Thiotepa-busulfan-fludarabine Compared to Treosulfan-based Conditioning for Haploidentical Transplant With Posttransplant Cyclophosphamide in Patients With Acute Myeloid Leukemia in Remission: A Study From the Acute Leukemia Working Party of the EBMT

We conducted a registry analysis including adult acute myeloid leukemia (AML) patients in remission who had received thiotepa, busulfan, and fludarabine (TBF) or treosulfan-based (Treo) conditioning for haplo-hematopoietic stem cell transplant (HSCT) with posttransplant cyclophosphamide (PTCy) between 2010 and 2020. A total of 1123 patients met the inclusion criteria (968 received TBF and 155 received Treo). A 1:1 matched-pair analysis was performed on 142 TBF and 142 Treo patients. In the Treo group, 68% of patients received treosulfan at a dose ≥36 g/m2 and 54% of patients received a second alkylator (thiotepa or melphalan). We observed a trend toward increased incidence of grade II-IV acute (a) graft-versus-host disease (GVHD) at 180 days in the TBF group compared with Treo (29% versus 20%; P = 0.08), while incidence of grade III-IV aGVHD was not statistically different. Similarly, the incidence of chronic (c) GVHD was not statistically different in the 2 groups. Incidence of nonrelapse mortality at 2 years was 19% in TBF and 14% in Treo (P = 0.4). Relapse incidence at 2 years was not statistically different in the 2 groups (16% and 18% in TBF and Treo, respectively; P = 0.9). Leukemia-free survival, overall survival, and GVHD-free, relapse-free survival was 65% versus 68% (P = 0.6), 73% versus 76% (P = 0.5), and 54% versus 53% (P = 0.8) in TBF versus Treo, respectively. In conclusion, we did not find a significant difference between the 2 conditioning in the present study; Treo and TBF represent 2 valid alternative regimens for haplo-HSCT with PTCy for AML in remission

Raising The Level Of Abstraction In Online Education: The Context

A commonly accepted definition of online learning is that students have access to learning experiences in: time, place, pace, learning style, content, assessment, and pathways (Chen, 2003). Although this is true, there is a considerable concern about the level of abstraction involved in online education. Critics of flexible learning call it just another fad (Zemsky & Massy, 2004). These criticisms are founded in claims that online learning failed to launch a pedagogical revolution or attract students in masses. Further, some argue that it is a training and not educational tool.  With all the buzz of successes and failures, flexible learning will continue to have an increasingly important role in higher education. Given the many fallacies about online learning, this paper argues that flexibility and transferability are prevailing traits in this explosion of knowledge. There is, simultaneously, a growing concern that online or flexible education has not raised learners’ level of abstraction. This paper concludes with a call for further investigation into flexibility/transferability and the effectiveness of institutions to align faculty development models and infrastructure with the new science of learning as well as to equip faculty with techniques to enhance level of abstraction

Experimental and calculated circular dichroism spectra of monoaza[5]helicenes

Circular dichroism (CD) spectra have been measured in the range of 400–200 nm on CH3OH solutions of both enantiomers for the almost complete series of monoaza[5]helicenes, namely the molecules where the hetero N atom occupies positions 1, 3, 4, 5, 6, and 7, respectively (the 2 isomer is missing due to difficulties in the synthesis). CD spectra recorded at controlled room temperature allow one to define precise racemization rates, that are nicely interpreted on the basis of DFT molecular orbital calculations. Time-dependent DFT methods provide us with calculated CD and UV spectra, that are compared with the corresponding experimental data. We discuss the role of the N atom in determining the height of the racemization barrier and in shaping the appearance of the CD spectra

Intraguild predation is increased in areas of low prey diversity in a generalist predator community

1. Niche differentiation and intraguild predation (IGP) can allow ecologically similar species to coexist, although it is unclear which coexistence mechanism predominates in consumer communities. Until now, a limited ability to quantify diets from metabarcoding data has precluded the use of sequencing data to determine the relative importance of these mechanisms. 2. Here, we pair a recent metabarcoding quantification approach with stable isotope analysis to examine diet composition in a wolf spider community. 3. We compare the prevalence of resource partitioning and IGP in these spiders and test whether factors that influence foraging performance, including individual identity, morphology, prey community and environmental conditions, can explain variation in diet composition and IGP. 4. Extensive IGP is likely the primary coexistence mechanism in this community, and other factors to which foraging variation is often attributed do not explain diet composition and IGP here. Rather, IGP increases as prey diversity decreases. 5. Foragers are driven to IGP where resource niches are limited. We highlight the need to examine how drivers of predator–prey interaction strengths translate into foraging in natural systems

Exploring noise effects in chaotic optical networks

We report the experimental evidence coherence and stochastic resonance in a dynamics of fast chaotic spiking of a semiconductor laser with optical feedback using an external nonwhite noise in the pumping current. We characterize both coherence and stochastic resonance in the time and frequency domain. We show that the regularity of the chaotic pulses in the intensity of laser diod increases when adding noise and it is optimal for some intermediate value of the noise intensity. We find that the power spectrum of the signal develops a peak at a finite frequency at intermediate values of the noise. The results show that noise may help in extracting the periodic signal without synchronization in chaotic communication. Then we reported the effect of external noise numerically on a single system by using bifurcation diagram. Finally, we considered Chaos synchronization in a network of 28 distinct chaotic systems with independent initial conditions when a normal Gaussian noise is added. The transition between non-synchronization to synchronization states using a suitable spatio-temporal representation has been reported. The role of coherence has also been considered. Keywords: Coherence resonance, Stochastic resonance, Control, Nois

Recursos didácticos y contextos usados por futuros profesores de matemáticas

Este documento informa sobre los recursos didácticos y contextos utilizados por futuros profesores de matemáticas durante el período de prácticas estipulado en su formación inicial. Se propone una definición operativa de recurso y de contexto, con la cual se identifican los recursos y los contextos que usan cuatro futuros profesores durante su práctica docente. La investigación es cualitativa y se usa un enfoque fenomenológico-hermenéutico para identificar e interpretar la actividad docente de los estudiantes en tanto que identifican, adecuan y usan recursos. Durante la investigación se registraron en el diario de campo los diferentes recursos que apoyan la enseñanza y se recopilan actividades que los futuros profesores presentan a los estudiantes. Se evidencia que los futuros profesores recurren a diferentes recursos y contextos de aplicación en la enseñanza de los conceptos y procedimientos matemáticos

Novel JAK inhibitors to reduce graft-versus-host disease after allogeneic hematopoietic cell transplantation in a preclinical mouse model

Allogeneic hematopoietic cell transplantation (allo-HCT) is a highly effective, well-established treatment for patients with various hematologic malignancies and non-malignant diseases. The therapeutic benefits of allo-HCT are mediated by alloreactive T cells in donor grafts. However, there is a significant risk of graft-versus-host disease (GvHD), in which the donor T cells recognize recipient cells as foreign and attack healthy organs in addition to malignancies. We previously demonstrated that targeting JAK1/JAK2, mediators of interferon-gamma receptor (IFNGR) and IL-6 receptor signaling, in donor T cells using baricitinib and ruxolitinib results in a significant reduction in GvHD after allo-HCT. Furthermore, we showed that balanced inhibition of JAK1/JAK2 while sparing JAK3 is important for the optimal prevention of GvHD. Thus, we have generated novel JAK1/JAK2 inhibitors, termed WU derivatives, by modifying baricitinib. Our results show that WU derivatives have the potential to mitigate GvHD by upregulating regulatory T cells and immune reconstitution while reducing the frequencies of antigen-presenting cells (APCs) and CD80 expression on these APCs in our preclinical mouse model of allo-HCT. In addition, WU derivatives effectively downregulated CXCR3 and T-bet in primary murine T cells. In summary, we have generated novel JAK inhibitors that could serve as alternatives to baricitinib or ruxolitinib

CHAOS CONTROL BY DIRECTLY MODULATED OPTO ELECTRONIC FEEDBACK IN SEMICONDUCTOR LASER

Nonlinear dynamic behavior of a directly modulated delayed optoelectronic feedback semiconductor laser has been studied numerically. The variation of small window of modulation current with the delayed optoelectronic feedback produces chaotic behavior of the laser output. The dynamics is completely determined by the variation of the injecting modulated amplitude (A). The chaotic spiking was observed at (A = 0.060). Excitability of the laser diode under directly modulation current with GHz was demonstrated by bifurcation diagram so the modulation amplitude is sensitive in output dynamic of the laser diode

(-)-Pentazocine induces visceral chemical antinociception, but not thermal, mechanical, or somatic chemical antinociception, in μ-opioid receptor knockout mice

<p>Abstract</p> <p>Background</p> <p>(-)-Pentazocine has been hypothesized to induce analgesia via the κ-opioid (KOP) receptor, although the involvement of other opioid receptor subtypes in the effects of pentazocine remains unknown. In this study, we investigated the role of the μ-opioid (MOP) receptor in thermal, mechanical, and chemical antinociception induced by (-)-pentazocine using MOP receptor knockout (MOP-KO) mice.</p> <p>Results</p> <p>(-)-Pentazocine-induced thermal antinociception, assessed by the hot-plate and tail-flick tests, was significantly reduced in heterozygous and abolished in homozygous MOP-KO mice compared with wildtype mice. The results obtained from the (-)-pentazocine-induced mechanical and somatic chemical antinociception experiments, which used the hind-paw pressure and formalin tests, were similar to the results obtained from the thermal antinociception experiments in these mice. However, (-)-pentazocine retained its ability to induce significant visceral chemical antinociception, assessed by the writhing test, in homozygous MOP-KO mice, an effect that was completely blocked by pretreatment with nor-binaltorphimine, a KOP receptor antagonist. <it>In vitro </it>binding and cyclic adenosine monophosphate assays showed that (-)-pentazocine possessed higher affinity for KOP and MOP receptors than for δ-opioid receptors.</p> <p>Conclusions</p> <p>The present study demonstrated the abolition of the thermal, mechanical, and somatic chemical antinociceptive effects of (-)-pentazocine and retention of the visceral chemical antinociceptive effects of (-)-pentazocine in MOP-KO mice. These results suggest that the MOP receptor plays a pivotal role in thermal, mechanical, and somatic chemical antinociception induced by (-)-pentazocine, whereas the KOP receptor is involved in visceral chemical antinociception induced by (-)-pentazocine.</p