25,917 research outputs found
Haploidentical Transplantation
No full textHaploidentical hemopoietic cell transplantation (haplo-SCT) is a therapeutic option in patients with acquired severe aplastic anemia (SAA); failure of one course of immune suppressive therapy (IST) with antithymocyte globulin (ATG) and the lack of an HLA-matched related or unrelated donor are accepted criteria for considering haplo-SCT treatment. Prevention of graft-versus-host disease (GvHD) in haplo-SCT is provided both by ex vivo T-cell depletion and by extensive drug GvHD prophylaxis after unmanipulated graft. Haploidentical transplant for IST-refractory SAA is a clinical option offered in centers with established experience in haplo-SCT and should be applied within clinical protocol aimed at maximally preventing graft rejection and GvHD
Single- and Multi-carrier Quadrature Amplitude Modulation: Principles and Applications for Personal Communications, WATM and Broadcasting: 2nd
No full textSingle- and Multi-carrier Quadrature Amplitude Modulation Principles and Applications for Personal Communications, WLANs and Broadcasting L. Hanzo Department of Electronics and Computer Science, University of Southampton, UK W. Webb Motorola, Arlington Heights, USA formerly at Multiple Access Communications Ltd, Southampton, UK T. Keller Ubinetics, Cambridge Technology Centre, Melbourn, UK formerly at Department of Electronics and Computer Science, University of Southampton, UK Motivated by the rapid evolution of wireless communication systems, this expanded second edition provides an overview of most major single- and multi-carrier Quadrature Amplitude Modulation (QAM) techniques commencing with simple QAM schemes for the uninitiated through to complex, rapidly-evolving areas, such as arrangements for wide-band mobile channels. Targeted at the more advanced reader, the multi-carrier modulation based second half of the book presents a research-orientated outlook using a variety of novel QAM-based arrangements. * Features six new chapters dealing with the complexities of multi-carrier modulation which has found applications ranging from Wireless Local Area Networks (WLAN) to Digital Video Broadcasting (DVB) * Provides a rudimentary introduction for readers requiring a background in the field of modulation and radio wave propagation * Discusses classic QAM transmission issues relevant to Gaussian channels * Examines QAM-based transmissions over mobile radio channels * Incorporates QAM-related orthogonal techniques, considers the spectral efficiency of QAM in cellular frequency re-use structures and presents a QAM-based speech communications system design study * Introduces Orthogonal Frequency Division Multiplexing (OFDM) over both Gaussian and wideband fading channels By providing an all-encompassing self-contained treatment of single- and multi- carrier QAM based communications, a wide range of readers including senior undergraduate and postgraduate students, practising engineers and researchers alike will all find the coverage of this book attractive
CPX-351 and allogeneic stem cell transplant for a therapy-related acute myeloid leukemia that developed after treatment of acute promyelocytic leukemia: a case report and review of the literature
No full textTherapy-related myeloid neoplasms (t-MNs), which develop after cytotoxic, radiation, or immunosuppressive therapy for an unrelated disease, account for 7%–8% of acute myeloid leukemia (AML). Worse outcomes and consequently shortened survival are associated with t-MNs as compared with de novo AML. Therapy-related MNs are being reported with increasing frequency in successfully treated acute promyelocytic leukemia (APL), in particular, before the introduction of all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO). Considering the high curability of APL, t-MNs represent one of the prognosis-limiting factors in this setting of leukemia. We report our experience with a patient who developed t-AML 15 years after treatment for APL. Treatment included three cycles of chemotherapy with CPX-351 (Vyxeos, Jazz Pharmaceuticals) followed, as in remission, by an allogeneic hematopoietic stem cell transplant. A review of available literature was also included
DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire
No full textThe majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire
The long-wavelength view of GG Tau A: rocks in the ring world
No full textWe present the first detection of GG Tau A at centimetre wavelengths, made with the Arcminute Microkelvin Imager Large Array at a frequency of 16 GHz (λ = 1.8 cm). The source is detected at >6 σrms with an integrated flux density of S16GHz = 249 ± 45 µJy. We use these new centimetre-wave data, in conjunction with additional measurements compiled from the literature, to investigate the long-wavelength tail of the dust emission from this unusual protoplanetary system. We use an MCMC-based method to determine maximum likelihood parameters for a simple parametric spectral model and consider the opacity and mass of the dust contributing to the microwave emission. We derive a dust mass of Md ~ 0.1 Msun, constrain the dimensions of the emitting region and find that the opacity index at λ > 7 mm is less than unity, implying a contribution to the dust population from grains exceeding ~4 cm in size. We suggest that this indicates coagulation within the GG Tau A system has proceeded to the point where dust grains have grown to the size of small rocks with dimensions of a few centimetres. Considering the relatively young age of the GG Tau association in combination with the low derived disc mass, we suggest that this system may provide a useful test case for rapid core accretion planet formation models
Model Based Building Chilled Water Loop Delta-T Fault Diagnosis
No full textImproving chilled water delta-T, which is the temperature difference of chilled water supply and return temperature, in campus buildings that are connected to a central distribution loop will not only improve the power consumption of the building through reduced tertiary (building) pumping power but the impact on the central distribution system and chiller efficiencies will be even greater. A degraded delta-T is almost inevitable and it can be expected to fall to about one-half to two-thirds of design at low loads (Taylor, 2002) due to various causes, such as air entering and leaving temperatures, chilled water supply temperature, type and effectiveness of flow control valves, tertiary connection configuration types and operation, coil cooling loads, air economizers, etc. However, in most variable-flow chilled water with 2-way control valve systems, the root cause of low delta-T is at coil side (Zhang, 2012), for example the geometric configuration of coil. This paper firstly discusses chilled water coil heat exchanger model results to help define methods for detecting opportunities for improved delta-T when analyzing campus building systems for performance optimization measures. Meanwhile, the author developed an effectiveness-NTU cooling coil models for a case study building containing chilled water coils with a range of design configurations to study cooling coil delta-T characteristics under various conditions in order to diagnose the low delta-T imposed on the chilled water distribution loop by the building's chilled water system under various loading conditions. The results show model-based building chilled water Loop delta-T fault diagnosis is an effective way to evaluate existing building chilled water loop delta-T performance and identify avoidable or resoluble causes for improving chilled water loop delta-T
Hundreds of variants clustered in genomic loci and biological pathways affect human height
No full textMost common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits(1), but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait(2,3). The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways
Aminosalicylates and other anti-inflammatory compounds for irritable bowel syndrome
No full textGrowing evidence suggests that gastrointestinal immune activation may affect intestinal function and sensory perception, which contribute to symptom generation in patients with irritable bowel syndrome (IBS). The identification of higher counts of immunocytes (e.g. T cells and mast cells), mucosal and systemic immune activation, and increased mucosal permeability in patients with IBS has stimulated interest in the potential development of therapeutic approaches aimed at targeting the immune system and inflammation. Although an initial attempt in a pilot trial with steroids in patients with post-infective IBS failed, there has been renewed interest for mast cell stabilizers and the therapeutic potential of aminosalicylates. A recent randomized, double-blind, placebo-controlled pilot trial assessed the effect of mesalazine on intestinal immune cells and symptom perception in patients with IBS. Mesalazine markedly reduced mucosal immune cells and mast cells in particular, compared to placebo. In addition, mesalazine significantly improved general well-being. Mesalazine may enhance epithelial barrier function, and preliminary data suggest that it may alter faecal bacterial profiles in IBS patients. Nevertheless, the exact mechanism through which this drug affects immune activation in the intestine of patients with IBS remains unknown. There is a need for further studies to prove the efficacy of mesalazine for IBS. Further studies aimed at assessing the role of aminosalicylates and other approaches with potential anti-inflammatory activity, including probiotics, non-absorbable antibiotics, histamine receptor antagonists and protease inhibitors on IBS symptoms or pathophysiology are now warranted.Growing evidence suggests that gastrointestinal immune activation may affect intestinal function and sensory perception, which contribute to symptom generation in patients with irritable bowel syndrome (IBS). The identification of higher counts of immunocytes (e.g. T cells and mast cells), mucosal and systemic immune activation, and increased mucosal permeability in patients with IBS has stimulated interest in the potential development of therapeutic approaches aimed at targeting the immune system and inflammation. Although an initial attempt in a pilot trial with steroids in patients with post-infective IBS failed, there has been renewed interest for mast cell stabilizers and the therapeutic potential of aminosalicylates. A recent randomized, double-blind, placebo-controlled pilot trial assessed the effect of mesalazine on intestinal immune cells and symptom perception in patients with IBS. Mesalazine markedly reduced mucosal immune cells and mast cells in particular, compared to plac..
Corrigendum to ‘Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI)’: (ESMO Open (2021) 6(2), (S2059702921000089), (10.1016/j.esmoop.2021.100054))
No full textThe authors regret that at the time the article was published the following two authors were missing from the author list: R. Caputo and D. Cianniello. Both authors affiliation is the Breast Oncology Department, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy. The updated author list is as follows: C. De Angelis, D. Bruzzese, A. Bernardo, E. Baldini, L. Leo, A. Fabi, T. Gamucci, P. De Placido, F. Poggio, S. Russo, V. Forestieri, R. Lauria, I. De Santo, R. Caputo, D. Cianniello, A. Michelotti, L. Del Mastro, M. De Laurentiis, M. Giuliano, S. De Placido, G. Arpino. The authors would like to apologise for any inconvenience caused
Auswirkungen der Einbringung von Buche (Fagus sylvatica L.) auf die Artendiversität und Naturnähe von Nadelholzbeständen in Niedersachsen
No full textThe promotion and extension of continuous cover mixed stands with a simultaneous reduction of conifer-monocultures play a major role in current silvicultural practices in Central Europe. It is assumed that the admixture of the natural dominant beech (Fagus sylvatica) in pure non site-specific conifer stands automatically indicates better conditions in terms of nature conservation and forest management. To test this hypothesis three different conifer-beech-comparisons of pure and mixed stands in Lower Saxony are studied, analyzing plant species diversity and naturalness of understory vegetation as one important indicator for the ecological status of forests. Each comparison includes pure coniferous stands (Picea abies, Pinus sylvestris, Pseudotsuga menziesii), mixed coniferous-beech-stands, and pure beech stands on similar acidic mineral soils where the potential natural vegetation will be an oligotrophic beech forest (L u z u l o - Fa g e t um). The age of stands varies between 50 and 150 years. To specify tree species influence on site conditions and vegetation, the study also includes light climate and soil data of the stands. It is observed that, with regard to all comparisons, the admixture of beech reduces plant species diversity but increases naturalness of the stands. The intensity of beech admixture effects differs. While in Scots pine stands the impact of admixed beech is very noticeable, with the mixed stands being nearly identical with pure beech stands, the species change in Douglas-fir and Norway spruce stands proceeds more slowly. Assuming that the status in nature conservation and forest management is improving with increasing plant species diversity and increasing naturalness, the results of this study show a contrary development on a stand scale, as the potential natural vegetation of the L u z u l o - F a g e t u m is in its self very species poor on vascular plants.Die Förderung und Ausweitung von Mischwäldern bei gleichzeitiger Reduktion reiner Nadelholz-Bestände spielt aktuell eine große Rolle im mitteleuropäischen Waldbau. Gemeinhin wird angenommen, dass die Beimischung der standortsgemäßen Buche (Fagus sylvatica) in standortsfremden Nadelholz Monokulturen die Bedingungen im Sinne des Naturschutzes und der Forstwirtschaft verbessert. Diese Hypothese wird auf der Grundlage von drei unterschiedlichen Nadelholz- Buchen-Versuchsreihen geprüft. Im Mittelpunkt steht dabei die Bodenvegetation als wichtiger und sensitiver Indikator für den ökologischen Zustand von Wäldern. Jede Versuchsreihe umfasst reine Nadelholz-Bestände (Picea abies, Pinus sylvestris, Pseudotsuga menziesii), Nadelholz-Buchen- Mischbestände und reine Buchen-Bestände auf sauren Mineralböden, auf denen von Natur aus nährstoffarme Buchenwälder (L u z u l o - Fa g e t um) vorherrschen würden. Das Alter der Bestände variiert zwischen 50 und 150 Jahren. Schwerpunkte der Analyse sind die Artenvielfalt und Naturnähe der Bodenvegetation. Um den Einfluss der Baumarten auf den Standort und die Vegetation zu bewerten, werden die Licht- und Bodenverhältnisse der Bestände charakterisiert. Es zeigt sich, dass mit der Beimischung der Buche in allen Versuchsreihen die Pflanzenartenvielfalt abnimmt und die Naturnähe zunimmt. Unterschiedlich ist dabei die Intensität der Veränderungen. Zwischen den Kiefern-Buchen-Mischbeständen und den Kiefern-Reinbeständen bestehen sehr deutliche Unterschiede im Aufbau der Bodenvegetation, so dass die Mischbestände den Buchen-Reinbeständen bereits sehr ähnlich sind. In den Douglasien- und Fichten-Versuchsreihen vollzieht sich der Artenwechsel vergleichsweise unauffällig und kontinuierlich. Wenn man davon ausgeht, dass der naturschutzfachliche und waldbauliche Status sich sowohl mit zunehmender Phytodiversität als auch bei zunehmender Naturnähe verbessert, so zeigen diese Ergebnisse auf Bestandesebene eine gegenläufige Entwicklung, da das in der Region der potenziell natürlichen Vegetation entsprechende L u z u l o - Fa g e tum von Natur aus sehr artenarm an Gefäßpflanzen ist
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