Conversion of ethanol, ethyl acetate and acetone over hydroxyapatite

Orientador: Gustavo Paim ValençaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia QuímicaResumo: Combustíveis renováveis têm conquistado um papel importante no contexto ambiental e socioeconômico mundial. O bio-óleo possui grande potencial para ser usado como bicombustível, mas devido ao elevado teor de oxigênio é necessário refinar o bio-óleo por desoxigenação catalítica. Esse trabalho se propôs a investigar a aplicação do catalisador hidroxiapatita (HAP) na conversão catalítica de moléculas plataforma do bio-óleo (etanol, acetato de etila e acetona). O catalisador foi sintetizado pelo método de precipitação química em meio básico. Após calcinação, o sólido foi caracterizado pelas seguintes análises: difração de raios X (XRD), espectroscopia de infravermelho (FT-IR), adsorção de N2 a 77 K e dessorção a temperatura programada (TPD) de CO2 e NH3. A análise físico-química indicou a formação de HAP e a presença de sítios ácidos e básicos capazes de atuar como um catalisador bifuncional. Os testes catalíticos foram realizados em reator de leito fixo, a 250, 300 e 350 °C, concentrações de reagente de 109, 145 e 180 mmHg e fluxo de gás de arraste (N2) de 60 mL min-1. Os produtos da reação foram identificados por cromatógrafo a gás acoplado a detector do tipo FID. As reações foram conduzidas de modo a apresentar conversões abaixo de 10 %, de forma que fosse possível considerar o reator de leito fixo como reator diferencial. Foram identificados produtos C2 a C6 na conversão de etanol. A HAP foi eficiente para reação de acoplamento de etanol via mecanismo de Guerbet, por meio de reações de condensação aldólica, desidrogenação e desidratação. Já nas reações de acetato de etila, foram identificados etanol, etileno, propeno, 2-propanol e acetona como produtos. Na conversão de acetato de etila sobre HAP foi observado que ocorrem reações em série e paralelo por meio de desidratação e descarboxilação. Por fim, na conversão de acetona foram identificados óxido de mesitila (MO), DAA (diacetona álcool), MIBK (metil isobutil cetona) e outros produtos pesados. Verificou-se que reações de acoplamento e desidratação ocorrem na conversão de catalítica de acetona sobre HAP. A temperatura de reação e a relação de sítios ácidos e básicos fracos e médios do catalisador é um fator determinante para seletividade dos produtos. A HAP pode ser considerada um catalisador potencial para reações de desoxigenação como desidratação, desoxigenação e descarboxilaçãoAbstract: Renewable fuels have been playing an important role in the global environmental and socio-economic context. Bio-oil has great potential to be used as bio-fuel, but due to the high oxygen content it is necessary a bio-oil upgrading to biofuel by catalytic deoxygenation. The aim of this work is investigate the application of hydroxyapatite (HAP) in the catalytic conversion of bio-oil platform molecules (ethanol, ethyl acetate and acetone). The catalyst was synthesized by basic precipitation method. The catalyst was synthesized by precipitation method. After heat treatment, the solid was characterized by X-ray diffraction (XRD), infrared spectroscopy (FT-IR), N2 adsorption at 77 K and programmed temperature desorption (TPD) of CO2 and NH3. The physical chemical analysis indicated the formation of HAP and the presence of acid and basic surface sites being able to act as a bifunctional catalyst. The catalytic tests were performed in a fixed bed reactor at 250, 300 and 350 °C, reactant pressures of 109, 145 and 180 mmHg and carrier gas flow (N2) of 60 mL min-1. The reaction products were identified by a GC-FID. The reactions were conducted in order to present conversions below 10%, so that it was possible to consider the fixed bed reactor as a differential reactor. Products C2 to C6 were identified at ethanol conversion. HAP was efficient for ethanol coupling reaction via Guerbet reaction, through aldol condensation, dehydrogenation and dehydration reactions. In addition, ethanol, ethylene, propene, 2-propanol and acetone were identified as products for ethyl acetate conversion. In the conversion of ethyl acetate over HAP, series and parallel reactions occur through dehydration and decarboxylation. Finally, in the conversion of acetone mesityl oxide (MO), DAA (diacetone alcohol), MIBK (methyl isobutyl ketone) and other heavy products were identified. It has been found that acetone coupling and dehydration reactions occur in the conversion of acetone over HAP. The reaction temperature and the ratio of weak acid and base sites of the catalyst is a determining factor for product selectivity. HAP can be considered a potential catalyst for deoxygenation reactions such as dehydration and decarboxylationMestradoEngenharia QuímicaMestra em Engenharia Química132112/2017-5CNP

ネパール都市部における医療費自己負担と対処戦略に関する研究

学位の種別:課程博士University of Tokyo(東京大学

Genotype prevalence and age distribution of human papillomavirus from infection to cervical cancer in Japanese women: A systematic review and meta-analysis

Background: National HPV vaccination coverage in Japan is less than one percent of the eligible population and cervical cancer incidence and mortality are increasing. This systematic review and meta-analysis aimed to provide a comprehensive estimate of HPV genotype prevalence for Japan. Methods: English and Japanese databases were searched to March 2021 for research reporting HPV genotypes in cytology and histology samples from Japanese women. Summary estimates were calculated by disease stage from cytology only assessment – Normal, ASCUS, LSIL, HSIL and from histological assessment – CIN1, CIN2, CIN3/AIS, ICC (ICC-SCC, and ICC-ADC), and other. A random-effects meta–analysis was used to calculate summary prevalence estimates of any-HPV, high-risk (HR) and low-risk (LR) vaccine types, and vaccine genotypes (bivalent, quadrivalent, or nonavalent). This study was registered with PROSPERO: CRD42018117596. Results: A total of 57759 women with normal cytology, 1766 ASCUS, 3764 LSIL, 2017 HSIL, 3130 CIN1, 1219 CIN2, 869 CIN3/AIS, and 4306 ICC (which included 1032 ICC-SCC, and 638 ICC-ADC) were tested for HPV. The summary estimate of any-HPV genotype in women with normal cytology was 15·6% (95% CI: 12·3–19·4) and in invasive cervical cancer (ICC) was 85·6% (80·7–89·8). The prevalence of HR-HPV was 86·0% (95% CI: 73·9–94·9) for cytological cases of HSIL, 76·9% (52·1–94·7) for histological cases of CIN3/AIS, and 75·7% (68·0–82·6) for ICC. In women with ICC, the summary prevalence of bivalent vaccine genotypes was 58·5% (95% CI: 52·1–64·9), for quadrivalent genotypes was 58·6% (52·2–64·9) and for nonavalent genotypes was 71·5% (64·9–77·6), and of ICC cases that were HPV positive over 90% of infections are nonavalent vaccine preventable. There was considerable heterogeneity in all HPV summary estimates and for ICC, this heterogeneity was not explained by variability in study design, sample type, HPV assay type, or HPV DNA detection method, although studies published in the 1990s had lower prevalence estimates of any-HPV and HR HPV genotypes. Interpretations: HPV prevalence is high among Japanese women. The nonavalent vaccine is likely to have the greatest impact on reducing cervical cancer incidence and mortality in Japan

Кривичните аспекти на азил во меѓународното и македонското кривично право“

Краток извадок Меѓународниот институт азил, како и неговата меѓународна кривичноправна рамка, е област на постојано надополнување и акумулација на материјални и формално - правни факти, со цел за изградба на универзален кривичноправен систем на азил кој би имал широкоопфатна примена. Теоретската рамка на поставениот проблем, низ годините на историјата, постојано била надополнувана во егзактните моменти на проблеми со именуваниот институт. Целта на мојот труд е искористување на изворите на правото и политиките на азил, нивна структурна анализа и дефиниција на имплементација. Миграцијата е поим тесно поврзан со азилот. Токму затоа, не може а да не се спомене нејзиното влијание врз правната форма на азилот како институт. Човештвото, во својата еволуција, тенденциозно дејствува кон создавање на универзални, регионални и национални правни лица кои ја претставуваат унилатералната желба за солидарност и сплотеност. Ваквите организации неопходно бараат консолидирано законодавство, во сите сегменти на општествениот живот. Токму затоа, анализата на ваквите организации во мојот труд е со цел да покаже во колкава мера и каква форма се конструираат и имплементираат правните норми на азилот. Исто така, ќе покаже во колкав капацитет е легислативата на азилот и од каде треба да се продолжи надградбата на правниот систем. Надградбата на системот на азил е сеопфатна и ги засега сите. Како европска држава со мултилатерални односи и желба за членство во евроатланската и европската заедница, Република Македонија настојува да го надградува својот правен систем секогаш кога ќе ѝ се овозможи терен за такво нешто. Мојата анализа го води трудот и до разградба на македонскиот правен систем, воочување на фактичката состојба во однос на азилот и привремената заштита, и критички анализирајќи ја поврзаноста на материјално - правните и формално - правните аспекти на азилните норми. Заклучокот на сето ова мора да биде објективен и во согласност со позитивното право, без остапување од начелата на непристрасност, јасност, еквивалентност, совестност и чесност. Клучни зборови: миграција, азил, кривично право, бегалци, бегалска криза, меѓународни организации

Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer

Background Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX. Methods We compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 [SD260] vs Medium: 220 mg/m2 [MD220] vs Low: 180 mg/m2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was 1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded. Results One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180. Conclusions Intravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC

Long-term efficacy and safety of tofacitinib in patients with ulcerative colitis: 3-year results from a real-world study

Background/Aims The efficacy and safety of tofacitinib for the treatment of refractory ulcerative colitis (UC) has been demonstrated in clinical trials. Although, a series of reports with real-world evidence of its short-term efficacy and safety profiles have already been published, reports of long-term real-world data have been limited. We aimed to show our 3-year evidence on the clinical use of tofacitinib for the treatment of UC, focusing on its efficacy and safety profiles. Methods A retrospective observational study was conducted on patients who started tofacitinib for active refractory UC at our hospital. The primary outcome was the retention rate until 156 weeks after initiating tofacitinib. The secondary outcomes were short-term efficacy at 4, 8, and 12 weeks; long-term efficacy at 52, 104, and 156 weeks; prognostic factors related to the cumulative retention rate; loss of response; and safety profile, including adverse events. Results Forty-six patients who were able to be monitored for up to 156 weeks after tofacitinib initiation, were enrolled in this study. Continuation of tofacitinib was possible until 156 weeks in 54.3%, with > 50% response rates and > 40% remission rates. Among patients in whom response or remission was achieved and tofacitinib was deescalated after 8 weeks of induction treatment, 54.3% experienced relapse but were successfully rescued by and retained on reinduction treatment, except for 1 patient. No serious AEs were observed in the study. Conclusions Tofacitinib is effective and safe as long-term treatment in a refractory cohort of UC patients in real-world clinical practice

Effect and cost-effectiveness of national gastric cancer screening in Japan: a microsimulation modeling study

Background A national endoscopic screening program for gastric cancer was rolled out in Japan in 2015. We used a microsimulation model to estimate the cost-effectiveness of current screening guidelines and alternative screening strategies in Japan. Methods We developed a microsimulation model that simulated a virtual population corresponding to the Japanese population in risk factor profile and life expectancy. We evaluated 15 endoscopic screening scenarios with various starting ages, stopping ages, and screening intervals. The primary outcomes were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratio. Cost-effective screening strategies were determined using a willingness-to-pay threshold of $50,000 per QALY gained. One-way sensitivity and probabilistic sensitivity analyses were done to explore model uncertainty. Results Using the threshold of$50,000 per QALY, a triennial screening program for individuals aged 50 to 75 years was the cost-effective strategy, with an incremental cost-effectiveness ratio of $45,665. Compared with no endoscopic screening, this strategy is predicted to prevent 63% of gastric cancer mortality and confer 27.2 QALYs gained per 1000 individuals over a lifetime period. Current screening guidelines were not on the cost-effectiveness efficient frontier. The results were robust on one-way sensitivity analyses and probabilistic sensitivity analysis. Conclusions This modeling study suggests that the endoscopic screening program in Japan would be cost-effective when implemented between age 50 and 75 years, with the screening repeated every 3 years. These findings underscore the need for further evaluation of the current gastric cancer screening recommendations

Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients

Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients’ quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001−3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01)