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1
Hole, Kjell Jorgen. "Management of hidden risks." Computer 46, no. 1 (January 2013): 65–70. http://dx.doi.org/10.1109/mc.2012.397.
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McGraw, G. "Managing software security risks." Computer 35, no. 4 (2002): 99–101. http://dx.doi.org/10.1109/mc.2002.993782.
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Dacorogna, Michel, Laila Elbahtouri, and Marie Kratz. "Validation of aggregated risks models." Annals of Actuarial Science 12, no. 2 (December 4, 2017): 433–54. http://dx.doi.org/10.1017/s1748499517000227.
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AbstractValidation of risk models is required by regulators and demanded by management and shareholders. Those models rely in practice heavily on Monte Carlo (MC) simulations. Given their complexity, the convergence of the MC algorithm is difficult to prove mathematically. To circumvent this problem and nevertheless explore the conditions of convergence, we suggest an analytical approach. Considering standard models, we compute, via mixing techniques, closed form formulas for risk measures as Value-at-Risk (VaR) VaR or Tail Value-at-Risk (TVaR) TVaR on a portfolio of risks, and consequently for the associated diversification benefit. The numerical convergence of MC simulations of those various quantities is then tested against their analytical evaluations. The speed of convergence appears to depend on the fatness of the tail of the marginal distributions; the higher the tail index, the faster the convergence. We also explore the behaviour of the diversification benefit with various dependence structures and marginals (heavy and light tails). As expected, it varies heavily with the type of dependence between aggregated risks. The diversification benefit is also studied as a function of the risk measure, VaR or TVaR.
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Gaff, Brian M. "Corporate Risks from Social Media." Computer 47, no. 1 (January 2014): 13–15. http://dx.doi.org/10.1109/mc.2014.9.
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Hong, J. I. "Minimizing security risks in ubicomp systems." Computer 38, no. 12 (December 2005): 118–19. http://dx.doi.org/10.1109/mc.2005.416.
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Oppliger, Rolf, Gunther Pernul, and Sokratis Katsikas. "New Frontiers: Assessing and Managing Security Risks." Computer 50, no. 4 (April 2017): 48–51. http://dx.doi.org/10.1109/mc.2017.93.
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McGraw, Gary, Richie Bonett, Victor Shepardson, and Harold Figueroa. "The Top 10 Risks of Machine Learning Security." Computer 53, no. 6 (June 2020): 57–61. http://dx.doi.org/10.1109/mc.2020.2984868.
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Kroll, Joshua A., James Bret Michael, and David B. Thaw. "Enhancing Cybersecurity via Artificial Intelligence: Risks, Rewards, and Frameworks." Computer 54, no. 6 (June 2021): 64–71. http://dx.doi.org/10.1109/mc.2021.3055703.
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Xiao, Chan-Chan, Mao-Jian Chen, Fan-Biao Mei, Xiang Fang, Tian-Ren Huang, Ji-Lin Li, Wei Deng, and Yuan-Dong Li. "Influencing factors and health risk assessment of microcystins in the Yongjiang river (China) by Monte Carlo simulation." PeerJ 6 (November 16, 2018): e5955. http://dx.doi.org/10.7717/peerj.5955.
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The Yongjiang river is a large, shallow, hyper-trophic, freshwater river in Guangxi, China. To investigate the presence of microcystin-RR, microcystin-LR, and microcystin-YR (MC-RR, MC-LR, and MC-YR) in the Yongjiang river and describe their correlation with environmental factors, as well as, assess health risk using Monte Carlo simulation, 90 water samples were collected at three sample points from March to December 2017. Results showed that during the monitoring period, total concentrations of MC-RR (TMC-RR), MC-YR (TMC-YR), and MC-LR (TMC-LR) varied from 0.0224 to 0.3783 μg/L, 0.0329 to 0.1433 μg/L, and 0.0341 to 0.2663 μg/L, respectively. Total phosphorus (TP) content appeared to be related to TMC-LR and the total concentrations of microcystins (TMCs), while pH and total nitrogen (TN)/TP ratio appeared to be related to TMC-RR and TMC-YR, respectively. Using the professional health risk assessment software @Risk7.5, the risks of dietary intake of microcystins (MCs), including the carcinogenic risk and non-carcinogenic risk, were evaluated. It was found that the carcinogenic risk of MC-RR from drinking water was higher than MC-LR and MC-YR, and the presence of MCs would lead to high potential health risks, especially in children. The carcinogenic risk of MC-RR to children was >1 × 10−4, the maximum allowance level recommended by the US Environmental Protection Agency; as for adults, it was >5 × 10−5, the maximum allowance level recommended by the International Commission on Radiological Protection. The non-carcinogenic hazard index (HI) of MC-RR, MC-YR, and MC-LR increased successively, indicating that MC-LR was more hazardous to human health than MC-YR and MC-RR, but its HI was <1. This suggests that MCs pose less risk to health. However, it is necessary to strengthen the protection and monitoring of drinking water source for effective control of water pollution and safeguarding of human health.
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Munck, Jan Christoph, Alexander Tkotz, Sven Heidenreich, and Andreas Wald. "The performance effects of management control instruments in different stages of new product development." Journal of Accounting & Organizational Change 16, no. 2 (June 26, 2020): 259–84. http://dx.doi.org/10.1108/jaoc-09-2019-0101.
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Purpose The study builds on existing research in management control (MC) and innovation management. The purpose of this study is to identify patterns in the application of MC instruments which contribute to successful innovation. The application of MC instruments can reduce potential risks and make the new product development (NPD) process more transparent and efficient. Design/methodology/approach The authors use dyadic data to determine the effect of 58 MC instruments on NPD process stage-specific performance and subsequent innovation and firm success. To provide empirical evidence of each MC instrument’s effectiveness, three importance-performance matrix analyses were conducted that assess the impact of each MC instrument. Findings The authors identify patterns in the application of MC instruments which contribute to successful innovation activities and the authors determine the impact of MC instruments on NPD performance, innovation performance and firm performance in different stages of the NPD process. Practical implications The authors provide knowledge that can be used by managers to review their actual application of MC in the NPD process and to select their instrument set. Originality/value The authors contribute to the MC literature by examining data from a cross-industry study on the effects of MC instruments during the NPD process. The authors include a comprehensive set of MC instruments and show how their effect changes between the different stages of the NPD process.
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Simiyu, Benard, Steve Oduor, Thomas Rohrlack, Lewis Sitoki, and Rainer Kurmayer. "Microcystin Content in Phytoplankton and in Small Fish from Eutrophic Nyanza Gulf, Lake Victoria, Kenya." Toxins 10, no. 7 (July 3, 2018): 275. http://dx.doi.org/10.3390/toxins10070275.
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The human health risks posed by exposure to cyanobacterial toxins such as microcystin (MC) through water and fish consumption remain poorly described. During the last two decades, coastal regions of Lake Victoria such as Nyanza Gulf (Kisumu Bay) have shown severe signs of eutrophication with blooms formed by Microcystis producing MC. In this study, the spatial variability in MC concentration in Kisumu Bay was investigated which was mostly caused by Microcystis buoyancy and wind drifting. Small fish (<6 cm) mainly composed of Rastrineobola argentea were examined for MC content by means of biological methods such as ELISA and protein phosphatase inhibition assay (PPIA) and partly by chemical-analytical methods such as LC-MS/MS. Overall, the MC content in small fish was related to the MC content observed in the seston. When comparing the MC content in the seston in relation to dry weight with the MC content in small fish the latter was found three orders of magnitude decreased. On average, the ELISA-determined MC contents exceeded the PPIA-determined MC contents by a factor of 8.2 ± 0.5 (SE) while the MC contents as determined by LC-MS/MS were close to the detection limit. Using PPIA, the MC content varied from 25–109 (mean 62 ± 7) ng/g fish dry weight in Kisumu Bay vs. 14 ± 0.8 ng MC/g in the more open water of L. Victoria at Rusinga channel. Drying the fish under the sun showed little effect on MC content, although increased humidity might indirectly favor photocatalyzed MC degradation.
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Xiang, Lei, Yan-Wen Li, Zhen-Ru Wang, Bai-Lin Liu, Hai-Ming Zhao, Hui Li, Quan-Ying Cai, Ce-Hui Mo, and Qing X. Li. "Bioaccumulation and Phytotoxicity and Human Health Risk from Microcystin-LR under Various Treatments: A Pot Study." Toxins 12, no. 8 (August 14, 2020): 523. http://dx.doi.org/10.3390/toxins12080523.
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Microcystin-LR (MC-LR) is prevalent in water and can be translocated into soil-crop ecosystem via irrigation, overflow (pollution accident), and cyanobacterial manure applications, threatening agricultural production and human health. However, the effects of various input pathways on the bioaccumulation and toxicity of MCs in terrestrial plants have been hardly reported so far. In the present study, pot experiments were performed to compare the bioaccumulation, toxicity, and health risk of MC-LR as well as its degradation in soils among various treatments with the same total amount of added MC-LR (150 μg/kg). The treatments included irrigation with polluted water (IPW), cultivation with polluted soil (CPS), and application of cyanobacterial manure (ACM). Three common leaf-vegetables in southern China were used in the pot experiments, including Ipomoea batatas L., Brassica juncea L., and Brassica alboglabra L. All leaf vegetables could bioaccumulate MC-LR under the three treatments, with much higher MC-LR bioaccumulation, especially root bioconcentration observed in ACM treatment than IPW and CPS treatments. An opposite trend in MC-LR degradation in soils of these treatments indicated that ACM could limit MC-LR degradation in soils and thus promote its bioaccumulation in the vegetables. MC-LR bioaccumulation could cause toxicity to the vegetables, with the highest toxic effects observed in ACM treatment. Similarly, bioaccumulation of MC-LR in the edible parts of the leaf-vegetables posed 1.1~4.8 fold higher human health risks in ACM treatment than in IPW and CPS treatments. The findings of this study highlighted a great concern on applications of cyanobacterial manure.
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Trung, Bui, Thanh-Son Dao, Elisabeth Faassen, and Miquel Lürling. "Cyanobacterial Blooms and Microcystins in Southern Vietnam." Toxins 10, no. 11 (November 14, 2018): 471. http://dx.doi.org/10.3390/toxins10110471.
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Studies on cyanobacteria in Vietnam are limited and mainly restricted to large reservoirs. Cyanobacterial blooms in small water bodies may pose a health risk to local people. We sampled 17 water bodies in the vicinity of urban settlements throughout the Mekong basin and in southeast Vietnam. From these, 40 water samples were taken, 24 cyanobacterial strains were isolated and 129 fish, 68 snail, 7 shrimp, 4 clam, and 4 duck samples were analyzed for microcystins (MCs). MCs were detected up to 11,039 µg/L or to 4033 µg/g DW in water samples. MCs were detected in the viscera of the animals. MC-LR and MC-RR were most frequently detected, while MC-dmLR, MC-LW, and MC-LF were first recorded in Vietnam. Microcystis was the main potential toxin producer and the most common bloom-forming species. A potential health hazard was found in a duck–fish pond located in the catchment of DauTieng reservoir and in the DongNai river where raw water was collected for DongNai waterwork. The whole viscera of fish and snails must be completely removed during food processing. Cyanobacterial monitoring programs should be established to assess and minimize potential public health risks.
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Esterhuizen, Maranda, and Stephan Pflugmacher. "Large-Scale Green Liver System for Sustainable Purification of Aquacultural Wastewater: Construction and Case Study in a Semiarid Area of Brazil (Itacuruba, Pernambuco) Using the Naturally Occurring Cyanotoxin Microcystin as Efficiency Indicator." Toxins 12, no. 11 (October 30, 2020): 688. http://dx.doi.org/10.3390/toxins12110688.
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The aquaculture industry in Brazil has grown immensely resulting in the production of inefficiently discarded wastewater, which causes adverse effects on the aquatic ecosystem. The efficient treatment of aquaculture wastewater is vital in reaching a sustainable and ecological way of fish farming. Bioremediation in the form of the Green Liver System employing macrophytes was considered as wastewater treatment for a tilapia farm, COOPVALE, in Itacuruba, Brazil, based on previously demonstrated success. A large-scale system was constructed, and the macrophytes Azolla caroliniana, Egeria densa, Myriophyllum aquaticum, and Eichhornia crassipes were selected for phytoremediation. As cyanobacterial blooms persisted in the eutrophic wastewater, two microcystin congeners (MC-LR and -RR) were used as indicator contaminants for system efficiency and monitored by liquid-chromatography–tandem-mass-spectrometry. Two trial studies were conducted to decide on the final macrophyte selection and layout of the Green Liver System. In the first trial, 58% MC-LR and 66% MC-RR were removed and up to 32% MC-LR and 100% MC-RR were removed in the second trial. Additional risks that were overcome included animals grazing on the macrophytes and tilapia were spilling over from the hatchery. The implementation of the Green Liver System significantly contributed to the bioremediation of contaminants from the fish farm.
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Simatupang, Erwinton, and Vandy Yoga Swara. "Membaca Arena Baru Subpolitik Anak Muda dalam Memaknai Risiko Industri Ekstraktif." Jurnal Studi Pemuda 8, no. 2 (October 11, 2019): 99. http://dx.doi.org/10.22146/studipemudaugm.48429.
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This article reveals the dynamics of youth subpolitics engagement amidst concern about environmental, social and economic risks of extractive industry operations. By focusing specifically on one of industrial locations as a case study, we explore how young people reflect nowadays and future various risks. This research uses a qualitative method with descriptive approach. Data is collected through focus group discussion (FGD), interview, and documentation. Behind youth subpolitics engagement discourse, we found that a change designed by young people leads to the risks. At this point, youth subpolitics engagement attempts to capitalize the risks that they initially against. At micro level, it turns out that a dominant actor controls youth subpolitics engagement. Applying the theoretical approach of strategic action fields developed by Neil Fligstein and Doug Mc Adam, we analyze how the dominant actor changes an arena of youth subpolitics engagement in dealing with the risks of extractive industry. As a result, young people depend on extractive industry operations.
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Brózman, Ondřej, Barbara Kubickova, Pavel Babica, and Petra Laboha. "Microcystin-LR Does Not Alter Cell Survival and Intracellular Signaling in Human Bronchial Epithelial Cells." Toxins 12, no. 3 (March 7, 2020): 165. http://dx.doi.org/10.3390/toxins12030165.
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Changes in ecological and environmental factors lead to an increased occurrence of cyanobacterial water blooms, while secondary metabolites-producing cyanobacteria pose a threat to both environmental and human health. Apart from oral and dermal exposure, humans may be exposed via inhalation and/or swallowing of contaminated water and aerosols. Although many studies deal with liver toxicity, less information about the effects in the respiratory system is available. We investigated the effects of a prevalent cyanotoxin, microcystin-LR (MC-LR), using respiratory system-relevant human bronchial epithelial (HBE) cells. The expression of specific organic-anion-transporting polypeptides was evaluated, and the western blot analysis revealed the formation and accumulation of MC-LR protein adducts in exposed cells. However, MC-LR up to 20 μM neither caused significant cytotoxic effects according to multiple viability endpoints after 48-h exposure, nor reduced impedance (cell layer integrity) over 96 h. Time-dependent increase of putative MC-LR adducts with protein phosphatases was not associated with activation of mitogen-activated protein kinases ERK1/2 and p38 during 48-h exposure in HBE cells. Future studies addressing human health risks associated with inhalation of toxic cyanobacteria and cyanotoxins should focus on complex environmental samples of cyanobacterial blooms and alterations of additional non-cytotoxic endpoints while adopting more advanced in vitro models.
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Santarém, Vamilton Alvares, Flávia Noris Chagas Leli, Guita Rubinsky-Elefant, and Rogério Giuffrida. "Protective and risk factors for toxocariasis in children from two different social classes of Brazil." Revista do Instituto de Medicina Tropical de São Paulo 53, no. 2 (April 2011): 66–72. http://dx.doi.org/10.1590/s0036-46652011000200002.
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The aim of this study was to analyze the prevalence of Toxocara spp. antibodies in children from two different socioeconomic classes in the Presidente Prudente municipality, São Paulo State, Brazil, and the protective and risk factors associated with toxocariasis. One hundred and twenty-six middle-class (MC) and 126 disadvantaged children (DC) were included in this study. Anti-Toxocara ELISA test was performed in order to evaluate seroprevalence. A survey was applied to the children's guardians/parents in order to analyze the protective and risk factors. The overall prevalence was 11.1%, and of 9.5% (12/126) and 12.7% (16/126) for MC and DC subgroups, respectively. Toxocara seropositivity was inversely proportional to the family income. A high household income was considered a protective factor for toxocariasis in the total population and in both MC and DC subgroups. Being a girl was considered a protective factor for the total population and for both subgroups. Whilst being an owner of cat was a risk factor for children belonging to the total and for both MC and DC subgroups, having dog was considered as a risk factor for only the MC. Epidemiologic protective/factor risks can be distinct depending on the strata of the same population. Thus, it is relevant to evaluate these factors independently for different socioeconomic classes in order to design future investigations and programs for preventing the infection of human beings by Toxocara spp. and other geohelminths.
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Pan, Chun, Minghao Yan, Haibo Jin, Hongqian Guo, and Xiaodong Han. "Chronic exposure to MC-LR increases the risks of microcytic anemia: Evidence from human and mice." Environmental Pollution 288 (November 2021): 117966. http://dx.doi.org/10.1016/j.envpol.2021.117966.
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Işık, E., A. Büyüksaraç, E. Avşar, M. F. Kuluöztürk, and M. Günay. "Characteristics and properties of Bitlis ignimbrites and their environmental implications." Materiales de Construcción 70, no. 338 (April 6, 2020): 214. http://dx.doi.org/10.3989/mc.2020.06519.
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Bitlis rock is used as a construction material and comes from the lava emitted by volcanoes and their subsequent transformation into ignimbrites. This type of rocks has been characterized physically, chemically, toxicologically and radioactively using different procedures including determination of the coefficient of thermal conductivity, gamma spectrometry, ultrasonic speed test, ICP masses and metal extraction. The results indicate that Bitlis rocks have an ACI greater than 1, although their content of radon is lower than other rocks of volcanic origin. Leaching of metals from these rocks indicates that Pb and Cd can provide an infiltration level in the field higher than the level permitted by TCLP and they have undesired toxicological risks. The percentages of extraction of other metals also point to this infiltration problem. Despite this, the material offers good qualities for usage as a building material such as its thermal coefficients.
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Muoio, Francesco, Stefano Panella, Matias Lindner, Valentin Jossen, Yves Harder, Tiziano Moccetti, Regine Eibl, Michele Müller, and Tiziano Tallone. "Development of a Biodegradable Microcarrier for the Cultivation of Human Adipose Stem Cells (hASCs) with a Defined Xeno- and Serum-Free Medium." Applied Sciences 11, no. 3 (January 20, 2021): 925. http://dx.doi.org/10.3390/app11030925.
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Stirred single-use bioreactors in combination with microcarriers (MCs) have established themselves as a technology that has the potential to meet the demands of current and future cell therapeutic markets. However, most of the published processes have been performed using fetal bovine serum (FBS) containing cell culture medium and non-biocompatible MCs. This approach has two significant drawbacks: firstly, the inevitable potential risks associated with the use of FBS for clinical applications; secondly, non-biocompatible MCs have to be removed from the cell suspension before implantation, requiring a step that causes loss of viable cells and adds further costs and complications. This study aimed to develop a new platform based on a chemically defined xeno- and serum-free cell culture medium and biodegradable MC that can support the growth of human adipose stem cells (hASCs) while still preserving their undifferentiated status. A specific combination of components and manufacturing parameters resulted in a MC prototype, called “BR44”, which delivered the desired functionality. MC BR44 allows the hASCs to stick to its surface and grow in a chemically defined xeno- and serum-free medium (UrSuppe). Although the cells’ expansion rate was not as high as with a commercial non-biodegradable standard MC, those cultured on BR44 maintained a better undifferentiated status in both static and dynamic conditions than those cultured on traditional 2D surfaces.
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Oppio, Alessandra, Marta Bottero, and Valentina Ferretti. "Multicriteria Spatial Analysis for Competitive Cultural Heritage in Fringe Areas: The Case of Valle d’Aosta Vastles." Advanced Engineering Forum 11 (June 2014): 579–84. http://dx.doi.org/10.4028/www.scientific.net/aef.11.579.
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The Alpine territories show a strong potential in reaching the targets set out by the European policies related to smart, sustainable and inclusive growth. The present paper reflects about the role of cultural heritage in supporting local development processes in mountain areas. In particular, Valle d’Aosta castles’ system (Italy) is considered in the study, with particular reference to the analysis of the opportunities and the risks at the regional scale. The results of the work delineate how Multicriteria-Spatial Decision Support Systems (MC-SDSS) can support the definition of enhancement strategies by providing a wide and integrated knowledge of the cultural heritage under investigation. The introduction of MC-SDSS in the field of historical assets’ conservation is quite innovative. Differently from the traditional analysis, the use of such an integrated approach allows decision maker to consider the spatial features of each development option and to evaluate simultaneously their multidimensional impacts.
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Khosrawipour, Tanja, Alessio Pigazzi, Haris Chaudhry, Agata Mikolajczyk, Justyna Schubert, and Veria Khosrawipour. "Occupational health risk of pressurized intra-peritoneal aerosol chemotherapy (PIPAC) via endoscopical microcatheter system." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e14231-e14231. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e14231.
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e14231 Background: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is becoming an increasingly widespread approach for delivering intra-peritoneal chemotherapy (IPC) by means of a chemoaerosol. In current studies, a flexible and easy-to-handle endoscopic microcatheter (MC) approach has been introduced to replace the conventional micropump used in PIPAC. While this new method has many advantages such as wide availability, cost effectiveness and improved drug distribution, its possible occupational health risks remain unknown. Methods: PIPAC was performed on three post mortem swine using the MC device. According to standard protocol in patients, solutions of doxorubicin and oxaliplatin were aerosolized in a standardized procedure room with laminar flow. Multiple probes of all surgical material including instruments and sutures, surrounding area surfaces and the operating personals’ items such as gloves and gowns were collected. Moreover, the air filter of the operating room was examined for doxorubicin and oxaliplatin concentrations. Results: The majority of probes showed no measurable doxorubicin or oxaliplatin concentrations. No exposure was detected on the operating personals’ gowns as well as the surrounding area surfaces. While a few of the surgical materials as well as the personals’ gloves and the main part of the application system showed low drug exposure, no drug exposure was measurable in the room filter. Conclusions: Our ex-vivo data suggest that PIPAC delivered via MC is safe and does not exhibit any major occupational hazards if the safety protocol is followed. MC offers an improved, easy-to-handle and cost-effective alternative to the micropump used in conventional PIPAC. Furthermore, the MC offers the great advantage of flexibility which allows access even in anatomically difficult situations and reduces the surgical point of entry to only one abdominal trocar placement.
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Hayashi, Michihiro, Tetsunosuke Shimizu, Fumitoshi Hirokawa, Yoshihiro Inoue, Koji Komeda, Mitsuhiro Asakuma, Yoshiharu Miyamoto, Atsushi Takeshita, Yuro Shibayama, and Nobuhiko Tanigawa. "Clinicopathological Risk Factors for Recurrence within One Year after Initial Hepatectomy for Hepatocellular Carcinoma." American Surgeon 77, no. 5 (May 2011): 572–78. http://dx.doi.org/10.1177/000313481107700516.
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Hepatocellular carcinoma (HCC) shows a high rate of recurrence after hepatectomy; predictive factors for early recurrence would help determine optimal therapeutic and management strategies. Among 163 patients with HCC undergoing hepatectomy with curative intent, 46 patients developed recurrence within 1 year. Clinicopathological data were retrospectively analyzed to identify predictive parameters for early recurrence. Survival rates in cases of recurrence within 1 year were worse than those of no recurrence within 1 year or recurrence after 1 year. Protein induced by vitamin K absence/antagonist II (PIVKA-II) greater than 150, positive fucosylated alpha-fetoprotein (L3-AFP), and deviancy from Milan criteria (MC) on preoperative imaging were associated with high risk of early recurrence and total number of these three risk factors predicted the survival. With multivariate analysis, 1) preoperatively, positive factors of two or more among three items of PIVKA-II, L3-AFP, and deviancy from MC; 2) and postoperatively, pathological cancer spread (microscopic vascular invasion and/or intrahepatic metastasis) both represented risks for early recurrence. A combination of three preoperative factors, PIVKA-II, L3-AFP, and MC status, in conjunction with the postoperative factor of cancer spread status represents a significant indicator for recurrence within 1 year. Improving the prognosis of patients with HCC would depend on how to adequately treat those at high risk of early recurrence.
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de Montera, B., D. El Zeihery, S. Müller, H. Jammes, G. Brem, H. D. Reichenbach, F. Scheipl, et al. "27 HIGHLY VARIABLE EPIGENOMES IN HEALTHY ADULT BOVINE CLONES." Reproduction, Fertility and Development 21, no. 1 (2009): 114. http://dx.doi.org/10.1071/rdv21n1ab27.
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Somatic cell nuclear transfer (SCNT) cloning requires epigenetic reprogramming of a differentiated donor cell nucleus. Incorrect reprogramming of epigenetic marks such as methylation of cytosine (5 mC) is associated with compromised development. Clones that survive into adulthood, in contrast, are assumed to be normal and are expected to be used in global food production. However, the epigenetic status of such healthy adult clones has never been investigated. We used a capillary electrophoresis technique to measure 5 mC content in leukocyte DNA from 38 healthy female clones at 1 to 8 years of age. Fibroblasts from 9 adults were used to generate 2 to 9 clones per donor. Four of the studied clone genotypes were from the Holstein breed, and 5 were from the Simmental breed. Individual 5 mC levels ranged from 4.4 to 6.9% with significant differences in mean 5 mC levels of Holstein and Simmental clones (6.50 ± 0.01% and 5.09 ± 0.02%, P < 0.001). The observed variances in 5 mC between clone genotypes of both breeds were similar (0.0204 and 0.0164), and we computed exact restricted likelihood ratio tests on the basis of linear mixed effects models to test for the presence of variability between genotypes. We found that the estimated variance in 5 mC level within clone genotypes from both breeds (0.104) was higher than the estimated variance between clone genotypes (<10–10). Three Holstein donors were analyzed for the 5 mC level of their genome together with their clones. Two donors exhibited the lowest 5 mC levels of the respective genotypes. The 5 mC level of the third nuclear donor was identical to 1 of its 8 clones, higher than 5 of them, and lower than the 2 remaining ones. This clearly demonstrates that the functional reprogramming of a given donor genotype is compatible with a highly flexible methylation status of its DNA and that genomic copies of adult animals have to be considered as epigenome variants. To quantify the contribution of SCNT to the observed variability between clones, we compared Simmental clones with female Simmental monozygotic twins of similar age that were generated by bisection of fertilized embryos. The estimated variability of 5 mC levels within 5 genotypes of clones (0.0636, n = 19) was clearly higher than in 12 twin pairs (0.0091). In clones, the estimated variability within genotypes (0.0636) was thus higher than between (<10–10) genotypes. In contrast, the variability within twin genotypes (0.0091) was lower than between twin genotypes (0.0136). Absolute deviations of 5 mC values of SCNT clones from their genotype means were 5-fold increased as compared with twins, whereas deviations of genotype means from group means were similar for clones and twins. The comparison with twins confirmed a SCNT cloning effect illustrated by a clone-specific variability of DNA methylation and provided new evidence of DNA hypermethylation by SCNT. Our data show that SCNT cloning can no longer be considered (epi)genetically neutral in apparently healthy adult animals. This raises new scientific and regulatory questions about the risks of disseminating cloned (epi)genetics into animal populations. Supported by EU (SABRE), DFG, INRA, and MRES.
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Massey, Isaac Yaw, Pian Wu, Jia Wei, Jiayou Luo, Ping Ding, Haiyan Wei, and Fei Yang. "A Mini-Review on Detection Methods of Microcystins." Toxins 12, no. 10 (October 4, 2020): 641. http://dx.doi.org/10.3390/toxins12100641.
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Cyanobacterial harmful algal blooms (CyanoHABs) produce microcystins (MCs) which are associated with animal and human hepatotoxicity. Over 270 variants of MC exist. MCs have been continually studied due of their toxic consequences. Monitoring water quality to assess the presence of MCs is of utmost importance although it is often difficult because CyanoHABs may generate multiple MC variants, and their low concentration in water. To effectively manage and control these toxins and prevent their health risks, sensitive, fast, and reliable methods capable of detecting MCs are required. This paper aims to review the three main analytical methods used to detect MCs ranging from biological (mouse bioassay), biochemical (protein phosphatase inhibition assay and enzyme linked immunosorbent assay), and chemical (high performance liquid chromatography, liquid chromatography-mass spectrometry, high performance capillary electrophoresis, and gas chromatography), as well as the newly emerging biosensor methods. In addition, the current state of these methods regarding their novel development and usage, as well as merits and limitations are presented. Finally, this paper also provides recommendations and future research directions towards method application and improvement.
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Uehara, Yuya, Kana Ishizuka, Yuko Shimamura, Michiko Yasuda, Kayoko Shimoi, and Shuichi Masuda. "Adsorptive Property of Food Materials and Chemicals to Cesium and Strontium." Natural Product Communications 12, no. 2 (February 2017): 1934578X1701200. http://dx.doi.org/10.1177/1934578x1701200232.
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In March, 2011, large amounts of radioactive materials were released from the Fukushima Daiichi nuclear power plant after the nuclear accident. Especially, for humans, internal exposure to 137Cs and 90Sr radionuclides presents very high risks because of their very long physical half-lives (137Cs: 30.2 years, 90Sr: 28.9 years). Therefore, it is important to inhibit the absorption of radioactive materials and to promote the excretion of them from the body through feces. The aim of this study was to explore foods, their components and various chemicals showing adsorption properties to Cs and Sr. Sodium alginate (ALA-Na) strongly adsorbed Cs and Sr compared with other samples. Chondroitin sulfate, carboxymethyl cellulose sodium (CMC-Na), methyl cellulose (MC) and apple polyphenols (AP; high molecule weight) also showed adsorption potency to Cs in that order. For Sr adsorption, kelp, CMC-Na, MC, AP (high molecule weight), laminaran and Jew's mallow exhibited adsorbing effects in that order. These samples might be useful and safe tools to protect from the adverse effects induced by internal exposure to these radioactive materials.
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Napier, Gary, Duncan Lee, Chris Robertson, and Andrew Lawson. "A Bayesian space–time model for clustering areal units based on their disease trends." Biostatistics 20, no. 4 (June 18, 2018): 681–97. http://dx.doi.org/10.1093/biostatistics/kxy024.
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Summary Population-level disease risk across a set of non-overlapping areal units varies in space and time, and a large research literature has developed methodology for identifying clusters of areal units exhibiting elevated risks. However, almost no research has extended the clustering paradigm to identify groups of areal units exhibiting similar temporal disease trends. We present a novel Bayesian hierarchical mixture model for achieving this goal, with inference based on a Metropolis-coupled Markov chain Monte Carlo ((MC)$^3$) algorithm. The effectiveness of the (MC)$^3$ algorithm compared to a standard Markov chain Monte Carlo implementation is demonstrated in a simulation study, and the methodology is motivated by two important case studies in the United Kingdom. The first concerns the impact on measles susceptibility of the discredited paper linking the measles, mumps, and rubella vaccination to an increased risk of Autism and investigates whether all areas in the Scotland were equally affected. The second concerns respiratory hospitalizations and investigates over a 10 year period which parts of Glasgow have shown increased, decreased, and no change in risk.
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Muñiz, Rubén, Juan Díaz, Juan A. Martínez, Fernando Nuño, Julio Bobes, Mᵃ Paz García-Portilla, and Pilar A. Sáiz. "A Smart Band for Automatic Supervision of Restrained Patients in a Hospital Environment." Sensors 20, no. 18 (September 12, 2020): 5211. http://dx.doi.org/10.3390/s20185211.
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Mechanical contention (MC) is a restrictive, vital but controversial measure, prescribed in the majority of EU countries to handle patients with psycho-motor agitation that do not respond to other types of intervention, with an imminent risk of physical violence and aggression involved. This last resort approach implies risks for the somatic health of the contained individual that go from trauma injuries to, in some extreme cases, sudden death. Despite these risks, somatic supervision and the monitoring of patients under MC is limited, being periodically and manually carried out by nursing personnel with portable equipment. In this context, ensuring continuous monitoring using fully automated equipment is an uncovered yet urgent need. There are several devices already in the market capable of monitoring vital signs, but they are not specifically designed for these type of patients and they can be expensive and/or difficult to integrate with other systems from a software perspective. The work described in this paper gives answers to these necessities with the introduction of a low-cost system, targeted at psychiatric patients, for the acquisition and wireless transmission in real-time of physiological parameters, making use of micro-controllers for collecting and processing sensor data, and WiFi technology to upload the information to the server where a patient’s profile with all the relevant vital parameters resides. In addition to data collection and processing, an application aimed at use by nursing staff has also been developed to raise alerts in case any critical condition is detected.
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Chang, Young, Yuri Cho, Jeong-Hoon Lee, Yun Bin Lee, Eun Ju Cho, Su Jong Yu, Dong Hyun Sinn, et al. "Comparison of Models for Tumor Recurrence after Liver Transplantation for the Patients with Hepatocellular Carcinoma: A Multicenter Long-Term Follow-Up Study." Cancers 11, no. 9 (September 3, 2019): 1295. http://dx.doi.org/10.3390/cancers11091295.
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Background and Aims: Several models have been developed to predict tumor the recurrence of hepatocellular carcinoma (HCC) after liver transplantation besides the conventional Milan criteria (MC), including the MoRAL score. This study aimed to compare the prognostication power of the MoRAL score to most models designed so far in the Eastern and Western countries. Methods: This study included 564 patients who underwent living donor liver transplantation (LDLT) in three large-volume hospitals in Korea. The primary and secondary endpoints were time-to-recurrence, and overall survival (OS), respectively. The performance of the MoRAL score was compared with those of other various Liver transplantation (LT) criteria, including the Milan criteria, University of California San Francisco (UCSF) criteria, up-to-seven criteria, Kyoto criteria, AFP model, total tumor volume/AFP criteria, Metroticket 2.0 model, and Weill Cornell Medical College group model. Results: The median follow-up duration was 78.1 months. Among all models assessed, the MoRAL score showed the best discrimination function for predicting the risk of tumor recurrence after LT, with c-index of 0.78, compared to other models (all p < 0.001). The MoRAL score also represented the best calibration function by Hosmer-Lemeshow test (p = 0.15). Especially in the beyond-MC sub-cohort, the MoRAL score predicted tumor recurrence (c-index, 0.80) and overall survival (OS) (c-index, 0.70) significantly better than any other models (all p < 0.001). When the MoRAL score was low (<314.8), the five-year cumulative risks of tumor recurrence and death were excellent in beyond-MC (27.8%, and 20.5%, respectively) and within-MC (16.3%, and 21.1%, respectively) sub-cohorts. Conclusions: The MoRAL score provides the most refined prognostication for predicting HCC recurrence after LDLT.
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Handa, Hiroshi, Itsumi Suda, Ayaka Kaneko, Yuta Masuda, Kei Kimura, Yuko Kuroda, Tetsuhiro Kasamatsu, et al. "Methylation and Hydroxymethylation Status of Tumor Suppressor Genes and Common Fragile Sites Genes in Acute Myeloid Leukemia." Blood 124, no. 21 (December 6, 2014): 3535. http://dx.doi.org/10.1182/blood.v124.21.3535.3535.
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Abstract Background: 5-methylation (5-mC) is the predominant epigenetic mark in mammalian genomic DNA. When promoter region of certain gene is hypermethylated, the gene becomes transcription silent. Promoter of tumor suppressor genes (TSG) usually exists in CpG islands, and silencing of TSGs in cancer cells is often associated with hypermethylation. p15, CDH1 are frequently methylated in myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Common Fragile Site (CFS) is a fragile site on the chromosomes easy to produce gap and break, and it contains putative TSGs. FHIT, WWOX and PARK2 are the CFS genes known to be frequently methylated in solid tumors, but their status of hematologic malignancies has not been fully elucidated yet. 5-hydroxymethylaiton (5-hmC) is a newly discovered epigenetic modification that is presumably generated by oxidation of 5-mC by the TET family of cytosine oxygenases. Techniques identifying 5-mC cannot distinguish between 5-mC and 5-hmC, therefore 5-hmC status of the genes have not fully elucidated yet too. Recently it has been demonstrated that mutation of epigenetic modifiers (DNMT3A, TET2, IDH1/2) play important role on AML pathogenesis. We tried to clarify 5-mC and 5-hmC status of TSG p15, CDH1 and CFS genes FHIT, WWOX and PARK2 by using new techniques and the relationships with expression levels of epigenetic modifiers in AML. Methods: BM samples obtained from 74 of AML patients are subjected to the study after informed consent. This study was approved by IRB of Gunma University Hospital. DNA, RNA were extracted from BM mononuclear cells. Methylation specific PCR (MSP) was carried out to assay 5-mC of p15, CDH1, WWOX, PARK2. Quantification of 5-mC and 5-hmC (except PARK2) was carried out by methylation sensitive restriction enzyme assay (MSRE) with glucosylation and Q-PCR. Total DNA 5-mC and 5-hmC were analyzed by ELISA. The mRNA expression levels of p15, CDH1, FHIT, WWOX, PARK2, DNMT1, 3A, TET2 were quantified by Q-PCR. Results: MSP revealed that p15, CDH1, WWOX and PARK2 were methylated in 43.1%, 94.3%, 35.7% and 36.9% of AML, respectively. PARK2 methylation was not found in t(15;17) APL, but in 32% of normal karyotype AML (NK-AML), in 67% of t(8;21) CBF-AML. In contrast, the p15 methylation was found in 83.3% of APL, 45.5% of NK-AML, 50% of CBF-AML. WWOX methylation was found in 42.9% of APL, in 16% of NK-AML and 66.7% of CBF-AML. Adverse karyotype AML (adv-AML) tended to show lower % of WWOX, PARK2 and p15 methylation with 15.8%, 21.1% and 18.8% compare to good risk karyotype. The frequency of the methylation of PARK2 and WWOX were varied among karyotypes and the methylation was mutually exclusive. ELISA demonstrated that mean % of total 5-mC DNA was 1.08% and ratio of 5-hmC in 5-mC was 0.95% in AML. Interestingly, 5-hmC was 0% in adv-AML although 5-mC existed (mean: 1.05%). Locus specific MSRE-QPCR demonstrated that mean % of 5-mC of p15, CDH1, WWOX and FHIT were 6.62%, 1.25%, 8.33%, 2.88%, respectively., In adv-AML, 5-hmC of CDH1, WWOX and FHIT were not detected, although 5-mC of these genes were detected (0.41%, 9.0%, 2.14%) in accordance with whole DNA analysis. In good and intermediate AML, 5-hmC of these genes was 3.44%, 1.07%, 2.69% ,respectively. RQ-PCR demonstrated that CDH1, p15, WWOX, PARK2 and epigenetic modifier DNMT1, DNMT3A and TET2 expression were not different among various karyotype risks, but only FHIT expression significantly higher in good risk group (p=0.047). The expression levels of the genes were not significantly different between mentylated and unmethylated. The ratio of 5-hmC/5-mC of the TSGs tended to be associated with the expression levels of the corresponding genes, but the association did not reach statistical significance. DNMT3A expression in AML with 5-mC PARK2 was higher than in other AML (p=0.016). Contrary to the intuition, DNMT3A expression was positively correlated with FHIT, PARK2 expression (r=0.776, p<0.001, r=0.689, p<0.001). CDH1 expression was positively correlated with DNMT1 and negatively correlated with TET2 expression (r=0.447, p=0.009, r=-0.349, p=0.022). OS and EFS were not different among the methylation status of these genes. Conclusion: CFS genes are selectively methylated in AML. MSRE-QPCR can distinguish 5-mC and 5-hmC and quantify the ratio of them with locus specific manner. The relationship between gene expression and 5-hmC, 5-mC should be pursued. Disclosures No relevant conflicts of interest to declare.
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Mallia, Vittoria, Lada Ivanova, Gunnar S. Eriksen, Emma Harper, Lisa Connolly, and Silvio Uhlig. "Investigation of In Vitro Endocrine Activities of Microcystis and Planktothrix Cyanobacterial Strains." Toxins 12, no. 4 (April 4, 2020): 228. http://dx.doi.org/10.3390/toxins12040228.
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Cyanobacteria are cosmopolitan photosynthetic prokaryotes that can form dense accumulations in aquatic environments. They are able to produce many bioactive metabolites, some of which are potentially endocrine disrupting compounds, i.e., compounds that interfere with the hormonal systems of animals and humans. Endocrine disruptors represent potential risks to both environmental and human health, making them a global challenge. The aim of this study was to investigate the potential endocrine disrupting activities with emphasis on estrogenic effects of extracts from cultures of Microcystis or Planktothrix species. We also assessed the possible role of microcystins, some of the most studied cyanobacterial toxins, and thus included both microcystin-producing and non-producing strains. Extracts from 26 cyanobacterial cultures were initially screened in estrogen-, androgen-, and glucocorticoid-responsive reporter-gene assays (RGAs) in order to identify endocrine disruption at the level of nuclear receptor transcriptional activity. Extracts from selected strains were tested repeatedly in the estrogen-responsive RGAs, but the observed estrogen agonist and antagonist activity was minor and similar to that of the cyanobacteria growth medium control. We thus focused on another, non-receptor mediated mechanism of action, and studied the 17β-estradiol (natural estrogen hormone) biotransformation in human liver microsomes in the presence or absence of microcystin-LR (MC-LR), or an extract from the MC-LR producing M. aeruginosa PCC7806 strain. Our results show a modulating effect on the estradiol biotransformation. Thus, while 2-hydroxylation was significantly decreased following co-incubation of 17β-estradiol with MC-LR or M. aeruginosa PCC7806 extract, the relative concentration of estrone was increased.
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Ghavami, Seyed, Hosein Ghiasi, and Asghar Mesbahi. "Monte Carlo modeling of the Yttrium-90 nanospheres application in the liver radionuclide therapy and organs doses calculation." Nuclear Technology and Radiation Protection 31, no. 1 (2016): 89–96. http://dx.doi.org/10.2298/ntrp1601089g.
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Using the nano-scaled radionuclides in the radionuclide therapy significantly reduces the particles trapping in the organs vessels and avoids thrombosis formations. Additionally, uniform distribution in the target organ may be another benefit of the nanoradionuclides in the radionuclide therapy. Monte Carlo simulation was conducted to model a mathematical humanoid phantom and the liver cells of the simulated phantom were filled with the 90Y nanospheres. Healthy organs doses, fatal and nonfatal risks of the surrounding organs were estimated. The estimations and calculations were made in four different distribution patterns of the radionuclide seeds. Maximum doses and risks estimated for the surrounding organs were obtained in the high edge concentrated distribution model of the liver including the nanoradionuclides. For the dose equivalent, effective dose, fatal and non-fatal risks, the values obtained as 7.51E-03 Sv/Bq, 3.01E-01 Sv/Bq, and 9.16E-01 cases/104 persons for the bladder, colon, and kidney of the modeled phantom, respectively. The mentioned values were the maximum values among the studied modeled distributions. Maximum values of Normal Tissue Complication Probability for the healthy organs calculated as 5.9-8.9 %. Result of using nanoparticles of the 90Y provides promising dosimetric properties in MC simulation results considering non-toxicity reports for the radionuclide.
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España, P., A. Sanchez, P. Espinosa, V. Massip, R. Perez-Maestu, M. Yebra, A. Hurtado, et al. "Analysis of competing risks of causes of death and their variation over different time periods in Hodgkin disease." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 18528. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.18528.
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18528 Background: Hodgkin’s disease is put forward as a model of curable illness. However, long-term studies show an excessive mortality in relation to the general population. The only way for detecting these causes are the long-term follow-up clinical studies, even these long-term follow-ups may not be fully representative of current causes of death. Methods: All patients diagnosed with HD at the University Hospital “Clínica Puerta de Hierro” between 1967 and 2003 were included. The competing risks of causes of death and the vital situation were examined in three time periods. Three cohorts were compared: cohort A with patients treated before 1980, B with those treated 1981–1986 and C from 1986 on. Results: We studied 534 patients, with a median follow-up time of 9.1 years for the whole cohort. The 5, 15 and 20-year Kaplan-Meier survival estimates for all patients were 81%, 72% and 65%, respectively. At the close of the study, 337 (63.1%) were alive and 170 (31.8%) had died. In general, the most common cause was the progress of Hodgkin’s disease, followed by deaths due to a second tumor. By time periods, we found statistically significant differences between cohort A and the other two cohorts, with less LD and MC histology, fewer advanced stages and fewer combined treatments in the latter. Between cohorts B and C there were only differences in the histological results, with less LD and MC and increased NS in the latter. Survival was significantly worse in the first period than in the other two (p<0.001) and in the three periods the main cause of death was tumor progression. Conclusions: The progression of Hodgkin’s disease is the main cause of death in all the periods studied. Over time a clear reduction in death related to the toxicity of treatments was seen. In the light of our results, the question is posed as to whether the survival and causes of death series for those patients treated since the 1970s are telling us about a real situation. Patients die now for reasons that are different from in the 1970s and this is important when planning preventive and clinical research activity. No significant financial relationships to disclose.
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Quaas, Philipp, and Filiz Markfeld-Erol. "‘TRAP-ped with an Acardius’: Case Series of Twin Reversed Arterial Perfusion (TRAP) Sequence and Review of Literature." Journal of Fetal Medicine 8, no. 1 (February 8, 2021): 27–33. http://dx.doi.org/10.1007/s40556-020-00286-z.
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AbstractTwin reversed arterial perfusion (TRAP) sequence is a rare but severe condition that affects monochorionic (MC) multifetal pregnancies. In twin pregnancies, it is characterized by a normally developed twin and another twin with missing heart function (acardiac twin or TRAP twin). A variety of risks and complications may affect the normal twin. Management of such pregnancies can be either expectant or interventional. We report four cases of TRAP sequence treated in our institutions and supply an overview on currently existing literature. This case series demonstrates the heterogeneity in manifestations and clinical course of patients affected by this condition. Furthermore, it includes an acardius amorphous of considerable size delivered at 35.6 weeks of gestation.
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Tøndevold, Niklas, Markus Lastikka, Thomas Andersen, Martin Gehrchen, and Ilkka Helenius. "Should instrumented spinal fusion in nonambulatory children with neuromuscular scoliosis be extended to L5 or the pelvis?" Bone & Joint Journal 102-B, no. 2 (February 2020): 261–67. http://dx.doi.org/10.1302/0301-620x.102b2.bjj-2019-0772.r2.
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Aims It is uncertain whether instrumented spinal fixation in nonambulatory children with neuromuscular scoliosis should finish at L5 or be extended to the pelvis. Pelvic fixation has been shown to be associated with up to 30% complication rates, but is regarded by some as the standard for correction of deformity in these conditions. The incidence of failure when comparing the most caudal level of instrumentation, either L5 or the pelvis, using all-pedicle screw instrumentation has not previously been reported. In this retrospective study, we compared nonambulatory patients undergoing surgery at two centres: one that routinely instrumented to L5 and the other to the pelvis. Methods In all, 91 nonambulatory patients with neuromuscular scoliosis were included. All underwent surgery using bilateral, segmental, pedicle screw instrumentation. A total of 40 patients underwent fusion to L5 and 51 had their fixation extended to the pelvis. The two groups were assessed for differences in terms of clinical and radiological findings, as well as complications. Results The main curve (MC) was a mean of 90° (40° to 141°) preoperatively and 46° (15° to 82°) at two-year follow-up in the L5 group, and 82° (33° to 116°) and 19° (1° to 60°) in the pelvic group (p < 0.001 at follow-up). Correction of MC and pelvic obliquity (POB) were statistically greater in the pelvic group (p < 0.001). There was no statistically significant difference in the operating time, blood loss, or complications. Loss of MC correction (> 10°) was more common in patients fixated to the pelvis (23% vs 3%; p = 0.032), while loss of pelvic obliquity correction was more frequent in the L5 group (25% vs 0%; p = 0.007). Risk factors for loss of correction (either POB or MC) included preoperative coronal imbalance (> 50 mm, odds ratio (OR) 11.5, 95%confidence interval (CI) 2.0 to 65; p = 0.006) and postoperative sagittal imbalance (> 25 mm, OR 11.0, 95% CI1.9 to 65; p = 0.008). Conclusion We found that patients undergoing pelvic fixation had a greater correction of MC and POB. The rate of complications was not different. Preoperative coronal and postoperative sagittal imbalance were associated with increased risks of loss of correction, regardless of extent of fixation. Therefore, we recommend pelvic fixation in all nonambulatory children with neuromuscular scoliosis where coronal or sagittal imbalance are present preoperatively. Cite this article: Bone Joint J 2020;102-B(2):261–267.
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Revuelta Crespo, D., D. M. Prada Betancourt, L. Fernández Luco, and L. Vega Catalán. "Riesgos para el consumidor y productor en función de los criterios de aceptación o rechazo de hormigón preparado según distintos reglamentos (parte I)." Materiales de Construcción 55, no. 280 (December 30, 2005): 71–78. http://dx.doi.org/10.3989/mc.2005.v55.i280.208.
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Shafiekhani, Soraya, and Griffiths G. Atungulu. "Effect of Rice Chilling on Drying, Milling, and Quality Characteristics." Applied Engineering in Agriculture 36, no. 5 (2020): 767–76. http://dx.doi.org/10.13031/aea.13895.
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HighlightsThis study experimentally simulated drying of rough rice subjected to various cold storage/chilling conditions.The rice was dried using slightly-heated air and high temperature air with procedures set to mimic those practiced by commercial systems.The moisture removal, drying rate constant, material state transition, milling and quality characteristics of rice upon drying conditions was investigated.The study provides important reference information for growers and rice processors using the relatively new rice cooling technology.Abstract. High temperature (field heat) and moisture content of freshly harvested rough rice promote excessive respiration and microbial growth. Therefore, the rice risks significant deterioration of quality due to delayed drying at peak harvest time when drying capacity becomes limited. The U.S. rice industry has identified that cooling/chilling the rice prior to drying to remove the excess heat, immediately after harvest, significantly preserves the quality of milled rice. This study experimentally simulated drying of rough rice after cold storage/chilling. The rice was dried using slightly-heated air and high temperature air with procedures set to mimic those practiced by commercial systems. Rough rice at moisture contents (MCs) of 16%, 19%, and 21% (wet basis) were stored at storage temperature (Ts) of 10°C, 15°C, and 20°C for up to 4 months. Following retrieval, the samples were dried at drying temperature (Td) of 35°C, 45°C, and 60°C and relative humidity (RH) of 20%. Each drying run comprised of two 20-min drying passes with the rice tempered at the drying Td for a duration of 4 h following every drying pass. Following the drying, the rice was conditioned in an equilibrium MC chamber (T=26°C, RH=56%) to 12.5% MC and then milled to evaluate milled rice yield and quality characteristics. The highest percentage points of MC removal (6.77% points) occurred following drying at air temperature of 60°C for samples with initial MC at 21% and stored at 20°C. Drying with air at 60°C decreased head rice yield (HRY) especially for samples with initial MC at 21% and stored at 10°C (HRY=51.4% versus those at 45°C and 35°C, HRY=55.95% and HRY=58.8%, respectively). Drying air temperatures studied (35°C, 45°C, 60°C) had no significant effect of causing discoloration of samples within the range of the studied initial MCs and storage temperatures. Peak and final viscosities of samples with different initial MCs (16%, 19%, and 21%) stored at 20°C followed by high temperature air drying (60°C) were significantly different from those of samples stored at 10°C and 15°C. The results provided insight into the drying, milling, and quality characteristics of rice after cold storage/chilling. The information provide foundation for development of new recommendations to improve quality of milled rice. Keywords: Conventional drying, Cooling/chilling, Milling quality, Rough rice, Storage.
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Irani, Mazda. "Predicting Geomechanical Dynamics of the Steam-Assisted-Gravity-Drainage Process. Part I: Mohr-Coulomb (MC) Dilative Model." SPE Journal 23, no. 04 (February 21, 2018): 1223–47. http://dx.doi.org/10.2118/189976-pa.
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Summary In the steam-assisted-gravity-drainage (SAGD) recovery process, the injection of high-pressure/high-temperature steam causes significant stress changes at the edge of the heated zone or steam chamber. These stress changes include shear dilation, which can both enhance the absolute permeability and result in horizontal and vertical formation displacements. The importance of considering geomechanical effects in thermal-recovery processes has been extensively discussed in the literature, but the prediction and surveillance of the resulting effects, such as the impact on production enhancement and reservoir displacement, have in many cases been neglected. Furthermore, issues related to these geomechanical effects on thermal production have been the subject of considerable debate in the industry with no conclusive, meaningful assessments of the effect on reservoir deliverability and production, or of the associated risks that such geomechanical effects have on wellbore and caprock integrity. This study will focus on identification of the main findings from an extensive monitoring program conducted on the original SAGD pilot project conducted at the Underground Test Facility (UTF) in the late 1980s and a seismic program conducted during the last several years by an SAGD operator at a commercial thermal-recovery project. The measured displacements and identified dilation shear zones in these applications were compared with a Mohr-Coulomb (MC) dilative model. This paper illustrates some of the pros and cons of using such analytical models through comparison of the results based on field evidence of the dilation and shearing effects, and how these mechanisms affect both reservoir productivity (revenue) and wellbore and caprock integrity. Although the discussion on the geomechanical effects in thermal-recovery processes will no doubt continue, this study will provide field-supported results to illustrate both beneficial and potentially challenging impacts that these geomechanical effects can have in a thermal-recovery project.
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Rossi, Giovanni, Angelo Michele Carella, Maria Marta Minervini, Lucia Savino, Andrea Fontana, Fabio Pellegrini, Michele Mario Greco, et al. "Minimal Residual Disease After Allogeneic Stem Cell Transplantation: A Comparison Among Multiparameter Flow Cytometry, Wilms Tumor 1 Expression and Chimerism Status (Complete vs Low-Level Mixed Chimerism) in Patients with Acute Leukemia." Blood 120, no. 21 (November 16, 2012): 1971. http://dx.doi.org/10.1182/blood.v120.21.1971.1971.
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Abstract Abstract 1971 Introduction. Relapse represents the main cause of treatment failure after allogeneic stem cell transplantation (allo-SCT). Thus, monitoring of minimal residual disease (MRD) in allografted patients allows an early detection of recurrence and a subsequent intervention prior to florid relapse. Multiparameter Flow Cytometry (MFC), chimerism, cytogenetics and molecular analysis have been widely used for this purpose, although the gold standard needs to be established yet. The evaluation of fusion transcripts represents the most sensitive method but more than 65% of patients do not demonstrate a molecular target. WT1 mRNA is over expressed in > 90% of patients with acute myeloid leukemia (AML) but it is not so expressed in acute lymphoblastic leukemia (ALL). On the MFC analysis instead, the complexity of maturational patterns and phenotypic shifts after therapy may underestimate residual leukemic cells. Finally, previous papers reported that a state of mixed chimerism (MC) in RT-PCR may identify higher risk of relapse in patients with AML. However, the test has a low sensitivity (from 0,1% to 1%) and recipient cells are not necessarily linked to disease recurrence. Hypothesizing the presence of blast cells in the low-level mixed chimerism (MC, 1%<MC<5% of autologous cells) but not in the complete chimerism (CC, no evidence of autologous cells) status, we used these two ranges as markers of positive and negative MRD, respectively. The aim of our study was twofold. Firstly, to assess the overall agreement among chimerism, MFC and WT1 mRNA methods in monitoring MRD. Secondly, to investigate whether such methods were associated to patient' s relapse-free survival. Methods. Fresh BM samples from 24 patients (17 AML and 7 ALL) in both morphological CR and CC or low-level MC status after allo-SCT were investigated. MRD with MFC, WT1 mRNA expression and chimerism analysis was evaluated at different time points: +1, +3, +6,+12,+18,+24 months after allo-SCT. The immunophenotypic analysis was performed using a six-color combinations and acquiring 250.000 events. RQ- PCR to test WT1 mRNA expression was made according to the standardized and quality-controlled method. Chimerism studies were performed with a multiplex amplification of 16 (STR). The agreement between two methods in monitoring MRD after allo-SCT was assessed by Kappa statistic. Moreover, time-to-event analyses were performed using Cox proportional-hazard models with time-dependent covariates. Risks were reported as hazards ratios (HR) along with their 95% confidence interval (95% CI). Results. Comparisons among results of MFC, RQ-PCR for WT1 mRNA and Chimerism were performed in all 67 serial samples obtained from 24 patients. A significant moderate agreement between MFC and WT1 mRNA evaluations was found (k= 0.463, p<0.001) as well as fair agreement between chimerism and MFC (k= 0.284, p=0.009) and chimerism and WT1 mRNA (k= 0.197, p=0.073). These results suggested a concordance among the three investigated techniques. In particular, the low-level MC would well detect the presence of leukemic cells, since the proportion of positive samples for MFC was not statistically different to the proportion of positive samples for WT1 mRNA within samples with low-level MC. Indeed, among 12 samples with low-level MC, 9 samples (75.0%) were also positive for MFC and 7(58.3%) were also positive for WT1 mRNA. Cut-off of 0.1% and 0.01% for MFC, 83.5 × 104 ABL for WT1 mRNA and 96%-99% of donor cells for chimerism were selected. The median follow-up times for relapse-free was 12.8 mths and the overall estimated relapse-free survival after 36 mths was 66.5%. At the end of follow- up, 5 patients relapsed and 4 patients died. Although not significant, the detection of a positive MRD for all methods were associated to a higher incidence of relapse than the negative MRD. Similar HRs were observed in the analysis of MFC(HR = 6.55, 95%CI= 0.71–60.17, p=0.096) and WT1 mRNA (HR= 7.17, 95% CI=0.77–66.42, p=0.083) whilst a slighter HR was found for the chimerism analysis (HR= 0.40, 95%CI= 0.04–4.44, p=0.456). Conclusions. According to our study MFC, WT1 mRNA and CC or low-level MC displayed an overall agreement in monitoring MRD. In particular, the agreement on the low-level MC may suggest the presence of leukemic cells. The detection of a positive MRD by MFC and WT1 mRNA similarly identified higher risk of relapse in patients with acute leukemia (AL) undergone to allo-SCT. Disclosures: No relevant conflicts of interest to declare.
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Lee, Sarah, Nathaniel Rosko, Janice Reed, Mary Ann Karam, Beth Faiman, Saveta Mathur, Kimberly Hamilton, et al. "Improving time to start bone modifying agents in newly diagnosed multiple myeloma patients." Journal of Clinical Oncology 37, no. 27_suppl (September 20, 2019): 65. http://dx.doi.org/10.1200/jco.2019.37.27_suppl.65.
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65 Background: Current ASCO and IMWG guidelines recommend all patients (pts) on active myeloma therapy receive concurrent supportive care with a bone modifying agent (BMA) to decrease the risk of skeletal related events (SRE). Unfortunately, recent data shows only 51% of Medicare pts with myeloma received a BMA within 90 days of first chemotherapy. We implemented a quality improvement project to identify the average time to BMA initiation at all Cleveland Clinic affiliated sites, with the primary goal to improve time to start BMA in newly diagnosed multiple myeloma (NDMM) pts by 4 weeks at Cleveland Clinic Main Campus (MC). Methods: Barriers to start BMA were identified using quality improvement tools developed at ASCO Quality Training Program. The first PDSA cycle ran from Sept 2018–Jan 2019 with an emphasis on education. This included review of updated guidelines, literature review of risks and toxicities associated with BMAs, and strategies for choosing BMA based on pt factors. Baseline data on time to start BMA and data to evaluate impact of PDSA intervention was done by chart review. Results: 161 NDMM pts were evaluated from 2015–2018 at all sites. The average time difference between the start of myeloma therapy and the start date of BMA in NDMM pts was 10.5 weeks. Subset analysis based on whether pts were treated at MC vs affiliate site was 10.6 weeks vs 9.1 weeks, respectively. During the first PDSA cycle, 14 NDMM pts were treated at MC. 86% (12/14) pts were treated with BMA. The average time between cycle 1 day 1 of first line treatment and first dose BMA was 4.3 weeks (range 4-12 weeks). Conclusions: With increased physician education and awareness of internal baseline data, we achieved our initial goal and observed a significant improvement in time to start BMA from 10.5 weeks to 4.3 weeks. Obstacles regarding effective communication with patients on the benefit of BMAs as well as need for dental clearance were barriers identified early on. We plan to incorporate BMA guidelines in our institutional care path with the goal to decrease time to initiation at all affiliated practices. Further mechanisms to ensure reinforcement of BMA initiation in NDMM patients is warranted to maintain therapeutic benefit.
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Campos, Alvaro, Alberto Llana, Rafael Molina, Ana Alises, Rebeca Gomez, and Carmen Castillo. "OVERTOPPING CHARACTERIZATION FOR THE ELABORATION OF VULNERABILITY MAPS IN PORTS FACILITIES." Coastal Engineering Proceedings 1, no. 33 (October 25, 2012): 26. http://dx.doi.org/10.9753/icce.v33.posters.26.
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Overtopping has been widely studied (European project CLASH 2000-2010), and mean and maximum overtopping discharge values have already been proposed. However, fundamental variables for determining overtopping affections and risks, such as the shape and energy of the overtopped water mass and how it is distributed in the possible affected zones (vulnerable areas), are not yet defined.
This study focuses on getting deeper comprehension of the flow-structure interaction. Different overtopping types have been characterized and a first step in the extension of the parametric map proposed by Mc Conel (1998) by including an overtopping term has been done. Also, a new mean overtopping rate (qnew) has been proposed, taking into account just the total overtopping time instead of the total test’s duration (q). This new way of measuring the mean overtopping rate seems to permit a more realistic characterization of overtopping as it gives a clue of the individual volumes of each overtopping event, which is fundamental for a risk evaluation.
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Baldini, Luca, Maria Goldaniga, Andrea Guffanti, Chiara Broglia, Sergio Cortelazzo, Andrea Rossi, Enrica Morra, et al. "Immunoglobulin M Monoclonal Gammopathies of Undetermined Significance and Indolent Waldenström's Macroglobulinemia Recognize the Same Determinants of Evolution Into Symptomatic Lymphoid Disorders: Proposal for a Common Prognostic Scoring System." Journal of Clinical Oncology 23, no. 21 (July 20, 2005): 4662–68. http://dx.doi.org/10.1200/jco.2005.06.147.
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Purpose To evaluate the clinicohematologic variables at diagnosis that are prognostically related to neoplastic progression in patients with immunoglobulin M (IgM) monoclonal gammopathies of undetermined significance (MGUS), and indolent Waldenström's macroglobulinemia (IWM), and propose a scoring system to identify subsets of patients at different risk. Patients and Methods We evaluated 217 patients with IgM MGUS and 201 with IWM (male-female ratio, 131:86 and 117:84; mean age, 63.7 and 63.6 years, respectively) diagnosed on the basis of serum monoclonal component (MC) levels and bone marrow lymphoplasmacytic infiltration degree. The variables selected by univariate analyses were multivariately investigated; on the basis of their individual relative hazards, a scoring system was devised to identify subsets of patients at different risk of evolution. Results After a median follow-up of 56.1 and 60.2 months, 15 of 217 MGUS and 45 of 201 IWM patients, respectively, required chemotherapy for symptomatic WM (13 and 36), non-Hodgkin's lymphoma (2 and 6) and amyloidosis (0 and 3). The median time to evolution (TTE) was not reached for MGUS and was 141.5 months for IWM. The variables adversely related to evolution were qualitatively the same in both groups: MC levels, Hb concentrations and sex. A scoring system based on these parameters identified three risk groups with highly significant differences in TTE in both groups (P < .0001). Conclusion MGUS and IWM identify disease entities with different propensities for symptomatic neoplastic evolution. As both have the same prognostic determinants of progression, we propose a practical scoring system that, identifying different risks of malignant evolution, may allow an individualized clinical approach.
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Baldini, L., A. Guffanti, BM Cesana, M. Colombi, O. Chiorboli, I. Damilano, and AT Maiolo. "Role of different hematologic variables in defining the risk of malignant transformation in monoclonal gammopathy." Blood 87, no. 3 (February 1, 1996): 912–18. http://dx.doi.org/10.1182/blood.v87.3.912.bloodjournal873912.
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The presenting clinico-hematologic features of 386 patients with nonmyelomatous monoclonal gammopathy (MG) were correlated with the frequency of malignant transformation to evaluate the most important variables conditioning its evolution into multiple myeloma (MM) or Waldenstrom macroglobulinemia (WM). Most of the patients (335) had monoclonal gammopathy of undetermined significance (MGUS: 39 IgA, 242 IgG, 54 IgM): the remaining 51 patients (12 IgA, 39 IgG) fulfilled all of the MGUS diagnostic criteria (according to Durie) except that bone marrow plasma cell (BMPC) content was 10% to 30%, and so they were defined as having monoclonal gammopathy of borderline significance (MGBS). There were no significant differences between the MGUS and MGBS groups in terms of age, sex, or median follow-up. After a median follow- up of 70 and 53 months, respectively, 23 of 335 MGUS and 19 of 51 MGBS patients had undergone a malignant evolution. Univariate analysis of the IgA and IgG patients showed that the cumulative probability of the disease evolving into MM correlated with diagnostic definition (MGBS v MGUS), BMPC content (> or = 10% v < 5% and < or = 5% v > 5%) and reduced serum polyclonal Ig. In the IgG cases, there was also a significant correlation with detectable Bence Jones proteinuria, serum monoclonal component (MC) levels and age at diagnosis (> 70 v < = or 55 years). In the IgG cases as a whole, the same variables remained in the Cox model where the BMPC percentage was considered after natural logarithmic transformation and the monoclonal component as g/dL value. The relative risks of developing MM are the following: 2.4 for each 1 g/dL increase of IgG, serum MC, 3.5 for detectable light chain proteinuria, 4.4 for the increase of 1 unit in log. BMPC percentage, 6.1 for age > 70, 3.6 and 13.1 for a reduction in one or two polyclonal Ig. In conclusion, our study allows the identification of a particular subset of MGUS patients (MC < = or 1.5 g/dL, BMPC < 5%, no reduction in polyclonal Ig and no detectable light chain proteinuria) at very low- risk of evolution, who can be considered as having benign monoclonal gammopathies. We also describe a previously undefined group of MG patients (with monoclonal gammopathy of borderline significance) who are at high-risk of malignant evolution. These findings could have a considerable impact on the cost/benefit ratio of monitoring programs in these patients.
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Rosko, Nathaniel, Sarah Lee, Christy Joy Samaras, Alex V. Mejia, Faiz Anwer, Beth Faiman, Saveta Mathur, et al. "Improving time to initiation of bone modifying agents in patients with newly diagnosed multiple myeloma." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 6528. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.6528.
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6528 Background: Current ASCO and IMWG guidelines recommend that all patients (pts) on active anti-myeloma therapy receive concurrent supportive care treatment with a bone modifying agent (BMA) to decrease the risk of skeletal related events (SRE). Unfortunately, recent data shows only 51% of Medicare pts with myeloma received a BMA within 90 days of first chemotherapy. We implemented a quality improvement project to identify the average time to BMA initiation at all Cleveland Clinic affiliated sites, with the primary goal to improve time to initiation of BMA in newly diagnosed multiple myeloma (NDMM) pts by 4 weeks at Cleveland Clinic Main Campus (MC). Methods: Barriers with BMA initiation were identified using quality improvement tools developed at the ASCO Quality Training Program. The first PDSA cycle was implemented between September 2018 – January 2019 with an emphasis on education. This included review of updated guidelines, literature review of risks and toxicities associated with BMAs, and strategies for choosing BMA based on pt factors. Baseline data on time to start BMA and data to evaluate impact of PDSA intervention was completed via chart review. Results: 161 NDMM pts were evaluated between 2015 to 2018 at all sites. The average time difference between the start of anti-myeloma therapy and the start date of a BMA in NDMM pts was 10.5 weeks. Subset analysis based on whether pts were treated at MC vs affiliate sites was 10.6 weeks vs 9.1 weeks, respectively. During the first PDSA cycle, 14 NDMM pts were treated at MC. 86% (12/14) pts were treated with a BMA. The average time between cycle 1 day 1 of first line treatment and first dose BMA was 4.3 weeks (range 4-12 weeks). Conclusions: With increased physician education and awareness of internal baseline data, we achieved our initial goal and observed a significant improvement in time to initiation of BMA from 10.5 weeks to 4.3 weeks. Obstacles regarding effective communication with patients on the benefit of BMAs as well as need for dental clearance were barriers identified early on. We plan to incorporate BMA guidelines in our institutional care path with the goal to decrease time to initiation at all affiliated practices. Further mechanisms to ensure reinforcement of BMA initiation in NDMM patients is warranted to maintain therapeutic benefit.
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Krzemień, Leszek, Marcin Strojecki, Sebastian Wroński, Jacek Tarasiuk, and Michał Łukomski. "Dynamic response of earlywood and latewood within annual growth ring structure of Scots pine subjected to changing relative humidity." Holzforschung 69, no. 5 (July 1, 2015): 555–61. http://dx.doi.org/10.1515/hf-2014-0132.
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Abstract Scots pine (Pinus sylvestris L.) was subjected to relative humidity (RH) changes, and the dynamic strain field on the surface and in the bulk wood was monitored by digital speckle pattern interferometry and X-ray computed microtomography assisted by digital volume correlation. If a freely shrinking specimen was subjected to an RH decrement, earlywood (EW) and latewood (LW) at the surface layer were deformed in the opposite directions at the beginning of drying due to moisture gradient across the specimen. As a result, the surface and core behaved as independent sub-components, with the surface restrained in its response by the dimensionally unchanged core. With time, both LW and EW shrank as moisture content (MC) became uniform across the specimen. When an entire wood specimen was restrained from movement and desiccated in ambient RH, EW was stretched to compensate for the considerable shrinkage of LW. Knowledge about surface deformation at the annual ring level as a function of varying RH may be helpful to assess the risks associated with the damage of paint layers caused by fluctuations of ambient RH.
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Chen, Rongda, and Huanhuan Yu. "Risk Measurement for Portfolio Credit Risk Based on a Mixed Poisson Model." Discrete Dynamics in Nature and Society 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/597814.
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Experiences manifest the importance of comovement and communicable characters among the risks of financial assets. Therefore, the portfolio view considering dependence relationship among credit entities is at the heart of risk measurement. This paper introduces a mixed Poisson model assuming default probabilities of obligors depending on a set of common economic factors to construct the dependence structure of obligors. Further, we apply mixed Poisson model into an empirical study with data of four industry portfolios in the financial market of China. In the process of model construction, the classical structural approach and option pricing formula contribute to estimate dynamic default probabilities of single obligor, which helps to obtain the dynamic Poisson intensities under the model assumption. Finally, given the values of coefficients in this model calculated by a nonlinear estimation, Monte Carlo technique simulates the progress of loss occurrence. Relationship between default probability and loss level reflected through the MC simulation has practical features. This study illustrates the practical value and effectiveness of mixed Poisson model in risk measurement for credit portfolio.
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Abrosimova, O. N., and M. A. Burakova. "Scaling of the Granulation Process in the Conditions of GMP Training Center and Assessment of Possible Risks." Drug development & registration 10, no. 3 (August 28, 2021): 131–37. http://dx.doi.org/10.33380/2305-2066-2021-10-3-131-137.
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Introduction. The stage of wet granulation is often used in the technology of solids. The method of wet granulation in a mixer-granulator with high shear force can be regarded as the most complicated method of its implementation from the engineering and technological point of view. The mixer-granulator has two mixers located in mutually perpendicular planes. Using an impeller, dry components are mixed, and the chopper, turning on when spraying a humidifier, ensures the formation of granules. By setting different chopper rotational speed, granules of different sizes can be obtained. This granulator has the following advantages: it provides a high product yield (≥ 99 %), takes up small workspaces, and the closed design ensures environmental protection.Aim. The aim of the research is to scale the granulation process, on the example of the solids production technology, using the wet granulation stage - in a mixer-granulator with high shear force.Materials and methods. Dry extract «N» and auxiliary substances were used as a pharmaceutical substance: lactose monohydrate, microcrystalline cellulose (MCC) (MICROCEL® MC-102), potato starch, povidone (Plasdone™ K-29/32), calcium stearate. Granulate under scaling conditions was produced in a mixer-granulator with high shear force. Technological properties of dry extract «N» and granulate were determined by the methods described in National pharmacopeia XIV.Results and discussion. On the basis of experimental studies, it was found that the resulting granulate, both when obtained under laboratory conditions and under scaling conditions, has good flowability, and also has a homogeneous fractional composition. The presence of a grinder in the mixer-granulator made it possible to obtain a more uniform fractional composition of the granulate. A 10-fold increase in loading did not affect the composition of the granulate. When scaling the pelletizing process, a risk analysis was carried out, factors influencing the technological process were identified and structured. It turned out that the most important stages are mixing and the actual granulation. To obtain a homogeneous mixture, additional equipment was used - a mixer.Conclusion. As a result of scaling up the granulation process, the parameters of wet granulation in the mixer-granulator (optimal loading, impeller and grinder rotation frequency), technological properties of the resulting granulate, and risks affecting the technological process were selected. were evaluated and a causal diagram (Ishikawa diagram) was drawn.
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Bernaudin, Francoise, Dominique Bories, Jean-Hugues Dalle, Marie Robin, Regis Peffault de Latour, Benedicte Neven, Yves Bertrand, et al. "Sickle Cell Anemia and HSCT: Relation Between ATG, Chimerism, Gvhd and Outcome In Myeloablative Genoidentical Transplants For The SFGM-TC." Blood 122, no. 21 (November 15, 2013): 971. http://dx.doi.org/10.1182/blood.v122.21.971.971.
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Abstract Background Sickle Cell Anemia (SCA) remains a disease with high risk of morbidity and early death. HSCT is currently the only curative treatment for SCA, but its use has been limited by the risks of transplant-related mortality (TRM) and GVHD. We have previously demonstrated that antithymocyte globulin (ATG) efficiently decreases the rejection rate in HSCT for SCA; however, its optimal dose has not been defined, prompting us to retrospectively analyse outcomes in patients from the SFGM-TC cohort receiving different ATG doses. Patients and Methods The cohort includes 236 SCA-patients (109F, 127M), (229 SS, 5 Sb0, 2 SDPunjab) transplanted in France (1988-2012) with geno-identical donors after homogeneous myeloablative conditioning regimen (CR; BU-CY), and rabbit ATG (n=215) at 5-15 mg/kg (n=35), 20 mg/kg (n=160) or no ATG (n=20). Cell sources were bone marrow (BM, n=197), cord blood (CB, n=30), CB+BM (n=8), and peripheral blood cells (PBC, n=1). Chimerism was assessed by quantitative real-time PCR from PBC at Day-30, 60, 90, Month-6, 12 and every year post-transplant, and defined as total donor chimerism (TDC): >95% donor (D); low (5-50%D) or high (50-95%D) mixed chimerism (MC),; or rejection (< 5%D). Disease-free survival (DFS) was defined as the absence of HSCT-related death and rejection. GVHD prophylaxis consisted of CSA-short MTX for BMT and CSA alone for CBT. Results Mean age at transplant was 9.7yr (range: 2.2-28.9), with 33 patients older than 15. With a mean follow-up of 5.6yr (range 0.5-22.5), TRM was not different with or without ATG (3.4%; 0.8-6%) whereas DFS was higher (p=0.004) with ATG (95.4%; 92-4-98.4) than without (72.7%; 51.7-93.7), due to differences in rejection rates (p<0.001). DFS was similar whether the cell source was CB or BM. No lymphoma was observed, and only one post-transplant death at 5m was virus-related (adenoviral meningo-encephalitis). Incidences of AGVH ≥2, 3-4 and chronic-GVHD (cGVHD) were 19%, 6% and 8.7%, respectively. Univariate Cox analysis showed that significant risk factors affecting DFS were low dose of ATG, AGVH grade, and cGVHD, whereas cell source, ABO compatibility, donor’s and recipient’s (DR) age, and CMV status were not. Risk factors associated with cGVHD (Logistic regression) were ATG dose (20% incidence with no ATG, 15.6% with 5-15 mg/kg and only 6.4% with 20), DR age (even after exclusion of CBT), whereas DR genders, DR CMV status, and cell source doses (NC, CD34, CD3+) were not. Multivariate analysis only retained ATG dose (OR=0.9/mg/kg increase, 95% CI:0.8-1, p=0.007) and donor’s age>15 (OR=7.9, 95%CI: 2.5-25.6,p<0.001) as significant independent risk factors for cGVHD. Chimerisms (n=165) (Figure) were significantly associated with ATG dose and cGVHD occurrence. Among the 6 patients with low MC at 1yr, 3 had not received ATG and rejected at 2, 2.2 and 8yr post-HSCT whereas the 3 others who had received ATG remained stable. All patients with high MC at 1yr (n=54) and TDC (n=80) are doing well with the same electrophoretic profile as their donor, excepted one patient who experienced appearance of MC with hemolysis (D/R group U+/U-) 5yr post-CBT, requiring donor lymphocyte infusion (DLI), which reversed chimerism to TDC but induced cGVHD. Conclusion This study confirms that myeloablative CR with ATG offers 95% DFS to SCA-patients and that stable MC in absence of SCA-symptoms does not require intervention such as DLI. It reports for the first time in HSCT for SCA that donor’s age significantly increases GVHD risk, suggesting to choose the youngest sibling when possible, and that high ATG dose (20 mg/kg), which significantly reduces cGVHD risk without enhancing viral risk, should be recommended. Disclosures: Bernaudin: Novartis: Research Funding. Bertrand:ERYTECH Pharma: Principal Investigator Other. Gluckman:Cord use: Honoraria; gamida: Honoraria.
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Yadav, Ashwani Kumar, Basilia Quispe Huillcara, Pablo Víctor Cerón Ramírez, Modesto Antonio Sosa Aquino, and Miguel Ángel Vallejo Hernández. "Structural Shielding Design of CT Facility using Monte Carlo Simulation." Journal of Nuclear Physics, Material Sciences, Radiation and Applications 8, no. 2 (February 10, 2021): 143–47. http://dx.doi.org/10.15415/jnp.2021.82018.
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Radiation application in medicine offers extraordinary benefits. But radiation is like a double-edged sword, it has both benefits and associated risks on the community in contact. To justify the safety of workers and members of the public, regulated use of radiation is assessed by the radiation protection protocols. The aim of this study is to design a Computed Tomography (CT) facility with a simplified model of CT scanner, whose shielding follows the guidelines of National Council on Radiation Protection and Measurements (NCRP) Report No. 147. To design the study model, Monte Carlo (MC) radiation transport code in MCNPX 2.6.0 was used for the simulation. Furthermore, MCNPX was used to measure the photon flux in a vicinity or the detector cell. To validate the functioning of the X-ray tube, the experimental results were compared with the X-ray Transition Energies Database of National Institute of Standards and Technology, U.S. Department of Commerce. The results obtained were within 0.60% of relative error. To confirm the functioning of shielding design, radiation protection quantity, air kerma was measured at several points outside, and inside of the CT room and they were under the radiation dose recommended by NCRP, which demonstrates that the shielding design wassuccessful in blocking the radiation. The study can be used for an easy evaluation of any CT room within the framework of the model of the study.
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Nagaraj, Rajini, Trevor Stack, Sijia Yi, Benjamin Mathew, Kenneth R. Shull, Evan A. Scott, Mathew T. Mathew, and Divya Rani Bijukumar. "High Density Display of an Anti-Angiogenic Peptide on Micelle Surfaces Enhances Their Inhibition of αvβ3 Integrin-Mediated Neovascularization In Vitro." Nanomaterials 10, no. 3 (March 22, 2020): 581. http://dx.doi.org/10.3390/nano10030581.
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Diabetic retinopathy (DR), Retinopathy of Pre-maturity (ROP), and Age-related Macular Degeneration (AMD) are multifactorial manifestations associated with abnormal growth of blood vessels in the retina. These three diseases account for 5% of the total blindness and vision impairment in the US alone. The current treatment options involve heavily invasive techniques such as frequent intravitreal administration of anti-VEGF (vascular endothelial growth factor) antibodies, which pose serious risks of endophthalmitis, retinal detachment and a multitude of adverse effects stemming from the diverse physiological processes that involve VEGF. To overcome these limitations, this current study utilizes a micellar delivery vehicle (MC) decorated with an anti-angiogenic peptide (aANGP) that inhibits αvβ3 mediated neovascularization using primary endothelial cells (HUVEC). Stable incorporation of the peptide into the micelles (aANGP-MCs) for high valency surface display was achieved with a lipidated peptide construct. After 24 h of treatment, aANGP-MCs showed significantly higher inhibition of proliferation and migration compared to free from aANGP peptide. A tube formation assay clearly demonstrated a dose-dependent angiogenic inhibitory effect of aANGP-MCs with a maximum inhibition at 4 μg/mL, a 1000-fold lower concentration than that required for free from aANGP to display a biological effect. These results demonstrate valency-dependent enhancement in the therapeutic efficacy of a bioactive peptide following conjugation to nanoparticle surfaces and present a possible treatment alternative to anti-VEGF antibody therapy with decreased side effects and more versatile options for controlled delivery.