Sunset haematology: improving the end-of-life journey for patients and caregivers, in patients with haematologic malignancies

BACKGROUND AND AIM Haematologic Malignancies (HM) are diverse diseases with differing illness trajectories and therapeutic pathways. Unfortunately HM patients may rapidly and unexpectedly clinically deteriorate, resulting in suboptimal engagement of palliative and end-of-life (EOL) care.  Compared to patients with solid tumours, HM patients have many different factors affecting their end-of-life (EOL) journey. Uniquely, a subset of HM patients with bone marrow failure (BMF) can be supported for significant, but highly variable, periods of time with red blood cell transfusions (RBCT), platelet transfusions (PT) and prophylactic antibiotics.  Availability of chronic RBCTs and PTs make HM patients with BMF similar to elderly and poor prognosis patients with end stage kidney disease (ESKD). Multidisciplinary Palliative Supportive Care programs have been shown to be effective for these EKSD patients and may serve as supportive care models for EOL journey in HM patients. This project is  a pilot study aiming to provide a template for management of EOL for patients with HM with BMF, and their care-givers. METHODS Three components are being developed: 1) Survey of patient opinions around treatment decision-making. 2) Analyses of the impact of patient, disease and treatment factors on the probability of survival from start of PT, to inform patients. 3) Collaborative involvement between Haematology and Palliative Care staff involved in the local ESKD program, to develop a template for earlier EOL pathway planning in HM patients. CONCLUSION Progress of work to date will be presented including preliminary findings and next steps

MPSoCs for Reconfigurable Modular Spacecraft

Modular, reconfigurable spacecraft offer a new approach to extending mission capability and maximising the lifetime of a spacecraft. Future uses of space robotics such as in-orbit construction and servicing allow faulty or obsolete parts of a modular spacecraft to be replaced by servicer spacecraft that dock with their targets and perform upgrades and maintenance. Such manoeuvres will require a high degree of autonomy from both platforms and thus will need to leverage high-performance onboard computing for both the robotic control and manipulation of service spacecraft but also for managing Thales Alenia Space in the UK (TAS UK) and The University of York (UoY) are involved in projects towards this goal and are collaborating to research autonomous network reconfiguration and fault tolerance of the onboard network based on existing space technology (SpaceWire, SpaceFibre). Both organisations have identified FPGA based MPSoCs as a solution for providing the high-performance computing that autonomous robotic systems require, using the FPGA fabric for mission-phase related hardware accelerators (e.g. vision soft co- processors) that can be swapped as the construction or maintenance task demands. In this presentation we will describe the modular spacecraft avionics unit that TAS UK is developing for the H2020 MOSAR project. This is based on the Xilinx Ultrascale+ MPSoC and uses the “big-little” architecture to provide a split between the spacecraft module’s mission functionality (executing on the “big” quad-core A53) and the support functions to provide: the communication network, module-to-module docking management and the module power management functions of the spacecraft (implemented on the “little” dual-core R5 cores). Details on our development of an AXI4 compatible SpaceWire and RMAP IP core will also be included. RMAP forms an important part of the MOSAR fault management strategy and this core allows processor-transparent RMAP access to the full MPSoC address range, with automatic DMA descriptors for all other SpaceWire traffic. The AXI4 interface simply allows it to be dropped into any Ultrascale+, Zynq 7000 and NG-ultra based design and several configuration options allow options such as SpW front end type (oversampling /clock recovery) and output data path width (32-bit/16bit) to be selected. We will also present details of research by the University of York on using RMAP in a MPSoC environment. Access to the full address space of a MPSoC via RMAP brings security and fault management concerns to complex SoCs and hardware security based approaches (e.g. ARM’s TrustZone) could be used in future MP- SoC architectures to protect against damage by either corrupt RMAP packets, damage from failure modes of RMAP initiators or malicious/compromised spacecraft modules. To tackle autonomy challenges UoY is cur- rently developing a reasoner based, reconfigurable modular robotic platform that can cope with uncertain environments that arise in space applications using FPGA based MPSoC and soft-processor technologies. MOSAR has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant agreement No. 821996. Part of this work is funded by EPSRC and Innovate UK under grant KTP12066

Global Research Alliance N2O chamber methodology guidelines: considerations for automated flux measurement

Nitrous oxide (N2O) emissions are highly episodic in response to nitrogen additions and changes in soil moisture. Automated gas sampling provides the necessary high temporal frequency to capture these emission events in real time, ensuring the development of accurate N2O inventories and effective mitigation strategies to reduce global warming. This paper outlines the design and operational considerations of automated chamber systems including chamber design and deployment, frequency of gas sampling, and options in terms of the analysis of gas samples. The basic hardware and software requirements for automated chambers are described, including the major challenges and obstacles in their implementation and operation in a wide range of environments. Detailed descriptions are provided of automated systems that have been deployed to assess the impacts of agronomy on the emissions of N2O and other significant greenhouse gases. This information will assist researchers across the world in the successful deployment and operation of automated N2O chamber systems

Comparing Outcomes with Bone Marrow or Peripheral Blood Stem Cells as Graft Source for Matched Sibling Transplants in Severe Aplastic Anemia across Different Economic Regions

Bone marrow (BM) is the preferred graft source for hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) compared to mobilized peripheral blood stem cells (PBSC). We hypothesized that this recommendation may not apply to those regions where patients present later in their disease course, with heavier transfusion load and with higher graft failure rates. Patients with SAA who received HSCT from an HLA-matched sibling donor from 1995 to 2009 and reported to the Center for International Blood and Marrow Transplant Research or the Japan Society for Hematopoietic Cell Transplantation were analyzed. The study population was categorized by gross national income per capita (GNI) and region/countries into four groups. Groups analyzed were high income countries (HIC), which were further divided into US-Canada (N=486) and other HIC (N=1264), upper middle-income (UMIC) (N=482), and combined lower middle, low income countries (LM-LIC) (N=142). In multivariate analysis, overall survival (OS) was highest with BM as graft source in HIC compared to PBSC in all countries or BM in UMIC or LM-LIC (p<0.001). There was no significant difference in OS between BM and PBSC in UMIC (p=0.32) or LM-LIC (p=0.23). In LM-LIC the 28-day neutrophil engraftment was higher with PBSC compared to BM (97% vs. 77%, p<0.001). Chronic GVHD was significantly higher with PBSC in all groups. Whereas BM should definitely be the preferred graft source for HLA-matched sibling HSCT in SAA, PBSC may be an acceptable alternative in countries with limited resources when treating patients at high risk of graft failure and infective complications

Idarubicin dose escalation during consolidation therapy for adult acute myeloid leukemia

Purpose Higher doses of the anthracycline daunorubicin during induction therapy for acute myeloid leukemia (AML) have been shown to improve remission rates and survival. We hypothesized that improvements in outcomes in adult AML may be further achieved by increased anthracycline dose during consolidation therapy. Patients and Methods Patients with AML in complete remission after induction therapy were randomly assigned to receive two cycles of consolidation therapy with cytarabine 100 mg/m daily for 5 days, etoposide 75 mg/m daily for 5 days, and idarubicin 9 mg/m daily for either 2 or 3 days (standard and intensive arms, respectively). The primary end point was leukemia-free survival (LFS). Results Two hundred ninety-three patients 16 to 60 years of age, excluding those with core binding factor AML and acute promyelocytic leukemia, were randomly assigned to treatment groups (146 to the standard arm and 147 to the intensive arm). Both groups were balanced for age, karyotypic risk, and FLT3–internal tandem duplication and NPM1 gene mutations. One hundred twenty patients in the standard arm (82%) and 95 patients in the intensive arm (65%) completed planned consolidation (P, .001). Durations of severe neutropenia and thrombocytopenia were prolonged in the intensive arm, but there were no differences in serious nonhematological toxicities. With a median follow-up of 5.3 years (range, 0.6 to 9.9 years), there was a statistically significant improvement in LFS in the intensive arm compared with the standard arm (3-year LFS, 47% [95% CI, 40% to 56%] v 35% [95% CI, 28% to 44%]; P = .045). At 5 years, the overall survival rate was 57% in the intensive arm and 47% in the standard arm (P = .092). There was no evidence of selective benefit of intensive consolidation within the cytogenetic or FLT3–internal tandem duplication and NPM1 gene mutation subgroups. Conclusion An increased cumulative dose of idarubicin during consolidation therapy for adult AML resulted in improved LFS, without increased nonhematologic toxicity