ALBERT

Description: Technology of light sensors, due to the wide range of applications, is a dynamically developing branch of both science and industry. This work presents concept of photodetectors based on a metal-ferroelectric-insulator-semiconductor, a structure which has not been thoroughly explored in the field of photodetectors. Functionality of the presented light sensor exploits the effects of photocapacitive phenomena, ferroelectric polarization, and charge trapping. This is accomplished by an interplay between polarization alignment, subsequent charge distribution, and charge trapping processes under given illumination condition and gate voltage. Change of capacitance serves as a read out parameter indicating the wavelength and intensity of the illuminating light. The operational principle of the proposed photocapacitive light sensor is demonstrated in terms of capacitance-voltage and capacitance-time characteristics of an Al/YMnO 3 /SiN x /p-Si structure exposed to green, red, and near infrared light. Obtained results are discussed in terms of optical properties of YMnO 3 and SiN x layers contributing to the performance of photodetectors. Presented concept of light sensing might serve as the basis for the development of more advanced photodetectors.

Description: Introduction: Insufficient yield of Peripheral Blood Progenitor Cells (PBPC) from healthy donors can result in higher mortality after allogeneic transplantation. Plerixafor (Mozobil®) is approved for the mobilization of PBPC in combination with G-CSF for collection and subsequent autologous transplantation in patients with non-Hodgkin lymphoma and multiple myeloma. Clinical data on G-CSF and Plerixafor in healthy donors are still limited. In a prospective single arm phase 2 trial we investigated the safety and efficacy of a single dose of Plerixafor as a salvage regimen in poor mobilizing allogeneic PBPC donors (NCT01954914). Methods: We enrolled healthy unrelated PBPC donors who had received G-CSF (Lenograstim) at a targed dose of 10 µg/kg bodyweight (bw) for five days but donated less than 2x 106 CD34+ cells/kg recipient bw during the 1st apheresis on day 5 of the mobilization regimen. Plerixafor was injected subcutaneously at a dose of 240µg/kg once on day 5 in the evening before the second leukapheresis. The target for the processed blood volume during each apheresis procedure was 3x donor blood volume +/- 25%. Mobilization success was defined by a donation of more than 4.5x 106CD34+ cells/kg recipient bw. Primary endpoint was the number of mobilization successes. The null hypothesis (success rate of less than 50%) was tested with an exact single sample binomial test at a one-sided significance level of 5%. Results : Between 1/2014 and 12/2015 37 allogeneic unrelated PBPC donors (54% women, 46% men, median age 34 years) were enrolled into the study. The median donor bw was 69 kg (IQR, 61 kg to 76 kg) and the median recipient bw was 85 kg (IQR, 74 kg to 102 kg). Application of Plerixafor was well tolerated in most donors with only moderate side effects such as nausea, diarrhea and occasional vomiting. The median CD34+ count in peripheral blood was 15.4/µl (IQR, 12.0-18.3) on day 5 after G-CSF alone and 44.0/µl (IQR, 38.0-60.5) on day 6 after G-CSF plus Plerixafor. The collected total nucleated cell count was 187 x 106 (IQR, 159.9-223.4) cells per ml volume of the apheresis product on day 5 and 289 x 106 (IQR, 248.0-348.0) cells per ml volume of the apheresis product on day 6. The yield of CD34+ cells in the apheresis products was 1.05 x 108 (range, 0.21-1.80) on day 5 and 2.8 x108(range, 0.93-5.26) on day 6. The percentage of CD3+ cells per TNC was 31% (IQR 27%-40%) and 31% (IQR, 23% - 35%) on days 5 and 6, respectively. In total, a median number of 5.16 x 106 CD34+ cells (IQR 3.06-6.10) per kg recipient weight were collected during both aphereses. Twenty-one out of 37 donors reached the target cell count (56.8%, 95% confidence interval (CI) 39.5% - 72.9%) by donating a CD34+ cell dose of 〉4.5x 106 CD34+ cells per kg recipient bw. Nine donors had donated ≤0.8 106 CD34+ cells per kg recipient bw during their first leukaphersis after stimulation with G-CSF alone. Notably, only one out of these nine very poor mobilizing donors failed to donate at least 2.0 x 106CD 34+ cells per kg recipient bw after salvage mobilization with Plerixafor. Nevertheless, the null hypothesis (H0: rate of mobilization success 4.5x 106 CD34+ cells per kg recipient bw) was 56.8% (95%-CI 39.5% - 72.9%) after a single dose of Plerixafor on day 5 of G-CSF administration. After injection of Plerixafor the CD34+count in the peripheral blood and the yield of CD34+ cells in the leukapheresis product increased by more than factor 2. The application of G-CSF and Plerixafor was well tolerated by most of the donors. Like for autologous donors, the administration of Plerixafor appears promising to optimize PBPC mobilization in allogeneic poor mobilizing donors. Disclosures Hoelig: Janssen Cilag GmbH: Honoraria; Therakos: Honoraria, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Schetelig:Sanofi: Honoraria.

Description: Background Graft versus host disease (GVHD) is the principal cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo HCT) and is associated with intestinal microbial dysbiosis. Administration of microbial metabolite butyrate or microbial cocktails of butyrogenic bacteria reduce the severity of acute GVHD in mice. Furthermore, this intestinal microbiome-metabolome axis can be manipulated via dietary intervention in healthy humans with supplementation by defined quantities of resistant potato starch (RPS), an indigestible carbohydrate that is metabolized by intestinal anaerobic commensal bacteria to produce butyrate1. Hereon we aimed to study the feasibility and tolerability of RPS in allo HCT recipients to test the hypothesis that the patients' intestinal microbiome and butyrate levels could be rationally modified by administration of defined quantities of RPS. Methods Between May 8, 2017 and September 30, 2018, we performed a single-center prospective, single arm, pilot study. We recruited adults who were undergoing human leukocyte antigen-matched, related-donor myeloablative allo HCT. Participants received RPS (Bob's Red Mill®) 20 g package orally, once/day for the first 3 days followed by twice daily, from day -7 through day 100 after allo HCT. Feasibility was defined as adherence to ≥ 70 % of scheduled doses in ≥ 60 % of patients. The primary objective was to test adherence to scheduled doses of RPS. Secondary endpoints included assessing tolerability of RPS and its ability to alter representation of RPS-degrading and butyrate-producing bacteria as well as butyrate levels in the intestines of allo HCT recipients. Stool samples were collected in the OMNIgene-Gut® (DNA Genotek) collection kit at baseline before intake of RPS, at time of nadir (day 7-10), engraftment (day 12-18), at day 100, and additional samples were also collected. Fecal microbiome was determined by 16S rRNA gene sequencing and butyrate by liquid chromatography. Results Ten subjects were enrolled. The median age was 57 years (range 52-62 years). All subjects received GVHD prophylaxis with tacrolimus and methotrexate as well as antibiotic prophylaxis with levaquin, and were treated for neutropenic fever with IV cefepime (90%) or IV vancomycin along with IV aztreonam (10%). One patient developed biopsy proven stage I acute GI GVHD with overall grade II acute GVHD (10%). Feasibility exceeded the preset goal of ≥ 70% adherence to scheduled dosages in ≥ 60 % of patients as 8 of the 10 patients (80%) received ≥ 70 % of scheduled doses (Figure 1A). No adverse effects/toxicities attributed to RPS were observed and longitudinal specimens were collected successfully. There was greater abundance of intestinal RPS-degraders such as Ruminococcus bromii, R. lactaris, R. gnavus, and Bifidobacterium spp and butyrate-producers such as Roseburia spp, Faecalibacterium prausnitzii, Eubacterium rectale, and Anaerostipes spp in the 10 patients receiving RPS compared to 15 historical controls after allo HCT (Figure 1B). Butyrate levels were significantly higher in the participants when they were on RPS as compared to pre RPS intake [median (interquartile range): 10.76 (7.62, 19.05) vs. 3.06 (2.32, 6.21) mmoL/kg, p

Description: Key Points MYD88 mutation analysis significantly improves the detection rate of vitreoretinal B-cell lymphoma. The high frequency of MYD88 mutations in primary VRL provides further evidence that VRL and primary CNS lymphoma represent the same entity.