Discussion: This is the first documented case of asymptomatic AMR associated with Q fever. The patient’s lack of autoantibodies challenges the established understanding of Q fever endocarditis and suggests potential alternative mechanisms. Conclusion: This case report expands our understanding of the multi-systemic impact of Q fever, highlighting the need for comprehensive clinical evaluation and including retinal screening in the setting of acute infection. The disease's underlying mechanism for ocular involvement is not yet established.

Keywords: Coxiella Burnetti, Q fever, ocular manifestation, acute multifocal retintis, endocarditis

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Authors: Rachelle McFarlane

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The Second Decade of Action Road Safety has begun with increased focus on countries who are disproportionately affected by road fatalities. Researchers highlight the low effectiveness of road safety campaigns in Latin America and the Caribbean (LAC) still reporting approximately 130,000 deaths and six million injuries annually. The regional fatality rate 19.2 per 100,000 with heightened concern for persons 15 to 44 years. In 2021, 483 Jamaicans died in 435 crashes, with 33% of these fatalities occurring during Covid-19 curfew hours. The study objective is to conduct a systemic safety review of Jamaican road crashes and provide a framework for its use in complementing traditional methods. The methodology involves the use of the FHWA Systemic Safety Project Selection Tool for analysis. This tool reviews systemwide data in order to identify risk factors across the network associated with severe and fatal crashes, rather that only hotspots. A total of 10,379 crashes with 745 fatalities and serious injuries were reviewed. Of the focus crash types listed, 50% of ‘Pedestrian Accidents’ resulted in fatalities and serious injuries, followed by 32% ‘Bicycle’, 24% ‘Single’ and 12% of ‘Head-on’. This study seeks to understand the associated risk factors with these priority crash types across the network and recommend cost-effective countermeasures across common sites. As we press towards Vision Zero, the inclusion of the systemic safety review method, complementing traditional methods, may create a wider impact in reducing road fatalities and serious injury by targeting issues across network with similarities; focus crash types and contributing factors.

Keywords: systemic safety review, risk factors, road crashes, crash types

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Authors: Farhad Reyazat, Richard Werner

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This paper contributes to the existent literature by developing a framework that explains how to monitor potential threats to banking sector stability. The study explores structural vulnerabilities at the country level, but also look at bilateral exposures within a network context. The study contributes in analysing of the European banking systemic risk at aggregated level, which integrates the characteristics of bank size, and interconnectedness relative to the size of the economy which ultimate risk belong to, taking to account the concentration ratio of the banking industry within the whole economy. The nature of the systemic risk depends on the interplay of the network topology with the nature of financial transactions over the network, assets and buffer stemming from bank size, correlations, and the nature of the shocks to the financial system. The study’s results illustrate the contribution of banks’ size, size of economy and concentration of counterparty exposures to a given country’s banks in explaining its systemic importance, how much the banking network depends on a few traditional hubs activities and the changes of this dependencies over the last 9 years. The role of few of traditional hubs such as Swiss banks and British Banks and also Irish banks- where the financial sector is fairly new and grew strongly between 1990s till 2008- take the fourth position on 2014 reducing the relative size since 2006 where they had the first position. In-degree concentration index analysis in the study shows concentration index of banking network was not changed since financial crisis 2007-8. In-degree concentration index on first quarter of 2014 indicates that US, UK and Germany together, getting over 70% of the network exposures. The result of comparing the in-degree concentration index with 2007-4Q, shows the same group having over 70% of the network exposure, however the UK getting more important role in the hub and the market share of US and Germany are slightly diminished.

Keywords: systemic risk, counterparty risk, financial stability, interconnectedness, banking concentration, european banks risk, network effect on systemic risk, concentration risk

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Authors: Rizwan H. Khan, Saima Nusrat

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Despite the fact that amyloid associated neurodegenerative diseases and non-neuropathic systemic amyloidosis have allured the research endeavors, as no curative drugs have been proclaimed up till now except for symptomatic cure. Therapeutic compounds which can diminish or disaggregate such toxic oligomers and fibrillar species have been examined and more are on its way. In the present study, we had reported an extensive biophysical, microscopic and computational study, revealing that L-3, 4-dihydroxyphenylalanine (L-Dopa) possess undeniable potency to inhibit heat induced human lysozyme (HL) amyloid fibrillation and also retain the fibril disaggregating potential. L-Dopa interferes in the amyloid fibrillogenesis process by interacting hydrophobically and also by forming hydrogen bonds with the amino acid residues found in amyloid fibril forming prone region of HL as elucidated by molecular docking results. L-Dopa also disaggregates the mature amyloid fibrils into some unorganised species. Thus, L-Dopa and related compounds can work as a promising inhibitor for the therapeutic advancement prospective against systemic amyloidosis.

Keywords: amyloids, disaggregation, human lysozyme, molecular docking

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Authors: Taurino S. R. Neto, Epitácio D. S. Neto, Flávio Signorelli, Gustavo G. M. Balbi, Alex H. Higashi, Mário Luiz R. Monteiro, Eloisa Bonfá, Danieli C. O. Andrade, Leandro C. Zacharias

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Purpose: To perform a multimodal evaluation, including the use of Optical Coherence Angiotomography (OCTA), in patients with primary antiphospholipid syndrome (PAPS) without ocular complaints and to compare them with healthy individuals. Methods: A complete structural and functional ophthalmological evaluation using OCTA and microperimetry (MP) exam in patients with PAPS, followed at a tertiary rheumatology outpatient clinic, was performed. All ophthalmologic manifestations were recorded and then statistical analysis was performed for comparative purposes; p <0.05 was considered statistically significant. Results: 104 eyes of 52 subjects (26 patients with PAPS without ocular complaints and 26 healthy individuals) were included. Among PAPS patients, 21 were female (80.8%) and 21 (80.8%) were Caucasians. Thrombotic PAPS was the main clinical criteria manifestation (100%); 65.4% had venous and 34.6% had arterial thrombosis. Obstetrical criteria were present in 34.6% of all thrombotic PAPS patients. Lupus anticoagulant was present in all patients. 19.2% of PAPS patients presented ophthalmologic findings against none of the healthy individuals. The most common retinal change was paracentral acute middle maculopathy (PAMM) (3 patients, 5 eyes), followed by drusen-like deposits (1 patient, 2 eyes) and pachychoroid pigment epitheliopathy (1 patient, 1 eye). Systemic hypertension and hyperlipidaemia were present in 100% of the PAPS patients with PAMM, while only six patients (26.1%) with PAPS without PAMM presented these two risk factors together. In the quantitative OCTA evaluation, we found significant differences between PAPS patients and controls in both the superficial vascular complex (SVC) and deep vascular complex (DVC) in the high-speed protocol, as well as in the SVC in the high-resolution protocol. In the analysis of the foveal avascular zone (FAZ) parameters, the PAPS group had a larger area of FAZ in the DVC using the high-speed method compared to the control group (p=0.047). In the quantitative analysis of the MP, the PAPS group had lower central (p=0.041) and global (p<0.001) retinal sensitivity compared to the control group, as well as in the sector analysis, with the exception of the inferior sector. In the quantitative evaluation of fixation stability, there was a trend towards worse stability in the PAPS subgroup with PAMM in both studied methods. Conclusions: PAMM was observed in 11.5% of PAPS patients with no previous ocular complaints. Systemic hypertension concomitant with hyperlipidemia was the most commonly associated risk factor for PAMM in patients with PAPS. PAPS patients present lower vascular density and retinal sensitivity compared to the control group, even in patients without PAMM.

Keywords: antiphospholipid syndrome, optical coherence angio tomography, optical coherence tomography, retina

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Authors: Ender Su, Kai Wen Wong, I-Ling Ju, Ya-Ling Wang

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In this study, the systemic risk change of Taiwan’s banking sector is analyzed during the financial crisis. The risk expose of each financial institutions to the whole Taiwan banking systemic risk or vice versa under financial distress are measured by conditional Value-at-Risk (CoVaR) and conditional coherent expected shortfall (CoES). The CoVaR and CoES are estimated by using vector quantile autoregression (MVMQ-CaViaR) with the daily stock returns of each banks included domestic and foreign banks in Taiwan. The daily in-sample data covered the period from 05/20/2002 to 07/31/2007 and the out-of-sample period until 12/31/2013 spanning the 2008 U.S. subprime crisis, 2010 Greek debt crisis, and post risk duration. All banks in Taiwan are categorised into several groups according to their size of market capital, leverage and domestic/foreign to find out what the extent of changes of the systemic risk as the risk changes between the individuals in the bank groups and vice versa. The final results can provide a guidance to financial supervisory commission of Taiwan to gauge the downside risk in the system of financial institutions and determine the minimum capital requirement hold by financial institutions due to the sensibility changes in CoVaR and CoES of each banks.

Keywords: bank financial distress, vector quantile autoregression, CoVaR, CoES

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Authors: Geum Yeon Sim, Jasal Patel, Anand Kumthekar, Stanley Wainapel

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A 65-year-old right-hand dominant African-American man, formerly employed as a security guard, was referred to Rehabilitation Medicine with bilateral hand stiffness and weakness. His past medical history was only significant for myelofibrosis, diagnosed 4 years earlier, for which he was receiving scheduled blood transfusions. Approximately 2 years ago, he began to notice stiffness and swelling in his non-dominant hand that progressed to pain and decreased strength, limiting his hand function. Similar but milder symptoms developed in his right hand several months later. There was no history of prior injury or exposure to cold. Physical examination showed enlargement of metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints with finger flexion contractures, Swan-neck and Boutonniere deformities, and associated joint tenderness. Changes were more prominent in the left hand. X-rays showed mild osteoarthritis of several bilateral PIP joints. Anti-nuclear antibodies, rheumatoid factor, and cyclic citrullinated peptide antibodies were negative. MRI of the hand showed no erosions or synovitis. A rheumatology consultation was obtained, and the cause of his symptoms was attributed to myelofibrosis-related arthropathy with secondary osteoarthritis. The patient was tried on diclofenac cream and received a few courses of Occupational Therapy with limited functional improvement. Primary myelofibrosis (PMF) is a rare myeloproliferative neoplasm characterized by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency. Rheumatic manifestations of malignancies include direct invasion, paraneoplastic presentations, secondary gout, or hypertrophic osteoarthropathy. PMF causes gradual bone marrow fibrosis with extramedullary metaplastic hematopoiesis in the liver, spleen, or lymph nodes. Musculoskeletal symptoms are not common and are not well described in the literature. The first reported case of myelofibrosis related arthritis was seronegative arthritis due to synovial invasion of myeloproliferative elements. Myelofibrosis has been associated with autoimmune diseases such as systemic lupus erythematosus, progressive systemic sclerosis, and rheumatoid arthritis. Gout has been reported in patients with myelofibrosis, and the underlying mechanism is thought to be related to the high turnover of nucleic acids that is greatly augmented in this disease. X-ray findings in these patients usually include erosive arthritis with synovitis. Treatment of underlying PMF is the treatment of choice, along with anti-inflammatory medications. Physicians should be cognizant of recognizing this rare entity in patients with PMF while maintaining clinical suspicion for more common causes of joint deformities, such as rheumatic diseases.

Keywords: myelofibrosis, arthritis, arthralgia, malignancy

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Authors: Soumaya Mrabet, Imen Akkari, Amira Atig, Elhem Ben Jazia

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Introduction: Primary biliary cirrhosis (PBC) is a cholestatic cholangitis of unknown etiology. It is frequently associated with autoimmune diseases, which explains their systematic screening. The aim of our study was to determine the prevalence and the type of autoimmune disorders associated with PBC and to assess their impact on the prognosis of the disease. Material and methods: It is a retrospective study over a period of 16 years (2000-2015) including all patients followed for PBC. In all these patients we have systematically researched: dysthyroidism (thyroid balance, antithyroid autoantibodies), type 1 diabetes, dry syndrome (ophthalmologic examination, Schirmer test and lip biopsy in case of Presence of suggestive clinical signs), celiac disease(celiac disease serology and duodenal biopsies) and dermatological involvement (clinical examination). Results: Fifty-one patients (50 women and one men) followed for PBC were collected. The Mean age was 54 years (37-77 years). Among these patients, 30 patients(58.8%) had at least one autoimmune disease associated with PBC. The discovery of these autoimmune diseases preceded the diagnosis of PBC in 8 cases (26.6%) and was concomitant, through systematic screening, in the remaining cases. Autoimmune hepatitis was found in 12 patients (40%), defining thus an overlap syndrome. Other diseases were Hashimoto's thyroiditis (n = 10), dry syndrome (n = 7), Gougerot Sjogren syndrome (n=6), celiac disease (n = 3), insulin-dependent diabetes (n = 1), scleroderma (n = 1), rheumatoid arthritis (n = 1), Biermer Anemia (n=1) and Systemic erythematosus lupus (n=1). The two groups of patients with PBC with or without associated autoimmune disorders were comparable for bilirubin levels, Child-Pugh score, and response to treatment. Conclusion: In our series, the prevalence of autoimmune diseases in PBC was 58.8%. These diseases were dominated by autoimmune hepatitis and Hashimoto's thyroiditis. Even if their association does not seem to alter the prognosis, screening should be systematic in order to institute an early and adequate management.

Keywords: autoimmune diseases, autoimmune hepatitis, primary biliary cirrhosis, prognosis

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Authors: Bahar Tunctan, Sefika Pinar Kucukkavruk, Meryem Temiz-Resitoglu, Demet Sinem Guden, Ayse Nihal Sari, Seyhan Sahan-Firat

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We hypothesized that rexinoids such as bexarotene, a selective retinoid X receptor α (RXRα) agonist, may be beneficial for preventing mortality due to inflammation associated with increased expression/activity of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS). Therefore, we investigated effects of bexarotene on the changes in circulating protein levels of iNOS (an index for systemic iNOS expression), myeloperoxidase (MPO) (an index for systemic inflammation), and lactate dehydrogenase (LDH) (an index for systemic tissue injury) in LPS-induced systemic inflammation model resulting in septic shock in rats. Rats were injected with saline (4 ml/kg; i.p.), LPS (10 mg/kg; i.p.), dimethylsulphoxide (4 ml/kg, 0.1%; s.c.) at time 0. Mean arterial blood pressure and heart rate were measured using a tail-cuff device. Bexarotene (0.03, 0.1, 0.3, and 1 mg/kg; s.c.) was administered to separate groups of rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and blood was collected for measurement of serum iNOS, MPO, and LDH protein levels. Blood pressure decreased by 31 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. Bexarotene at 0.3 and 1 mg/kg doses caused 20% mortality 4 h after LPS injection. In the LPS-treated rats, serum iNOS, MPO, and LDH protein levels were increased. Bexarotene only at 0.1 mg/kg dose prevented the LPS-induced hypotension and increased in iNOS, MPO, and LDH protein levels. These data are consistent with the view that a decrease in systemic iNOS levels contributes to the beneficial effect of bexarotene to prevent the hypotension associated with inflammation and tissue injury during rat endotoxemia. [This work was financially supported by The Scientific and Technological Research Council of Turkey (SBAG-109S121)].

Keywords: bexarotene, inflammation, iNOS, lipopolisaccharide, RXRa

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Authors: Rahmoune Abdelhaq

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Systemic risk is a key concern for central banks charged with safeguarding overall financial stability. In this work, we investigate how systemic risk is affected by the structure of the financial system. We construct banking systems that are composed of a number of banks that are connected by interbank linkages. We then vary the key parameters that define the structure of the financial system — including its level of capitalization, the degree to which banks are connected, the size of interbank exposures and the degree of concentration of the system — and analyses the influence of these parameters on the likelihood of contagious (knock-on) defaults. First, we find that the better-capitalized banks are, the more resilient is the banking system against contagious defaults and this effect is non-linear. Second, the effect of the degree of connectivity is non-monotonic, that is, initially a small increase in connectivity increases the contagion effect; but after a certain threshold value, connectivity improves the ability of a banking system to absorb shocks. Third, the size of interbank liabilities tends to increase the risk of knock-on default, even if banks hold capital against such exposures. Fourth, more concentrated banking systems are shown to be prone to larger systemic risk, all else equal. In an extension to the main analysis, we study how liquidity effects interact with banking structure to produce a greater chance of systemic breakdown. We finally consider how the risk of contagion might depend on the degree of asymmetry (tier) inherent in the structure of the banking system. A number of our results have important implications for public policy, which this paper also draws out. This paper also discusses why bank risk management is needed to get the optimal one.

Keywords: financial stability, contagion, liquidity risk, optimal risk

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Authors: Rim Sghiri, Samia Al Shouli, Hana Benhassine, Nejla Elamri, Zahid Shakoor, Foued Slama, Adel Almogren, Hala Zeglaoui, Elyes Bouajina, Ramzi Zemni

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Objectives: Little is known about genes predisposing to systemic bone loss (SBL) in rheumatoid arthritis (RA). Therefore, we examined the association between SBL and a variant of CD40 gene, which is known to play a critical role in both immune response and bone homeostasis among patients with RA. Methods: CD40 rs48104850 was genotyped in 176 adult RA patients. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). Results: Low BMD was observed in 116 (65.9%) patients. Among them, 60 (34.1%) had low femoral neck (FN) Z score, 72 (40.9%) had low total femur (TF) Z score, and 105 (59.6%) had low lumbar spine (LS) Z score. CD40 rs4810485 was found to be associated with reduced TF Z score with the CD40 rs4810485 T allele protecting against reduced TF Z score (OR = 0.40, 95% CI = 0.23-0.68, p = 0.0005). This association was confirmed in the multivariate logistic regression analysis (OR=0.31, 95% CI= 0.16-0.59, p=3.84 x 10₋₄). Moreover, median FN BMD was reduced among RA patients with CD40 rs4810485 GG genotype compared to RA patients harbouring CD40 rs4810485 TT and GT genotypes (0.788± 0.136 versus 0.826± 0.146g/cm², p=0.001). Conclusion: This study, for the first time ever, demonstrated an association between a CD40 genetic variant and SBL among patients with RA.

Keywords: rheumatoid arthritis, CD40 gene, bone mineral density, systemic bone loss, rs48104850

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Authors: Cunyu Zhang

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Based on Systemic Functional Linguistics, this paper aims to explore the complex aspectuality system of English. This study shows that the complex aspectuality is classified into complex viewpoint aspect which refers to the homogeneous or heterogeneous ways continuously viewing on the same situation by the speaker and complex situation aspect which is the combined configuration of the internal time schemata of situation. Through viewpoint shifting and repeating, the complex viewpoint aspect is formed in two combination ways. Complex situation aspect is combined by the way of hypotactic verbal complex and the limitation of participant and circumstance in a clause.

Keywords: aspect series, complex situation aspect, complex viewpoint aspect, systemic functional linguistics

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Authors: Maryam Radan, Fereshteh Nejad Dehbashi, Vahid Bayati, Mahin Dianat, Seyyed Ali Mard, Zahra Mansouri

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Pulmonary emphysema is a pathological respiratory condition identified by alveolar destruction which leads to limitation of airflow and diminished lung function. A substantial body of evidence suggests that mesenchymal stem cells (MSCs) have the ability to induce tissue repair primarily through a paracrine effect. In this study, we aimed to determine the efficacy of Intratracheal adipose-derived mesenchymal stem cells (ADSCs) therapy in comparison to this approach with that of Intravenous (Systemic) therapy. Fifty adult male Sprague–Dawley rats weighing between 180 and 200 g were used in this experiment. The animals were randomized to Control groups (Intratracheal or Intravenous vehicle), Elastase group (intratracheal administration of porcine pancreatic elastase; 25 U/kg on day 0 and day 10th), Elastase+Intratracheal ADSCs therapy (1x107 Cells, on day 28) and Elastase+Systemic ADSCs therapy (1x107 Cells, on day 28). The rats which not subjected to any treatment, considered as the control. All rats were sacrificed 3 weeks later. Morphometric findings in lung tissues (Mean linear intercept) confirmed the establishment of the emphysema model via alveolar disruption. Contrarily, ADSCs administration partially restored alveolar architecture. These results were associated with improving arterial oxygenation, reducing lung edema, and decreasing lung inflammation with higher significant effects in the Intratracheal therapy route. These results documented that the efficacy of intratracheal ADSCs was comparable with intravenous ADSCs therapy. Accordingly, the obtained data suggested that intratracheal delivery of ADSCs would enhance lung repair in pulmonary emphysema. Moreover, this method provides benefits over a systemic administration, such as the reduction of cell number and the low risk to engraft other organs.

Keywords: mesenchymal stem cell, emphysema, Intratracheal, systemic

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Authors: Mohamed Hendawy Mousa, Warda Youssef Mohamed Morsy

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Background: Sepsis is a major cause of mortality and morbidity in trauma patients. Body mass index as an indicator of nutritional status was reported as a predictor of injury pattern and complications among critically ill injured patients. Aim: The aim of this study is to investigate the relationship between body mass index and the development of sepsis, systemic inflammatory response syndrome among adult trauma patients at emergency hospital - Cairo University. Research design: Descriptive correlational research design was utilized in the current study. Research questions: Q1. What is the body mass index profile of adult trauma patients admitted to the emergency hospital at Cairo University over a period of 6 months?, Q2. What is the frequency of systemic inflammatory response syndrome and sepsis among adult trauma patients admitted to the emergency hospital at Cairo University over a period of 6 months?, and Q3. What is the relationship between the development of sepsis, systemic inflammatory response syndrome and body mass index among adult trauma patients admitted to the emergency hospital at Cairo University over a period of 6 months?. Sample: A purposive sample of 52 adult male and female trauma patients with revised trauma score 10 to 12. Setting: The Emergency Hospital affiliated to Cairo University. Tools: Four tools were utilized to collect data pertinent to the study: Socio demographic and medical data tool, Systemic inflammatory response syndrome assessment tool, Revised Trauma Score tool, and Sequential organ failure assessment tool. Results: The current study revealed that, (61.5 %) of the studied subjects had normal body mass index, (25 %) were overweight, and (13.5 %) were underweight. 84.6% of the studied subjects had systemic inflammatory response syndrome and 92.3% were suffering from mild sepsis. No significant statistical relationship was found between body mass index and occurrence of Systemic inflammatory response syndrome (2= 2.89 & P = 0.23). However, Sequential organ failure assessment scores were affected significantly by body mass index was found mean of initial and last Sequential organ failure assessment score for underweight, normal and obese where t= 7.24 at p = 0.000, t= 16.49 at p = 0.000 and t= 9.80 at p = 0.000 respectively. Conclusion: Underweight trauma patients showed significantly higher rate of developing sepsis as compared to patients with normal body weight and obese. Recommendations: based on finding of this study the following are recommended: replication of the study on a larger probability sample from different geographical locations in Egypt; Carrying out of further studies in order to assess the other risk factors influencing trauma outcome and incidence of its complications; Establishment of standardized guidelines for managing underweight traumatized patients with sepsis.

Keywords: body mass index, sepsis, systemic inflammatory response syndrome, adult trauma

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Authors: Azmi Ilmi Aziz, Wisnu Sadasih, Rizal Fanany

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Purpose: This study describes systemic factors, intraocular lens (IOL), and ocular abnormalities in patients with IOL glistening at a tertiary hospital in Semarang. Methods: A retrospective, with a descriptive approach on patients with IOL glistening who visited the eye clinic between August 2019 to June 2023. Results: Twenty-five patients were examined; 11 patients (44%) had IOL glistening in their right eye, 4 patients (16%) in their left eye, and 10 patients (40%) in both eyes. The gender of patients consisted of 12 male patients (48%) and 13 female patients (52%). The median age of the patients was 68 years. The mean onset was 4.44 years after the first cataract surgery. Hypertension was found in 13 patients (52%), and diabetes was found in 9 patients (36%). Nine patients (36%) were identified with a foldable IOL with a closed loop design, and 1 patient (4%) with a PMMA IOL with an iris-fixated IOL design, while 15 other patients’ IOL were unrecorded. Glaucoma was found in 3 patients (12%). Conclusions: The result of this study showed that more than half of the patients were hypertensive, and some were glaucomatous, which had been discussed relevant in previous studies. Most IOL that could be identified was foldable IOL with a closed loop design. To our knowledge, the design of an IOL to glistening had never been explored. A longer study involving larger subjects is needed to better describe the systemic factors, IOL, and ocular abnormalities in patients with IOL glistening.

Keywords: glistening, intraocular lens, foldable IOL, PMMA IOL

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

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Objectives. Gastrointestinal involvement is one of the most common manifestations of systemic sclerosis (SSc). The aim of our study was to assess the frequency of gastrointestinal manifestations in SSc patients (pts) with interstitial lung disease (ILD) and their changes to rituximab (RTX) therapy. Methods. There were 103 pts with SSc in this study. The mean follow-up period was 12.6±10.7 months. The mean age was 47±12.9 years, females - 87 pts (84%), and the diffuse cutaneous subset of the disease 55 pts (53%). The mean disease duration was 6.2±5.5 years. All pts had ILD and were positive for ANA. 67% of them were positive for anti-topoisomerase-1. All patients received prednisolone at a dose of 11.3±4.5 mg/day, and immunosuppressants at inclusion received 47% of them. Pts received RTX due to the ineffectiveness of previous therapy for ILD. The cumulative mean dose of RTX was 1.7±0.6 grams. 90% of pts received omeprazole at a dose of 20-40 mg/day. Results. At inclusion, dysphagia was observed in 76 pts (74%), early satiety or vomiting in 32 pts (31%), and diarrhea in 20 pts (19%). We didn't observe any changes in gastrointestinal manifestation during RTX therapy. There was a decrease in the number of pts with dysphagia from 76 (74%) to 66 (64%), but it was insignificant. The number of pts with early satiety or vomiting and diarrhea didn't change. Conclusion. In our study, gastrointestinal involvement was observed in most of the pts with SSc-ILD. We didn't find any significant changes in gastrointestinal manifestations during RTX therapy. RXT does not worsen gastrointestinal manifestations in SSc-ILD.

Keywords: systemic sclerosis, dysphagia, rituximab, gastrointestinal manifestations

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Authors: İlhami Karahanoglu, Oguz Ceylan

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As its well-known definitions; systemic risk refers to whole economic system down-turn movement even collapse together in very severe cases. In fact, it points out the contagion effects of the defaults. Such a risk is can be depicted with the famous Chinese game of falling domino stones. During and after the Bear & Sterns and Lehman Brothers cases, it was well understood that there is a very strong effect of systemic risk in financial services sector. In this study, we concentrate on the existence of systemic risk in Turkish Banking Sector based upon the Halkbank Case during the end month of 2013; there was a political turmoil in Turkey in which the close relatives of the upper politicians were involved in illegal trading activities. In that operation, the CEO of Halkbank was also arrested and in investigation, Halkbank was considered as part of such illegal actions. That operation had an impact on Halkbanks stock value. The Halkbank stock value during that time interval decreased remarkably, the distributional profile of stock return changed and became more volatile as well as more skewed. In this study, the daily returns of 5 leading banks in Turkish banking sector were used to obtain 48 return distributions (for each month, 90-days-back stock value returns are used) of 5 banks for the period 12/2011-12/2013 (pre operation period) and 12/2013-12/2015 (post operation period). When those distributions are compared with timely manner, interestingly; the distribution of the 5 other leading banks in Turkey, public or private, had also distribution profiles which was different from the past 2011-2013 period just like Halkbank. Those 5 big banks, whose stock values are monitored with sub index in Istanbul stock exchange (BIST) as BN10, had more skewed distribution just following the Halkbank stock return movement during the post operation period, with lover mean value and as well higher volatility. In addition, the correlation between the stock value return distributions of the leading banks after Halkbank case, where the returns are more skewed to the left, increased (which is measured in monthly base before and after the operation). The dependence between those banks was stronger under the case where the stock values were falling compared with the normal market condition. Such distributional effect of stock returns between the leading banks in Turkey, which is valid for down sub-market (financial/banking sector) condition, can be evaluated as an evidence for the existence of contagious effect and systemic risk.

Keywords: financial risk, systemic risk, banking sector, return distribution, dependency structure

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Authors: Fenni Sim

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Background: The application of systemic family therapy approaches to community health cases have not gathered traction. In National Kidney Foundation, Singapore, the belief is that community support has great potential in helping End Stage Renal Failure (ESRF) patients manage the demands of their treatment regime, whether Hemodialysis (HD) or Peritoneal Dialysis(PD) and sustain them on the treatment. However, the current community support does not include family interventions and is largely nursing based. Although nursing support is well provided to patients, and their family members in issues related to treatment and compliance, complex family issues and dynamics arising from caregiver strain or pre-dialysis relationship strain might deter efforts in managing the challenges of the treatment. Objective: The objective of the study is to understand the potential scope of work provided by a social worker who is trained in systemic family therapy and the effects of these interventions. Methodology: 3 families on HD and 3 families on PD who have been receiving family intervention for the past 6 months would be chosen for the study. A qualitative interview would be conducted to review the effectiveness for the family. Scales such as SCORE-15, PHQ-9, and Zarit Burden were used to measure family functioning, depression, and caregiver’s burden for the families. Results: The research is still in preliminary phase. Conclusion: The study highlights the importance of family intervention for families with multiple stressors on different treatment modalities who might have different needs and challenges. Nursing support needs to be complemented with family-based support to manage complex family issues in order to achieve better health outcomes and improved family coping.

Keywords: complementing nursing support, end stage renal failure, healthcare, systemic approaches

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Authors: Lin Tang, Xiaoxia Guo, Lingling Zhang

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Recent vaccine scandals overshadowed China’s accomplishment of public health, triggering discussions on the causes of vaccine incidents. Through legal interpretation of selected vaccine incidents and analysis of systemic vulnerabilities in vaccine circulation and lot release, a panoramic review of legislative progresses in the vaccine administration sheds the light on this debate. In essence, it is the combination of the lagging legal system and the absence of information technology infrastructure in the process of vaccine administration reform that has led to the recurrence of vaccine incidents. These findings have significant implications for further improvement of vaccine administration and China’s participation in global healthcare.

Keywords: legislation, lot release, public health, reform, vaccine administration, vaccine circulation

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Authors: Mostafa Najim, Alaa Rahhal, Fadi Khir, Safae Abu Yousef, Amer Aljundi, Feryal Ibrahim, Aliaa Amer, Ahmed Soliman Mohamed, Samira Saleh, Dekra Alfaridi, Ahmed Mahfouz, Sumaya Al-Yafei, Faraj Howady, Mohamad Yahya Khatib, Samar Alemadi

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Background: Coronavirus disease 2019 (COVID-19) increases the risk of coagulopathy among critically ill patients. Although the presence of antiphospholipid antibodies (aPLs) has been proposed as a possible mechanism of COVID-19 induced coagulopathy, their clinical significance among critically ill patients with COVID-19 remains uncertain. Methods: This prospective observational study included patients with COVID-19 admitted to intensive care units (ICU) to evaluate the prevalence and clinical significance of aPLs, including anticardiolipin IgG/IgM, anti-β2-glycoprotein IgG/IgM, and lupus anticoagulant. The study outcomes included the prevalence of aPLs, a primary composite outcome of all-cause mortality, and arterial or venous thrombosis among aPLs positive patients versus aPLs negative patients during their ICU stay. Multiple logistic regression was used to assess the influence of aPLs on the primary composite outcome of mortality and thrombosis. Results: A total of 60 critically ill patients were enrolled. Of whom, 57 (95%) were male, with a mean age of 52.8 ± 12.2 years, and the majority were from Asia (68%). Twenty-two patients (37%) were found to have positive aPLs; of whom 21 patients were positive for lupus anticoagulant, whereas one patient was positive for anti-β2-glycoprotein IgG/IgM. The composite outcome of mortality and thrombosis during ICU did not differ among patients with positive aPLs compared to those with negative aPLs (4 (18%) vs. 6 (16%), aOR= 0.98, 95% CI 0.1-6.7; p-value= 0.986). Likewise, the secondary outcomes, including all-cause mortality, venous thrombosis, arterial thrombosis, discharge from ICU, time to mortality, and time to discharge from ICU, did not differ between those with positive aPLs upon ICU admission in comparison to patients with negative aPLs. Conclusion: The presence of aPLs does not seem to affect the outcomes of critically ill patients with COVID-19 in terms of all-cause mortality and thrombosis. Therefore, clinicians may not screen critically ill patients with COVID-19 for aPLs unless deemed clinically appropriate.

Keywords: antiphospholipid antibodies, critically ill patients, coagulopathy, coronavirus

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Authors: Karissa A. Graham

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Pyoderma gangrenosum (PG) is a prototypic autoinflammatory neutrophilic dermatosis that is a rare disorder. It presents a diagnostic challenge owing to its variable presentation, clinical overlap with other conditions, it is often associated with other systemic conditions, and there is no definitive histological or laboratory characteristic. The Delphai consensus for PG includes the presence of at least one ulcer on the anterior lower limb. Systemic corticosteroids and immunosuppressive therapies are the mainstay treatment for PG. We describe a case report of delayed diagnosis of ulcerative pyoderma gangrenosum in a 44-year-old male on his forearm. The patient presented with an infected ulcer on his right forearm that had been present for over three years. The patient was a Type 2 Diabetic with no personal or family history of inflammatory bowel disease or other autoimmune diseases. The patient was initially investigated for malignancy, but biopsies returned as chronic inflammatory tissue with neutrophilic infiltrate and no malignancy. The patient was commenced on systemic prednisone for the treatment of pyoderma gangrenosum. The diagnosis of ulcerative PG poses a challenge given the vast differential diagnosis for a cutaneous ulcer (i.e., malignant, vascular, autoimmune, trauma, infective, etc.). Diagnostic accuracy is important given that the treatment for PG with steroids does not go without risks and indeed may be contraindicated in other potential causes of the ulcer. Indeed, more common and more sinister causes of ulcers should be investigated first, as death from PG is quite rare.

Keywords: dermatological diagnosis, dermatosis, pyoderma gangrenosum, rare presentation

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Authors: Iván González, Pablo Andrés Maya, Sebastián Jaén

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Eco-industrial parks (EIPs) work as networks for the exchange of by-products, such as materials, water, or energy. This research identifies the relevant factors in the formation of EIPs in different industrial environments around the world. Then an aggregation of these factors is carried out to reduce them from 50 to 17 and classify them according to 5 fundamental axes. Subsequently, the Vester Sensitivity Model (VSM) systemic methodology is used to determine the influence of the 17 factors on an EIP system and the interrelationship between them. The results show that the sequence of effects between factors: Trust and Cooperation → Business Association → Flows → Additional Income represents the “backbone” of the system, being the most significant chain of influences. In addition, the Organizational Culture represents the turning point of the Industrial Symbiosis on which it must act correctly to avoid falling into unsustainable economic development. Finally, the flow of Information should not be lost since it is what feeds trust between the parties, and the latter strengthens the system in the face of individual or global imbalances. This systemic understanding will enable the formulation of pertinent policies by the actors that interact in the formation and permanence of the EIP. In this way, it seeks to promote large-scale sustainable industrial development, integrating various community actors, which in turn will give greater awareness and appropriation of the current importance of sustainability in industrial production.

Keywords: critical factors, eco-industrial park, industrial symbiosis, system methodology

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Authors: Cherif Y., Ghariani R., Derbal S., Farhati S., Ben Dahmen F., Abdallah M.

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Introduction: Tuberculosis (TBC) is a frequent infection and is still a major public health problem in Tunisia. The aim of this work is to focus on diagnostic and therapeutic characteristics of TBC in patients referred to our internal medicine department. Patients and Methods: The study was retrospective and descriptive of a cohort of consecutive cases treated from January 2016 to December 2019, collecting patients with latent or patent TBC. Twenty-eight medical records of adults diagnosed with TBC were reviewed. Results: Twenty-eight patients, including 18 women and 10 men, were diagnosed with TBC. Their mean age is 48 years (range: 22-78 years). Five patients have a medical history of diabetes mellitus, 1 patient was followed for systemic lupus erythematosus treated with corticosteroids and immunosuppressant drugs, and another was treated with corticosteroids for Mac Duffy syndrome. The TBC is latent in 12 cases and patent in 16 cases. The most common symptoms were fever and weight loss and were found in 10 cases, a cough in 2 cases, sputum in 3 cases, lymph nodes in 4 cases, erythema nodosum in 2 cases, and neurological signs in 3 cases. Lymphopenia is noticed in 3 cases and a biological inflammatory syndrome in 18 of the cases. The purified protein derivate reaction was positive in 17 cases, anergic in 3 cases, negative in 5 cases, and not done in 3 cases. The acid-fast bacilli stain culture was strongly positive in one patient. The histopathological study was conclusive in 11 patients and showed granulomatosis with caseous necrosis. TBC was pulmonary in 7 patients, lymph node in 7 cases, peritoneal in 7 cases, digestive in 1 case, neuromeningeal in 3 cases, and thyroïd in 1 case. Seven patients had multifocal TBC. All the patients received anti-tuberculosis treatment with a mean duration of 8 months with no failure or relapse with an average follow-up time of 10.58 months. Conclusion: Diagnosis and management of TBC remain essential to avoid serious complications. The survey is necessary to ensure timely detection and treatment of infected adults to decrease its incidence. The best treatment remains preventive through vaccination and improving social and economic conditions.

Keywords: tuberculosis, infection, autoimmune disease, granulomatosis

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Authors: Xueying Li

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Different from English, it is common to observe Chinese clauses logically related in an implicit way without any conjunctions. This typological difference has posed a great challenge for Chinese-English translators, as 1) translators may interpret logical meaning in different ways when there are no conjunctions in Chinese Source Text (ST); 2) translators may have questions whether to make Chinese implicit logical meaning explicit or to remain implicit in Target Text (TT), and whether other dimensions of logical meaning (e.g., type of logical meaning) should be shifted or not. Against this background, this study examines a comprehensive arrange of Chinese-English translation choices of logical meaning to deal with this challenge in a systematic way. It compiles several ST-TT passages from a set of translation textbooks in a corpus, namely Ying Yu Bi Yi Shi Wu (Er Ji)) [Translation Practice between Chinese and English: Intermediate Level] and its supportive training book, analyzes how logical meaning in ST are translated in TT in texts across different text types with Systemic Functional Linguistics (SFL) as the theoretical framework, and finally draws a system network of translation choices of logical meaning from Chinese into English. Since translators may probably think about semantic meaning rather than lexico-grammatical resources in translation, this study goes away from traditional lexico-grammatical choices, but rather describing translation choices from the semantic level. The findings in this study can provide some help and support for translation practitioners so that they can understand that besides explicitation, there are a variety of possible linguistic choices available for making informed decisions when translating Chinese logical meaning into English.

Keywords: Chinese-English translation, logical meaning, systemic functional linguistics, translation choices

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Authors: Ratna Kuswardani

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This paper aims to study the impact of recent Global Financial Crisis (GFC) on 6 selected emerging Asian economies (Indonesia, Malaysia, Thailand, Philippines, Singapore, and South Korea). We first figure out the contagion of GFC from the US and Europe to the selected emerging Asian countries by studying the tail dependence of market stock returns between those countries. We apply the concept of Extreme Value Theory (EVT) to model the dependence between multiple returns series of variables under examination. We explore the factors causing the contagion between the regions. We find dependencies between markets that are influenced by their size, especially for large markets in emerging Asian countries that tend to have a higher dependency to the market in the more advanced country such as the U.S. and some countries in Europe. The results also suggest that the dependencies between market returns and bank stock returns in the same region tend to be higher than dependencies between these returns across two different regions. We extend our analysis by studying the impact of GFC on the systemic in the banking system. We also find that larger institution has more dependencies with the market stock, suggesting that larger size bank can cause disruption in the market. Further, the higher probability of extreme loss can be seen during the crisis period, which is shown by the non-linear dependency between the pre-crisis and the post-crisis period. Finally, our analysis suggests that systemic risk appears in the domestic banking systems in emerging Asia, as shown by the extreme dependencies within banks in the system. Overall, our results provide caution to policy makers and investors alike on the possible contagion of the impact of global financial crisis across different markets.

Keywords: contagion, extreme value theory, global financial crisis, systemic risk

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Authors: Rachel Jones

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Systemic Family therapy in the Queensland Foster Care System is the implementation of Integrative Practice as a purposeful intervention implemented with complex ‘family’ systems (by expanding the traditional concept of family to include all relevant stakeholders for a child) and is shown to improve the overall wellbeing of children (with developmental delays and trauma) in Queensland out of home care contexts. The importance of purposeful integrative practice in the field of systemic family therapy has been highlighted in achieving change in complex family systems. Essentially, it is the purposeful use of multiple interventions designed to meet the myriad of competing needs apparent for a child (with developmental delays resulting from early traumatic experiences - both in utero and in their early years) and their family. In the out-of-home care context, integrative practice is particularly useful to promote positive change for the child and what is an extended concept of whom constitutes their family. Traditionally, a child’s family may have included biological and foster care family members, but when this concept is extended to include all their relevant stakeholders (including biological family, foster carers, residential care workers, child safety, school representatives, Health and Allied Health staff, police and youth justice staff), the use of integrative family therapy can produce positive change for the child in their overall wellbeing, development, risk profile, social and emotional functioning, mental health symptoms and relationships across domains. By tailoring therapeutic interventions that draw on systemic family therapies from the first and second-order schools of family therapy, neurobiology, solution focussed, trauma-informed, play and art therapy, and narrative interventions, disability/behavioural interventions, clinicians can promote change by mixing therapeutic modalities with the individual and their stakeholders. This presentation will unpack the implementation of systemic family therapy using this integrative approach to formulation and treatment for a child in out-of-home care in Queensland (experiencing developmental delays resulting from trauma). It considers the need for intervention for the individual and in the context of the environment and relationships. By reviewing a case example, this study aims to highlight the simultaneous and successful use of pharmacological interventions, psychoeducational programs for carers and school staff, parenting programs, cognitive-behavioural and trauma-informed interventions, traditional disability approaches, play therapy, mapping genograms and meaning-making, and using family and dyadic sessions for the system associated with the foster child. These elements of integrative systemic family practice have seen success in the reduction of symptoms and improved overall well-being of foster children and their stakeholders. Accordingly, a model for best practice using this integrative systemic approach is presented for this population group and preliminary findings for this approach over four years of local data have been reviewed.

Keywords: systemic family therapy, treating families of children with delays, trauma and attachment in families systems, improving practice and functioning of children and families

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Authors: Gerard Bray, Arya Bahadori, Sachinka Ranasinghe

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Renal cell carcinoma (RCC) is among the top 10 most common cancers worldwide, where metastatic disease carries a poor prognosis. Herein, we present a 74-year-old male presenting with asymptomatic solitary metachronous metastasis to the gall bladder 4 years following nephrectomy for clear cell RCC. Solitary RCC metastasis to the gall bladder following nephrectomy is rarely reported in the literature and brings with it a clinical conundrum of whether surgical resection or systemic therapy should be utilized. In this case, surgical excision with cholecystectomy was employed without systemic therapy. We, therefore, contribute a rare and interesting case that highlights that metastasectomy of a solitary metastasis can improve survival according to current literature.

Keywords: renal cell carcinoma, gall bladder metastasis, solitary metastasectomy, metachronous

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Authors: Jadwiga Królikowska, Andrzej Królikowski, Jarosław Bajer

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The work delineates the threats of maladjustment of the capacity of rain canals, designed and built in the early 20th century, in connection to heavy rainfall, especially in summer. This is the cause of the so called 'urban floods.' It directly relates to fierce raise of paving in the cities. Resolving this problem requires a change in philosophy of draining the rainfall by wider use of retention, infiltration and usage of rainwater. In systemic approach to managing the safety of urban drainage systems the risk, which is directly connected to safety failures, has been accepted as a measure. The risk level defines the probability of occurrence of losses greater than the ones forecast for a given time frame. The procedure of risk modelling, enabling its numeric analysis by using appropriate weights, is a significant issue in this paper.

Keywords: risk management, drainage system, urban areas, urban floods

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