Search results for: Burak Kaplan

Authors: Philip Friedlander, John Rutledge, Jason Suh

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Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.

Keywords: angiotensin, cancer, immunotherapy, PD-1, efficacy

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Authors: Sara Ataei, Molouk Hadjibabaie, Amirhossein Moslehi, Maryam Taghizadeh-Ghehi, Asieh Ashouri, Elham Amini, Kheirollah Gholami, Alireza Hayatshahi, Mohammad Vaezi, Ardeshir Ghavamzadeh

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Acute kidney injury (AKI) is one of the complications of hematopoietic stem cell transplantation and is associated with increased mortality. N-acetylcysteine (NAC) is a thiol compound with antioxidant and vasodilatory properties that has been investigated for the prevention of AKI in several clinical settings. In the present study, we evaluated the effects of intravenous NAC on the prevention of AKI in allogeneic hematopoietic stem cell transplantation patients. A double-blind randomized placebo-controlled trial was conducted, and 80 patients were recruited to receive 100 mg/kg/day NAC or placebo as intermittent intravenous infusion from day -6 to day +15. AKI was determined on the basis of the Risk-Injury-Failure-Loss-Endstage renal disease and AKI Network criteria as the primary outcome. We assessed urine neutrophil gelatinase-associated lipocalin (uNGAL) on days -6, -3, +3, +9, and +15 as the secondary outcome. Moreover, transplant-related outcomes and NAC adverse reactions were evaluated during the study period. Statistical analysis was performed using appropriate parametric and non-parametric methods including Kaplan–Meier for AKI and generalized estimating equation for uNGAL. At the end of the trial, data from 72 patients were analyzed (NAC: 33 patients and placebo: 39 patients). Participants of each group were not different considering baseline characteristics. AKI was observed in 18% of NAC recipients and 15% of placebo group patients, and the occurrence pattern was not significantly different (p = 0.73). Moreover, no significant difference was observed between groups for uNGAL measures (p = 0.10). Transplant-related outcomes were similar for both groups, and all patients had successful engraftment. Three patients did not tolerate NAC because of abdominal pain, shortness of breath and rash with pruritus and were dropped from the intervention group before transplantation. However, the frequency of adverse reactions was not significantly different between groups. In conclusion, our findings could not show any clinical benefits from high-dose NAC particularly for AKI prevention in allogeneic hematopoietic stem cell transplantation patients.

Keywords: acute kidney injury, N-acetylcysteine, hematopoietic stem cell transplantation, urine neutrophil gelatinase-associated lipocalin, randomized controlled trial

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Authors: Getahun Nigusie Demise

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Background; antiretroviral treatment reduce HIV-related morbidity, and prolonged survival of patients however, there is lack of up-to-date information concerning the treatment long term effect on the survival of HIV positive children especially in the study area. Objective: The aim of this study is to assess the incidence and predictors of mortality among HIV positive children on antiretroviral therapy (ART) in public hospitals of Harer town who were enrolled from 2011 to 2021. Methodology: Institution based retrospective cohort study was conducted among 429 HIV positive children enrolled in ART clinic from January 1st 2011 to December30th 2021. Data were collected from medical cards by using a data extraction form, Descriptive analyses were used to Summarized the results, and life table was used to estimate survival probability at specific point of time after introduction of ART. Kaplan Meier survival curve together with log rank test was used to compare survival between different categories of covariates, and Multivariate Cox-proportional hazard regression model was used to estimate adjusted Hazard rate. Variables with p-values ≤0.25 in bivariable analysis were candidates to the multivariable analysis. Finally, variables with p-values < 0.05 were considered as significant variables. Results: The study participants had followed for a total of 2549.6 child-years (30596 child months) with an overall mortality rate of 1.5 (95% CI: 1.1, 2.04) per 100 child-years. Their median survival time was 112 months (95% CI: 101–117). There were 38 children with unknown outcome, 39 deaths, and 55 children transfer out to different facility. The overall survival at 6, 12, 24, 48 months were 98%, 96%, 95%, 94% respectively. being in WHO clinical Stage four (AHR=4.55, 95% CI:1.36, 15.24), having anemia(AHR=2.56, 95% CI:1.11, 5.93), baseline low absolute CD4 count (AHR=2.95, 95% CI: 1.22, 7.12), stunting (AHR=4.1, 95% CI: 1.11, 15.42), wasting (AHR=4.93, 95% CI: 1.31, 18.76), poor adherence to treatment (AHR=3.37, 95% CI: 1.25, 9.11), having TB infection at enrollment (AHR=3.26, 95% CI: 1.25, 8.49),and no history of change their regimen(AHR=7.1, 95% CI: 2.74, 18.24), were independent predictors of death. Conclusion: more than half of death occurs within 2 years. Prevalent tuberculosis, anemia, wasting, and stunting nutritional status, socioeconomic factors, and baseline opportunistic infection were independent predictors of death. Increasing early screening and managing those predictors are required.

Keywords: human immunodeficiency virus-positive children, anti-retroviral therapy, survival, treatment, Ethiopia

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Authors: Taleb Lotfi, Benarbia Maheidine, Allam Hamza, Boutira Fatima, Boukerche Abdelbaki

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Introduction and purpose of the study: This is a retrospective single-center study with an analytical aim to determine the prognostic factors for relapse in patients treated with radiotherapy after total laryngectomy with lymph node dissection for laryngeal cancer at the Emir Abdelkader cancer center in Oran (Algeria). Material and methods: During the study period from January 2014 to December 2018, eighty-nine patients (n=89) with squamous cell carcinoma of the larynx were treated with postoperative radiotherapy. Relapse-free survival was studied in the univariate analysis according to pre-treatment criteria using Kaplan-Meier survival curves. We performed a univariate analysis to identify relapse factors. Statistically significant factors have been studied in the multifactorial analysis according to the Cox model. Results and statistical analysis: The average age was 62.7 years (40-86 years). It was a squamous cell carcinoma in all cases. Postoperatively, the tumor was classified as pT3 and pT4 in 93.3% of patients. Histological lymph node involvement was found in 36 cases (40.4%), with capsule rupture in 39% of cases, while the limits of surgical excision were microscopically infiltrated in 11 patients (12.3%). Chemotherapy concomitant with radiotherapy was used in 67.4% of patients. With a median follow-up of 57 months (23 to 104 months), the probabilities of relapse-free survival and five-year overall survival are 71.2% and 72.4%, respectively. The factors correlated with a high risk of relapse were locally advanced tumor stage pT4 (p=0.001), tumor site in case of subglottic extension (p=0.0003), infiltrated surgical limits R1 (p=0.001), l lymph node involvement (p=0.002), particularly in the event of lymph node capsular rupture (p=0.0003) as well as the time between surgery and adjuvant radiotherapy (p=0.001). However, in the subgroup analysis, the major prognostic factors for disease-free survival were subglottic tumor extension (p=0.001) and time from surgery to adjuvant radiotherapy (p=0.005). Conclusion: Combined surgery and postoperative radiation therapy are effective treatment modalities in the management of laryngeal cancer. Close cooperation of the entire cervicofacial oncology team is essential, expressed during a multidisciplinary consultation meeting, with the need to respect the time between surgery and radiotherapy.

Keywords: laryngeal cancer, laryngectomy, postoperative radiotherapy, survival

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Authors: Omar Nouri, Wafa Mnejja, Nejla Fourati, Fatma Dhouib, Wicem Siala, Ilhem Charfeddine, Afef Khanfir, Jamel Daoud

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Background and objective: Induction chemotherapy (IC) followed by concomitant chemo radiotherapy with intensity modulated radiation (IMRT) technique is actually the recommended treatment modality for locally advanced nasopharyngeal carcinomas (NPC). The aim of this study was to evaluate the prognostic factors predicting loco regional relapse with this new treatment protocol. Patients and methods: A retrospective study of 52 patients with NPC treated between June 2016 and July 2019. All patients received IC according to the protocol of the Head and Neck Radiotherapy Oncology Group (Gortec) NPC 2006 (3 TPF courses) followed by concomitant chemo radiotherapy with weekly cisplatin (40 mg / m2). Patients received IMRT with integrated simultaneous boost (SIB) of 33 daily fractions at a dose of 69.96 Gy for high-risk volume, 60 Gy for intermediate risk volume and 54 Gy for low-risk volume. Median age was 49 years (19-69) with a sex ratio of 3.3. Forty five tumors (86.5%) were classified as stages III - IV according to the 2017 UICC TNM classification. Loco regional relapse (LRR) was defined as a local and/or regional progression that occurs at least 6 months after the end of treatment. Survival analysis was performed according to Kaplan-Meier method and Log-rank test was used to compare anatomy clinical and therapeutic factors that may influence loco regional free survival (LRFS). Results: After a median follow up of 42 months, 6 patients (11.5%) experienced LRR. A metastatic relapse was also noted for 3 of these patients (50%). Target volumes coverage was optimal for all patient with LRR. Four relapses (66.6%) were in high-risk target volume and two (33.3%) were borderline. Three years LRFS was 85,9%. Four factors predicted loco regional relapses: histologic type other than undifferentiated (UCNT) (p=0.027), a macroscopic pre chemotherapy tumor volume exceeding 100 cm³ (p=0.005), a reduction in IC doses exceeding 20% (p=0.016) and a total cumulative cisplatin dose less than 380 mg/m² (p=0.0.34). TNM classification and response to IC did not impact loco regional relapses. Conclusion: For nasopharyngeal carcinoma, tumors with initial high volume and/or histologic type other than UCNT, have a higher risk of loco regional relapse. Therefore, they require a more aggressive therapeutic approaches and a suitable monitoring protocol.

Keywords: loco regional relapse, modulation intensity radiotherapy, nasopharyngeal carcinoma, prognostic factors

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Authors: Ben Cheikh Asma, Bouafia Nabiha, Ammar Asma, Ezzi Olfa, Meddeb Khaoula, Chouchène Imed, Boussarsar Hamadi, Njah Mansour

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Background: Hospital Acquired Infection (HAI) constitutes an important worldwide health problem. It was associated with high mortality rate in intensive care units (ICU). This study aimed to determine HAI mortality rate in Tunisian intensive care units and identify its risk factors. Methods: We conducted a prospective observational cohort study over a 12 months period (September 15th 2015 to September 15 th 2016) in the adult medical ICU of University Hospital-Farhat Hached (Sousse-Tunisia). All patients admitted in the ICU for more than 48 hours were included in the study. We used an anonymous standardized survey record form to collect data by a medical hygienist assisted by an intensivist. We adopted definitions of Center for Diseases Control and prevention of Atlanta to detect HAI, Kaplan Meier survival analysis and Cox proportional hazard regression to identify independent risk factor of HAI mortality. Results: Of 171 patients, 67 developed ICU-acquired infection (global incidence rate=39.2%). The mean age of patients was 59 ± 21.2 years and 60.8% were male. The most frequently identified infections were pulmonary acquired infection (ventilator associated pneumonia (VAP) and infected atelectasis with density rates 21.4 VAP/1000 days of mechanical ventilation and 9.4 infected atelectasis /1000 days of mechanical ventilation; respectively) and central venous catheter associated infection (CVC - AI) with density rate 28.4 CVC-AI / 1000 CVC-days). HAI mortality rate was 66.7% (n=44). The median survival was 20 days 3.36, 95% Confidential Interval [13.39 – 26.60]. Specific mortality rates according to infectious site were 65.5%, 36.4% and 4.5% respectively for VAP, CVC associated infection and infected atelectasis. In univariate analysis, a significant associations between mortality and cardiovascular history (p=0.04) tracheotomy (p=0.00), peripheral venous catheterization (p=0.04), VAP (p=0.04) and infected atelectasis (p=0.04) were detected. Independent risk factors for HAI mortality were VAP with Hazard Ratio = 3.14, 95% Confidential Interval [1.63 – 6.05] (p=0.001) and tracheotomy (Hazard Ratio=0.22, 95% Confidential Interval [0.10 – 0.44], p=0.000). Conclusions: In the present study, hospital acquired infection mortality rate was relatively high. We need to intensify the fight against these infections especially ventilator-associated pneumonia that is associated with higher risk of mortality in many studies. Thus, more effective infection control interventions were necessary in our hospital.

Keywords: hospital acquired infection, intensive care unit, mortality, risk factors

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Authors: Nurdan Olguncelik Kaplan, Aysen Akay

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Nowadays soil pollution has become a global problem. External added polluters to the soil are destroying and changing the structure of the soil and the problems are becoming more complex and in this sense the correction of these problems is going to be harder and more costly. Cadmium has got a fast mobility in the soil and plant system because of that cadmium can interfere very easily to the human and animal food chain and in the same time this can be very dangerous. The cadmium which is absorbed and stored by the plants is causing to many metabolic changes of the plants like; protein synthesis, nitrogen and carbohydrate metabolism, enzyme (nitrate reductase) activation, photo and chlorophyll synthesis. The biological function of cadmium is not known over the plants and it is not a necessary element. The plant is generally taking in small amounts the cadmium and this element is competing with the zinc. Cadmium is causing root damages. Buckwheat (Fagopyrum esculentum) is an important nutraceutical because of its high content of flavonoids, minerals and vitamins, and their nutritionally balanced amino-acid composition. Buckwheat has relatively high biomass productivity, is adapted to many areas of the world, and can flourish in sterile fields; therefore buckwheat plants are widely used for the phytoremediation process.The aim of this study were to evaluate the phytoremediation capacity of the high-yielding plant Buckwheat (Fagopyrum esculentum) in soils contaminated with Cd and Zn. The soils were applied to differrent doses cd(0-12.5-25-50-100 mg Cd kg−1 soil in the form of 3CdSO4.8H2O ) and Zn (0-10-30 mg Zn kg−1 soil in the form of ZnSO4.7H2O) and incubated about 60 days. Later buckwheat seeds were sown and grown for three mounth under greenhouse conditions. The test plants were irrigated by using pure water after the planting process. Buckwheat seeds (Gunes and Aktas species) were taken from Bahri Dagdas International Agricultural Research. After harvest, Cd and Zn concentrations of plant biomass and grain, yield and translocation factors (TFs) for Cd and Cd were determined. Cadmium accumulation in biomass and grain significantly increased in dose-dependent manner. Long term field trials are required to further investigate the potential of buckwheat to reclaimed the soil. But this could be undertaken in conjunction with actual remediation schemes. However, the differences in element accumulation among the genotypes were affected more by the properties of genotypes than by the soil properties. Gunes genotype accumulated higher lead than Aktas genotypes.

Keywords: buckwheat, cadmium, phytoremediation, zinc

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Authors: Zeytu G. Asfaw, Serkalem K. Abrha, Demisew G. Degefu

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Background: HIV/AIDS remains a major public health problem in Ethiopia and heavily affecting people of productive and reproductive age. We aimed to compare the performance of Parametric Survival Analysis and Bayesian Survival Analysis using simulations and in a real dataset application focused on determining predictors of HIV patient survival. Methods: A Parametric Survival Models - Exponential, Weibull, Log-normal, Log-logistic, Gompertz and Generalized gamma distributions were considered. Simulation study was carried out with two different algorithms that were informative and noninformative priors. A retrospective cohort study was implemented for HIV infected patients under Highly Active Antiretroviral Therapy in Alamata General Hospital, North Ethiopia. Results: A total of 320 HIV patients were included in the study where 52.19% females and 47.81% males. According to Kaplan-Meier survival estimates for the two sex groups, females has shown better survival time in comparison with their male counterparts. The median survival time of HIV patients was 79 months. During the follow-up period 89 (27.81%) deaths and 231 (72.19%) censored individuals registered. The average baseline cluster of differentiation 4 (CD4) cells count for HIV/AIDS patients were 126.01 but after a three-year antiretroviral therapy follow-up the average cluster of differentiation 4 (CD4) cells counts were 305.74, which was quite encouraging. Age, functional status, tuberculosis screen, past opportunistic infection, baseline cluster of differentiation 4 (CD4) cells, World Health Organization clinical stage, sex, marital status, employment status, occupation type, baseline weight were found statistically significant factors for longer survival of HIV patients. The standard error of all covariate in Bayesian log-normal survival model is less than the classical one. Hence, Bayesian survival analysis showed better performance than classical parametric survival analysis, when subjective data analysis was performed by considering expert opinions and historical knowledge about the parameters. Conclusions: Thus, HIV/AIDS patient mortality rate could be reduced through timely antiretroviral therapy with special care on the potential factors. Moreover, Bayesian log-normal survival model was preferable than the classical log-normal survival model for determining predictors of HIV patients survival.

Keywords: antiretroviral therapy (ART), Bayesian analysis, HIV, log-normal, parametric survival models

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Authors: S. Sakhri

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Background: The use of Zoledronic acid (ZA) is an established place in the treatment of malignant tumors with a predilection for the skeleton of interest (in particular metastasis). Although the main target of Zoledronic acid was osteoclasts, there are preclinical data suggest that Zoledronic acid may have an antitumor effect on cells other than osteoclasts, including tumor cells. Antitumor activity, including the inhibition of tumor cell growth and the induction of apoptosis of tumor cells, inhibition of tumor cell adhesion and invasion, and anti-angiogenic effects have been demonstrated. Methods. From (2012 to 2014), 438 patients were included respondents the inclusion criteria, respectively. This is a prospective study over a 4 year period. Of all patients (N=438), 432 received neoadjuvant chemotherapy with Zoledronic acid. The primary end point was the pathologic complete response in advancer breast cancer stage. The secondary end point is to evaluate Clinical response according to RECIST criteria; estimate the bone density before and at the end of chemotherapy in women with locally advanced breast cancer, Toxicity Evaluation and Overall survival using Kaplan-Meier and log test. Result: The Objective response rate was 97% after (C4) with 3% stabilizations and 99, 3% of which 0.7% C8 after stabilization. The clinical complete response was 28% after C4 respectively, and 46.8% after C8, the pathologic complete response rate was 40.13% according to the classification Sataloff. We observed that the pathologic complete response rate was the most raised in the group including Her2 (luminal Her2 and Her2) the lowest in the triple negative group as classified by Sataloff. We found that the pCR is significantly higher in the age group (35-50 years) with 53.17%. Those who have more than 50 years in 2nd place with 27.7% and the lower in young woman 35 years pCR was 19%, not statistically significant, -The pCR was also in favor of the menopausal group in 51, 4%, and 48, 55% for non-menopausal women. The average duration of overall survival was also significantly in the subgroup (Luminal -Her2, Her2) compared with triple negative. It is 47.18 months in the luminal group vs. 38.95 in the triple negative group. -Was observed in our study a difference in quality of life between (C1) was the admission of the patient, and after (C8), we found an increase in general signs and a deterioration in the psychological state C1, in contrast to the C8 these general signs and mental status improves, up to 12, and 24 months. Conclusion The results of this study suggest that the addition of ZA to néoadjuvant CT has potential anti-cancer benefit in patients (Luminal -Her2, Her2) compared with triple negative with or without menopause status.

Keywords: HER2+, RH+, breast cancer, tyrosine kinase

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Authors: Einat E. Peles, Shaul Schreiber, Miriam Adelson

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Background: Since established more than 50 years ago, methadone maintenance treatment (MMT) is the most effective treatment for opioid addiction, a chronic relapsing brain disorder that became an epidemic in western societies. Treatment includes daily individual optimal medication methadone dose (a long acting mu opioid receptor full agonist), accompanied with psychosocial therapy. It is well established that the longer retention in treatment the better outcome and survival occur. It reduces the likelihood to infectious diseases and overdose death that associated with drug injecting, enhanced social rehabilitation and eliminate criminal activity, and lead to healthy productive life. Aim: To evaluate predictors for long term retention in treatment we analyzed our prospective follow up of a major MMT clinic affiliated to a big tertiary medical center. Population Methods: Between June 25, 1993, and June 24, 2016, all 889 patients ( ≥ 18y) who ever admitted to the clinic were prospectively followed-up until May 2017. Duration in treatment from the first admission until the patient quit treatment or until the end of follow-up (24 years) was taken for calculating cumulative retention in treatment using survival analyses (Kaplan Meier) with log-rank and Cox regression for multivariate analyses. Results: Of the 889 patients, 25.2% were females who admitted to treatment at younger age (35.0 ± 7.9 vs. 40.6 ± 9.8, p < .0005), but started opioid usage at same age (22.3 ± 6.9). In addition to opioid use, on admission to MMT 58.5% had positive urine for benzodiazepines, 25% to cocaine, 12.4% to cannabis and 6.9% to amphetamines. Hepatitis C antibody tested positive in 55%, and HIV in 7.8% of the patients and 40%. Of all patients, 75.7% stayed at least one year in treatment, and of them, 67.7% stopped opioid usage (based on urine tests), and a net reduction observed in all other substance abuse (proportion of those who stopped minus proportion of those who have started). Long term retention up to 24 years was 8.0 years (95% Confidence Interval (CI) 7.4-8.6). Predictors for longer retention in treatment (Cox regression) were being older on admission ( ≥ 30y) Odds Ratio (OR) =1.4 (CI 1.1-1.8), not abusing opioids after one year OR=1.8 (CI 1.5-2.1), not abusing benzodiazepine after one year OR=1.7 (CI 1.4-2.1) and treating with methadone dose ≥ 100mg/day OR =1.8 (CI 1.5-2.3). Conclusions: Treating and following patients over 24 years indicate success of two main outcomes, high rate of retention after one year (75.7%) and high proportion of opiate abuse cessation (67.7%). As expected, longer cumulative retention was associated with patients treated with high adequate methadone dose that successfully result in opioid cessation. Based on these findings, in order to reduce morbidity and mortality, we find the establishment of more MMT clinics within a general hospital, a most urgent necessity.

Keywords: methadone maintenance treatment, epidemic, opioids, retention

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Authors: Lennart Dimberg, Lala Joulha Ian

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Introduction: Overweight (BMI 25-30) and obesity (BMI 30+) have consistently been associated with cardiovascular (CV) risk and death since the Framingham heart study in 1948, and BMI was included in the original Framingham risk score (FRS). Background: Myocardial infarction (MI) poses a serious threat to the patient's life. In addition to BMI, several other indices of overweight have been presented and argued to replace FRS as more relevant measures of CV risk. These indices include waist circumference (WC), waist/hip ratio (WHR), sagittal abdominal diameter (SAD), and sagittal abdominal diameter to height (SADHtR). Specific research question: The research question of this study is to evaluate the interrelationship between the various body measurements, BMI, WC, WHR, SAD, and SADHtR, and which measurement is strongly associated with MI and death. Methods: In 1993, 1,000 middle-aged Caucasian, randomly selected working men of the Swedish Volvo-Renault cohort were surveyed at a nurse-led health examination with a questionnaire, EKG, laboratory tests, blood pressure, height, weight, waist, and sagittal abdominal diameter measurements. Outcome data of myocardial infarction over 28 years come from Swedeheart (the Swedish national myocardial infarction registry) and the Swedish death registry. The Aalen-Johansen and Kaplan–Meier methods were used to estimate the cumulative incidences of MI and death. Multiple logistic regression analyses were conducted to compare BMI with the other four body measurements. The risk for the various measures of obesity was calculated with outcomes of accumulated first-time myocardial infarction and death as odds ratios (OR) in quartiles. The ORs between the 4th and the 1st quartile of each measure were calculated to estimate the association between the body measurement variables and the probability of cumulative incidences of myocardial infarction (MI) over time. Double-sided P values below 0.05 will be considered statistically significant. Unadjusted odds ratios were calculated for obesity indicators, MI, and death. Adjustments for age, diabetes, SBP, and the ratio of total cholesterol/HDL-C and blue/white collar status were performed. Results: Out of 1000 people, 959 subjects had full information about the five different body measurements. Of those, 90 participants had a first MI, and 194 persons died. The study showed that there was a high and significant correlation between the five different body measurements, and they were all associated with CVD risk factors. All body measurements were significantly associated with MI, with the highest (OR=3.6) seen for SADHtR and WC. After adjustment, all but SADHtR remained significant with weaker ORs. As for all-cause mortality, WHR (OR=1.7), SAD (OR=1.9), and SADHtR (OR=1.6) were significantly associated, but not WC and BMI. However, after adjustment, only WHR and SAD were significantly associated with death, but with attenuated ORs.

Keywords: BMI, death, epidemiology, myocardial infarction, risk factor, sagittal abdominal diameter, sagittal abdominal diameter to height, waist circumference, waist-hip ratio

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Authors: Burak Oksuzoglu, Savas Yildirim, Ferhat Kutlu

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Opinion mining (OM) is one of the natural language processing (NLP) problems to determine the polarity of opinions, mostly represented on a positive-neutral-negative axis. The data for OM is usually collected from various social media platforms. In an era where social media has considerable control over companies’ futures, it’s worth understanding social media and taking actions accordingly. OM comes to the fore here as the scale of the discussion about companies increases, and it becomes unfeasible to gauge opinion on individual levels. Thus, the companies opt to automize this process by applying machine learning (ML) approaches to their data. For the last two decades, OM or sentiment analysis (SA) has been mainly performed by applying ML classification algorithms such as support vector machines (SVM) and Naïve Bayes to a bag of n-gram representations of textual data. With the advent of deep learning and its apparent success in NLP, traditional methods have become obsolete. Transfer learning paradigm that has been commonly used in computer vision (CV) problems started to shape NLP approaches and language models (LM) lately. This gave a sudden rise to the usage of the pretrained language model (PTM), which contains language representations that are obtained by training it on the large datasets using self-supervised learning objectives. The PTMs are further fine-tuned by a specialized downstream task dataset to produce efficient models for various NLP tasks such as OM, NER (Named-Entity Recognition), Question Answering (QA), and so forth. In this study, the traditional and modern NLP approaches have been evaluated for OM by using a sizable corpus belonging to a large private company containing about 76,000 comments in Turkish: SVM with a bag of n-grams, and two chosen pre-trained models, multilingual universal sentence encoder (MUSE) and bidirectional encoder representations from transformers (BERT). The MUSE model is a multilingual model that supports 16 languages, including Turkish, and it is based on convolutional neural networks. The BERT is a monolingual model in our case and transformers-based neural networks. It uses a masked language model and next sentence prediction tasks that allow the bidirectional training of the transformers. During the training phase of the architecture, pre-processing operations such as morphological parsing, stemming, and spelling correction was not used since the experiments showed that their contribution to the model performance was found insignificant even though Turkish is a highly agglutinative and inflective language. The results show that usage of deep learning methods with pre-trained models and fine-tuning achieve about 11% improvement over SVM for OM. The BERT model achieved around 94% prediction accuracy while the MUSE model achieved around 88% and SVM did around 83%. The MUSE multilingual model shows better results than SVM, but it still performs worse than the monolingual BERT model.

Keywords: BERT, MUSE, opinion mining, pretrained language model, SVM, Turkish

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Authors: Fatih Kılıç, Burak Birol, Necmettin Maraşlı

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The directional solidification process is generally used for homogeneous compound production, single crystal growth, and refining (zone refining), etc. processes. The most important two parameters that control eutectic structures are temperature gradient and grain growth rate which are called as solidification parameters The solidification behavior and microstructure characteristics is an interesting topic due to their effects on the properties and performance of the alloys containing eutectic compositions. The solidification behavior of multicomponent and multiphase systems is an important parameter for determining various properties of these materials. The researches have been conducted mostly on the solidification of pure materials or alloys containing two phases. However, there are very few studies on the literature about multiphase reactions and microstructure formation of multicomponent alloys during solidification. Because of this situation, it is important to study the microstructure formation and the thermodynamical, thermophysical and microstructural properties of these alloys. The production process is difficult due to easy oxidation of magnesium and therefore, there is not a comprehensive study concerning alloys containing high Mg (> 30 wt.% Mg). With the increasing amount of Mg inside Al alloys, the specific weight decreases, and the strength shows a slight increase, while due to formation of β-Al8Mg5 phase, ductility lowers. For this reason, production, examination and development of high Mg containing alloys will initiate the production of new advanced engineering materials. The original value of this research can be described as obtaining high Mg containing (> 30% Mg) Al based multicomponent alloys by melting under vacuum; controlled directional solidification with various growth rates at a constant temperature gradient; and establishing relationship between solidification rate and microstructural, mechanical, electrical and thermal properties. Therefore, within the scope of this research, some > 30% Mg containing ternary or quaternary Al alloy compositions were determined, and it was planned to investigate the effects of directional solidification rate on the mechanical, electrical and thermal properties of these alloys. Within the scope of the research, the influence of the growth rate on microstructure parameters, microhardness, tensile strength, electrical conductivity and thermal conductivity of directionally solidified high Mg containing Al-32,2Mg-0,37Si; Al-30Mg-12Zn; Al-32Mg-1,7Ni; Al-32,2Mg-0,37Fe; Al-32Mg-1,7Ni-0,4Si; Al-33,3Mg-0,35Si-0,11Fe (wt.%) alloys with wide range of growth rate (50-2500 µm/s) and fixed temperature gradient, will be investigated. The work can be planned as; (a) directional solidification of Al-Mg based Al-Mg-Si, Al-Mg-Zn, Al-Mg-Ni, Al-Mg-Fe, Al-Mg-Ni-Si, Al-Mg-Si-Fe within wide range of growth rates (50-2500 µm/s) at a constant temperature gradient by Bridgman type solidification system, (b) analysis of microstructure parameters of directionally solidified alloys by using an optical light microscopy and Scanning Electron Microscopy (SEM), (c) measurement of microhardness and tensile strength of directionally solidified alloys, (d) measurement of electrical conductivity by four point probe technique at room temperature (e) measurement of thermal conductivity by linear heat flow method at room temperature.

Keywords: directional solidification, electrical conductivity, high Mg containing multicomponent Al alloys, microhardness, microstructure, tensile strength, thermal conductivity

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Authors: CA Kishore S. Peshori

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Introduction: India, a country with vast diversity and huge population is going to have largest young population by 2020. Higher education has and will always be the basic requirement for making a developing nation to a developed nation. To improve any system it needs to be bench-marked. There have been various tools for bench-marking the systems. Education is delivered in India by universities which are mainly funded by government. This universities for delivering the education sets up colleges which are again funded mainly by government. Recently however there has also been autonomy given to universities and colleges. Moreover foreign universities are waiting to enter Indian boundaries. With a large number of universities and colleges it has become more and more necessary to measure this institutes for bench-marking. There have been various tools for measuring the institute. In India college assessments have been made compulsory by UGC. Naac has been offically recognised as the accrediation criteria. The Naac criteria has been based on seven criterias namely: 1. Curricular assessments, 2. Teaching learning and evaluation, 3. Research Consultancy and Extension, 4. Infrastructure and learning resources, 5. Student support and progression, 6. Governance leadership and management, 7. Innovation and best practices. The Naac tries to bench mark the institution for identification, sustainability, dissemination and adaption of best practices. It grades the institution according to this seven criteria and the funding of institution is based on these grades. Many of the colleges are struggling to get best of grades but they have not come across a systematic tool to achieve the results. Balanced Scorecard developed by Kaplan has been a successful tool for corporates to develop best of practices so as to increase their financial performance and also retain and increase their customers so as to grow the organization to next level.It is time to test this tool for an educational institute. Methodology: The paper tries to develop a prototype for college based on the secondary data. Once a prototype is developed the researcher based on questionnaire will try to test this tool for successful implementation. The success of this research will depend on its implementation of BSC on an institute and its grading improved due to this successful implementation. Limitation of time is a major constraint in this research as Naac cycle takes minimum 4 years for accreditation and reaccreditation the methodology will limit itself to secondary data and questionnaire to be circulated to colleges along with the prototype model of BSC. Conclusion: BSC is a successful tool for enhancing growth of an organization. Educational institutes are no exception to these. BSC will only have to be realigned to suit the Naac criteria. Once this prototype is developed the success will be tested only on its implementation but this research paper will be the first step towards developing this tool and will also initiate the success by developing a questionnaire and getting and evaluating the responses for moving to the next level of actual implementation

Keywords: balanced scorecard, bench marking, Naac, UGC

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Authors: İsmail Kavdır, M. Burak Büyükcan, Ferhat Kurtulmuş

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Table olive is a valuable product especially in Mediterranean countries. It is usually consumed after some fermentation process. Defects happened naturally or as a result of an impact while olives are still fresh may become more distinct after processing period. Defected olives are not desired both in table olive and olive oil industries as it will affect the final product quality and reduce market prices considerably. Therefore it is critical to sort table olives before processing or even after processing according to their quality and surface defects. However, doing manual sorting has many drawbacks such as high expenses, subjectivity, tediousness and inconsistency. Quality criterions for green olives were accepted as color and free of mechanical defects, wrinkling, surface blemishes and rotting. In this study, it was aimed to classify fresh table olives using different classifiers and NIR spectroscopy readings and also to compare the classifiers. For this purpose, green (Ayvalik variety) olives were classified based on their surface feature properties such as defect-free, with bruised defect and with fly defect using FT-NIR spectroscopy and classification algorithms such as artificial neural networks, ident and cluster. Bruker multi-purpose analyzer (MPA) FT-NIR spectrometer (Bruker Optik, GmbH, Ettlingen Germany) was used for spectral measurements. The spectrometer was equipped with InGaAs detectors (TE-InGaAs internal for reflectance and RT-InGaAs external for transmittance) and a 20-watt high intensity tungsten–halogen NIR light source. Reflectance measurements were performed with a fiber optic probe (type IN 261) which covered the wavelengths between 780–2500 nm, while transmittance measurements were performed between 800 and 1725 nm. Thirty-two scans were acquired for each reflectance spectrum in about 15.32 s while 128 scans were obtained for transmittance in about 62 s. Resolution was 8 cm⁻¹ for both spectral measurement modes. Instrument control was done using OPUS software (Bruker Optik, GmbH, Ettlingen Germany). Classification applications were performed using three classifiers; Backpropagation Neural Networks, ident and cluster classification algorithms. For these classification applications, Neural Network tool box in Matlab, ident and cluster modules in OPUS software were used. Classifications were performed considering different scenarios; two quality conditions at once (good vs bruised, good vs fly defect) and three quality conditions at once (good, bruised and fly defect). Two spectrometer readings were used in classification applications; reflectance and transmittance. Classification results obtained using artificial neural networks algorithm in discriminating good olives from bruised olives, from olives with fly defect and from the olive group including both bruised and fly defected olives with success rates respectively changing between 97 and 99%, 61 and 94% and between 58.67 and 92%. On the other hand, classification results obtained for discriminating good olives from bruised ones and also for discriminating good olives from fly defected olives using the ident method ranged between 75-97.5% and 32.5-57.5%, respectfully; results obtained for the same classification applications using the cluster method ranged between 52.5-97.5% and between 22.5-57.5%.

Keywords: artificial neural networks, statistical classifiers, NIR spectroscopy, reflectance, transmittance

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Authors: Pedro Gomes, Luís Sá Castelo, António Lopes, Marta Maio, Pedro Mota, Adélia Avelar, António Marques Dias

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Introduction: Total Knee Arthroplasty (TKA) has contributed to improvement of patient`s quality of life, although it has been associated with some complications including component loosening and polyethylene wear. To prevent these complications various fixation techniques have been employed. Hybrid TKA with cemented tibial and cementless femoral components have shown favourable outcomes, although it still lack of consensus in the literature. Objectives: To evaluate the clinical and radiographic results of hybrid versus cemented TKA with an average 5 years follow-up and analyse the survival rates. Methods: A retrospective study of 125 TKAs performed in 92 patients at our institution, between 2006 to 2008, with a minimum follow-up of 2 years. The same prosthesis was used in all knees. Hybrid TKA fixation was performed in 96 knees, with a mean follow-up of 4,8±1,7 years (range, 2–8,3 years) and 29 TKAs received fully cemented fixation with a mean follow-up of 4,9±1,9 years (range, 2-8,3 years). Selection for hybrid fixation was nonrandomized and based on femoral component fit. The Oxford Knee Score (OKS 0-48) was evaluated for clinical assessment and Knee Society Roentgenographic Evaluation Scoring System was used for radiographic outcome. The survival rate was calculated using the Kaplan-Meier method, with failures defined as revision of either the tibial or femoral component for aseptic failures and all-causes (aseptic and infection). Analysis of survivorship data was performed using the log-rank test. SPSS (v22) was the computer program used for statistical analysis. Results: The hybrid group consisted of 72 females (75%) and 24 males (25%), with mean age 64±7 years (range, 50-78 years). The preoperative diagnosis was osteoarthritis (OA) in 94 knees (98%), rheumatoid arthritis (RA) in 1 knee (1%) and Posttraumatic arthritis (PTA) in 1 Knee (1%). The fully cemented group consisted of 23 females (79%) and 6 males (21%), with mean age 65±7 years (range, 47-78 years). The preoperative diagnosis was OA in 27 knees (93%), PTA in 2 knees (7%). The Oxford Knee Scores were similar between the 2 groups (hybrid 40,3±2,8 versus cemented 40,2±3). The percentage of radiolucencies seen on the femoral side was slightly higher in the cemented group 20,7% than the hybrid group 11,5% p0.223. In the cemented group there were significantly more Zone 4 radiolucencies compared to the hybrid group (13,8% versus 2,1% p0,026). Revisions for all causes were performed in 4 of the 96 hybrid TKAs (4,2%) and 1 of the 29 cemented TKAs (3,5%). The reason for revision was aseptic loosening in 3 hybrid TKAs and 1 of the cemented TKAs. Revision was performed for infection in 1 hybrid TKA. The hybrid group demonstrated a 7 years survival rate of 93% for all-cause failures and 94% for aseptic loosening. No significant difference in survivorship was seen between the groups for all-cause failures or aseptic failures. Conclusions: Hybrid TKA yields similar intermediate-term results and survival rates as fully cemented total knee arthroplasty and remains a viable option in knee joint replacement surgery.

Keywords: hybrid, survival rate, total knee arthroplasty, orthopaedic surgery

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Authors: Çağrı Bekir Baysal, Göktuğ Burak Çalık

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Armored vehicles may have different traction layouts as a result of terrain capabilities and mobility needs. Two main categories of layouts can be separated as wheeled and tracked. Tracked vehicles have superior off-road capabilities but what they gain on terrain performance they lose on mobility front. Wheeled vehicles on the other hand do not have as good terrain capabilities as tracked vehicles but they have superior mobility capabilities such as top speed, range and agility with respect to tracked vehicles. Conventional armored vehicles employ a diesel ICE as main power source. In these vehicles ICE is mechanically connected to the powertrain. This determines the ICE rpm as a result of speed and torque requested by the driver. ICE efficiency changes drastically with torque and speed required and conventional vehicles suffer in terms of fuel consumption because of this. Hybrid electric vehicles employ at least one electric motor in order to improve fuel efficiency. There are different types of hybrid vehicles but main types are Series Hybrid, Parallel Hybrid and Series-Parallel Hybrid. These vehicles introduce an electric motor for traction and also can have a generator electric motor for range extending purposes. Having an electric motor as the traction power source brings the flexibility of either using the ICE as an alternative traction source while it is in efficient range or completely separating the ICE from traction and using it solely considering efficiency. Hybrid configurations have additional advantages for armored vehicles in addition to fuel efficiency. Heat signature, silent operation and prolonged stationary missions can be possible with the help of the high-power battery pack that will be present in the vehicle for hybrid drivetrain. Because of the reasons explained, hybrid armored vehicles are becoming a target area for military and also for vehicle suppliers. In order to have a better idea and starting point when starting a hybrid armored vehicle design, hybrid drivetrain configuration has to be selected after performing a trade-off study. This study has to include vehicle mobility simulations, integration level, vehicle level and performance level criteria. In this study different hybrid traction configurations possible for an 8x8 vehicle is compared using above mentioned criteria set. In order to compare hybrid traction configurations ease of application, cost, weight advantage, reliability, maintainability, redundancy and performance criteria have been used. Performance criteria points have been defined with the help of vehicle simulations and tests. Results of these simulations and tests also help determining required tractive power for an armored vehicle including conditions like trench and obstacle crossing, gradient climb. With the method explained in this study, each configuration is assigned a point for each criterion. This way, correct configuration can be selected objectively for every application. Also, key aspects of armored vehicles, mine protection and ballistic protection will be considered for hybrid configurations. Results are expected to vary for different types of vehicles but it is observed that having longitudinal differential locking capability improves mobility and having high motor count increases complexity in general.

Keywords: armored vehicles, electric drivetrain, electric mobility, hybrid vehicles

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Authors: Shenlun Chen, Leonard Wee

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Tumor grading is an essential reference for colorectal cancer (CRC) staging and survival prognostication. The widely used World Health Organization (WHO) grading system defines histological grade of CRC adenocarcinoma based on the density of glandular formation on whole slide images (WSI). Tumors are classified as well-, moderately-, poorly- or un-differentiated depending on the percentage of the tumor that is gland forming; >95%, 50-95%, 5-50% and <5%, respectively. However, manually grading WSIs is a time-consuming process and can cause observer error due to subjective judgment and unnoticed regions. Furthermore, pathologists’ grading is usually coarse while a finer and continuous differentiation grade may help to stratifying CRC patients better. In this study, a deep learning based automatic differentiation grading algorithm was developed and evaluated by survival analysis. Firstly, a gland segmentation model was developed for segmenting gland structures. Gland regions of WSIs were delineated and used for differentiation annotating. Tumor regions were annotated by experienced pathologists into high-, medium-, low-differentiation and normal tissue, which correspond to tumor with clear-, unclear-, no-gland structure and non-tumor, respectively. Then a differentiation prediction model was developed on these human annotations. Finally, all enrolled WSIs were processed by gland segmentation model and differentiation prediction model. The differentiation grade can be calculated by deep learning models’ prediction of tumor regions and tumor differentiation status according to WHO’s defines. If multiple WSIs were possessed by a patient, the highest differentiation grade was chosen. Additionally, the differentiation grade was normalized into scale between 0 to 1. The Cancer Genome Atlas, project COAD (TCGA-COAD) project was enrolled into this study. For the gland segmentation model, receiver operating characteristic (ROC) reached 0.981 and accuracy reached 0.932 in validation set. For the differentiation prediction model, ROC reached 0.983, 0.963, 0.963, 0.981 and accuracy reached 0.880, 0.923, 0.668, 0.881 for groups of low-, medium-, high-differentiation and normal tissue in validation set. Four hundred and one patients were selected after removing WSIs without gland regions and patients without follow up data. The concordance index reached to 0.609. Optimized cut off point of 51% was found by “Maxstat” method which was almost the same as WHO system’s cut off point of 50%. Both WHO system’s cut off point and optimized cut off point performed impressively in Kaplan-Meier curves and both p value of logrank test were below 0.005. In this study, gland structure of WSIs and differentiation status of tumor regions were proven to be predictable through deep leaning method. A finer and continuous differentiation grade can also be automatically calculated through above models. The differentiation grade was proven to stratify CAC patients well in survival analysis, whose optimized cut off point was almost the same as WHO tumor grading system. The tool of automatically calculating differentiation grade may show potential in field of therapy decision making and personalized treatment.

Keywords: colorectal cancer, differentiation, survival analysis, tumor grading

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Authors: Elena Filova, Ondrej Kaplan, Marie Markova, Helena Dragounova, Roman Matejka, Eduard Brynda, Lucie Bacakova

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Decellularized vessels have been evaluated as small-diameter vascular prostheses. Reseeding autologous cells onto decellularized tissue prior implantation should prolong prostheses function and make them living tissues. Suitable cell types for reseeding are both endothelial cells and bone marrow-derived stem cells, with a capacity for differentiation into smooth muscle cells upon mechanical loading. Endothelial cells assure antithrombogenicity of the vessels and MSCs produce growth factors and, after their differentiation into smooth muscle cells, they are contractile and produce extracellular matrix proteins as well. Fibrin is a natural scaffold, which allows direct cell adhesion based on integrin receptors. It can be prepared autologous. Fibrin can be modified with bound growth factors, such as basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF). These modifications in turn make the scaffold more attractive for cells ingrowth into the biological scaffold. The aim of the study was to prepare thin surface-attached fibrin assemblies with bound FGF-2 and VEGF, and to evaluate growth and differentiation of bone marrow-derived mesenchymal stem cells on the fibrin (Fb) assemblies. Following thin surface-attached fibrin assemblies were prepared: Fb, Fb+VEGF, Fb+FGF2, Fb+heparin, Fb+heparin+VEGF, Fb+heparin+FGF2, Fb+heparin+FGF2+VEGF. Cell culture poly-styrene and glass coverslips were used as controls. Human MSCs (passage 3) were seeded at the density of 8800 cells/1.5 mL alpha-MEM medium with 2.5% FS and 200 U/mL aprotinin per well of a 24-well cell culture. The cells have been cultured on the samples for 6 days. Cell densities on day 1, 3, and 6 were analyzed after staining with LIVE/DEAD cytotoxicity/viability assay kit. The differentiation of MSCs is being analyzed using qPCR. On day 1, the highest density of MSCs was observed on Fb+VEGF and Fb+FGF2. On days 3 and 6, there were similar densities on all samples. On day 1, cell morphology was polygonal and spread on all sample. On day 3 and 6, MSCs growing on Fb assemblies with FGF2 became apparently elongated. The evaluation of expression of genes for von Willebrand factor and CD31 (endothelial cells), for alpha-actin (smooth muscle cells), and for alkaline phosphatase (osteoblasts) is in progress. We prepared fibrin assemblies with bound VEGF and FGF-2 that supported attachment and growth of mesenchymal stem cells. The layers are promising for improving the ingrowth of MSCs into the biological scaffold. Supported by the Technology Agency of the Czech Republic TA04011345, and Ministry of Health NT11270-4/2010, and BIOCEV – Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University” project (CZ.1.05/1.1.00/02.0109), funded by the European Regional Development Fund for their financial supports.

Keywords: fibrin assemblies, FGF-2, mesenchymal stem cells, VEGF

Procedia PDF Downloads 325

Authors: Richard Abel

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In the United States, increased incarceration rates have caused many adolescents to feel the strain of parental absence. This absence is then manifest through adolescent feelings of parental rejection. Additionally, upon reentry maternal incarceration may be related to adolescents experienced perceived excessive disciple. It is possible parents engage in this manner of discipline attempting to prevent the child from taking the same path to incarceration as the parent. According to General Strain Theory, adolescents encountering strain are likely to experience negative emotions. The emotion that is most likely to lead to delinquency is anger through reduced inhibitions and motivation to act. Additionally, males are more likely to engage in delinquent behavior, regardless of experiencing strain. This is not the case for every male who experiences maternal incarceration, parental rejection, excessive discipline, or anger. There are protective factors that enable agency within individuals. One such protective factor is mastery, or the perception that one is in control of his or her own future. The model proposed in this research suggests maternal incarceration is associated with increased parental rejection and excessive discipline in males. Males experiencing parental rejection and excessive discipline are likely to experience increased anger, which is then associated with increases in delinquent behavior. This model explores whether agency, in the form of mastery, mediates the relationship between strains and negative emotions, or between negative emotions and delinquent behavior. The Kaplan Longitudinal and Multigenerational Study (KLAMS) dataset is uniquely situated to analyze this model providing longitudinal data collected from both parents and their offspring. Maternal incarceration is constructed using parental responses such that the mother was incarcerated after the child’s birth, and any incarceration that happened prior to birth is excluded. The remaining variables of the study are all constructed from varying waves of the adolescent survey. Parental rejection, along with control variables for age, race, parental socioeconomic status, neighborhood effects, delinquent peers, and prior delinquent behavior are all constructed using Wave I data. To increase causal inference, the negative emotion of anger and the mediating variable of mastery are measured during Wave II. Lastly, delinquent behavior is measured at Wave III. Results of the analysis show expected relationships such that adolescent males encountering maternal incarceration show increased perception of parental rejection and excessive discipline. Additionally, there is a positive relationship between parental rejection and excessive discipline at Wave I and feelings of anger at Wave II for males. For males experiencing either of these strains in Wave I, feelings of anger in Wave II are found to be associated with increased delinquent behavior in Wave III. Mastery was found to mediate the relationship between both parental rejection and excessive discipline and anger, but no such mediation occurs in the relationship between anger and delinquency, regardless of the strain being experienced. These findings suggest adolescent males who feel they are in control of their own lives are less likely to experience negative emotions produced by the occurrence of strain, thereby decreasing male engagement in delinquent behavior later in life.

Keywords: delinquency, mastery, maternal incarceration, strain

Procedia PDF Downloads 133

Authors: Omar Nouri, Wafa Mnejja, Fatma Dhouib, Syrine Zouari, Wicem Siala, Ilhem Charfeddine, Afef Khanfir, Leila Farhat, Nejla Fourati, Jamel Daoud

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Purpose and Objective: Intensity modulated radiation (IMRT) technique, associated with induction chemotherapy (IC) and/or concomitant chemotherapy (CC), is actually the recommended treatment modality for nasopharyngeal carcinomas (NPC). The aim of this study was to evaluate the therapeutic results and the patterns of relapse with this treatment protocol. Material and methods: A retrospective monocentric study of 145 patients with NPC treated between June 2016 and July 2021. All patients received IMRT with integrated simultaneous boost (SIB) of 33 daily fractions at a dose of 69.96 Gy for high-risk volume, 60 Gy for intermediate risk volume and 54 Gy for low-risk volume. The high-risk volume dose was 66.5 Gy in children. Survival analysis was performed according to the Kaplan-Meier method, and the Log-rank test was used to compare factors that may influence survival. Results: Median age was 48 years (11-80) with a sex ratio of 2.9. One hundred-twenty tumors (82.7%) were classified as stages III-IV according to the 2017 UICC TNM classification. Ten patients (6.9%) were metastatic at diagnosis. One hundred-thirty-five patient (93.1%) received IC, 104 of which (77%) were TPF-based (taxanes, cisplatin and 5 fluoro-uracil). One hundred-thirty-eight patient (95.2%) received CC, mostly cisplatin in 134 cases (97%). After a median follow-up of 50 months [22-82], 46 patients (31.7%) had a relapse: 12 (8.2%) experienced local and/or regional relapse after a median of 18 months [6-43], 29 (20%) experienced distant relapse after a median of 9 months [2-24] and 5 patients (3.4%) had both. Thirty-five patients (24.1%) died, including 5 (3.4%) from a cause other than their cancer. Three-year overall survival (OS), cancer specific survival, disease free survival, metastasis free survival and loco-regional free survival were respectively 78.1%, 81.3%, 67.8%, 74.5% and 88.1%. Anatomo-clinic factors predicting OS were age > 50 years (88.7 vs. 70.5%; p=0.004), diabetes history (81.2 vs. 66.7%; p=0.027), UICC N classification (100 vs. 95 vs. 77.5 vs. 68.8% respectively for N0, N1, N2 and N3; p=0.008), the practice of a lymph node biopsy (84.2 vs. 57%; p=0.05), and UICC TNM stages III-IV (93.8 vs. 73.6% respectively for stage I-II vs. III-IV; p=0.044). Therapeutic factors predicting OS were a number of CC courses (less than 4 courses: 65.8 vs. 86%; p=0.03, less than 5 courses: 71.5 vs. 89%; p=0.041), a weight loss > 10% during treatment (84.1 vs. 60.9%; p=0.021) and a total cumulative cisplatin dose, including IC and CC, < 380 mg/m² (64.4 vs. 87.6%; p=0.003). Radiotherapy delay and total duration did not significantly affect OS. No grade 3-4 late side effects were noted in the evaluable 127 patients (87.6%). The most common toxicity was dry mouth which was grade 2 in 47 cases (37%) and grade 1 in 55 cases (43.3%).Conclusion: IMRT for nasopharyngeal carcinoma granted a high loco-regional control rate for patients during the last five years. However, distant relapses remain frequent and conditionate the prognosis. We identified many anatomo-clinic and therapeutic prognosis factors. Therefore, high-risk patients require a more aggressive therapeutic approach, such as radiotherapy dose escalation or adding adjuvant chemotherapy.

Keywords: therapeutic results, prognostic factors, intensity-modulated radiotherapy, nasopharyngeal carcinoma

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Authors: Evonne Kaplan-Liss, Val Lantz-Gefroh

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Arts and humanities are often incorporated into medical education to help deepen understanding of the human condition and the ability to communicate from a place of compassion. However, a gap remains in our knowledge of compassionate communication training for postgraduate medical professionals (as opposed to students and residents); how training opportunities include and impact the artists themselves, and how train-the-trainer models can support learners to become teachers. In this report, the authors present results from a pilot evaluation of the UC San Diego Health: Sanford Compassionate Communication Fellowship, a 60-hour experiential program that uses theater, narrative reflection, poetry, literature, and journalism techniques to train a multidisciplinary cohort of medical professionals and artists in compassionate communication. In the culminating project, fellows design and implement their own projects as teachers of compassionate communication in their respective workplaces. Qualitative methods, including field notes and 30-minute Zoom interviews with each fellow, were used to evaluate the impact of the fellowship. The cohort included both artists (n=2) and physicians representing a range of specialties (n=7), such as occupational medicine, palliative care, and pediatrics. The authors coded the data using thematic analysis for evidence of how the multidisciplinary nature of the fellowship impacted the fellows’ experiences. The findings show that the multidisciplinary cohort contributed to a greater appreciation of compassionate communication in general. Fellows expressed that the ability to witness how those in different fields approached compassionate communication enhanced their learning and helped them see how compassion can be expressed in various contexts, which was both “exhilarating” and “humbling.” One physician expressed that the fellowship has been “really helpful to broaden my perspective on the value of good communication.” Fellows shared how what they learned in the fellowship translated to increased compassionate communication, not only in their professional roles but in their personal lives as well. A second finding was the development of a supportive community. Because each fellow brought their own experiences and expertise, there was a sense of genuine ability to contribute as well as a desire to learn from others. A “brave space” was created by the fellowship facilitators and the inclusion of arts-based activities: a space that invited vulnerability and welcomed fellows to make their own meaning without prescribing any one answer or right way to approach compassionate communication. This brave space contributed to a strong connection among the fellows and reports of increased well-being, as well as multiple collaborations post-fellowship to carry forward compassionate communication training at their places of work. Results show initial evidence of the value of a multidisciplinary fellowship for promoting compassionate communication for both artists and physicians. The next steps include maintaining the supportive fellowship community and collaborations with a post-fellowship affiliate faculty program; scaling up the fellowship with non-physicians (e.g., nurses and physician assistants); and collecting data from family members, colleagues, and patients to understand how the fellowship may be creating a ripple effect outside of the fellowship through fellows’ compassionate communication.

Keywords: compassionate communication, communication in healthcare, multidisciplinary learning, arts in medicine

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Authors: M. Markova, E. Filova, O. Kaplan, R. Matejka, L. Bacakova

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The porcine pericardium is used as a material for cardiac and aortic valves substitutes. Current biological aortic heart valve prosthesis have a limited lifetime period because they undergo degeneration. In order to make them more biocompatible and prolong their lifetime it is necessary to reseed the decellularized prostheses with endothelial cells and with valve interstitial cells. The endothelialization of the prosthesis-surface may be supported by suitable chemical surface modification of the prosthesis. The aim of this study is to prepare bioactive fibrin layers which would both support endothelialization of porcine pericardium and enhance differentiation and maturation of the endothelial cells seeded. As a material for surface adjustments we used layers of fibrin with/without heparin and some of them with adsorbed or chemically bound FGF2, VEGF or their combination. Fibrin assemblies were prepared in 24-well cell culture plate and were seeded with HSVEC (Human Saphenous Vein Endothelial Cells) at a density of 20,000 cells per well in EGM-2 medium with 0.5% FS and without heparin, without FGF2 and without VEGF; medium was supplemented with aprotinin (200 U/mL). As a control, surface polystyrene (PS) was used. Fibrin was also used as homogeneous impregnation of the decellularized porcine pericardium throughout the scaffolds. Morphology, density, and viability of the seeded endothelial cells were observed from micrographs after staining the samples by LIVE/DEAD cytotoxicity/viability assay kit on the days 1, 3, and 7. Endothelial cells were immunocytochemically stained for proteins involved in cell adhesion, i.e. alphaV integrin, vinculin, and VE-cadherin, markers of endothelial cells differentiation and maturation, i.e. von Willebrand factor and CD31, and for extracellular matrix proteins typically produced by endothelial cells, i.e. type IV collagen and laminin. The staining intensities were subsequently quantified using a software. HSVEC cells grew on each of the prepared surfaces better than on control surface. They reached confluency. The highest cell densities were obtained on the surface of fibrin with heparin and both grow factors used together. Intensity of alphaV integrins staining was highest on samples with remained fibrin layer, i.e. on layers with lower cell densities, i.e. on fibrin without heparin. Vinculin staining was apparent, but was rather diffuse, on fibrin with both FGF2 and VEGF and on control PS. Endothelial cells on all samples were positively stained for von Willebrand factor and CD31. VE-cadherin receptors clusters were best developed on fibrin with heparin and growth factors. Significantly stronger staining of type IV collagen was observed on fibrin with heparin and both growth factors. Endothelial cells on all samples produced laminin-1. Decellularized pericardium was homogeneously filled with fibrin structures. These fibrin-modified pericardium samples will be further seeded with cells and cultured in a bioreactor. Fibrin layers with/without heparin and with adsorbed or chemically bound FGF2, VEGF or their combination are good surfaces for endothelialization of cardiovascular prostheses or porcine pericardium based heart valves. Supported by the Ministry of Health, grants No15-29153A and 15-32497A, and the Grant Agency of the Czech Republic, project No. P108/12/G108.

Keywords: aortic valves prosthesis, FGF2, heparin, HSVEC cells, VEGF

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Authors: Delphine Ribes Lemay, Valentine Bernasconi, André Andrade, Lara DéFayes, Mathieu Salzmann, FréDéRic Kaplan, Nicolas Henchoz

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Digitization and preservation of large heritage induce high maintenance costs to keep up with the technical standards and ensure sustainable access. Creating impactful usage is instrumental to justify the resources for long-term preservation. The Museum für Gestaltung of Zurich holds one of the biggest poster collections of the world from which 52’000 were digitised. In the process of building a digital installation to valorize the collection, one objective was to develop an algorithm capable of predicting the next poster to show according to the ones already displayed. The work presented here describes the steps to build an algorithm able to automatically create sequences of posters reflecting associations performed by curator and professional designers. The exposed challenge finds similarities with the domain of song playlist algorithms. Recently, artificial intelligence techniques and more specifically, deep-learning algorithms have been used to facilitate their generations. Promising results were found thanks to Recurrent Neural Networks (RNN) trained on manually generated playlist and paired with clusters of extracted features from songs. We used the same principles to create the proposed algorithm but applied to a challenging medium, posters. First, a convolutional autoencoder was trained to extract features of the posters. The 52’000 digital posters were used as a training set. Poster features were then clustered. Next, an RNN learned to predict the next cluster according to the previous ones. RNN training set was composed of poster sequences extracted from a collection of books from the Gestaltung Museum of Zurich dedicated to displaying posters. Finally, within the predicted cluster, the poster with the best proximity compared to the previous poster is selected. The mean square distance between features of posters was used to compute the proximity. To validate the predictive model, we compared sequences of 15 posters produced by our model to randomly and manually generated sequences. Manual sequences were created by a professional graphic designer. We asked 21 participants working as professional graphic designers to sort the sequences from the one with the strongest graphic line to the one with the weakest and to motivate their answer with a short description. The sequences produced by the designer were ranked first 60%, second 25% and third 15% of the time. The sequences produced by our predictive model were ranked first 25%, second 45% and third 30% of the time. The sequences produced randomly were ranked first 15%, second 29%, and third 55% of the time. Compared to designer sequences, and as reported by participants, model and random sequences lacked thematic continuity. According to the results, the proposed model is able to generate better poster sequencing compared to random sampling. Eventually, our algorithm is sometimes able to outperform a professional designer. As a next step, the proposed algorithm should include a possibility to create sequences according to a selected theme. To conclude, this work shows the potentiality of artificial intelligence techniques to learn from existing content and provide a tool to curate large sets of data, with a permanent renewal of the presented content.

Keywords: Artificial Intelligence, Digital Humanities, serendipity, design research

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Authors: Briohny H. Spencer, Russ Chess-Williams, Catherine McDermott, Shailendra Anoopkumar-Dukie, David Christie

Abstract:

Background: Prostate cancer is the second most common cancer diagnosed in men worldwide and the most prevalent in Australian men. In 2015, it was estimated that approximately 18,000 new cases of prostate cancer were diagnosed in Australia. Currently, for localised disease, androgen depravation therapy (ADT) and radiotherapy are a major part of the curative management of prostate cancer. ADT acts to reduce the levels of circulating androgens, primarily testosterone and the locally produced androgen, dihydrotestosterone (DHT), or by preventing the subsequent activation of the androgen receptor. Thus, the growth of the cancerous cells can be reduced or ceased. Radiation techniques such as brachytherapy (radiation delivered directly to the prostate by transperineal implant) or external beam radiation therapy (exposure to a sufficient dose of radiation aimed at eradicating malignant cells) are also common techniques used in the treatment of this condition. Radiotherapy (RT) has significant limitations, including reduced effectiveness in treating malignant cells present in hypoxic microenvironments leading to radio-resistance and poor clinical outcomes and also the significant side effects for the patients. Alpha1-adrenoceptor antagonists are used for many prostate cancer patients to control lower urinary tract symptoms, due to the progression of the disease itself or may arise as an adverse effect of the radiotherapy treatment. In Australia, a significant number (not a majority) of patients receive a α1-ADR antagonist and four drugs are available including prazosin, terazosin, alfuzosin and tamsulosin. There is currently limited published data on the effects of α1-ADR antagonists during radiotherapy, but it suggests these medications may improve patient outcomes by enhancing the effect of radiotherapy. Aim: To determine the impact of α1-ADR antagonists treatments on time to biochemical relapse following radiotherapy. Methods: A retrospective study of male patients receiving radiotherapy for biopsy-proven localised prostate cancer was undertaken to compare cancer outcomes for drug-naïve patients and those receiving α1-ADR antagonist treatments. Ethical approval for the collection of data at Genesis CancerCare QLD was obtained and biochemical relapse (defined by a PSA rise of >2ng/mL above the nadir) was recorded in months. Rates of biochemical relapse, prostate specific antigen doubling time (PSADT) and Kaplan-Meier survival curves were also compared. Treatment groups were those receiving α1-ADR antagonists treatment before or concurrent with their radiotherapy. Data was statistically analysed using One-way ANOVA and results expressed as mean ± standard deviation. Major findings: The mean time to biochemical relapse for tamsulosin, prazosin, alfuzosin and controls were 45.3±17.4 (n=36), 41.5±19.6 (n=11), 29.3±6.02 (n=6) and 36.5±17.6 (n=16) months respectively. Tamsulosin, prazosin but not alfuzosin delayed time to biochemical relapse although the differences were not statistically significant. Conclusion: Preliminary data for the prior and/or concurrent use of tamsulosin and prazosin showed a positive trend in delaying time to biochemical relapse although no statistical significance was shown. Larger clinical studies are indicated and with thousands of patient records yet to be analysed, it may determine if there is a significant effect of these drugs on control of prostate cancer.

Keywords: alpha1-adrenoceptor antagonists, biochemical relapse, prostate cancer, radiotherapy

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Authors: Zuzana Tatarkova, Ivana Pilchova, Michal Cibulka, Martin Kolisek, Peter Racay, Peter Kaplan

Abstract:

Introduction: Normal functioning of mitochondria is crucial for cardiac performance. Mitochondria undergo mitophagy and biogenesis, and mitochondrial proteins are subject to extensive post-translational modifications. The state of mitochondrial homeostasis reflects overall cellular fitness and longevity. Perturbed mitochondria produce less ATP, release greater amounts of reactive molecules, and are more prone to apoptosis. Therefore mitochondrial turnover is an integral aspect of quality control in which dysfunctional mitochondria are selectively eliminated through mitophagy. Currently, the progressive deterioration of physiological functions is seen as accumulation of modified/damaged proteins with limiting regenerative ability and disturbance of such affected protein-protein communication throughout aging in myocardial cells. Methodologies: For our study was used immunohistochemistry, biochemical methods: spectrophotometry, western blotting, immunodetection as well as more sophisticated 2D electrophoresis and mass spectrometry for evaluation protein-protein interactions and specific post-translational modification. Results and Discussion: Mitochondrial stress response to reactive species was evaluated as electron transport chain (ETC) complexes, redox-active molecules, and their possible communication. Protein-protein interactions revealed a strong linkage between age and ETC protein subunits. Redox state was strongly affected in senescent mitochondria with shift in favor of more pro-oxidizing condition within cardiomyocytes. Acute myocardial ischemia and ischemia-reperfusion (IR) injury affected ETC complexes I, II and IV with no change in complex III. Ischemia induced decrease in total antioxidant capacity, MnSOD, GSH and catalase activity with recovery in some extent during reperfusion. While MnSOD protein content was higher in IR group, activity returned to 95% of control. Nitric oxide is one of the biological molecules that can out compete MnSOD for superoxide and produce peroxynitrite. This process is faster than dismutation and led to the 10-fold higher production of nitrotyrosine after IR injury in adult with higher protection in senescent ones. 2D protein profiling revealed 140 mitochondrial proteins, 12 of them with significant changes after IR injury and 36 individual nitrotyrosine-modified proteins further identified by mass spectrometry. Linking these two groups, 5 proteins were altered after IR as well as nitrated, but only one showed massive nitration per lowering content of protein after IR injury in adult. Conclusions: Senescent cells have greater proportion of protein content, which might be modulated by several post-translational modifications. If these protein modifications are connected to functional consequences and protein-protein interactions are revealed, link may lead to the solution. Assume all together, dysfunctional proteostasis can play a causative role and restoration of protein homeostasis machinery is protective against aging and possibly age-related disorders. This work was supported by the project VEGA 1/0018/18 and by project 'Competence Center for Research and Development in the field of Diagnostics and Therapy of Oncological diseases', ITMS: 26220220153, co-financed from EU sources.

Keywords: aging heart, mitochondria, proteomics, redox state

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Authors: Zeynep Busra Velioglu, Deniz Pulat, Beril Demirbakan, Burak Ozcan, Ece Bayrak, Cevat Erisken

Abstract:

Bone tissue has the ability to perform a wide array of functions including providing posture, load-bearing capacity, protection for the internal organs, initiating hematopoiesis, and maintaining the homeostasis of key electrolytes via calcium/phosphate ion storage. The most common cause for bone defects is extensive trauma and subsequent infection. Bone tissue has the self-healing capability without a scar tissue formation for the majority of the injuries. However, some may result with delayed union or fracture non-union. Such cases include reconstruction of large bone defects or cases of compromised regenerative process as a result of avascular necrosis and osteoporosis. Several surgical methods exist to treat bone defects, including Ilizarov method, Masquelete technique, growth factor stimulation, and bone replacement. Unfortunately, these are technically demanding and come with noteworthy disadvantages such as lengthy treatment duration, adverse effects on the patient’s psychology, repeated surgical procedures, and often long hospitalization times. These limitations associated with surgical techniques make bone substitutes an attractive alternative. Here, it was hypothesized that a 3D printed scaffold will mimic trabecular bone in terms of biomechanical properties and that such scaffolds will support cell attachment and survival. To test this hypothesis, this study aimed at fabricating poly(lactic acid), PLA, structures using 3D printing technology for trabecular bone defects, characterizing the scaffolds and comparing with bovine trabecular bone. Capacity of scaffolds on human bone marrow stem cell (hBMSC) attachment and survival was also evaluated. Cubes with a volume of 1 cm³ having pore sizes of 0.50, 1.00 and 1.25 mm were printed. The scaffolds/grafts were characterized in terms of porosity, contact angle, compressive mechanical properties as well cell response. Porosities of the 3D printed scaffolds were calculated based on apparent densities. For contact angles, 50 µl distilled water was dropped over the surface of scaffolds, and contact angles were measured using ‘Image J’ software. Mechanical characterization under compression was performed on scaffolds and native trabecular bone (bovine, 15 months) specimens using a universal testing machine at a rate of 0.5mm/min. hBMSCs were seeded onto the 3D printed scaffolds. After 3 days of incubation with fully supplemented Dulbecco’s modified Eagle’s medium, the cells were fixed using 2% formaldehyde and glutaraldehyde mixture. The specimens were then imaged under scanning electron microscopy. Cell proliferation was determined by using EZQuant dsDNA Quantitation kit. Fluorescence was measured using microplate reader Spectramax M2 at the excitation and emission wavelengths of 485nm and 535nm, respectively. Findings suggested that porosity of scaffolds with pore dimensions of 0.5mm, 1.0mm and 1.25mm were not affected by pore size, while contact angle and compressive modulus decreased with increasing pore size. Biomechanical characterization of trabecular bone yielded higher modulus values as compared to scaffolds with all pore sizes studied. Cells attached and survived in all surfaces, demonstrating higher proliferation on scaffolds with 1.25mm pores as compared with those of 1mm. Collectively, given lower mechanical properties of scaffolds as compared to native bone, and biocompatibility of the scaffolds, the 3D printed PLA scaffolds of this study appear as candidate substitutes for bone repair and regeneration.

Keywords: 3D printing, biomechanics, bone repair, stem cell

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