Scalable and Energy-Efficient Millimeter Massive MIMO Architectures: Reflect-Array and Transmit-Array Antennas

Hybrid analog-digital architectures are considered as promising candidates for implementing millimeter wave (mmWave) massive multiple-input multiple-output (MIMO) systems since they enable a considerable reduction of the required number of costly radio frequency (RF) chains by moving some of the signal processing operations into the analog domain. However, the analog feed network, comprising RF dividers, combiners, phase shifters, and line connections, of hybrid MIMO architectures is not scalable due to its prohibitively high power consumption for large numbers of transmit antennas. Motivated by this limitation, in this paper, we study novel massive MIMO architectures, namely reflect-array (RA) and transmit-array (TA) antennas. We show that the precoders for RA and TA antennas have to meet different constraints compared to those for conventional MIMO architectures. Taking these constraints into account and exploiting the sparsity of mmWave channels, we design an efficient precoder for RA and TA antennas based on the orthogonal matching pursuit algorithm. Furthermore, in order to fairly compare the performance of RA and TA antennas with conventional fully-digital and hybrid MIMO architectures, we develop a unified power consumption model. Our simulation results show that unlike conventional MIMO architectures, RA and TA antennas are highly energy efficient and fully scalable in terms of the number of transmit antennas.Comment: submitted to IEEE ICC 201

Intelligent Surface-Aided Transmitter Architectures for Millimeter Wave Ultra Massive MIMO Systems

In this paper, we study two novel massive multiple-input multiple-output (MIMO) transmitter architectures for millimeter wave (mmWave) communications which comprise few active antennas, each equipped with a dedicated radio frequency (RF) chain, that illuminate a nearby large intelligent reflecting/transmitting surface (IRS/ITS). The IRS (ITS) consists of a large number of low-cost and energy-efficient passive antenna elements which are able to reflect (transmit) a phase-shifted version of the incident electromagnetic field. Similar to lens array (LA) antennas, IRS/ITS-aided antenna architectures are energy efficient due to the almost lossless over-the-air connection between the active antennas and the intelligent surface. However, unlike for LA antennas, for which the number of active antennas has to linearly grow with the number of passive elements (i.e., the lens aperture) due to the non-reconfigurablility (i.e., non-intelligence) of the lens, for IRS/ITS-aided antennas, the reconfigurablility of the IRS/ITS facilitates scaling up the number of radiating passive elements without increasing the number of costly and bulky active antennas. We show that the constraints that the precoders for IRS/ITS-aided antennas have to meet differ from those of conventional MIMO architectures. Taking these constraints into account and exploiting the sparsity of mmWave channels, we design two efficient precoders; one based on maximizing the mutual information and one based on approximating the optimal unconstrained fully digital (FD) precoder via the orthogonal matching pursuit algorithm. Furthermore, we develop a power consumption model for IRS/ITS-aided antennas that takes into account the impacts of the IRS/ITS imperfections, namely the spillover loss, taper loss, aperture loss, and phase shifter loss.Comment: Journal version of arXiv:1811.0294

Haploidentical transplant with posttransplant cyclophosphamide vs matched related and unrelated donor transplant in acute myeloid leukemia and myelodysplastic neoplasm

Hematopoietic cell transplantation from haploidentical donors (haploHCT) has facilitated treatment of AML and MDS by increasing donor availability and became more feasible since the introduction of post-transplant cyclophosphamide (ptCY). In our single-center retrospective analysis including 213 patients with AML or MDS, we compare the outcome of haploHCT (n = 40) with ptCY with HCT from HLA-identical MRD (n = 105) and MUD (n = 68). At 2 years after transplantation, overall survival (OS) after haploHCT was not significantly different (0.59; 95% confidence interval 0.44-0.79) compared to MRD (0.77; 0.67-0.88) and MUD transplantation (0.72; 0.64-0.82, p = 0.51). While progression-free survival (PFS) was also not significantly different (haploHCT: 0.60; 0.46-0.78, MRD: 0.55; 0.44-0.69, MUD: 0.64; 0.55-0.74, p = 0.64), non-relapse mortality (NRM) was significantly higher after haploHCT (0.18; 0.08-0.33) vs. MRD (0.029; 0.005-0.09) and MUD (0.06; 0.02-0.12, p < 0.05). Higher NRM was mainly caused by a higher rate of fatal infections, while deaths related to GvHD or other non-relapse reasons were rare in all groups. As most fatal infections occurred early and were bacterial related, one potential risk factor among many was identified in the significantly longer time to neutrophil engraftment after haploHCT with a median of 16 days (interquartile range; 14.8-20.0) vs. 12 days (10.0-13.0) for MRD and 11 days (10.0-13.0) for MUD (p = 0.01)

Introducing innovative cellular therapies into the clinic: a 2-year retrospective experience of a chimeric antigen receptor T-cell programme at a single centre in Switzerland

AIM OF THE STUDY Chimeric antigen receptor T (CAR-T) cells are a powerful form of immune-cell therapy for patients with relapsed/refractory B-cell lymphoma and acute B lymphoblastic leukaemia. CAR-T cells have been commercially available in Switzerland since 2018. Because of the complexity and costs of this treatment it is critical to review patient outcomes in real-world settings, to examine whether the promising results from pivotal trials can be reproduced and to identify clinical parameters that determine their efficacy. METHODS Here we present results of a retrospective study analysing outcomes of patients treated with CAR-T cells in a single academic centre in Switzerland during the first two years after commercial approval (BASEC-No. 2020-02271). Cytokine release syndrome (CRS), immune-cell associated neurotoxicity syndrome (ICANS), responses to treatment, ancillary laboratory studies and administrative specifics of CAR-T treatment were examined and are discussed. RESULTS From October 2018 to August 2020 CAR-T cell therapy was evaluated in 34 patients, mostly with relapsed/refractory aggressive B-cell lymphoma (87% had refractory disease). Thirty-one patients underwent leukapheresis. Three of 31 patients (9.6%) died of rapid disease progression before the CAR-T cell product was delivered, two patients were enrolled into a clinical trial, three patients were not given CAR-T cells for other reasons. Ultimately, 23 patients were infused with a commercial CAR-T cell product and included in this analysis. Fourteen (61%) patients received bridging therapy while waiting for a median of 41 days (range 31-62) for delivery of the CAR-T cell product. Toxicity and severe side effects were rare (CRS >3 in 13%, ICANS > grade 3 in 10% of patients), manageable and resolved completely thereafter. The best overall response rate was 65%, with complete responses in 38% of lymphoma patients. At 12 months postinfusion, 61% of patients were alive and 35% progression free. With a median follow-up of 14 months, 13/23 (56%) patients were alive at the time of writing. CONCLUSION CAR-T cell therapy proved to be safe and manageable under adequate hospital conditions. Outcomes resemble results from pivotal trials. The majority of patients was heavily pretreated and refractory at the time of CAR-T cell infusion. Patient selection, time point of leukapheresis, bridging strategies and timing of CAR-T cell infusion may be critical to further improve outcomes

Resource utilization for chimeric antigen receptor T cell therapy versus autologous hematopoietic cell transplantation in patients with B cell lymphoma

CD19-directed chimeric antigen receptor T cells (CAR-T) have emerged as a highly efficacious treatment for patients with relapsed/refractory (r/r) B cell lymphoma (BCL). The value of CAR-T for these patients is indisputable, but one-off production costs are high, and little is known about the ancillary resource consumption associated with CAR-T treatment. Here, we compared the resource use and costs of CAR-T treatment with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) for patients with r/r BCL. Standard operating procedures were used to develop a process model in ClipMedPPM, which comprises all activities and processes to sustain or generate treatment components that together constitute a treatment path. The software allows a graphic representation and the use of standardized linguistic elements for comparison of different treatment paths. Detailed processes involved in CAR-T treatments (n = 1041 processes) and in ASCT (n = 1535) were analyzed for time consumption of treatment phases and personnel. Process costs were calculated using financial controlling data. CAR-T treatment required ~ 30% less staff time than ASCT (primarily nursing staff) due to fewer chemotherapy cycles, less outpatient visits, and shorter hospital stays. For CAR-T, production costs were ~ 8 × higher, but overall treatment time was shorter compared with ASCT (30 vs 48 days), and direct labor and overhead costs were 40% and 10% lower, respectively. Excluding high product costs, CAR-T uses fewer hospital resources than ASCT for r/r BCL. Fewer hospital days for CAR-T compared to ASCT treatment and the conservation of hospital resources are beneficial to patients and the healthcare system. Keywords: Aggressive B cell lymphoma; Autologous stem cell transplantation (ASCT); Chimeric antigen receptor T cells (CAR-T); Comparative cost analysis; Health care resource consumptio

Fulminant Cardiotoxicity in a Patient With Cardiac Lymphoma Treated With CAR-T Cells

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Molecular and phylogenetic characterization of the sieve element occlusion gene family in Fabaceae and non-Fabaceae plants

<p>Abstract</p> <p>Background</p> <p>The phloem of dicotyledonous plants contains specialized P-proteins (phloem proteins) that accumulate during sieve element differentiation and remain parietally associated with the cisternae of the endoplasmic reticulum in mature sieve elements. Wounding causes P-protein filaments to accumulate at the sieve plates and block the translocation of photosynthate. Specialized, spindle-shaped P-proteins known as forisomes that undergo reversible calcium-dependent conformational changes have evolved exclusively in the <it>Fabaceae</it>. Recently, the molecular characterization of three genes encoding forisome components in the model legume <it>Medicago truncatula </it>(<it>MtSEO1</it>, <it>MtSEO2 </it>and <it>MtSEO3</it>; SEO = sieve element occlusion) was reported, but little is known about the molecular characteristics of P-proteins in non-<it>Fabaceae</it>.</p> <p>Results</p> <p>We performed a comprehensive genome-wide comparative analysis by screening the <it>M. truncatula</it>, <it>Glycine max</it>, <it>Arabidopsis thaliana</it>, <it>Vitis vinifera </it>and <it>Solanum phureja </it>genomes, and a <it>Malus domestica </it>EST library for homologs of <it>MtSEO1</it>, <it>MtSEO2 </it>and <it>MtSEO3 </it>and identified numerous novel <it>SEO </it>genes in <it>Fabaceae </it>and even non-<it>Fabaceae </it>plants, which do not possess forisomes. Even in <it>Fabaceae </it>some <it>SEO </it>genes appear to not encode forisome components. All <it>SEO </it>genes have a similar exon-intron structure and are expressed predominantly in the phloem. Phylogenetic analysis revealed the presence of several subgroups with <it>Fabaceae</it>-specific subgroups containing all of the known as well as newly identified forisome component proteins. We constructed Hidden Markov Models that identified three conserved protein domains, which characterize SEO proteins when present in combination. In addition, one common and three subgroup specific protein motifs were found in the amino acid sequences of SEO proteins. <it>SEO </it>genes are organized in genomic clusters and the conserved synteny allowed us to identify several <it>M. truncatula </it>vs <it>G. max </it>orthologs as well as paralogs within the <it>G. max </it>genome.</p> <p>Conclusions</p> <p>The unexpected occurrence of forisome-like genes in non-<it>Fabaceae </it>plants may indicate that these proteins encode species-specific P-proteins, which is backed up by the phloem-specific expression profiles. The conservation of gene structure, the presence of specific motifs and domains and the genomic synteny argue for a common phylogenetic origin of forisomes and other P-proteins.</p