Pilot Study of Delayed ICOS/ICOS-L Blockade With alphaCD40 to Modulate Pathogenic Alloimmunity in a Primate Cardiac Allograft Model

Background: Inducible costimulator (ICOS) is rapidly upregulated with T-cell stimulation and may represent an escape pathway for T-cell costimulation in the setting of CD40/CD154 costimulation blockade. Induction treatment exhibited no efficacy in a primate renal allograft model, but rodent transplant models suggest that the addition of delayed ICOS/ICOS-L blockade may prolong allograft survival and prevent chronic rejection. Here, we ask whether ICOS-Ig treatment, timed to anticipate ICOS upregulation, prolongs NHP cardiac allograft survival or attenuates pathogenic alloimmunity. Methods: Cynomolgus monkey heterotopic cardiac allograft recipients were treated with alphaCD40 (2C10R4, d0-90) either alone or with the addition of delayed ICOS-Ig (d63-110). Results: Median allograft survival was similar between ICOS-Ig + alphaCD40 (120 days, 120-125 days) and alphaCD40 (124 days, 89-178 days) treated animals, and delayed ICOS-Ig treatment did not prevent allograft rejection in animals with complete CD40 receptor coverage. Although CD4(+) TEM cells were decreased in peripheral blood (115 +/- 24) and mLNs (49 +/- 1.9%) during ICOS-Ig treatment compared with monotherapy (214 +/- 27%, P = 0.01; 72 +/- 9.9%, P = 0.01, respectively), acute and chronic rejection scores and kinetics of alloAb elaboration were similar between groups. Conclusions: Delayed ICOS-Ig treatment with the reagent tested is probably ineffective in modulating pathogenic primate alloimmunity in this model

Metamorphosis of plasma turbulence-shear flow dynamics through a transcritical bifurcation

The structural properties of an economical model for a confined plasma turbulence governor are investigated through bifurcation and stability analyses. A close relationship is demonstrated between the underlying bifurcation framework of the model and typical behavior associated with low- to high-confinement transitions such as shear flow stabilization of turbulence and oscillatory collective action. In particular, the analysis evinces two types of discontinuous transition that are qualitatively distinct. One involves classical hysteresis, governed by viscous dissipation. The other is intrinsically oscillatory and non-hysteretic, and thus provides a model for the so-called dithering transitions that are frequently observed. This metamorphosis, or transformation, of the system dynamics is an important late side-effect of symmetry-breaking, which manifests as an unusual non-symmetric transcritical bifurcation induced by a significant shear flow drive.Comment: 17 pages, revtex text, 9 figures comprised of 16 postscript files. Submitted to Phys. Rev.

Allogeneic Hematopoietic Cell Transplantation Provides Effective Salvage Despite Refractory Disease or Failed Prior Autologous Transplant in Angioimmunoblastic T-Cell Lymphoma: A CIBMTR Analysis

Background: There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT. Methods: We evaluated 249 adult AITL patients who received their first allo-HCT during 2000–2016. Results: The median patient age was 56 years (range = 21–77). Majority of the patients were Caucasians (86%), with a male predominance (60%). Graft-versus-host disease (GVHD) prophylaxis was predominantly calcineurin inhibitor-based approaches while the most common graft source was peripheral blood (97%). Median follow-up of survivors was 49 months (range = 4–170 months). The cumulative incidence of grade 2–4 and grade 3–4 acute GVHD at day 180 were 36% (95% CI = 30–42) and 12 (95% CI = 8–17), respectively. The cumulative incidence of chronic GVHD at 1 year was 49% (95%CI 43–56). The 1-year non-relapse mortality (NRM) was 19% (95% CI = 14–24), while the 4-year relapse/progression, progression-free survival (PFS), and overall survival (OS) were 21% (95% CI = 16–27), 49% (95% CI = 42–56), and 56% (95% CI = 49–63), respectively. On multivariate analysis, chemoresistant status at the time of allo-HCT was associated with a significantly higher risk for therapy failure (inverse of PFS) (RR = 1.73 95% CI = 1.08–2.77), while KPS \u3c 90% was associated with a significantly higher risk of mortality (inverse of OS) (RR = 3.46 95% CI = 1.75–6.87). Conclusion: Our analysis shows that allo-HCT provides durable disease control even in AITL patients who failed a prior auto-HCT and in those subjects with refractory disease at the time of allografting

Allogeneic hematopoietic cell transplantation provides effective salvage despite refractory disease or failed prior autologous transplant in angioimmunoblastic T-cell lymphoma: a CIBMTR analysis

Abstract Background There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT. Methods We evaluated 249 adult AITL patients who received their first allo-HCT during 2000–2016. Results The median patient age was 56 years (range = 21–77). Majority of the patients were Caucasians (86%), with a male predominance (60%). Graft-versus-host disease (GVHD) prophylaxis was predominantly calcineurin inhibitor-based approaches while the most common graft source was peripheral blood (97%). Median follow-up of survivors was 49 months (range = 4–170 months). The cumulative incidence of grade 2–4 and grade 3–4 acute GVHD at day 180 were 36% (95% CI = 30–42) and 12 (95% CI = 8–17), respectively. The cumulative incidence of chronic GVHD at 1 year was 49% (95%CI 43–56). The 1-year non-relapse mortality (NRM) was 19% (95% CI = 14–24), while the 4-year relapse/progression, progression-free survival (PFS), and overall survival (OS) were 21% (95% CI = 16–27), 49% (95% CI = 42–56), and 56% (95% CI = 49–63), respectively. On multivariate analysis, chemoresistant status at the time of allo-HCT was associated with a significantly higher risk for therapy failure (inverse of PFS) (RR = 1.73 95% CI = 1.08–2.77), while KPS < 90% was associated with a significantly higher risk of mortality (inverse of OS) (RR = 3.46 95% CI = 1.75–6.87). Conclusion Our analysis shows that allo-HCT provides durable disease control even in AITL patients who failed a prior auto-HCT and in those subjects with refractory disease at the time of allografting.https://deepblue.lib.umich.edu/bitstream/2027.42/146782/1/13045_2018_Article_696.pd

Outcomes of Medicare-age eligible NHL patients receiving RIC allogeneic transplantation: a CIBMTR analysis

The application of allogeneic hematopoietic cell transplantation (allo-HCT) in non-Hodgkin lymphoma (NHL) patients ≥65 years in the United States is limited by lack of Medicare coverage for this indication. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we report allo-HCT outcomes of NHL patients aged ≥65 years (older cohort; n = 446) compared with a cohort of younger NHL patients aged 55-64 years (n = 1183). We identified 1629 NHL patients undergoing a first reduced-intensity conditioning (RIC) or nonmyeloablative conditioning allo-HCT from 2008 to 2015 in the United States. Cord blood or haploidentical transplants were excluded. The median age was 68 years (range 65-77) for the older cohort vs 60 years (range 55-64) in the younger cohort. The 4-year adjusted probabilities of nonrelapse mortality (NRM), relapse/progression (R/P), progression-free survival (PFS), and overall survival (OS) of the younger and older groups were 24% vs 30% (P = .03), 41% vs 42% (P = .82), 37% vs 31% (P = .03), and 51% vs 46% (P = .07), respectively. Using multivariate analysis, compared with the younger group, the older cohort was associated with increased NRM, but there was no difference between the 2 cohorts in terms of R/P, PFS, or OS. The most common cause of death was disease relapse in both groups. In NHL patients eligible for allo-HCT, there was no difference in OS between the 2 cohorts. Age alone should not determine allo-HCT eligibility in NHL, and Medicare should expand allo-HCT coverage to older adults

Чисельні рішення проблем утворення тріщин при формуванні еластомеру

Generically, thermoset elastomers are often referred to as rubber. It is characterized by the chemical bonding between polymer chains. One of the important problems that plague elastomer manufacturing and rubber parts under service is cracks. Predicting the main factors affecting crack propagation trajectories during forming and after curing time is an important challenge. For this purpose, numerical analysis was implemented by using the commercial ABAQUS/CAE software package. A three-dimensional model was established to predict the important factors that affect this process. During the analysis, the effect of forming velocity and the amount of kinetic energy on the distortion of rubber material and crack propagation is explored in detail by using different forming punch velocities. The drop velocity of the upper insert (punch) on the rubber pad was taken as 10 m/s, 7 m/s, and 5 m/s, respectively. Consequently, while each forming velocity will generate different kinetic energy between the interaction surfaces, the change in crack behavior and the normal stress can be monitored in different positions. As a result, among these velocities, it was found that the low forming velocity of the upper insert (punch) is better than the others in forming rubber where cracks and distortions were at minimum values. Also, the amount of kinetic energy is low enough in the case of low speeds and can affect the results significantly. In addition, it was found that the generated stresses have a significant impact on the crack development in a specific area, especially near the fillets and sharp edges. It was concluded that calculating the parameters affecting the crack growth and predicting the crack propagation trajectories using the finite element method is a significant method for predicting and solving crack problems before tool fabricationТермореактивні еластомери часто називають каучуком. Він характеризується хімічним зв’язком між полімерними ланцюгами. Однією з істотних проблем, з якими стикаються виробники еластомерів та експлуатовані деталі з каучуку, є утворення тріщин. Важливим завданням є прогнозування основних факторів, що впливають на траєкторії поширення тріщин під час формування та після затвердіння. Для цієї мети було проведено чисельний аналіз з використанням комерційного програмного пакету ABAQUS/CAE. Для прогнозування важливих факторів, що впливають на цей процес, була створена тривимірна модель. Аналіз детально вивчає вплив швидкості формування та кількості кінетичної енергії на деформацію каучукового матеріалу та поширення тріщин за допомогою різних швидкостей штампування. Швидкість падіння верхньої вставки (пуансона) на гумову прокладку прийнята рівною 10 м/с, 7 м/с та 5 м/с відповідно. Отже, у той час як кожна швидкість формування генеруватиме різну кінетичну енергію між поверхнями взаємодії, зміну поведінки тріщин і нормальне напруження можна відстежувати в різних положеннях. В результаті було виявлено, що серед даних швидкостей кращою є низька швидкість формування верхньої вставки (пуансона) при формуванні каучуку з мінімальними значеннями тріщин і деформацій. Крім того, кількість кінетичної енергії досить невелика у разі низьких швидкостей і може суттєво вплинути на результати. Також встановлено, що створювані напруження мають значний вплив на розвиток тріщин у певній області, особливо поблизу заокруглень і гострих кромок. Зроблено висновок, що розрахунок параметрів, що впливають на ріст тріщин, та прогнозування траєкторій поширення тріщин за допомогою методу кінцевих елементів є важливим способом прогнозування та вирішення проблем утворення тріщин до виготовлення інструмент

Impact of egg mass layers and scale thicknesses of the fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), on the parasitic performance of Trichogrammatoidea bactrae (Hymenoptera: Trichogrammatidae)

Abstract Background Fall armyworm (FAW), Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), is one of the new alien destructive pests of maize and other 350 economic crops. The majority of farmers are still depended upon chemical insecticides to suppress the pest, but S. frugiperda has succeeded to develop resistance against most of the chemical families. Improving an effective environmentally-friendly approach is highly recommended. Therefore, the egg parasitoids are the best weapon for managing the FAW in the early egg stage due to the feeding behavior of their larvae. In this regard, the impact of FAW egg mass layers and scale thicknesses, as physical barriers, on the parasitic performance of the egg-parasitoid species, Trichogrammatoidea bactrae Nagaraja (Hymenoptera: Trichogrammatidae), in non-choice and choice tests was assessed. Besides, the efficacy of FAW-produced adult wasps on the next generation based on the rates of parasitism, adults' emergence, and female progeny was determined. Results Obtained results exhibited that T. bactrae was able to parasitize all exposed FAW egg masses but with different rates related to the layers’ number and scales' thicknesses in both tests. One-layer (83.18, 78.24%) and two-layer egg masses (65.99, 76.42%) had significantly the highest parasitism rate, while three layers (42.15, 46.05%) was the least one, in both tests, respectively. All parasitoids emerged after 10–12 days with high rates (~ 88–98%) from all the tested egg masses, and the majority offspring were female-biased in both tests. Furthermore, parasitic performance in F1 progeny was similar with that recorded in parental generation in terms of parasitism rate, high parasitoid emergency (~ 87–95%), and strongly female-biased (~ 68–76%) in all the exposed egg masses. Conclusions The egg parasitoid, T. bactrae, could be an efficient and recommended bio-control agent against FAW as its greatest ability to overcome the layers’ number and scales’ thickness

Water sorption properties of room-temperature ionic liquids over the whole range of water activity and molecular states of water in these media

International audienc