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A deep-sea manganese nodules test miner has not only coupled relationship between system components but also various design requirements of each system to meet the specified multitasks. To accomplish the multiobjectives of complex systems, multidisciplinary design optimization (MDO) is performed. Metamodels such as the kriging model and the response surface model are employed to reduce computational costs for MDO and to integrate component systems in a design framework. After verifying the accuracy of each metamodel, metamodel-based MDO for a deep-ocean test miner is formulated and performed. Finally, results and advantages of the proposed design methodology are discussed.

Abstract Background Protein C (PC) and protein S (PS) determination is part of the thrombophilia investigation in patients with idiopathic venous thromboembolism (VTE). Based on scarce evidence it is a common notion that PC and PS levels decrease during the acute phase of VTE, necessitating delay of testing and temporary transition from warfarin to low molecular weight heparin. We have previously demonstrated that an abnormal PC or PS result determined within 24 hours of VTE diagnosis and before the initiation of warfarin needs to be repeated for confirmation ≥3 months after starting treatment and ≥14 days after stopping anticoagulation therapy. In the current study, we sought to show that normal PC and PS values determined during the acute phase of VTE are not false negatives. Methods 99 patients with acute idiopathic VTE who had normal PC and PS determination within the first 24 hours of presentation and who subsequently had their oral anticoagulation discontinued after six months of therapy. PC and PS determinations were repeated ≥6 months after starting treatment and ≥ 14 days after stopping warfarin. Proportions of patients who tested abnormal on the second test were calculated and 95% confidence intervals obtained using the Wilson's score method. Data from a previously published study on patients with abnormal initial tests was included for comparison. Results None of the 99 patients who had normal PC and PS initially had an abnormal result on repeated testing (0%; 95% CI 0 - 3.7%). Data from the previous study showed that, among patients who initially had abnormal results, 40% (95%CI 35.4-84.8%) were confirmed to have low PC and 63.6% (95%CI 16.8-68.7%) low PS on repeated testing. The difference between proportions was statistically significant (χ2 p-value < 0.001). Conclusion Our results suggest that PC and PS can be determined during the acute phase of VTE and whereas abnormal results need to be confirmed with repeat testing at a later date, a normal result effectively rules out deficiency with only one test.

Objective: To provide family physicians with an understanding of blood bank tests performed during pregnancy. The value of routine blood type and antibody tests, as well as the follow-up required when a patient develops a red blood cell antibody or experiences a fetal-maternal hemorrhage (FMH) will be reviewed., Sources of Information: The approach described is based on the authors' clinical expertise and peer-reviewed literature from 1967 to 2020., Main Message: An ABO and RhD group and antibody screen test is performed on every pregnant patient during the first trimester. Although antibodies to red blood cell antigens occur infrequently, some can lead to substantial adverse fetal or neonatal consequences including hemolytic disease of the fetus and newborn. Early identification and quantification of important antibodies ensures that at-risk mothers are referred to and followed by obstetricians experienced with high-risk care. Another valuable and related test is the FMH test. For RhD-negative women, these tests are performed at every delivery and following antepartum events that could contribute to FMH. This test determines the number of fetal red blood cells in the maternal circulation and is used to determine the dose of Rh immune globulin an RhD-negative mother requires to prevent alloimmunization to fetal RhD., Conclusion: An understanding of blood bank tests performed during pregnancy and their role and limitations is vital to optimal practice and aids clinicians in their decision making. When there is doubt or confusion regarding antenatal testing or immunoprophylaxis, consult the regional laboratory or transfusion medicine specialists for additional guidance., (Copyright© the College of Family Physicians of Canada.)

Background: Intravenous iron therapy is a treatment option for iron deficient patients who are intolerant to oral iron or where oral iron is ineffective, but with possible adverse effects. Currently, prospective studies comparing different intravenous iron formulations are needed to determine safety and efficacy of these agents., Methods: We conducted a prospective, double-blind, randomized controlled trial (RCT) to assess the feasibility of a trial comparing the safety of high molecular weight intravenous iron dextran, Infufer®, with intravenous iron sucrose, Venofer®, in non-hemodialysis adult outpatients. Primary outcome was the occurrence of immediate severe drug reactions., Results: We enrolled 143 patients in a one-year period. Overall, 45/143 (31.5 %) patients (20 iron dextran, 25 iron sucrose) developed 48 infusion reactions (14 immediate, 28 delayed, and 3 both). The risk of an immediate reaction was similar in both groups, 9/73 (12.3 %) iron dextran versus 8/70 (11.4 %) iron sucrose, RR = 0.93 (95 % CI; 0.38 to 2.27). The risk of a delayed reaction was significantly higher in the iron sucrose group 22/70 (31.4 %) versus the iron dextran group 9/73 (12.3 %), RR = 2.55 (95 % CI; 1.26 to 5.15; p = 0.0078)., Conclusion: In this limited feasibility study, no major differences in immediate reactions were seen, but a significantly higher number of delayed reactions were seen in the iron sucrose group. Further, under our assumptions and design a full RCT to evaluate the safety of different intravenous iron preparations is not feasible. Future studies should consider modifying the clinical outcomes, utilize multiple centers, and consider other emerging parenteral iron formulations. (ClinicalTrials.gov NCT005936197 January 3, 2008).

Background: Although prophylaxis is a standard of care for young children in developed countries, known to reduce the severity of hemophilic arthropathy, older adults with existing arthropathy have not traditionally used prophylaxis. Recent studies have shown that adults with hemophilia A are increasingly adopting prophylaxis but the characteristics of this treatment in older adults are not well understood. This multicenter observational study was conducted to describe how secondary/tertiary prophylaxis is being used in older adults (≥40 years of age) in comparison to younger adults with severe hemophilia A., Methods: Eligible adult (≥18 years of age) Canadian males with baseline FVIII:C ≤2% from the participating centres were observed over a 2 year period., Results: Of the 220 adult severe hemophilia patients enrolled, 70% (155/220) used prophylaxis during the observational period. Only 27% (60/220) are older adults with very few >60 years of age. A lower proportion of older adults use prophylaxis compared to younger adults (58% vs. 75%, p = 0.016), with most patients in both groups using continuous prophylaxis (92 and 94% respectively). When considering all treatment modalities together, younger subjects use more factor concentrate than older subjects (2437 u/kg/year vs. 1702 u/kg/year, p = 0.027); however, older subjects on prophylaxis use 3447 u/kg/year and had an ABR of 12 while those on demand use 560 u/kg/year and had an ABR of 13., Conclusion: A significant number of older adults use secondary/tertiary continuous prophylaxis in Canada, accounting for a significant fraction of factor concentrate utilization.

Prolymphocytic transformation of chronic lymphocytic leukemia is a rare but recognized entity. We present the case of a 76-year-old gentleman with a previous diagnosis of chronic lymphocytic leukemia who presented with fatigue, fever, and a white blood cell count of 500 000 with prolymphocytes on peripheral blood examination. Chlorambucil and dexamethasone were initiated. He developed progressive anemia during his admission with no clear cause on initial CT examination. Bilateral hip pain began several days later and he was unfortunately diagnosed with a large spontaneous retroperitoneal hemorrhage postmortem. This condition is rare and generally occurs in those receiving therapeutic anticoagulation or dialysis, with known bleeding disorders or vascular malformation, none of which were present in our patient. Pathology revealed marked leukemoid engorgement of the vessels of many organs with prolymphocytes. We discuss the potential etiologies and relationships between these critical diagnoses.

The recent completion of genome sequencing of 12 species of Drosophila has provided a powerful resource for hypothesis testing, as well as the development of technical tools. Here we take advantage of genome sequence data from two closely related species of Drosophila, Drosophila simulans and Drosophila sechellia, to quickly identify candidate molecular markers for genotyping based on expected insertion or deletion (indel) differences between species. Out of 64 candidate molecular markers selected along the second and third chromosome of Drosophila, 51 molecular markers were validated using PCR and gel electrophoresis. We found that the 20% error rate was due to sequencing errors in the genome data, although we cannot rule out possible indel polymorphisms. The approach has the advantage of being affordable and quick, as it only requires the use of bioinformatics tools for predictions and a PCR and agarose gel based assay for validation. Moreover, the approach could be easily extended to a wide variety of taxa with the only limitation being the availability of complete or partial genome sequence data.

Background: Protein C (PC) and protein S (PS) determination is part of the thrombophilia investigation in patients with idiopathic venous thromboembolism (VTE). Based on scarce evidence it is a common notion that PC and PS levels decrease during the acute phase of VTE, necessitating delay of testing and temporary transition from warfarin to low molecular weight heparin. We have previously demonstrated that an abnormal PC or PS result determined within 24 hours of VTE diagnosis and before the initiation of warfarin needs to be repeated for confirmation >/=3 months after starting treatment and >/=14 days after stopping anticoagulation therapy. In the current study, we sought to show that normal PC and PS values determined during the acute phase of VTE are not false negatives., Methods: 99 patients with acute idiopathic VTE who had normal PC and PS determination within the first 24 hours of presentation and who subsequently had their oral anticoagulation discontinued after six months of therapy. PC and PS determinations were repeated >/=6 months after starting treatment and >/= 14 days after stopping warfarin. Proportions of patients who tested abnormal on the second test were calculated and 95% confidence intervals obtained using the Wilson's score method. Data from a previously published study on patients with abnormal initial tests was included for comparison., Results: None of the 99 patients who had normal PC and PS initially had an abnormal result on repeated testing (0%; 95% CI 0 - 3.7%). Data from the previous study showed that, among patients who initially had abnormal results, 40% (95%CI 35.4-84.8%) were confirmed to have low PC and 63.6% (95%CI 16.8-68.7%) low PS on repeated testing. The difference between proportions was statistically significant (chi2 p-value < 0.001)., Conclusion: Our results suggest that PC and PS can be determined during the acute phase of VTE and whereas abnormal results need to be confirmed with repeat testing at a later date, a normal result effectively rules out deficiency with only one test.