bluuebunny/crossref_metadata_2025 huggingface dataset:
Microstructure and mechanical properties of the 316 stainless steel nuclear grade experimental component made by wire and arc additive manufacturing
Authors: Ye Changqing , Lu Guangyao , Peng Xiangyang , Hou Shuo , Zhou Jianming , Ni Liang
Published: April 2020

An experimental component of nuclear grade austenitic stainless steel 316 (SS316) shielding plate was manufactured by wire and arc additive manufacturing (WAAM) method. Its microstructure, tensile properties at room and high temperatures, Vickers hardness, and impact properties were analyzed. The results show that the microstructure of WAAM SS316 product is mainly composed of austenite (γ) and delta-ferrite (δ) phases. The δ exhibits a fine vermicular morphology in the austenite matrix and is distributed at the boundaries of and inside the grains. The tensile properties of WAAM SS316 product are comparable to those of wrought SS316 and exceed the corresponding requirements of the nuclear industry. WAAM SS316 product has good uniform impact toughness in all directions, and the impact energy can fully meet the technical requirements of the nuclear industry with excellent performance. The results of nondestructive testing show that the quality of the WAAM SS316 shield plate product meets the evaluation requirements of the nuclear industry.
East Asia’s retail revolution: Diffusion of organized retailing and varieties of market development in Korea and Taiwan
Authors: Shin Solee
Published: April 2020

Global diffusion of organized retailing over the last several decades brought extensive worldwide standardization of retail formats and technologies. Such development, however, has not led to the success of the same set of retailers but to varied prominence of core players across markets. Few studies comparatively analyse local market environments to assess this variation, and those that do rarely look beyond local policy measures or idiosyncratic consumer tastes. Presenting a sociological institutionalist alternative and comparing Korea’s and Taiwan’s paths to organized retail development, this article highlights how local business groups relied on network-hierarchy logics to coordinate and control new businesses amid MNC entry and global diffusion of retailing. The resulting dynamics of competition and cooperation illustrate the significance of institutionalized market environments for MNC performance. The study contributes to the comparative capitalism literature by highlighting institutionally embedded strategic behaviours of organizations as crucial contributors to continued national economic diversity amid heightening globalization.
Describing the role of the hematology/oncology clinical pharmacist in health information technology
Authors: Philippon Jennifer S , Kusoski Carolyn L , Kennerly-Shah Julie M , Barreto Janinah S
Published: April 2020

Purpose

To describe the role of hematology/oncology clinical pharmacists in health information technology as well as their perceptions of the impact of technology expansion on patient care.

Methods

A single-center, web-based survey was distributed to 30 hematology/oncology clinical pharmacists by email over the two-week-period of 24 September 2018 to 8 October 2018. The anonymous survey was composed of 19 questions, with varying formats including multiple choice, fill-in-the-blank, and rank order. Primary endpoints were quantification of time spent in the electronic health record and perceptions on how technology expansion has impacted the safety, quality, and efficiency of patient care.

Results

Twenty-seven hematology/oncology clinical pharmacists (90% response rate) completed the survey in its entirety. Respondents reported that they spend an average of 84.1% of their work day in the electronic health record. Based on a 40-h work week, clinical pharmacists indicated that they spend approximately 32.2 h each week performing direct patient care tasks in the electronic health record compared to 3.7 h on indirect patient care tasks. All respondents reported a greater utilization of technology over the last five years, and most respondents felt that patient care is safer, of better quality, and more efficient with technology expansion. The majority of respondents (81.5%) indicated that clinical pharmacists have the best understanding of the health information technology system, followed by generalist pharmacists and informatics pharmacists.

Conclusion

The hematology/oncology clinical pharmacist is well positioned to serve as a health information technology leader on the interdisciplinary healthcare team.
Who should be admitted? Conjoint analysis of South Korean attitudes toward immigrants
Authors: Denney Steven , Green Christopher
Published: April 2020

South Korea is slowly but steadily becoming a country of immigrants. In 1998, there were barely 300,000 foreign residents in South Korea. As of 2018, there were more than 2.3 million. The immigrant population has yet to reach 5% of the total population, but it is predicted to rise significantly in the years to come. Despite the increase in newcomers, it is not well understood who native South Koreans prefer as immigrants and why. Are immigrant attitudes motivated by co-ethnic solidarity, or are they primarily based on economic and sociotropic concerns? To isolate attitudes on these crucial questions, this research uses a conjoint experiment that simultaneously tests the influence of seven immigrant attributes in generating support for admission. Our results show that broad sociotropic concerns largely drive attitudes towards immigrants in South Korea, but an immigrant’s origin also matters. Prospective newcomers from culturally similar and higher-status countries who can speak Korean and have clear plans to work are most preferred. The research findings will be relevant to the comparative study of immigration attitudes, as well as to researchers interested in the specifics of the South Korean case.
Everyday action research for complex times: A peacebuilder’s guide
Authors: Pace Marie
Published: April 2020

In the midst of the increasing intensity of our world, peacebuilding practice is rapidly transforming. These changes come with a growing recognition that complexity is a new type of problem that requires new approaches and responses. As conflict resolution and peacebuilding actors are increasingly adopting complexity thinking and approaches to program implementation, I propose that we can learn to better master complexity by how we attend to our everyday experience. This, I suggest, is something that peacebuilding practitioners can do as a form of ongoing inquiry into the first-person territory of relational, contextual information that surrounds and includes the problems we care about and seek to address. I use a difficult incident from my experience to demonstrate some of what makes complexity so challenging and to explore ways we can learn to deal with these challenges. In keeping with the emancipatory and self-reflective traditions of action research and conflict resolution, an everyday action research is my way of harnessing inquiry and practice to expand capacities to meet the challenges we face in an increasingly complex world.
Preparation of electrospun silver/poly(vinyl alcohol) fibrous membranes and characterization of the effect of sterilization processes on the antibacterial activity
Authors: Chen Wen-Cheng , Ko Chia-Ying , Chang Kai-Chi , Chen Chih-Hua , Lin Dan-Jae
Published: April 2020

Silver ions (Ag+) and silver nanoparticles (AgNPs) are effective antimicrobial agents that act against a broad spectrum of bacteria. The releasing quantitation of free Ag+ is exclusively responsible for the biological toxicity, while limiting the free Ag+ in AgNPs or in polymers would largely ease the conditions. In this study, the different concentrations of silver nitrate (AgNO3) in poly(vinyl alcohol) (PVA) and an optional preheat treatment on the spinning solution before electrospinning to form the Ag+/AgNPs/PVA fibrous membranes through electrospinning technology were investigated. The morphologies, AgNPs dispersity within the PVA matrix, and the sterilizations (UV irradiation and autoclave) for Ag+/AgNPs/PVA fibrous membranes were characterized. The antibacterial activities of Ag/PVA composite membranes combined with the in-house prepared light-cured resin were also investigated. Results showed that the AgNPs/PVA fibrous membranes with antibacterial capability can be produced with the addition of at least 5 wt.% of AgNO3 to PVA. The antibacterial activities of Ag content in the PVA matrix were increased in the high presence of Ag. Noteworthy, the antibacterial enhancing effect was observed for the spinning solution groups after preheating treatment at 100°C for 1 h. The result suggests that Ag/PVA fibrous membranes sterilized by autoclave hindered antibacterial effectiveness due to the significant particle size changes in the generation of large-sized AgNPs. Nevertheless, the direct application of UV light irradiation to Ag/PVA fibrous membranes preserves their active antibacterial profile against Staphylococcus aureus and Escherichia coli. We also demonstrated that these designed AgNPs/PVA composite membranes can equip the resin with an active antibacterial capability, could benefit from the prevented bacteria breeding in microleakages and thus further reduce the possibility for secondary caries.
Importance of perceived teammate support as a predictor of student-athletes’ positive emotions and subjective well-being
Authors: Cho Heetae , Yi Tan Hui , Lee Eunsoon
Published: April 2020

Student-athletes may have high stress, and the level of their subjective well-being could be low due to the dual role of being a student and an athlete. In the field of sport psychology, social support has received focal attention to identifying its impact on individuals’ subjective well-being. However, there is a lack of research that focuses on teammate support and subjective well-being. Thus, this study examined how the perception of teammate support influences subjective well-being through positive emotions based on the environmental psychology model and the broaden-and-build theory of positive emotions. This study collected 313 responses from university student-athletes in Singapore and conducted a confirmatory factor analysis and structural equation modeling analysis. Results showed that perceived teammate support had a positive influence on subjective well-being through positive emotion. Also, there was a direct effect of perceived teammate support on subjective well-being. The results support the critical role of perceived teammate support in enhancing the student-athletes’ subjective well-being. The findings of this study are beneficial for coaches and student-leaders to design strategies to improve the subjective well-being of student-athletes.
A novel reverse design method of tag antenna based on image analysis
Authors: Liu Zhenlu , Zhao Zhimin , Yu Xiaolei , Liu Mengjie , Ji Rendong
Published: April 2020

Since the working efficiency of the entire radio frequency identification system depends on the performance of the radio frequency identification tag antenna, the research and design of the tag antenna have received attention, especially for radio frequency identification tags applied to special scenes. We mainly studied the effect of antenna bending on the performance of ultra-high frequency radio frequency identification systems, and combined the bent antenna with the impedance matching loop to achieve impedance matching between the chip and the antenna in the ultra-high frequency band. We analyzed the variation of tag antenna performance with antenna parameters by the simulation software High Frequency Structure Simulator (HFSS). At the same time, we propose a novel antenna reverse design method. Through the analysis of the antenna-specific absorption rate image, the antenna performance intensity is visually reflected. According to the image analysis result, the antenna parameters are corrected to improve the antenna matching performance. This design method is simpler and faster than other methods.
In vitro anti-adenoviral activities of ethanol extract, fractions, and main phenolic compounds of pomegranate (Punica granatumL.) peel
Authors: Karimi Ali , Moradi Mohammad-Taghi , Rabiei Mohammad , Alidadi Somayeh
Published: April 2020

Background

Adenovirus causes a number of diseases in human, and can cause serious infection in severely immunosuppressed individuals. Despite the seriousness of adenovirus infection, there is no definitely approved anti-adenoviral therapy. Many studies have shown that compounds derived from medicinal plants have antiviral activity. Therefore, this study evaluated in vitro anti-adenoviral activity of ethanol extract, fractions, and main phenolic compounds of pomegranate peel.

Methods

The ethanol extract of pomegranate peel was prepared with maceration method and fractionated by consecutive liquid/liquid partition. The cytotoxic and anti-adenovirus activities of the extract, fractions, and main phenolic compounds (ellagic acid, punicalagin and gallic acid) were evaluated on Hep-2 cell line using MTT assay. Inhibitory effect on adsorption and post-adsorption phases of the virus replication cycle was also evaluated.

Results

Pomegranate peel extract had a desirable effect against adenovirus with IC50of 5.77 µg/mL and selectivity index of 49.9. Among the fractions and compounds, the n-butanol fraction and gallic acid had the highest anti-adenoviral activity with IC50of 2.16 µg/mL and 4.67 µM and selectivity indices of 122.5 and 10.5, respectively. The crude extract, n-butanol fraction and gallic acid inhibited the virus replication in post-adsorption phase ( p <  0.01).

Conclusion

Pomegranate peel extract, especially its n-butanol fraction, could serve as a new promising anti-adenovirus agent due to high inhibitory effect against adenovirus replication. The effect of the n-butanol fraction may be related to the synergistic effect or other compounds of this fraction. Further understanding of the bioassay guided isolation of natural compounds of this fraction seems essential.
Ultrasound parameters of pelvic organs and their age-related changes in a cohort of asymptomatic postmenopausal women: A community-based study
Authors: Dias Thiran D , Palihawadana Thilina S , Patabendige Malitha , Motha Mary BC , de Silva Hithanadura J
Published: April 2020

Objective

To describe the ultrasound parameters of pelvic organs and their age-related changes in a cohort of asymptomatic postmenopausal women and to describe the prevalence of ultrasound-detected pathologies in a Sri Lankan population.

Study design

A large community-based longitudinal study using a randomly selected sample of postmenopausal women who have never used hormone replacement therapy.

Main outcome measures

Uterine, endometrial and ovarian measurements at pelvic ultrasonography as described by the International Endometrial Tumor Analysis and the International Ovarian Tumor Analysis groups.

Results

A total of 815 postmenopausal women were approached and all volunteered to participate. This included women between the ages of 45 and 74 years with a median (interquartile range (IQR)) of 62.0 (10.0) years. The median (IQR) uterine volume was 18.1 (17) ml, while the median (IQR) of right and left ovarian volumes were 17.3 (22.9) ml and 18.2 (21.5) ml. Both uterine and ovarian volumes showed an age-related decline (p < 0.01). Furthermore, the ovarian volumes demonstrated an increase in size with a higher body mass index (p < 0.03 for left and p < 0.01 for right, respectively). Median (IQR) endometrial thickness among the population was 3.0 (1.0) mm and there was no age-related change observed. Sixty-one women had an ultrasound-detected gynaecological pathology with a prevalence of 7.5% (95% confidence interval (CI) 5.6–9.5).

Conclusions

This study aimed at describing ultrasound parameters of pelvic organs among postmenopausal women of Sri Lanka was able to provide the reference values for uterine and ovarian volume among asymptomatic postmenopausal women. Both uterine and ovarian volumes demonstrated an age-related decline, whereas the endometrial thickness does not seem to relate to the age.
A Hypomorphic Cbfb Allele Reveals Requirements for the Development of T Lymphocytes, Granulocytes, and Monocytes/Macrophages, and for Maintaining Proper Numbers of Hematopoietic Progenitors.
Authors: Talebian Laleh , Li Zhe , Gallagher Torrey L. , Guo Yalin , Speck Caroline L. , Stacy Terryl , Speck Nancy A.
Published: April 2020

CBFβ is the non-DNA binding subunit of the core binding factors, and is required for both the functions of Runx1 in hematopoiesis and Runx2 in osteogenesis. Homozygous disruption of Cbfb results in embryonic lethality at mid-gestation and a severe impairment of fetal liver hematopoiesis, a phenotype similar to Runx1 deficiency. To examine Cbfb requirements at later stages of hematopoiesis, we generated a hypomorphic Cbfb allele (Cbfbrss). Mice homozygous for the Cbfbrss allele have a 4- to 5-fold reduction in CBFβ protein levels, while Cbfbrss/− mice have an 8- to 10-fold reduction in CBFβ concentration. Cbfbrss/rss and Cbfbrss/− mice die at P0 for unknown reasons and display minor defects in bone ossification. Granulocyte and macrophage differentiation at E17.5 is impaired in both Cbfbrss/rss and Cbfbrss/−animals, as evidenced by a 2- to 3- fold decrease in GR1+ and Mac1+ cells. The percentages of Ter119+, B220+, and CD19+ cells are normal. Fetal liver hematopoietic progenitor numbers, as determined by cell surface marker and functional analyses, are increased approximately 2-fold. The most severe defects are in the T cell lineage. Cbfbrss/rss fetuses have reduced thymus cellularity and lower numbers of CD8 SP T cells, consistent with a role for Runx1 and Runx3 in epigenetic CD4 silencing. A further 2-fold reduction in CBFβ levels in Cbfbrss/− fetuses results in an absence of CD4/8 SP and DP cells. These hematopoietic defects were also seen upon transplantation of Cbfbrss/rss and Cbfbrss/− fetal liver cells into congenic Ly5.1/5.2 mice. Our data indicate that the threshold level of CBFβ required for normal hematopoiesis, bone development, and postnatal viability is somewhere between 25%-50% of its normal concentration. The data demonstrate that T cell development is particularly sensitive to CBFβ levels, and both granulocyte and macrophage differentiation require CBFβ. Since the conditional knockout of Runx1 in the adult mouse reported by Ichikawa et al. (Nat Med.10, 299, 2004) did not cause either granulocyte or monocyte/macrophage defects, we hypothesize that Runx2 and/or Runx3 are also required in these lineages. Hemizygosity for CBFB-MYH11, the product of the inv(16), is associated with a more severe phenotype than is seen in the Cbfb rss/− fetuses (Castilla et al. Cell87, 687, 1996). We therefore conclude that the hematopoietic consequences for cells expressing the inv(16) are equivalent to a greater than 10-fold reduction in the level of functional CBFβ.
Adoptive Transfer of T Cell Help Breaks Tolerance in Endogenous, Tumor-Specific CD8+ T Cells Responding to a Growing Tumor.
Authors: Wang Jie , Aalamian Maryam , Jalla Sanju , Luznik Leo , Fuchs Ephraim J.
Published: April 2020

Patients who reject allogeneic blood or marrow grafts after non-myeloablative conditioning sometimes develop delayed or sustained clinical disease responses, raising the possibility that a transient graft-versus-host reaction rekindles dormant anti-tumor immunity by recipient T cells. More specifically, we postulate that endogenous tumor-specific CD8+ T cells are not irreversibly tolerant of a growing tumor, and can be activated to effector function by tumor antigen recognition in the presence of adoptively transferred CD4+ T cell help. We have tested this hypothesis by examining the response of influenza hemagglutinin (HA)-specific “endogenous” CD8+ T cells in HA-tumor-bearing mice treated with cyclophosphamide (Cy) and adoptive transfer of allogeneic or tumor-specific CD4+ T cells, with or without concomitant tumor vaccine administration. In these models, this combination therapy induced the clonal expansion of endogenous, tumor-specific CD8+ T cells, their secretion of interferon gamma, and in vivo cytolytic activity against HA-expressing cells. In separate experiments, adoptively transferred, major histocompatibility complex-mismatched CD4+ T cells induced the activation of recipient, CD11c+ dendritic cells, as demonstrated by enhanced expression of the costimulatory molecules CD80 and CD86. The administration of Cy followed by infusion of allogeneic T cells, with or without tumor vaccine administration, also induced regression of B cell leukemia/lymphoma or established prostate cancer. These results highlight the potential cooperation of donor CD4+ T cells and recipient CD8+ T cells in transient or stable mixed hematopoietic chimeras, and open new avenues for the immunotherapy of cancer in the clinic.
Elevation of Plasma Von Willebrand Factor and Tumor Necrosis Factor-α in Obese Subjects and Their Reduction by Low Molecular Weight Heparin.
Authors: Mousa Shaker A.
Published: April 2020

Background: Increased plasma-soluble von Willebrand factor (vWF) level, a marker of vascular endothelial cell dysfunction, is a predictor of atherosclerotic cardiovascular disease in the general population. We compared associations between vWF level and markers of inflammation as well as the effects of low molecular weight heparin (LMWH) in obese as compared to healthy human subjects.

Methods: Plasma samples were obtained from healthy volunteers (n = 32) and obese subjects (n = 12) before and after administration of a single subcutaneous (SC) dose of tinzaparin, given at a deep vein thrombosis (DVT) prophylaxis dose of 75 IU/kg once a day. These samples were analyzed for vWF and tumor necrosis factor-α (TNF-α) by ELISA. Also examined was the effect of different LMWH on the release of vWF from human umbilical vein endothelial cells (HUVEC) in response to various stimuli, such as oxidized low density lipoprotein (LDL) or endotoxin.

Results: Obese subjects showed higher plasma levels of TNF-α compared with normal-weight subjects. Regression analysis showed plasma vWF levels to be directly associated with the presence of higher plasma levels of TNF-α in these obese subjects. Tinzaparin, given at a prophylaxis dose for DVT (75 IU/kg, SC, QD), significantly reduced elevated plasma levels of endothelial dysfunction marker vWF associated with higher inflammatory TNF-α levels (P <0.01). HUVEC, when treated with oxidized LDL or endotoxin, demonstrated a significant elevation of vWF release into the medium in a time-dependent manner. Tinzaparin and enoxaparin significantly reduced this increased vWF release from HUVEC in the media.

Conclusion: Plasma values of vWF and TNF-α are higher in obese than in normal-weight individuals. Treatment with tinzaparin lowers plasma levels of TNF-α in both obese and normal-weight subjects. The levels of vWF were higher in obese subjects than in normal-weight ones because of the higher levels of circulating TNF-α. Tinzaparin reduced vWF levels in these obese subjects.

Table 1. Effect of Tinzaparin (75 IU/kg, SC, QD) on Plasma vWF in Obese and Normal-Weight Subjects

Table 2. Effect of Tinzaparin (75 IU/kg, SC) on Plasma TNF-α in Obese and Normal-Weight Subjects

Subjects Mean Plasma vWF (IU/mL) ± SD Pre-Tinzaparin Mean Plasma vWF (IU/mL) ± SD Post-Tinzaparin (2 h) * P <0.05 obese versus normal-weight subjects before treatment with tinzaparin; †P <0.01 post- versus pre-tinzaparin; vWF = von Willebrand factor. Normal body weight (n = 32) 0.44 ± 0.15 0.36 ± 0.12 Obese (n = 12) 0.68 ± 0.20* 0.29 ± 0.11† Subjects Mean Plasma TNF- α (pg/mL) ± SD Pre-Tinzaparin Mean Plasma TNF- α (pg/mL) ± SD Post-Tinzaparin * P <0.05 obese compared with normal-weight subjects before treatment with tinzaparin; †P <0.01 post- compared with pre-tinzaparin; TNF-α = tumor necrosis factor-α. Normal body weight (n = 32) 1.68 ± 0.55 1.37 ± 0.33 Obese (n = 32) 2.82 ± 0.38* 1.45 ± 0.25†
Correlation of Genetic Polymorphisms Detected by Geneohm EPLEX™ Electrochemical Platform with Functional Study for Venous Thrombosis.
Authors: Xu Bo , Thompson Steven , Koenigberger Carol , Pettay James , Silbergleit Arkadiy , Kawashima Tad , Kottke-Marchant Kandice , Tubbs Raymond R.
Published: April 2020

Venous thrombosis (VT) is a multi-factorial disorder with both congenital and acquired risk factors. Mutations in several genes, such as factor V, prothrombin and methylene tetrahydrofolate reductase (MTHFR), are considered risk factors for thrombophilia. Since multiple mutations compound the risk for (VT), simultaneous discovery of mutations could directly alter patient management. In this study, we employed the GeneOhm ePlex™ platform to simultaneously detect genetic polymorphisms for six markers: factor V Leiden (FVL) and HR2A45374G, prothrombin G20210A, MTHFR C677T and A1298C, and plasminogen activator inhibitor 1 (4G/5G). Fifty-one patient samples were selected. Each sample was genotyped for all six markers on the GeneOhm ePlex™ electrochemical array and data from functional studies were analyzed and compared to the genotyping results. Among the 51 patients, 16 were tested for activated protein C resistance and the average values were 1.22, 1.76 and 2.64 for FVL homozygous, heterozygous and wild type normal patients, respectively. In addition, the average plasma homocysteine levels measured in 17 patients were 15.40, 6.42 and 11.93, 12.63 mmol/L for MTHFR C677T homozygous, heterozygous and MTHFR A1298C heterozygous and C677T/A1298C double heterozygous, respectively. Furthermore, 10 out of 11 patients with history of deep venous thrombosis (DVT) and/or pulmonary embolism (PE) displayed genetic abnormalities in FVL or prothrombin G20210A. The other patient with history of both DVT and PE showed homozygous in MTHFR C677T with high plasma homocysteine level (22.3 mmol/L) and heterozygous mutation in PAI-1. This study demonstrates the principle of multiplexed molecular diagnostics for the polymorphisms associated with thrombophilia and the utility of the GeneOhm ePlex platform. The study is being expanded to test a larger set of samples to establish the relationship between genetic polymorphism and corresponding clinical outcome for all six markers.
Treatment of Deep Vein Thrombosis with Enoxaparin in Pediatric Cancer Patients Receiving Chemotherapy.
Authors: Stine Kimo , Saylors Robert , Saccente Suzanne , Becton David
Published: April 2020

Thrombosis is a known risk in pediatric patients with leukemia. This risk is increased when L-asparaginase is administered. However, children with cancer may have thrombotic complications similar to adults even in the absence of L-asparaginase. The risk may be related to the presence of central lines, surgery, immobilization, or inherited thrombophilia. Cancer in adult patients is also associated with an increased risk of thrombosis that may be related to the disease itself. Low molecular weight heparin such as enoxaparin has become widely used in adult patients with thrombosis. However, there is little data regarding the use of enoxaparin in children undergoing myelosuppressive therapy for malignancies. The purpose of this study was to review the utilization of low molecular weight heparin, enoxaparin (Lovenox), in children with cancer at our institution who had thrombosis while undergoing myelosuppressive chemotherapy. In particular we were interested in the efficacy of enoxaparin in these patients, and if these children were able to continue their chemotherapy without adjustment or interruption secondary to bleeding complications. We conducted a retrospective review from 1999 through April 1, 2004 which yielded seven patients with malignancies and a vascular thrombotic event. The age range was 4–17 years. Diagnosis include: B-precursor ALL (n=3), T-ALL, Hodgkin’s disease, Anaplastic large cell lymphoma, and rhabdomyosarcoma (n=1 each). Six patients developed a deep vein thrombus or clot of the vena cava. One of these 6 patients also had a pulmonary embolus. One patient presented with manifestations of a unilateral cerebral vascular accident without evidence of a DVT. U/S and CT/MRI were performed on patients when appropriate. All patients were screened for Protein C & S deficiency, ATIII deficiency, Factor V Leiden mutation, prothrombin 20210a mutation, and lupus anticoagulant. Treatment was enoxaparin, 1–1.5 mg/kg/dose twice daily to maintain a heparin anti-Xa level of 0.5-1.5 IU/mL. Once the clot had resolved, the enoxaparin was maintained daily for a total of 3–6 months of therapy. All patients had resolution of their thrombosis within 1–2 months of initiation of enoxaparin, and none required delays or dose-reduction of their chemotherapy regimens while on anti-coagulation. There were 10 documented occurences of thrombocytopenia (platelet count < 50,000) in 2 patients without bleeding complications. There was a minimum of 50 days of documented thrombocytopenia while on enoxaparin. We conclude that enoxaparin is effective and safe treatment for thrombotic complications in children undergoing cancer chemotherapy.
Incidence of Ex Vivo Expansion on the Capacity of Cord Blood Graft To Generate Immune Cells: Rational for Co-Infusion of Expanded and Non Expanded Fractions?.
Authors: Rosenzwajg Michelle , Giarratana Marie-Catherine , Gluckman Jean-Claude , Douay Luc , Kobari Ladan
Published: April 2020

The aim of our study was to determine whether ex vivo expansion of umbilical cord blood (UCB) progenitor cells induces changes in their capacity to generate immune cells. CD34+ CB cells were cultured for 14 days with SCF, FLT3-l, TPO and G-CSF, inducing a total cells, CD34+ and LTC-ICs increase of 1500, 120 and 8 fold respectively. Non expanded (d0) and 14-day expanded (d14) CD34+ cells were compared for their capacity to produce T lymphocytes (TLs) using the fetal thymus organ culture system and DCs generated from d0 and d14 CD34+ cells were compared for their differentiation, phenotype and function. Total percentages of CD4+, CD4+CD8− and CD4+CD8+ TLs obtained from d0 and d14 CD34+ cells were comparable. In both fractions, most of the CD4+ T cells co-expressed iCD3 but a lower proportion of d14 derived TLs expressed sCD3. However, there was no significant difference between d0 and d14 derived TLs in term of Vb chain representation, all TCR-Vb chains examined being represented in each case. These data indicate that d0 and d14 CD34+ cells have a similar capacity to generate TLs and that expansion does not induced any skewing of the TCR-Vb repertoire. D0 and d14 CD34+ cells were next cultured with SCF, FL, GM-CSF and TNF-a to compare their capacity to differentiate into DCs. Similar percentages of CD1a+ DCs expressing the same levels of HLA-DR and co stimulatory molecules were obtained. DCs derived from d14 CD34+ cells were less potent to stimulate allogeneic TLs, but the pattern of cytokines produced by stimulated TLs was similar and no shift towards a predominant Th1 or Th2 response was observed. Moreover, in spite of a quantitative increase (15 fold) related to the CD34 pool amplification, we observed a decreased capacity (13-fold) of d14 cells to generate DCs compared to d0 CD34+ cells.

Overall, these results indicate that ex vivo expansion of CD34+ cells doesn’t induce any major modification in T Lymphopoiesis capacity while alters somehow the capacity of the graft to generate DCs. We discuss in the context of UCB transplantation, the putative interest of co-infusion of expanded and non expanded fractions in view of improving myelopoiesis in the graft without subverting the immune reconstitution.
Benefit of Fondaparinux in Medical Patients: A Subgroup Analysis.
Authors: Cohen Alexander T. , Gallus Alexander S. , Davidson Bruce L. , Lassen Michael R. , Prins Martin H. , Tomkowski Witold , Turpie Alexander G.G. , Egberts Jan F.M. , Lensing Anthonie W.A.
Published: April 2020

Aim

In the ARTEMIS study fondaparinux 2.5mg reduced the overall incidence of venous thromboembolism (VTE) by 47% in general medical patients when compared to placebo. Our aim was to identify which medical patient populations with an acute medical illness or risk factor for VTE benefited from fondaparinux prophylaxis.

Method

A total of 849 patients were enrolled in 35 centres in 8 countries. Patients were randomised to receive placebo or fondaparinux 2.5mg subcutaneously once daily for 6 to 14 days. 644 (76%) patients were available for assessment of the primary outcome, occurrence of documented VTE between day 1 and day 15. We performed a subgroup analysis of the incidence of VTE in the placebo and fondaparinux 2.5mg treatment groups. The medical illness subgroups analysed were those predefined in the original study: acute heart failure only, respiratory disease only, infectious/inflammatory disease only and more than one disease.

Results

Conclusion

Fondaparinux 2.5mg is superior to placebo in preventing VTE in patients with acute medical illness. Similar point estimates and overlapping confidence intervals indicate that the results are consistent within all the predefined medical illness.

Population variable Placebo Fondaparinux 2.5mg Relative risk reduction 95% CI * P Value n/N % n/N % *exact CI for RRR based on standardized statistics and inverting a 2-sided test Acute heart failure (NYHA III/IV) 10/82 12.2 7/78 9.0 26.4% [−78.9%;69.7%] 0.61 Acute respiratory disease only 4/73 5.5 1/63 1.6 71.0% [−86.6%;97.7%] 0.37 Acute infectious/inflammatory disease only 10/88 11.4 4/77 5.2 54.3% [−33.1%;85.0%] 0.17 More than one disease 10/80 12.5 6/103 5.8 53.4% [−21.4%;83.4%] 0.12
Targeting the Risks of Specific Antiplatelet Alloimmunization in the Populations of Sub-Saharan Africa, Asia, and Oceania.
Authors: Kaplan-Gouet Cecile , Bigot Andre , Imandy Gisele , M’Bayo Ferdinand , Khanh Hoa B. , Tetaria Claude , Martageix Corinne , Halle Liliane
Published: April 2020

As specific antiplatelet alloimmunization directed against Human Platelet Antigens (HPA) during pregnancy or after platelet transfusion is not a rare event, this study aims at identifying such a risk in the context of the diversity caused by the population migrations we see today in our hospitals and particularly in the Sub-Saharan African (SSA), south East Asia and Polynesian populations. Samples were collected from 155 Beninese, 118 Cameroonian, 96 Congolese (Kinshasa), 107 Vietnamese and 81 Polynesian Ma’ohis, all unrelated, healthy blood donors. DNA was extracted by salting out method and the platelet genotype was determined by PCR-RFLP. We did not observe any significant deviation from the Hardy-Weinberg equilibrium. As opposed to Caucasian populations, the risk of anti HPA-1a alloimmunization is extremely low, due to the absence, or at least the low frequencies of HPA-1 b homozygous individuals in these populations (Cameroon 0.8 % and Benin 1.3 %). An important risk could be associated with HPA-2 immunization in the SSA population, as we observed a relatively high frequency of HPA-2b homozygous individuals. Moreover we noted the frequency of HPA-3b homozygous to be between 11 and 24%. Given that, as neonatal alloimmune thrombocytopenia (NAIT) caused by anti HPA-3a or 3b is similar in severity to disease caused by incompatibility of HPA-1a, this risk should not be ignored particularly in the Vietnamese population with 24.3 % of HPA3b homozygous. We noted the absence of HPA-4b allele. Finally, in contrast to the frequency of HPA-6 heterozygous in the Polynesian population (17%), we do not observe HPA-6b homozygous individuals, suggesting a small risk for that antigen to be implicated in alloimmunization. The repartition of HPA-15 alleles is heterogeneous in these populations. In conclusion: HPA-2 alloimmunization in SSA populations should be identified for platelet transfusion refractoriness or NAIT, similarly for HPA-3 especially in the Vietnamese population and to a lesser degree, HPA-5 in the Cameroon and in the Congo.

Genotype frequencies

HPA-1 HPA-2 HPA-3 HPA-5 HPA-6 HPA-15 bb ...ab ↑bb ...ab ↑bb ...ab ↑bb ↑ ...ab bb ↑ ...ab bb Viet Nam 0.0 ↑ 09.4 0.0 54. ↑24.3 05.6 ↑0.0 02.8 ↑0 ↑ 57.0 24.3 Polynesia 0.0 ↑ 16.3 0.0 ↑ 37.5 18.7 05. ↑0.0 ↑ 17.1 0 ↑ 52.4 28.4 Benin 1.3 ↑ 44.8 7.1 42.8 ↑11.1 34.1 ↑0.8 0.00 ↑0 ↑ 41.6 14.1 Cameroon 0.8 32.7 ↑7.8 ↑ 50.8 13.1 29.8 ↑6.4 ↑ 0.00 0 ↑ 41.2 10.9 Congo 0.0 40.0 ↑2.5 49. ↑18.6 45.2 ↑4.1 ↑ 0.00 0 ↑ 43.8 05.5
Establishing Safety in the Clinic for the First Lentiviral Vector To Be Tested in Humans.
Authors: Dropulic Boro , Humeau Laurent , Slepushkin Vladimir , Lu Xiaobin , Manilla Peter , Rebello Tessio , Afable Cathleen , Lacy Kim , Ybarra Cathy , Levine Bruce , June Carl , MacGregor Rob Roy
Published: April 2020

Lentiviral vectors (LV) offer improved therapeutic benefit of gene therapy applications as a result of their ability to stably transduce a wide range of cycling and non-cycling cells. The first Phase I clinical trial using a lentiviral vector, VRX496, was initiated in January of 2003. The vector evaluated is an HIV-1 based lentiviral vector, fully gutted but retaining the 5′ and 3′ long terminal repeats, the packaging sequence, cPPT/CTS, splice donor and splice acceptor, and rev response element (RRE). VRX496 contains a splice-independent 937-base antisense sequence targeting the envelope gene in the HIV genome, and a small 186-base tag derived from the GFP gene to serve as a molecular marker for vector in HIV infected patient cells. Five (5) HIV-infected patients with CD4 counts between 200 and 500, and viral loads above 5000 copies/ml, no history of opportunistic infections, who have failed two regiments of highly active antiretroviral therapy (HAART), were serially enrolled in the trial. After leukopheresis, patient’s CD4 T lymphocytes were isolated by negative selection of CD8+ cells, and then cultured for three days in the presence of immobilized CD3/28 beads, and VRX496. Thereafter, the vector and beads were removed, cells were expanded to the dose of 1 x 1010, and then given intravenously over 15 minutes. At the time of this abstract, 4 patients have been dosed and have passed the initial 21-day safety assessment; a fifth patient is scheduled for dosing. No serious adverse events have occurred. All patients have steady CD4 counts, and viral loads have decreased below baseline in all patients, notably from 218,000 pre dose to 36,000 1 year post dosing in the first patient, and from 22,000 pre dose to 1,625 at 9 months post dosing in the second patient; patients 3 and 4 are at 3 months and 21 days post-infusion, respectively. Importantly, persistence of vector-modified CD4 cells are detected in the peripheral blood out to 9 months post dosing. This trial establishes for the first time the safety of lentiviral vectors for clinical gene therapy application.
Emerging Viruses Are Inactivated by Pasteurization.
Authors: Groener Albrecht , Schäfer Wolfram , Nowak Thomas
Published: April 2020

Emerging zoonotic viruses as West Nile virus (WNV), SARS coronavirus, and avian influenza viruses have raised concern about their potential presence in blood/plasma. However, so far only WNV has been demonstrated to be transmitted via blood transfusion. Pasteurization (heat treatment in aqueous stabilized solution at 60°C for 10 hours) is an integral part of the manufacturing process of ZLB Behring’s coagulation factor concentrates such as Haemate P / Humate-P, Monoclate-P, Beriate P, and Berinin P as well as other plasma-derived medicinal products. Therefore, the virus inactivation capacity of this manufacturing step was evaluated utilizing these emerging viruses or appropriate model viruses in virus spiking studies in order to assess the safety of plasma derivatives. The studies demonstrated that WNV was inactivated very effectively by pasteurization in different plasma derivatives resulting in an inactivation factor of more than 7 log10 and that BVDV (bovine viral diarrhea virus, as WNV a member of the family Flaviviridae) is a suitable model virus for WNV. Furthermore, coronaviruses and influenza viruses, of both avian and human origin, were highly susceptible to inactivation by pasteurization resulting in complete inactivation of virus infectivity within a short period of time. In addition, feline calicivirus, a model virus for hepatitis E virus (HEV), was inactivated very effectively within a short period of time. We demonstrate that pasteurization is an effective method to inactivate the emerging viruses WNV, SARS coronavirus, and avian influenza viruses as well as HEV below detection limit of a sensitive cell culture infectivity assay resulting in a safe plasma derivative.
A Clinical Trial of VVR Rate in Preoperative Autologous Blood Donation by Adults and Pediatrics Patients with or without IV Fluid Infusion.
Authors: Kobayashi Sumiko , Sato Norihiro , Hashino Satoshi , Kondo Takeshi , Koike Takao
Published: April 2020

Background: There are no reports that compared with or without a simultaneous IV infusion in the autologous blood donation of adult patients and pediatric patients in the incidence of vasovagal reactions (VVR) rate. These reactions may decrease return donation and disrupt blood donation activities. Objectives:The purpose of our study is whether we can take autologous blood donation safely from the both groups of adults patients and pediatric patients. To determine whether a IV fluid infusion is required during the autologous blood donation in both of adult and pediatric patients and whether a IV infusion influences the incidence of VVR rate. Study design and Methods: Since 1999, a total of the 922patients (1,654 times donations) were enrolled including 40 pediatric patients: we investigated two groups such as with or without IV infusion. In pediatric patients, their original diseases were almost based on orthopedic disorders. We used exactly same size needle (17.5gage) to the adult and pediatric groups. Results: Ten of 394 times donations in 244 adults patients with the IV infusion group were shown in VVR (2.5%). The other group who had not taken an IV infusion in 375 times donation of 164 adult patients had 1.8% incidence rate of VVR (seven of 375 times donations) during autologous blood donation. There was no significant difference between with or without IV infusion groups of adults. In pediatric patients, one of the ten patients with IV infusion group occurred 10% of VVR and 3 of 30 times donations of without IV infusion occurred same percentage of incident rate (10%). We also investigated what is the risk factor of VVR in pediatric patients. What is the risk factor of pediatric patients? The result was that low hemoglobin data (mean 12.7g/dl vs 14.0g/dl) before donation and below 40kg were high risk groups in VVR incidence (P<0.01). Conclusion: Our study shows that there is no significant change between with or without IV fluid infusion in both groups of patients of adults or pediatrics in autologous blood donation before operations. Therefore it is useful that it can be done safely without IV prevention for VVR, particularly in cases of pediatrics patients.
Evaluation of the Sepacell RS-2000® (LeukoConnect) Sterile Dock Leukocyte Reduction Filter Set with Red Blood Cells Collected using Trima.
Authors: Campbell Sandy C. , Mauldin Jennifer E. , McShan Kristy L. , Elfath M. Dean
Published: April 2020

As automated red blood cell (RBC) collections become more prevalent, sterile dock filtration will continue to be an important means of leukoreduction (LR). This study evaluated the performance of the Baxter Sepacell RS-2000 sterile dock leukocyte reduction filter set with RBCs collected using Trima, which were filtered either immediately at ambient temperature, or refrigerated and then filtered 6–8 or 68–72 hours post-collection. 180 RBC units were collected using Trima (Gambro BCT, Lakewood, CO) and filtered with the Sepacell RS-2000 (Baxter Healthcare, Deerfield, IL). Units within Group A (n=60) were filtered at ambient temperature immediately after collection. Units within Group B (n=60) and C (n=60) were refrigerated and filtered at 6–8 or 68–72 hours post-collection respectively. Pre- and Post-filtration hematocrits were performed on the Cell-Dyn 3700 (Abbott Laboratories, Abbott Park, IL) to determine RBC percent recovery. Residual leukocytes in the final product were counted using either the FACSCalibur flow cytometer (BD Biosciences, San Jose, CA). Relevant data is presented in Table 1 below. This study demonstrated that the Sepacell RS-2000 (LeukoConnect) sterile dock filter yielded red cell units that met or exceeded the FDA and AABB standards for leukoreduction when filtering refrigerated red blood cell (RBC) units collected on Trima at 6–8 or 68–72 hours post-collection. 60 out of 60 (100%) LR-RBC units in Groups B and C contained residual white blood cell (WBC) counts at or below the limit of detection of 0.3 x 105. 55 of 60 (92%) LR-RBC units in Group A contained residual WBC < 5x106. 38 of 60 (63 %) LR-RBC units within this group contained residual WBC = 1x106. The hold-time prior to ambient filtration for Group A averaged 1:37 ± 0:18. Filtration was initiated < 3 hours post-collection for all units within this group. There is speculation that a correlation may exist between the temperature of the unit at the time of filtration and leukocyte reduction performance for this filtration condition. This correlation was not assessed by this study and warrants further investigation. It was also noted that 11 out of 180 total units (6%) achieved RBC recovery results slightly less than 85%. Unexpected variability in volume recovery for these units can be attributed to inadequate drainage time of the filter. Allowing additional time for complete drainage of the filter would be expected to result in all units achieving > 85% recovery. Table 1

Parameters Group A Group B Group C Mean ± SD (n=60) (n=60) (n=60) Storage & Filtration Condition Ambient (< 3hrs) 1–6°C (6–8hrs) 1–6°C (68–72hrs) Filtration Time (min) 11 ± 1 24 ± 5 27 ± 6 Residual WBC count (1x106) 1.81 ± 3.33 0.30 ± 0.00 0.30 ± 0.00 % RBC Recovery 88 ± 2 87 ± 2 88 ± 2