Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms' tumor: a CIBMTR retrospective analysis.

Despite the marked improvement in the overall survival (OS) for patients diagnosed with Wilms' tumor (WT), the outcomes for those who experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and were reported to the Center for International Blood and Marrow Transplantation Research. The 5-year estimates for event-free survival (EFS) and OS were 36% (95% confidence interval (CI); 29-43%) and 45% (95 CI; 38-51%), respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. As attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus HDT followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. As disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy

Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors

BACKGROUND Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia. METHODS We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37). RESULTS The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, −3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse. CONCLUSIONS We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute–National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.

Robot Drawing on a Moving Paperboard

Robustness to uncertainties is crucial to collaborative robot control, particularly when performing tasks under unpredictable external influences. One important class of challenging problems is controlling the robot to perform a specific task on a target that undergoes random movements. To address this challenge, we consider the problem of using a robot manipulator to draw a given shape on a paperboard that can have unpredictable small movements. An electromagnetic sensor is used to monitor the pose of the paperboard. We design an MPC (Model Predictive Control) controller and compared it with a few different feedback control strategies for the robot to draw the required shape on the paperboard. Simulations and physical experiments using a Dobot demonstrate that using the electromagnetic sensor information as feedback combined with different control strategies can allow for accurate drawing. A video of our experiments is available at https://youtu.be/Wmj0GU5CYH4?si=cgnN9D3VRr0ZLRlK

Modelling the impacts of policy interventions for food systems transformation in Indonesia – Governance and policy support: Report.

The Government of Indonesia and FAO have recognized the need for thorough analysis and modelling of Indonesia’s food systems to support food systems transformation efforts in the country. This is needed to provide a better understanding of the governance context in food systems, including the political economy dynamics influencing performance, as well as to identify synergies and trade-offs across different policy goals and optimal policy mixes for achieving multiple policy objectives. In this regard, FAO facilitated a project to pilot an innovative approach to modelling for food systems transformation. This modelling approach was developed and implemented by a team of researchers from IFPRI, IIASA, IISD and Christian-Albrechts-University of Kiel. It makes use of three different economic models to generate insights that can assist Indonesian policymakers in developing technically sound and politically feasible policy interventions for food systems transformation. This report provides context for food systems transformation in Indonesia and describes the overall modelling approach before synthesizing the results of the individual modelling activities and distilling these into the overall findings of the modelling. It concludes with implications from these findings for policymaking for food systems transformation in Indonesia and some suggestions for next steps. The results of this modelling and the insights drawn from these results are expected to support efforts to translate Indonesia’s commitments on food systems transformation into concrete policy interventions and to inform medium- and long-term development planning by the Indonesian Government

Harnessing the oloid shape in magnetically driven robots to enable high-resolution ultrasound imaging

Magnetic fields enable remote manipulation of objects and are ideal for medical applications because they pass through human tissue harmlessly. This capability is promising for surgical robots, allowing navigation deeper into the human anatomy and accessing organs beyond the reach of current technologies. However, magnetic manipulation is typically limited to a maximum two–degrees-of-freedom orientation, restricting complex motions, especially those including rolling around the main axis of the magnetic robot. To address this challenge, we introduce a robot design inspired by embodied intelligence and the unique geometry of developable rollers, leveraging the oloid shape. The oloid, with its axial asymmetry and sinusoidal motion, facilitates rolling when precisely controlled by an external magnetic field. We present a versatile closed-loop control model to ensure precise magnetic manipulation of an oloid-shaped robot. This capability was validated in endoluminal applications through the integration of a 28-megahertz micro-ultrasound array to perform virtual biopsies, noninvasive real-time histological imaging. Extensive in vitro and in vivo tests using a porcine model showed the robot’s ability to execute sweeping motions, identify lesions, and generate detailed three-dimensional scans of gastrointestinal subsurface tissue. This research not only restores a critical movement capability to magnetic medical robots but also enables additional clinical applications deep within the human body

Micellar structure and transformations in sodium alkylbenzenesulfonate (NaLAS) aqueous solutions: effects of concentration, temperature, and salt

We investigate the shape, dimensions, and transformation pathways of micelles of linear sodium alkylbenzenesulfonate (NaLAS), a common anionic surfactant, in aqueous solution. Employing Small Angle Neutron Scattering (SANS) and surface tensiometry, we quantify the effects of surfactant concentration (0.6–15 wt%), temperature (5–40 °C) and added salt (≤0.35 M Na2SO4). Spherical micelles form at low NaLAS (≤2.6 wt%) concentration in water, and become elongated with increasing concentration and decreasing temperature. Addition of salt reduces the critical micelle concentration (CMC) and thus promotes the formation of micelles. At fixed NaLAS concentration, salt addition causes spherical micelles to grow into cylindrical micelles, and then multilamellar vesicles (MLVs), which we examine by SANS and cryo-TEM. Above a threshold salt concentration, the MLVs reach diameters of 100 s of nm to few μm, eventually causing precipitation. While the salt concentrations associated with the micelle-to-cylinder transformation increase only slightly with temperature, those required for the cylinder-to-MLV transformation exhibit a pronounced, linear temperature dependence, which we examine in detail. Our study establishes a solution structure map for this model anionic surfactant in water, quantifying the combined roles of concentration, temperature and salt, at practically relevant conditions

Alterations of hemostatic parameters in the early development of allogeneic hematopoietic stem cell transplantation-related complications

Thrombotic events are common and potentially fatal complications in patients receiving hematopoietic stem cell transplantation (HSCT). Early diagnosis is crucial but remains controversial. In this study, we investigated the early alterations of hemostatic parameters in allogeneic HSCT recipients and determined their potential diagnostic values in transplantation-related thrombotic complications and other post-HSCT events. Results from 107 patients with allogeneic HSCT showed higher levels of plasma plasminogen activator inhibitor-1 (PAI-1), fibrinogen, and tissue-plasminogen activator (t-PA) and a lower level of plasma protein C after transplantation. No change was found for prothrombin time, antithrombin III, d-dimer, and activated partial thromboplastin time following HSCT. Transplantation-related complications (TRCs) in HSCT patients were defined as thrombotic (n = 8), acute graft-versus-host disease (aGVHD, n = 45), and infectious (n = 38). All patients with TRCs, especially the patients with thrombotic complications, presented significant increases in the mean and maximum levels of PAI-1 during the observation period. Similarly, a high maximum t-PA level was found in the thrombotic group. In contrast, apparent lower levels of mean and minimum protein C were observed in the TRC patients, especially in the aGVHD group. Therefore, the hemostatic imbalance in the early phase of HSCT, reflecting prothrombotic state and endothelial injury due to the conditioning therapy or TRCs, might be useful in the differential diagnosis of the thrombotic complication from other TRCs

Bordetella pertussis Infection or Vaccination Substantially Protects Mice against B. bronchiseptica Infection

Although B. bronchiseptica efficiently infects a wide range of mammalian hosts and efficiently spreads among them, it is rarely observed in humans. In contrast to the many other hosts of B. bronchiseptica, humans are host to the apparently specialized pathogen B. pertussis, the great majority having immunity due to vaccination, infection or both. Here we explore whether immunity to B. pertussis protects against B. bronchiseptica infection. In a murine model, either infection or vaccination with B. pertussis induced antibodies that recognized antigens of B. bronchiseptica and protected the lower respiratory tract of mice against three phylogenetically disparate strains of B. bronchiseptica that efficiently infect naïve animals. Furthermore, vaccination with purified B. pertussis-derived pertactin, filamentous hemagglutinin or the human acellular vaccine, Adacel, conferred similar protection against B. bronchiseptica challenge. These data indicate that individual immunity to B. pertussis affects B. bronchiseptica infection, and suggest that the high levels of herd immunity against B. pertussis in humans could explain the lack of observed B. bronchiseptica transmission. This could also explain the apparent association of B. bronchiseptica infections with an immunocompromised state

Molecular Evolution of the Two-Component System BvgAS Involved in Virulence Regulation in Bordetella

The whooping cough agent Bordetella pertussis is closely related to Bordetella bronchiseptica, which is responsible for chronic respiratory infections in various mammals and is occasionally found in humans, and to Bordetella parapertussis, one lineage of which causes mild whooping cough in humans and the other ovine respiratory infections. All three species produce similar sets of virulence factors that are co-regulated by the two-component system BvgAS. We characterized the molecular diversity of BvgAS in Bordetella by sequencing the two genes from a large number of diverse isolates. The response regulator BvgA is virtually invariant, indicating strong functional constraints. In contrast, the multi-domain sensor kinase BvgS has evolved into two different types. The pertussis type is found in B. pertussis and in a lineage of essentially human-associated B. bronchiseptica, while the bronchiseptica type is associated with the majority of B. bronchiseptica and both ovine and human B. parapertussis. BvgS is monomorphic in B. pertussis, suggesting optimal adaptation or a recent population bottleneck. The degree of diversity of the bronchiseptica type BvgS is markedly different between domains, indicating distinct evolutionary pressures. Thus, absolute conservation of the putative solute-binding cavities of the two periplasmic Venus Fly Trap (VFT) domains suggests that common signals are perceived in all three species, while the external surfaces of these domains vary more extensively. Co-evolution of the surfaces of the two VFT domains in each type and domain swapping experiments indicate that signal transduction in the periplasmic region may be type-specific. The two distinct evolutionary solutions for BvgS confirm that B. pertussis has emerged from a specific B. bronchiseptica lineage. The invariant regions of BvgS point to essential parts for its molecular mechanism, while the variable regions may indicate adaptations to different lifestyles. The repertoire of BvgS sequences will pave the way for functional analyses of this prototypic system