Search results for: plantation survival
902 Clinical Efficacy of Nivolumab and Ipilimumab Combination Therapy for the Treatment of Advanced Melanoma: A Systematic Review and Meta-Analysis of Clinical Trials
Authors: Zhipeng Yan, Janice Wing-Tung Kwong, Ching-Lung Lai
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Background: Advanced melanoma accounts for the majority of skin cancer death due to its poor prognosis. Nivolumab and ipilimumab are monoclonal antibodies targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocytes antigen 4 (CTLA-4). Nivolumab and ipilimumab combination therapy has been proven to be effective for advanced melanoma. This systematic review and meta-analysis are to evaluate its clinical efficacy and adverse events. Method: A systematic search was done on databases (Pubmed, Embase, Medline, Cochrane) on 21 June 2020. Search keywords were nivolumab, ipilimumab, melanoma, and randomised controlled trials. Clinical trials fulfilling the inclusion criteria were selected to evaluate the efficacy of combination therapy in terms of prolongation of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The odd ratios and distributions of grade 3 or above adverse events were documented. Subgroup analysis was performed based on PD-L1 expression-status and BRAF-mutation status. Results: Compared with nivolumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR in combination therapy were 0.64 (95% CI, 0.48-0.85; p=0.002), 0.84 (95% CI, 0.74-0.95; p=0.007) and 1.76 (95% CI, 1.51-2.06; p < 0.001), respectively. Compared with ipilimumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR were 0.46 (95% CI, 0.37-0.57; p < 0.001), 0.54 (95% CI, 0.48-0.61; p < 0.001) and 6.18 (95% CI, 5.19-7.36; p < 0.001), respectively. In combination therapy, the odds ratios of grade 3 or above adverse events were 4.71 (95% CI, 3.57-6.22; p < 0.001) compared with nivolumab monotherapy, and 3.44 (95% CI, 2.49-4.74; p < 0.001) compared with ipilimumab monotherapy, respectively. High PD-L1 expression level and BRAF mutation were associated with better clinical outcomes in patients receiving combination therapy. Conclusion: Combination therapy is effective for the treatment of advanced melanoma. Adverse events were common but manageable. Better clinical outcomes were observed in patients with high PD-L1 expression levels and positive BRAF-mutation.Keywords: nivolumab, ipilimumab, advanced melanoma, systematic review, meta-analysis
Procedia PDF Downloads 138901 Role of Human Epididymis Protein 4 as a Biomarker in the Diagnosis of Ovarian Cancer
Authors: Amar Ranjan, Julieana Durai, Pranay Tanwar
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Background &Introduction: Ovarian cancer is one of the most common malignant tumor in the female. 70% of the cases of ovarian cancer are diagnosed at an advanced stage. The five-year survival rate associated with ovarian cancer is less than 30%. The early diagnosis of ovarian cancer becomes a key factor in improving the survival rate of patients. Presently, CAl25 (carbohydrate antigen125) is used for the diagnosis and therapeutic monitoring of ovarian cancer, but its sensitivity and specificity is not ideal. The introduction of HE4, human epididymis protein 4 has attracted much attention. HE4 has a sensitivity and specificity of 72.9% and 95% for differentiating between benign and malignant adnexal masses, which is better than CA125 detection. Methods: Serum HE4 and CA -125 were estimated using the chemiluminescence method. Our cases were 40 epithelial ovarian cancer, 9 benign ovarian tumor, 29 benign gynaecological diseases and 13 healthy individuals. This group include healthy woman those who have undergoing family planning and menopause-related medical consultations and they are negative for ovarian mass. Optimal cut off values for HE4 and CA125 were 55.89pmol/L and 40.25U/L respectively (determined by statistical analysis). Results: The level of HE4 was raised in all ovarian cancer patients (n=40) whereas CA125 levels were normal in 6/40 ovarian cancer patients, which were the cases of OC confirmed by histopathology. There is a significant decrease in the level of HE4 with comparison to CA125 in benign ovarian tumor cases. Both the levels of HE4 and CA125 were raised in the nonovarian cancer group, which includes cancer of endometrium and cervix. In the healthy group, HE4 was normal in all patients except in one case of the rudimentary horn, and the reason for this raised HE4 level is due to the incomplete development of uterus whereas CA125 was raised in 3 cases. Conclusions: Findings showed that the serum level of HE4 is an important indicator in the diagnosis of ovarian cancer, and it also distinguishes between benign and malignant pelvic masses. However, a combination of HE4 and CA125 panel will be extremely valuable in improving the diagnostic efficiency of ovarian cancer. These findings of our study need to be validated in the larger cohort of patients.Keywords: human epididymis protein 4, ovarian cancer, diagnosis, benign lesions
Procedia PDF Downloads 131900 Grade and Maximum Tumor Dimension as Determinants of Lymphadenectomy in Patients with Endometrioid Endometrial Cancer (EEC)
Authors: Ali A. Bazzi, Ameer Hamza, Riley O’Hara, Kimberly Kado, Karen H. Hagglund, Lamia Fathallah, Robert T. Morris
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Introduction: Endometrial Cancer is a common gynecologic malignancy primarily treated with complete surgical staging, which may include complete pelvic and para-aortic lymphadenectomy. The role of lymphadenectomy is controversial, especially the intraoperative indications for the procedure. Three factors are important in decision to proceed with lymphadenectomy: Myometrial invasion, maximum tumor dimension, and histology. Many institutions incorporate these criteria in varying degrees in the decision to proceed with lymphadenectomy. This investigation assesses the use of intraoperatively measured MTD with and without pre-operative histologic grade. Methods: This study compared retrospectively EEC patients with intraoperatively measured MTD ≤2 cm to those with MTD >2 cm from January 1, 2002 to August 31, 2017. This assessment compared those with MTD ≤ 2cm with endometrial biopsy (EB) grade 1-2 to patients with MTD > 2cm with EB grade 3. Lymph node metastasis (LNM), recurrence, and survival were compared in these groups. Results: This study reviewed 222 patient cases. In tumors > 2 cm, LNM occurred in 20% cases while in tumors ≤ 2 cm, LNM was found in 6% cases (p=0.04). Recurrence and mean survival based on last follow up visit in these two groups were not statistically different (p=0.78 and 0.36 respectively). Data demonstrated a trend that when combined with preoperative EB International Federation of Gynecology and Obstetrics (FIGO) grade, a higher proportion of patients with EB FIGO Grade 3 and MTD > 2 cm had LNM compared to those with EB FIGO Grade 1-2 and MTD ≤ 2 cm (43% vs, 11%, p=0.06). LNM was found in 15% of cases in which lymphadenectomy was performed based on current practices, whereas if the criteria of EB FIGO 3 and MTD > 2 cm were used the incidence of LNM would have been 44% cases. However, using this criterion, two patients would not have had their nodal metastases detected. Compared to the current practice, the sensitivity and specificity of the proposed criteria would be 60% and 81%, respectively. The PPV and NPV would be 43% and 90%, respectively. Conclusion: The results indicate that MTD combined with EB FIGO grade can detect LNM in a higher proportion of cases when compared to current practice. MTD combined with EB FIGO grade may eliminate the need of frozen section sampling in a substantial number of cases.Keywords: endometrial cancer, FIGO grade, lymphadenectomy, tumor size
Procedia PDF Downloads 182899 A Profile of Out-of-Hospital Cardiac Arrest in ‘Amang’ Rodriguez Memorial Medical Center: A Prospective Cohort Study
Authors: Donna Erika E. De Jesus
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Introduction: Cardiac arrest occurs when abrupt cessation of cardiac function results in loss of effective circulation and complete cardiovascular collapse. For every minute of cardiac arrest without early intervention (cardiopulmonary resuscitation [CPR], defibrillation), chances of survival drop by 7-10%. It is crucial that CPR be initiated within 4-6 minutes to avoid brain death. Most out-of-hospital cardiac arrests (OHCA) occur in a residential setting where access to trained personnel and equipment is not readily available, resulting in poor victim outcomes. Methods: This is a descriptive study done from August to November 2021 using a prospective cohort design. Participants of the study include adult patients aged 18 years and above brought to the emergency room who suffered from out-of-hospital cardiac arrest. Out of the total 102 cases of OHCA, 63 participants were included in the study. Descriptive statistics were used to summarize the demographic and clinical characteristics of the patients. Results: 43 were male patients, comprising the majority at 73.02%. Hypertension was identified as the top co-morbidity, followed by diabetes mellitus, heart failure, and chronic kidney disease (CKD). Medical causes of arrest were identified in 96.83% of the cases. 90.48% of cardiac arrests occurred at home. Only 26 patients (41.27%) received pre-hospital intervention prior to ER arrival, which comprised only hands-only CPR. Twenty-three of which were performed by individuals with background knowledge of CPR. 60.32% were brought via self-conduction, the remainder by ambulances, which were noted to have no available equipment necessary to provide proper resuscitation. The average travel time from dispatch to ER arrival is 20 minutes. Conclusion: Overall survival of OHCA in our local setting remains dismal, as a return of spontaneous circulation was not achieved in any of the patients. The small number of patients having pre-hospital CPR indicates the need for emphasis on training and community education.Keywords: out-of-hospital cardiac arrest, cardiopulmonary resuscitation, basic life support, emergency medical services
Procedia PDF Downloads 108898 Management of Small-Scale Companies in Nigeria. Case Study of Problems Faced by Entrepreneurs
Authors: Aderemi, Moses Aderibigbe
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The supply chain of a manufacturing company can be classified into three categories, namely: 1) supplier chain, these are a network of suppliers of raw materials, machinery, and other requirements for daily operations for the company; 2) internal chain, which are departmental or functional relationships within the organization like production, finance, marketing, logistic and quality control departments all interacting together to achieve the goals and objective of the company; and 3) customer chain; these are networks used for products distribution to the final consumer which includes the product distributors and retailers in the marketplace as may be applicable. In a developing country like Nigeria, where government infrastructures are poor or, in some cases, none in existence, the survival of a small-scale manufacturing company often depends on how effectively its supply chain is managed. In Nigeria, suppliers of machinery and raw materials to most manufacturing companies are from low-cost but high-tech countries like China or India. The problem with the supply chain from these countries apart from the language barrier between these countries and Nigeria, is also that of product quality and after-sales support services. The internal chain also requires funding to employ an experienced and trained workforce to deliver the company’s goals and objectives effectively and efficiently, which is always a challenge for small-scale manufacturers, including product marketing. In Nigeria, the management of the supply chain by small-scale manufacturers is further complicated by unfavourable government policies. This empirical research is a review and analysis of the supply chain management of a small-scale manufacturing company located in Lagos, Nigeria. The company's performance for the past five years has been on the decline and company management thinks there is a need for a review of its supply chain management for business survival. The company’s supply chain is analyzed and compared with best global practices in this research, and recommendations are made to the company management. The research outcome justifies the company’s need for a strategic change in its supply chain management for business sustainability and provides a learning point to small-scale manufacturing companies from developing countries in AfricaKeywords: management, small scale, supply chain, companies, leaders
Procedia PDF Downloads 26897 Analysis of Bed Load Sediment Transport Mataram-Babarsari Irrigation Canal
Authors: Agatha Padma Laksitaningtyas, Sumiyati Gunawan
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Mataram Irrigation Canal has 31,2 km length, is the main irrigation canal in Special Region Province of Yogyakarta, connecting Progo River on the west side and Opak River on the east side. It has an important role as the main water carrier distribution for various purposes such as agriculture, fishery, and plantation which should be free from sediment material. Bed Load Sediment is the basic sediment that will make the sediment process on the irrigation canal. Sediment process is a simultaneous event that can make deposition sediment at the base of irrigation canal and can make the height of elevation water change, it will affect the availability of water to be used for irrigation functions. To predict the amount of drowning sediments in the irrigation canal using two methods: Meyer-Peter and Muller’s Method which is an energy approach method and Einstein Method which is a probabilistic approach. Speed measurement using floating method and using current meters. The channel geometry is measured directly in the field. The basic sediment of the channel is taken in the field by taking three samples from three different points. The result of the research shows that by using the formula Meyer -Peter Muller get the result of 60,75799 kg/s, whereas with Einsten’s Method get result of 13,06461 kg/s. the results may serve as a reference for dredging the sediments on the channel so as not to disrupt the flow of water in irrigation canal.Keywords: bed load, sediment, irrigation, Mataram canal
Procedia PDF Downloads 229896 Twist2 Is a Key Regulator of Cell Proliferation in Acute Lymphoblastic Leukaemia
Authors: Magdalena Rusady Goey, Gordon Strathdee, Neil Perkins
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Background: Acute lymphoblastic leukaemia (ALL) is the most frequent type of childhood malignancy, accounting for 25% of all cases. TWIST2, a basic helix-loop-helix transcription factor, has been implicated in ALL development. Prior studies found that TWIST2 undergoes epigenetic silencing in more than 50% cases of ALL through promoter hypermethylation and suggested that re-expression of TWIST2 may inhibit cell growth/survival of leukaemia cell lines. TWIST2 has also been implicated as a regulator of NF-kappaB activity, which is constitutively active in leukaemia. Here, we use a lentiviral transductions system to confirm the importance of TWIST2 in controlling leukaemia cell growth and to investigate whether this is achieved through altered regulation of NF-kappaB activity. Method: Re-expression of TWIST2 in leukaemia cell lines was achieved using lentiviral-based transduction. The lentiviral vector also expresses enhanced green fluorescent protein (eGFP), allowing transduced cells to be tracked using flow cytometry. Analysis of apoptosis and cell proliferation were done using annexinV and VPD450 staining, respectively. Result and Discussion: TWIST2-expressing cells were rapidly depleted from a mixed population in ALL cell lines (NALM6 and Reh), indicating that TWIST2 inhibited cell growth/survival of ALL cells. In contrast, myeloid cell lines (HL60 and K562) were comparatively insensitive to TWIST2 re-expression. Analysis of apoptosis and cell proliferation found no significant induction of apoptosis, but did find a rapid induction of proliferation arrest in TWIST2-expressing Reh and NALM6 cells. Initial experiment with NF-kappaB inhibitor demonstrated that inhibition of NF-kappaB has similar impact on cell proliferation in the ALL cell lines, suggesting that TWITST2 may induce cell proliferation arrest through inhibition of NF-kappaB. Conclusion: The results of this study suggest that epigenetic inactivation of TWIST2 in primary ALL leads to increased proliferation, potentially by altering the regulation of NF-kappaB.Keywords: leukaemia, acute lymphoblastic leukaemia, NF-kappaB, TWIST2, lentivirus
Procedia PDF Downloads 346895 Influence of IL-1β on Hamster Blastocyst Hatching via Regulation of Hatching Associated Proteases
Authors: Madhulika Pathak, Polani Seshagiri, Vani Venkatappa
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Blastocyst hatching is an indispensable process for successful implantation. One of the major reasons for implantation failure in IVF clinic is poor quality of embryo, which are not development/hatching-competent. Therefore, attempts are required to develop or enhance the culture system with a molecule recapitulating the autocrine/paracrine factors containing the environment of in-vivo endometrial milieu. We have tried to explore the functional molecules involved in the hamster hatching phenomenon. Blastocyst hatching is governed by several molecules that are entwined and regulate this process, among which cytokines are known to be expressed and are still least explored. Two of such cytokines we have used for our study are IL-1β and its natural antagonist IL-1ra to understand the functional dynamics of cytokines involved in the hatching process. Using hamster, an intriguing experimental model for hatching behavior, we have shown the mRNA (qPCR) and protein (ICC) expression of IL-1β, IL-1ra and IL-1 receptor type 1 throughout all the stages of morula, blastocyst and hatched blastocyst. Post-asserting the expression, the functional role is shown by supplementation studies, where IL-1β supplementation showed enhancement in hatching level (IL-1β treated: 84.1 ± 4.2% vs control: 63.7 ± 3.1 %, N=11), further confirmed by the diminishing effect of IL-1ra on hatching rate (IL-1ra treated: 27.5 ± 11.1% vs control: 67.9 ± 3.1%). The exogenous supplementation of IL-1ra decreased the survival rate of embryos and affected the viability in dose-dependent manner, establishing the importance of IL-1β in blastocyst cell survival. Previously, the cathepsin L and B were established as the proteases that were involved in the hamster hatching process. The inducing effect of IL-1β was correlated with enhanced mRNA level, as analyzed by qPCR, for both CAT L (by 1.9 ± 0.5 fold) and CAT B (by 3.5 ± 0.1) fold which was diminished in presence of IL-1ra (Cat L by 88 percent and Cat B by 94 percent. Moreover, using a specific fluorescent substrate-based assay kit, the enzymatic activity of these proteases was found to be increased in presence of IL-1β (Cat L by 2.1 ± 0.1 fold and CAT B by 2.3 ± 0.7 fold) and was curtailed in presence of IL-1ra. These observations provide functional insights with respect to the involvement of cytokines in the hatching process. This has implications in understanding the hatching biology and improving the embryo development quality in IVF clinics.Keywords: Blastocyst, Cytokines, Hatching, Interleukin
Procedia PDF Downloads 145894 Long Non-Coding RNAs Mediated Regulation of Diabetes in Humanized Mouse
Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo
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Long noncoding RNA (lncRNA) mediated post-transcriptional gene regulation, and their epigenetic landscapes have been shown to be involved in many human diseases. However, their regulation in diabetes through governing islet’s β-cell function and survival needs to be elucidated. Due to the technical and ethical constraints, it is difficult to study their role in β-cell function and survival in human under in vivo condition. In this study, humanized mice have been developed through transplanting human pancreatic islet under the kidney capsule of NOD.SCID mice and induced β-cell death leading to diabetes condition to study lncRNA mediated regulation. For this, human islets from 3 donors (3000 IEQ, purity > 80%) were transplanted under the kidney capsule of STZ induced diabetic NOD.scid mice. After at least 2 weeks of normoglycecemia, lymphocytes from diabetic NOD mice were adoptively transferred and islet grafts were collected once blood glucose reached > 200 mg/dl. RNA from human donor islets, islet grafts from humanized mice with either adoptive lymphocyte transfer (ALT) or PBS control (CTL) were ribodepleted; barcoded fragment libraries were constructed and sequenced on the Ion Proton sequencer. lncRNA expression in isolated human islets, islet grafts from humanized mice with and without induced β-cell death and their regulation in human islets function in vitro under glucose challenge, cytokine mediated inflammation and induced apoptotic condition were investigated. Out of 3155 detected lncRNAs, 299 that highly expressed in islets were found to be significantly downregulated and 224 upregulated in ALT compared to CTL. Most of these are found to be collocated within 5 kb upstream and 1 kb downstream of 788 up- and 624 down-regulated mRNAs. Genomic Regions Enrichment of Annotations Analysis revealed deregulated and collocated genes are related to pancreas endocrine development; insulin synthesis, processing, and secretion; pancreatitis and diabetes. Many of them, that found to be located within enhancer domains for islet specific gene activity, are associated to the deregulation of known islet/βcell specific transcription factors and genes that are important for β-cell differentiation, identity, and function. RNA sequencing analysis revealed aberrant lncRNA expression which is associated to the deregulated mRNAs in β-cell function as well as in molecular pathways related to diabetes. A distinct set of candidate lncRNA isoforms were identified as highly enriched and specific to human islets, which are deregulated in human islets from donors with different BMIs and with type 2 diabetes. These RNAs show an interesting regulation in cultured human islets under glucose stimulation and with induced β-cell death by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the media of islets cultured with cytokines. Results of this study suggest that the islet specific lncRNAs are deregulated in human islet with β-cell death, hence important in diabetes. These lncRNAs might be important for human β-cell function and survival thus could be used as biomarkers and novel therapeutic targets for diabetes.Keywords: β-cell, humanized mouse, pancreatic islet, LncRNAs
Procedia PDF Downloads 164893 Investigating Legal Consciousness Among Migrants in Greece: A Study of Migrant’s Views of Hate Crime and their Legal Rights
Authors: Violeta Kapageorgiadou
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Over the past decade, millions of individuals from middle-eastern and African countries have migrated to Europe to seek refuge. The majority of these refugees emigrate from Muslim majority countries and seek to integrate into European societies. Notably, Greece has hosted thousands of individuals seeking asylum since 2015. Many of these individuals have applied for asylum. They have sought to integrate into the Greek society and to navigate their way through the national and European legal systems with regard to their status. This paper, drawn from a PhD thesis project, focuses on the legal consciousness of migrants and the processes open to asylum seekers to assert their rights, notably with regard to incidents of hate crime and including their interactions with the legal authorities in Greece. The research seeks to capture the factors that influence the views and behaviors of migrants towards the law and their legal rights, using legal consciousness as a theoretical framework. The research findings indicate that asylum seekers have developed a multidimensional legal consciousness influenced by their religious and political background, legal knowledge, previous (negative) experiences with the legal system and their socio-economic status in Greece. Asylum seekers, while aware of the rights essential for their survival in the host country (such as applying for asylum to obtain a secure status, claiming for benefits and housing), were unaware of, and less willing to engage with, legal authorities and rights which they did not find essential for their survival. They viewed hate incidents against them as less important, not worth reporting and sometimes did not even consider these incidents as crimes. The research suggests that asylum seekers in Greece are a vulnerable population who need mechanisms to support them and raise their legal consciousness around their rights in order to better integrate, develop and thrive in the host society. Moving forwards, a better understanding of refugees' and asylum seekers’ reactions towards hate crime will help to create future policies and support mechanisms that could improve the lives of these individuals.Keywords: hate crime, legal consciousness, legal rights, migrations
Procedia PDF Downloads 223892 Proteomic Analysis of the Inhibition of Prolyl Oligopeptidase Induced by Z-Pro-Prolinal in Filarial Parasites
Authors: Mohit Wadhawan, Sushma Rathaur
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Lymphatic filariasis, also called elephantiasis is a tropical disease afflicting over 120 million people in 81 countries worldwide. Existing anti filarial drugs are effective against the larval stages of filarial parasites which call for an urgent need of drugs which are macrofilaricidal. Identification of molecular targets crucial for survival of filarial parasites is a prerequisite for drug designing. Prolyl oligopeptidase (POP) is one such crucial enzyme involved in the maturation and degradation of neuropeptides and peptide hormones. We have identified this peptidase in the bovine filarial parasite, Setaria cervi. Effect of inhibition of POP on the proteome profile of filarial parasite has been discussed in this study. Filarial parasites were exposed to Z-pro-prolinal (ZPP), a specific POP inhibitor for 8 h and the motility and viability of the parasites was observed. It significantly reduced the motility and viability of the parasites. To study the proteome profile, the cytosolic, endoplasmic reticulum (ER) and mitochondrial extracts of the adult female parasites were subjected to 2-dimensional electrophoresis. As analyzed by the PD-Quest software, the ZPP caused the alteration in the different subcellular proteins, and the significantly altered proteins were identified using MALDI-MS/MS spectrometry. The major proteins identified were found to play important role in diverse biological functions like signaling, redox regulation, energy metabolism, stress response, and cytoskeleton formation. Moreover, we found upregulation in the calcium binding proteins such as calreticulin, calponin, and calpain-6 suggesting that POP inhibition regulates calcium release. This relates to earlier reports that POP plays non-catalytic role in inositol 1,4,5-trisphosphate (IP3) signaling inducing release of calcium from ER. Taken together, the data demonstrated that inhibition of prolyl oligopeptidase alter the overall proteome signifying its role in survival of the filarial parasites. Thus this study provides a basis for the use of POP as a chemotherapeutic target for the treatment of lymphatic filariasis.Keywords: lymphatic filariasis, setaria cervi, prolyl oligopeptidase, proteomics
Procedia PDF Downloads 285891 Outcome of Unilateral Retinoblastoma: A Ten Years Experience of Children's Cancer, Hospital Egypt
Authors: Ahmed Elhussein, Hossam El-Zomor, Adel Alieldin, Mahmoud A. Afifi, Abdullah Elhusseiny, Hala Taha, Amal Refaat, Soha Ahmed, Mohamed S. Zagloul
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Background: A majority of children with retinoblastoma (60%) have a disease in one eye only (unilateral disease). This is a retrospective study to evaluate two different treatment modalities in those patients for saving their lives and vision. Methods: Four hundred and four patients were diagnosed with unilateral intraocular retinoblastoma at Children’s Cancer, Hospital Egypt (CCHE) through the period of July/2007 until December/2017. Management strategies included primary enucleation versus ocular salvage treatment. Results: Patients presented with mean age 24.5 months with range (1.2-154.3 months). According to the international retinoblastoma classification, Group D (n=172, 42%) was the most common, followed by group E (n=142, 35%), group C (n=63, 16%), and group B (n=27, 7%). All patients were alive at the end of the study except four patients who died, with 5-years overall survival 98.3% [CI, (96.5-100%)]. Patients presented with advanced disease and poor visual prognosis (n=241, 59.6%) underwent primary enucleation with 6 cycles adjuvant chemotherapy if they had high-risk features in the enucleated eye; only four patients out of 241 ended-up either with extraocular metastasis (n=3) or death (n=1). While systemic chemotherapy and focal therapy were the primary treatment for those who presented with favorable disease status and good visual prognosis (n=163, 40.4%); seventy-seven patients of them (47%) ended up with a pre-defined event (enucleation, EBRT, off protocol chemotherapy or 2ry malignancy). Ocular survival for patients received primary chemotherapy + focal therapy was [50.9% (CI, 43.5-59.6%)] at 3 years and [46.9% (CI,39.3-56%)] at 5 years. Comparison between upfront enucleation and primary chemotherapy for occurrence of extraocular metastasis revealed that there was no statistical difference between them except in group D (p value). While for occurrence of death, no statistical difference in all classification groups. Conclusion: In retinoblastoma, primary chemotherapy is a reasonable option and has a good probability for ocular salvage without increasing the risk of metastasis in comparison to upfront enucleation except in group D.Keywords: CCHE, chemotherapy, enucleation, retinoblastoma
Procedia PDF Downloads 155890 Evaluation of the Efficacy of Basic Life Support Teaching in Second and Third Year Medical Students
Authors: Bianca W. O. Silva, Adriana C. M. Andrade, Gustavo C. M. Lucena, Virna M. S. Lima
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Introduction: Basic life support (BLS) involves the immediate recognition of cardiopulmonary arrest. Each year, 359.400 and 275.000 individuals with cardiac arrest are attended in emergency departments in USA and Europe. Brazilian data shows that 200.000 cardiac arrests occur every year, and half of them out of the hospital. Medical schools around the world teach BLS in the first years of the course, but studies show that there is a decline of the knowledge as the years go by, affecting the chain of survival. The objective was to analyze the knowledge of medical students about BLS and the retention of this learning throughout the course. Methods: This study included 150 students who were at the second and third year of a medical school in Salvador, Bahia, Brazil. The instrument of data collection was a structured questionnaire composed of 20 questions based on the 2015 American Heart Association guideline. The Pearson Chi-square test was used in order to study the association between previous training, sex and semester with the degree of knowledge of the students. The Kruskal-Wallis test was used to evaluate the different yields obtained between the various semesters. The number of correct answers was described by average and quartiles. Results: Regarding the degree of knowledge, 19.6% of the female students reached the optimal classification, a better outcome than the achieved by the male participants. Of those with previous training, 33.33% were classified as good and optimal, none of the students reached the optimal classification and only 2.2% of them were classified as bad (those who did not have 52.6% of correct answers). The analysis of the degree of knowledge related to each semester revealed that the 5th semester had the highest outcome: 30.5%. However, the acquaintance presented by the semesters was generally unsatisfactory, since 50% of the students, or more, demonstrated knowledge levels classified as bad or regular. When confronting the different semesters and the achieved scores, the value of p was 0.831. Conclusion: It is important to focus on the training of medical professionals that are capable of facing emergency situations, improving the systematization of care, and thereby increasing the victims' possibility of survival.Keywords: basic life support, cardiopulmonary ressucitacion, education, medical students
Procedia PDF Downloads 187889 An Alternative Semi-Defined Larval Diet for Rearing of Sand Fly Species Phlebotomus argentipes in Laboratory
Authors: Faizan Hassan, Seema Kumari, V. P. Singh, Pradeep Das, Diwakar Singh Dinesh
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Phlebotomus argentipes is an established vector for Visceral Leishmaniasis in Indian subcontinent. Laboratory colonization of Sand flies is imperative in research on vectors, which requires a proper diet for their larvae and adult growth that ultimately affects their survival and fecundity. In most of the laboratories, adult Sand flies are reared on rabbit blood feeding/artificial blood feeding and their larvae on fine grinded rabbit faeces as a sole source of food. Rabbit faeces are unhygienic, difficult to handle, high mites infestation as well as owing to bad odour which creates menacing to human users ranging from respiratory problems to eye infection and most importantly it does not full fill all the nutrients required for proper growth and development. It is generally observed that the adult emergence is very low in comparison to egg hatched, which may be due to insufficient food nutrients provided to growing larvae. To check the role of food nutrients on larvae survival and adult emergence, a high protein rich artificial diet for sand fly larvae were used in this study. The composition of artificial diet to be tested includes fine grinded (9 gm each) Rice, Pea nuts & Soyabean balls. These three food ingredients are rich source of all essential amino acids along with carbohydrate and minerals which is essential for proper metabolism and growth. In this study artificial food was found significantly more effective for larval development and adult emergence than rabbit faeces alone (P value >0.05). The weight of individual larvae was also found higher in test pots than the control. This study suggest that protein plays an important role in insect larvae development and adding carbohydrate will also enhances the fecundity of insects larvae.Keywords: artificial food, nutrients, Phlebotomus argentipes, sand fly
Procedia PDF Downloads 307888 Caspase-11 and AIM2 Inflammasome are Involved in Smoking-Induced COPD and Lung Adenocarcinoma
Authors: Chiara Colarusso, Michela Terlizzi, Aldo Pinto, Rosalinda Sorrentino
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Cigarette smoking is the main cause and the most common risk factor for both COPD and lung cancer. In our previous studies, we proved that caspase-11 in mice and its human analogue, caspase-4, are involved in lung carcinogenesis and that AIM2 inflammasome might play a pro-cancerous role in lung cancer. Therefore, the aim of this study was to investigate potential crosstalk between COPD and lung cancer, focusing on AIM2 and caspase-11-dependent inflammasome signaling pathway. To mimic COPD, we took advantage of an experimental first-hand smoking mouse model and, to confirm what was observed in mice, we used human samples of lung adenocarcinoma patients stratified according to the smoking and COPD status. We demonstrated that smoke exposure led to emphysema-like features, bronchial tone impairment, and release of IL-1-like cytokines (IL-1α, IL-1β, IL-33, IL-18) in a caspase-1 independent manner in C57Bl/6N. Rather, a dysfunctional caspase-11 in smoke-exposed 129Sv mice was associated to lower bronchial inflammation, collagen deposition, and IL-1-like inflammation. In addition, for the first time, we found that AIM2 inflammasome is involved in lung inflammation in smoking and COPD, in that its expression was higher in smoke-exposed C57Bl/6N compared to 129Sv smoking mice, who instead did not show any alteration of AIM2 in both macrophages and dendritic cells. Moreover, we found that AIM2 expression in the cancerous tissue, albeit higher than non-cancerous tissue, was not statistically different according to the COPD and smoking status. Instead, the higher expression of AIM2 in non-cancerous tissue of smoker COPD patients than smokers who did not have COPD was correlated to a higher hazard ratio of poor survival rate than patients who presented lower levels of AIM2. In conclusion, our data highlight that caspase-11 in mice is associated to smoke-induced lung latent inflammation which could drive the establishment of lung cancer, and that AIM2 inflammasome plays a role at the crosstalk between smoking/COPD and lung adenocarcinoma in that its higher presence is correlated to lower survival rate of smoker COPD adenocarcinoma.Keywords: COPD, inflammasome, lung cancer, lung inflammation, smoke
Procedia PDF Downloads 156887 Effector and Memory Immune Responses Induced by Total Extracts of Naegleria fowleri Co-Administered with Cholera Toxin
Authors: Q. B. Maria de la Luz Ortega Juárez, Saúl Rojas Hernández, Itzel Berenice Rodríguez Mera, María Maricela Carrasco Yépez, Mara Gutierrez Sánchez
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Naegleria fowleri is a free-living amoeba found mainly in temperate freshwater and is the etiologic agent of primary amebic meningoencephalitis (PAM), a fatal acute disease with a mortality rate greater than 95%. At present, there are no treatments available for MAP, and the development of effective vaccines that generate long-term immunological memory allowing protection against MAP would be of great importance. The objective of this work was to analyze the effector and memory immune response in BALB/c mice immunized with total extract of N. fowleri co-administered with cholera toxin. In this study, BALB/c mice were immunized four times intranasally with ET of N. fowleri adjuvanted with CT with or without booster at three months and were challenged or not with the lethal dose of N. fowleri, determining survival, the humoral, effector and memory response, by ELISA and flow cytometry techniques. The results obtained showed that the survival of mice immunized with booster had 60% protection compared to the group without booster, which obtained 20% protection. Evaluating the humoral response, it was found that both IgG and IgA levels were higher in sera than in nasal washes in both treatments. In the cellular response, the increase in the percentage of positive cells was found for effector T and B lymphocytes in the nasal passages (NP) in the group with boost and nasopharynx-associated lymphoid tissue (NALT) in the group without boost and lymphocytes only. B in both treatments, as well as in memory cells treatment with boost T lymphocytes in PN and NALT and without boost in cervical lymph nodes (CG) with respect to B lymphocytes, in PN, GC and NALT in treatment with boost and NALT in treatment without booster. Therefore, the involvement of the effector immune response and memory play a fundamental role for protection against N. fowleri and for the development of vaccine candidates.Keywords: immune response, immunological memory, naegleria fowleri, primary amebic meningoencephalitis
Procedia PDF Downloads 78886 Enhanced Efficiency for Propagation of Phalaenopsis cornu-cervi (Breda) Blume & Rchb. F. Using Trimmed Leaf Technique
Authors: Suphat Rittirat, Sutha Klaocheed, Kanchit Thammasiri
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The effects of thidiazuron (TDZ) and benzyladenine (BA) on protocorm-like bodies (PLBs) induction from leaf explants was investigated. It was found that TDZ was superior to BA. The highest percentage and number of PLBs per leaf explant at 30 and 5.3 respectively were obtained on ½ MS medium supplemented with 9µM TDZ. The regenerated plantlets were potted and acclimatized in the greenhouse. These plants grew well and developed into normal plants after 3 month of transplantation. The 100% survival of plantlets was achieved when planted on pots containing sphagnum moss.Keywords: orchid, PLBs, sphagnum moss, thidiazuron
Procedia PDF Downloads 329885 Aboriginal Head and Neck Cancer Patients Have Different Patterns of Metastatic Involvement, and Have More Advanced Disease at Diagnosis
Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern
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Introduction: The mortality gap in Aboriginal Head and Neck Cancer is well known, but the reasons for poorer survival are not well established. Aim: We aimed to evaluate the locoregional and metastatic involvement, and stage at diagnosis, in Aboriginal compared with non-Aboriginal patients. Methods: We performed a retrospective cohort analysis of 320 HNC patients from a single centre in Western Australia, identifying 80 Aboriginal patients and 240 non-Aboriginal patients matched on a 1:3 ratio by sites, histology, rurality, and age. We collected data on the patient characteristics, tumour features, regions involved, stage at diagnosis, treatment history, and survival and relapse patterns, including sites of metastatic and locoregional involvement. Results: Aboriginal patients had a significantly higher incidence of lung metastases (26.3% versus 13.7%, p=0.009). Aboriginal patients also had a numerically but non-statistically significant higher incidence of thoracic nodal involvement (10% vs 5.8%) and malignant pleural effusions (3.8% vs 2.5%). Aboriginal patients also had a numerically but not statistically significantly higher incidence of adrenal and bony involvement. Interestingly, non-Aboriginal patients had an increased rate of cutaneous (2.1% vs 0%) and liver metastases (4.6% vs 2.5%) compared with Aboriginal patients. In terms of locoregional involvement, Aboriginal patients were more than twice as likely to have contralateral neck involvement (58.8% vs 24.2%, p<0.00001), and 30% more likely to have ipsilateral neck lymph node involvement (78.8% vs 60%, p=0.002) than non-Aboriginal patients. Aboriginal patients had significantly more advanced disease at diagnosis (p=0.008). Aboriginal compared with non-Aboriginal patients were less likely to present with stage I (7.5% vs 22.5%), stage II (11.3% vs 13.8%), or stage III disease (13.8% vs 17.1%), and more likely to present with more advanced stage IVA (42.5% vs 34.6%), stage IVB (15% vs 7.1%), or stage IVC (10% vs 5%) disease (p=0.008). Number of regions of disease involvement was higher in Aboriginal patients (median 3, mean 3.64, range 1-10) compared with non-Aboriginal patients (median 2, mean 2.80, range 1-12). Conclusion: Aboriginal patients had a significantly higher incidence of lung metastases, and significantly more frequent involvement of ipsilateral and contralateral neck lymph nodes. Aboriginal patients also had significantly more advanced disease at presentation with a higher stage at diagnosis. We are performing further analyses to investigate explanations for these findings.Keywords: head and neck cancer, Aboriginal, metastases, locoregional, pattern of relapse, sites of disease
Procedia PDF Downloads 70884 Standalone Docking Station with Combined Charging Methods for Agricultural Mobile Robots
Authors: Leonor Varandas, Pedro D. Gaspar, Martim L. Aguiar
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One of the biggest concerns in the field of agriculture is around the energy efficiency of robots that will perform agriculture’s activity and their charging methods. In this paper, two different charging methods for agricultural standalone docking stations are shown that will take into account various variants as field size and its irregularities, work’s nature to which the robot will perform, deadlines that have to be respected, among others. Its features also are dependent on the orchard, season, battery type and its technical specifications and cost. First charging base method focuses on wireless charging, presenting more benefits for small field. The second charging base method relies on battery replacement being more suitable for large fields, thus avoiding the robot stop for recharge. Existing many methods to charge a battery, the CC CV was considered the most appropriate for either simplicity or effectiveness. The choice of the battery for agricultural purposes is if most importance. While the most common battery used is Li-ion battery, this study also discusses the use of graphene-based new type of batteries with 45% over capacity to the Li-ion one. A Battery Management Systems (BMS) is applied for battery balancing. All these approaches combined showed to be a promising method to improve a lot of technical agricultural work, not just in terms of plantation and harvesting but also about every technique to prevent harmful events like plagues and weeds or even to reduce crop time and cost.Keywords: agricultural mobile robot, charging methods, battery replacement method, wireless charging method
Procedia PDF Downloads 153883 Defense Priming from Egg to Larvae in Litopenaeus vannamei with Non-Pathogenic and Pathogenic Bacteria Strains
Authors: Angelica Alvarez-Lee, Sergio Martinez-Diaz, Jose Luis Garcia-Corona, Humberto Lanz-Mendoza
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World aquaculture is always looking for improvements to achieve productions with high yields avoiding the infection by pathogenic agents. The best way to achieve this is to know the biological model to create alternative treatments that could be applied in the hatcheries, which results in greater economic gains and improvements in human public health. In the last decade, immunomodulation in shrimp culture with probiotics, organic acids and different carbon sources has gained great interest, mainly in larval and juvenile stages. Immune priming is associated with a strong protective effect against a later pathogen challenge. This work provides another perspective about immunostimulation from spawning until hatching. The stimulation happens during development embryos and generates resistance to infection by pathogenic bacteria. Massive spawnings of white shrimp L. vannamei were obtained and placed in experimental units with 700 mL of sterile seawater at 30 °C, salinity of 28 ppm and continuous aeration at a density of 8 embryos.mL⁻¹. The immunostimulating effect of three death strains of non-pathogenic bacterial (Escherichia coli, Staphylococcus aureus and Bacillus subtilis) and a pathogenic strain for white shrimp (Vibrio parahaemolyticus) was evaluated. The strains killed by heat were adjusted to O.D. 0.5, at A 600 nm, and directly added to the seawater of each unit at a ratio of 1/100 (v/v). A control group of embryos without inoculum of dead bacteria was kept under the same physicochemical conditions as the rest of the treatments throughout the experiment and used as reference. The duration of the stimulus was 12 hours, then, the larvae that hatched were collected, counted and transferred to a new experimental unit (same physicochemical conditions but at a salinity of 28 ppm) to carry out a challenge of infection against the pathogen V. parahaemolyticus, adding directly to seawater an amount 1/100 (v/v) of the live strain adjusted to an OD 0.5; at A 600 nm. Subsequently, 24 hrs after infection, nauplii survival was evaluated. The results of this work shows that, after 24 hrs, the hatching rates of immunostimulated shrimp embryos with the dead strains of B. subtillis and V. parahaemolyticus are significantly higher compared to the rest of the treatments and the control. Furthermore, survival of L. vanammei after a challenge of infection of 24 hrs against the live strain of V. parahaemolyticus is greater (P < 0.05) in the larvae immunostimulated during the embryonic development with the dead strains B. subtillis and V. parahaemolyticus, followed by those that were treated with E. coli. In summary superficial antigens can stimulate the development cells to promote hatching and can have normal development in agreeing with the optical observations, plus exist a differential response effect between each treatment post-infection. This research provides evidence of the immunostimulant effect of death pathogenic and non-pathogenic bacterial strains in the rate of hatching and oversight of shrimp L. vannamei during embryonic and larval development. This research continues evaluating the effect of these death strains on the expression of genes related to the defense priming in larvae of L. vannamei that come from massive spawning in hatcheries before and after the infection challenge against V. parahaemolyticus.Keywords: immunostimulation, L. vannamei, hatching, survival
Procedia PDF Downloads 143882 The Effect of the COVID-19 Pandemic on Frailty, Sarcopenia, and Other Comorbidities in Liver Transplant Candidates: A Retrospective Review of an Extensive Frailty Database
Authors: Sohaib Raza, Parvez Mantry
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Frailty is a multi-system impairment associated with stressors such as age, disease, and invasive surgical procedures. This multi-system impairment can lead to increased post-transplant mortality and functional decline. Additionally, the prevalence and/or severity of frailty increases when patient pre-habilitation is unsatisfactory or lacking. We conducted a retrospective study to examine whether the COVID-19 Pandemic, and subsequent lack of patient access to pre-habilitation and physical therapy resources, led to an increase in the prevalence and severity of frailty, sarcopenia, and other comorbidities including diabetes, hypertension, and COPD. Secondarily, we examined the correlation between patient survival rate and liver frailty index as well as muscle wasting/sarcopenia. Data were analyzed in order to correlate variables associated with these parameters. Three hundred sixty-nine liver transplant candidates at Methodist Dallas Medical Center were administered pre-transplant frailty assessments, which consisted of chair stands, grip strength, and position balance time. A frailty score less than 3.2 indicated a robust condition, a score from 3.3 to 4.4 indicated a pre-frail condition, and a score greater than 4.5 indicated a frail condition. Greater than 50 percent of patients were found to have muscle wasting in the COVID-19 period (March 13, 2020 to February 28, 2022), an increase of 16.5 percent from the pre-COVID period (April 1st, 2018 to March 12, 2020). Additionally, sarcopenia was associated with a two-fold increase in patient mortality rate. Furthermore, high liver frailty index scores were associated with increased patient mortality. However, there was no significant difference in liver frailty index or number of comorbidities between patients in the two cohorts. Conclusion: The COVID-19 Pandemic exacerbated sarcopenia-related muscle wasting in liver transplant candidates, and patient survival rate was directly correlated with liver frailty index score and the presence of sarcopenia.Keywords: frailty, sarcopenia, covid-19, patient mortality, pre-habilitation, liver transplant candidates
Procedia PDF Downloads 120881 Trans-Activator of Transcription-Tagged Active AKT1 Variants for Delivery to Mammalian Cells
Authors: Tarana Siddika, Ilka U. Heinemann, Patrick O’Donoghue
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Protein kinase B (AKT1) is a serine/threonine kinase and central transducer of cell survival pathways. Typical approaches to study AKT1 biology in cells rely on growth factor or insulin stimulation that activates AKT1 via phosphorylation at two key regulatory sites (Threonine308, Serine473), yet cell stimulation also activates many other kinases and fails to differentiate the effect of the two main activating sites of AKT1 on downstream substrate phosphorylation and cell growth. While both AKT1 activating sites are associated with disease and used as clinical markers, in some cancers, high levels of Threonine308 phosphorylation are associated with poor prognosis while in others poor survival correlates with high Serine473 levels. To produce cells with specific AKT1 activity, a system was developed to deliver active AKT1 to human cells. AKT1 phospho-variants were produced from Escherichia coli with programmed phosphorylation by genetic code expansion. Tagging of AKT1 with an N-terminal cell penetrating peptide tag derived from the human immunodeficiency virus trans-activator of transcription (TAT) helped to enter AKT1 proteins in mammalian cells. The TAT-tag did not alter AKT1 kinase activity and was necessary and sufficient to rapidly deliver AKT1 protein variants that persisted in human cells for 24 h without the need to use transfection reagents. TAT-pAKT1T308, TAT-pAKT1S473 and TAT-pAKT1T308S473 proteins induced selective phosphorylation of the known AKT1 substrate GSK-3αβ, and downstream stimulation of the AKT1 pathway as evidenced by phosphorylation of ribosomal protein S6 at Serine240/244 in transfected cells. Increase in cell growth and proliferation was observed due to the transfection of different phosphorylated AKT1 protein variants compared to cells with TAT-AKT1 protein. The data demonstrate efficient delivery of AKT1 with programmed phosphorylation to human cells, thus establishing a cell-based model system to investigate signaling that is dependent on specific AKT1 activity and phosphorylation.Keywords: cell penetrating peptide, cell signaling, protein kinase b (AKT1), phosphorylation
Procedia PDF Downloads 118880 Modern Sports and Imperial Solidarity: Sports, Mutiny and British Army in Colonial Malabar (1900-1930)
Authors: Anas Ali
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The British administration at Malabar, the southern coastal commercial outpost in the Indian Subcontinent, faced with a series of perpetual revolts from the Mappila Muslim peasants during the last decades of the 19th and early decades of the 20th century. The control of Malabar region was a concern for the British administrators as the region was a prime centre of spice trade and plantation products. The Madras government set up a special police battalion called the Malabar Special Police in 1884 and summoned different army battalions to Malabar to crush the revolts. The setting up of army camps in the rural Malabar led to the diffusion of modern sports as the army men played different games in the garrisons and with the local people. For the imperial army men deployed in Malabar, sports acted as a viable medium to strengthen solidarity with other European settlers. They actively participated in the ‘Canterbury Week’, an annual sporting event organized by the European planters and organized tournaments among themselves. This paper would argue that, sports enabled the imperial army men, European planters and British administrators to build camaraderie that enabled them to manifest their imperial solidarity during the time of these constant revolts. Based on newspaper reports and colonial memoirs, this paper would look at how modern sports enabled the imperial army men to be ‘good in health’ and create a feeling of ‘being at home’ during this period.Keywords: imperial army, Malabar, modern sports, mutiny
Procedia PDF Downloads 213879 Covariate-Adjusted Response-Adaptive Designs for Semi-Parametric Survival Responses
Authors: Ayon Mukherjee
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Covariate-adjusted response-adaptive (CARA) designs use the available responses to skew the treatment allocation in a clinical trial in towards treatment found at an interim stage to be best for a given patient's covariate profile. Extensive research has been done on various aspects of CARA designs with the patient responses assumed to follow a parametric model. However, ranges of application for such designs are limited in real-life clinical trials where the responses infrequently fit a certain parametric form. On the other hand, robust estimates for the covariate-adjusted treatment effects are obtained from the parametric assumption. To balance these two requirements, designs are developed which are free from distributional assumptions about the survival responses, relying only on the assumption of proportional hazards for the two treatment arms. The proposed designs are developed by deriving two types of optimum allocation designs, and also by using a distribution function to link the past allocation, covariate and response histories to the present allocation. The optimal designs are based on biased coin procedures, with a bias towards the better treatment arm. These are the doubly-adaptive biased coin design (DBCD) and the efficient randomized adaptive design (ERADE). The treatment allocation proportions for these designs converge to the expected target values, which are functions of the Cox regression coefficients that are estimated sequentially. These expected target values are derived based on constrained optimization problems and are updated as information accrues with sequential arrival of patients. The design based on the link function is derived using the distribution function of a probit model whose parameters are adjusted based on the covariate profile of the incoming patient. To apply such designs, the treatment allocation probabilities are sequentially modified based on the treatment allocation history, response history, previous patients’ covariates and also the covariates of the incoming patient. Given these information, an expression is obtained for the conditional probability of a patient allocation to a treatment arm. Based on simulation studies, it is found that the ERADE is preferable to the DBCD when the main aim is to minimize the variance of the observed allocation proportion and to maximize the power of the Wald test for a treatment difference. However, the former procedure being discrete tends to be slower in converging towards the expected target allocation proportion. The link function based design achieves the highest skewness of patient allocation to the best treatment arm and thus ethically is the best design. Other comparative merits of the proposed designs have been highlighted and their preferred areas of application are discussed. It is concluded that the proposed CARA designs can be considered as suitable alternatives to the traditional balanced randomization designs in survival trials in terms of the power of the Wald test, provided that response data are available during the recruitment phase of the trial to enable adaptations to the designs. Moreover, the proposed designs enable more patients to get treated with the better treatment during the trial thus making the designs more ethically attractive to the patients. An existing clinical trial has been redesigned using these methods.Keywords: censored response, Cox regression, efficiency, ethics, optimal allocation, power, variability
Procedia PDF Downloads 165878 Targeting Glucocorticoid Receptor Eliminate Dormant Chemoresistant Cancer Stem Cells in Glioblastoma
Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu
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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.
Procedia PDF Downloads 85877 Climate Change: Affecting Basic Human Rights in Bangladesh
Authors: Shekh Shadi Rahaman
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In Bangladesh, basic human rights more specifically right to food and right to shelter are being adversely affected by the consequences of climate change. Over the last two decades, a considerable number of environmental studies revealed that basic human rights, more specifically, the right to food and right to a shelter are going to be seriously affected by climate change. Agriculture, forestry, and fisheries and livestock, which are most sensitive to climate change, are key sources interconnected with food security and the security of shelter. Consequences of climate change affecting these key sources, and with the change of time, climate change is turning into a gigantic challenge towards ensuring basic human rights in Bangladesh. This study was carried out by employing a general review of literature on climate change, focusing on effects of climate change on basic two major human rights in Bangladesh. Upon analysis of existing researches, it is found very few researches focused on correlating climate change and right to food and right to shelter. This study shows how the consequences of climate change affects food production and abode of people of Bangladesh. This study recommends that tree plantation, floating agricultural practice, co-operation with international organization, developing environment friendly institutions, increased use of renewable energy, proper management of wetlands and forests, shelter for climate induced migrated people, encouraging research and public awareness are key issues to be followed for combating climate change and protecting basic human right to food and shelter.Keywords: achievements, agriculture and forestry, fisheries and livestock, renewable energy
Procedia PDF Downloads 137876 Resin-coated Controlled Release Fertilizer (CRF) for Oil Palm: Laboratory and Main Nursery Evaluation
Authors: Umar Adli Amran, Tan Choon Chek, Mohd Shahkhirat Norizan, Then Kek Hoe
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Controlled release fertilizer (CRF) enables a regulated nutrients release for more efficient plant uptake compared to the normal granular fertilizer. It reduces nutrients loss via surface run-off and leaching, hence promotes sustainable agriculture. Although the performance of CRF in providing consistent and timely nutrients supply is well known, its expensive price limits it usage in a large scale plantation. This study is conducted to evaluate the properties and performance of bio-based polyurethane (PU)-coated CRF via laboratory and oil palm main nursery trial. The CRF is produced by coating of a normal commercial compound granular fertilizer from FGV Fertiliser Sdn. Bhd., namely Felda 10 (10.5-8-20-3+0.5B), and designated as CRF FGV10. Based on laboratory evaluation, the CRF FGV10 can sustain nutrients release for more than 6 months. Vegetative growth parameters such as girth size, palm height, third frond length, and the total number of fronds produced were recorded. Besides that, dry biomass of the oil palm seedlings was also determined. From the evaluation, it is proved that at 50% reduction of nutrients application rate and for only two times application (T3), CRF FGV10 enabled the oil palm seedlings to achieve similar vegetative growth with the control samples (T1). It is also proven that only PU-coated CRF FGV10 had allowed the reduction of fertilizer rate and application rounds.Keywords: nutrition, oil palm seedlings, polyurethane, sustainable manuring, vegetative growth
Procedia PDF Downloads 63875 Spatial Analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) Patients in Lagos, Nigeria
Authors: Akinsola Oluwatosin, Udofia Samuel, Odofin Mayowa
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The study is aimed at assessing the Geographic Information System (GIS)-based spatial analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) cases for Lagos, Nigeria, with an objective to inform priority areas for public health planning and resource allocation. Multi-drug resistant tuberculosis (MDR-TB) develops due to problems such as irregular drug supply, poor drug quality, inappropriate prescription, and poor adherence to treatment. The shapefile(s) for this study were already georeferenced to Minna datum. The patient’s information was acquired on MS Excel and later converted to . CSV file for easy processing to ArcMap from various hospitals. To superimpose the patient’s information the spatial data, the addresses was geocoded to generate the longitude and latitude of the patients. The database was used for the SQL query to the various pattern of the treatment. To show the pattern of disease spread, spatial autocorrelation analysis was used. The result was displayed in a graphical format showing the areas of dispersing, random and clustered of patients in the study area. Hot and cold spot analysis was analyzed to show high-density areas. The distance between these patients and the closest health facility was examined using the buffer analysis. The result shows that 22% of the points were successfully matched, while 15% were tied. However, the result table shows that a greater percentage of it was unmatched; this is evident in the fact that most of the streets within the State are unnamed, and then again, most of the patients are likely to supply the wrong addresses. MDR-TB patients of all age groups are concentrated within Lagos-Mainland, Shomolu, Mushin, Surulere, Oshodi-Isolo, and Ifelodun LGAs. MDR-TB patients between the age group of 30-47 years had the highest number and were identified to be about 184 in number. The outcome of patients on ART treatment revealed that a high number of patients (300) were not ART treatment while a paltry 45 patients were on ART treatment. The result shows the Z-score of the distribution is greater than 1 (>2.58), which means that the distribution is highly clustered at a significance level of 0.01.Keywords: tuberculosis, patients, treatment, GIS, MDR-TB
Procedia PDF Downloads 154874 Geospatial Land Suitability Modeling for Biofuel Crop Using AHP
Authors: Naruemon Phongaksorn
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The biofuel consumption has increased significantly over the decade resulting in the increasing request on agricultural land for biofuel feedstocks. However, the biofuel feedstocks are already stressed of having low productivity owing to inappropriate agricultural practices without considering suitability of crop land. This research evaluates the land suitability using GIS-integrated Analytic Hierarchy Processing (AHP) of biofuel crops: cassava, at Chachoengsao province, in Thailand. AHP method that has been widely accepted for land use planning. The objective of this study is compared between AHP method and the most limiting group of land characteristics method (classical approach). The reliable results of the land evaluation were tested against the crop performance assessed by the field investigation in 2015. In addition to the socio-economic land suitability, the expected availability of raw materials for biofuel production to meet the local biofuel demand, are also estimated. The results showed that the AHP could classify and map the physical land suitability with 10% higher overall accuracy than the classical approach. The Chachoengsao province showed high and moderate socio-economic land suitability for cassava. Conditions in the Chachoengsao province were also favorable for cassava plantation, as the expected raw material needed to support ethanol production matched that of ethanol plant capacity of this province. The GIS integrated AHP for biofuel crops land suitability evaluation appears to be a practical way of sustainably meeting biofuel production demand.Keywords: Analytic Hierarchy Processing (AHP), Cassava, Geographic Information Systems, Land suitability
Procedia PDF Downloads 205873 Association of a Genetic Polymorphism in Cytochrome P450, Family 1 with Risk of Developing Esophagus Squamous Cell Carcinoma
Authors: Soodabeh Shahid Sales, Azam Rastgar Moghadam, Mehrane Mehramiz, Malihe Entezari, Kazem Anvari, Mohammad Sadegh Khorrami, Saeideh Ahmadi Simab, Ali Moradi, Seyed Mahdi Hassanian, Majid Ghayour-Mobarhan, Gordon A. Ferns, Amir Avan
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Background Esophageal cancer has been reported as the eighth most common cancer universal and the seventh cause of cancer-related death in men .recent studies have revealed that cytochrome P450, family 1, subfamily B, polypeptide 1, which plays a role in metabolizing xenobiotics, is associated with different cancers. Therefore in the present study, we investigated the impact of CYP1B1-rs1056836 on esophagus squamous cell carcinoma (ESCC) patients. Method: 317 subjects, with and without ESCC were recruited. DNA was extracted and genotyped via Real-time PCR-Based Taq Man. Kaplan Meier curves were utilized to assess overall and progression-free survival. To evaluate the relationship between patients clinicopathological data, genotypic frequencies, disease prognosis, and patients survival, Pearson chi-square and t-test were used. Logistic regression was utilized to assess the association between the risk of ESCC and genotypes. Results: the genotypic frequency for GG, GC, and CC are respectively 58.6% , 29.8%, 11.5% in the healthy group and 51.8%, 36.14% and 12% in ESCC group. With respect to the recessive genetic inheritance model, an association between the GG genotype and stage of ESCC were found. Also, statistically significant results were not found for this variation and risk of ESCC. Patients with GG genotype had a decreased risk of nodal metastasis in comparison with patients with CC/CG genotype, although this link was not statistically significant. Conclusion: Our findings illustrated the correlation of CYP1B1-rs1056836 as a potential biomarker for ESCC patients, supporting further studies in larger populations in different ethnic groups. Moreover, further investigations are warranted to evaluate the association of emerging marker with dietary intake and lifestyle.Keywords: Cytochrome P450, esophagus squamous cell carcinoma, dietary intake, lifestyle
Procedia PDF Downloads 202