Combining BeEAM with Brentuximab Vedotin for High-Dose Therapy in CD30 Positive Lymphomas before Autologous Transplantation-A Phase I Study.

The prognosis for patients with CD30+ lymphomas (Hodgkin lymphoma and various T-cell lymphomas) relapsing after autologous stem cell transplantation (ASCT) is critical. Brentuximab vedotin (BV), an ADC targeting CD30, is an obvious candidate for inclusion into high-dose chemotherapy (HDCT) regimens to improve outcomes. This single center phase I trial investigated 12 patients with CD30+ lymphoma (AITL: n = 5; relapsed HL: n = 7; median of two previous treatment lines) undergoing ASCT. In a 3 + 3 dose escalation design, 12 patients received a single BV dose at three dose levels (DL) (0.9/1.2/1.8 mg/kg b.w.) prior to standard BeEAM. All patients were treated as planned; no dose limiting toxicities (DLTs) occurred at DL 1 and 2. At DL 3, one DLT (paralytic ileus, fully recovering) occurred. Grade III febrile neutropenia occurred in one patient, and two others had septic complications, all fully recovering. Median hospitalization was 23 days. Hematologic recovery was normal. Six of twelve (50%) patients achieved CR. PFS and OS at 1 year were 67% (n = 8/12) and 83% (n = 10/12), respectively. The addition of brentuximab to standard BeEAM HDCT seems to be safe. We observed a CR rate of 75% post-ASCT in a highly pretreated population. The efficacy of this novel HDCT combination with BV at a 1.8 mg/kg dose level needs to be explored in larger studies

Environmental Factors Affecting the Expression of pilAB as Well as the Proteome and Transcriptome of the Grass Endophyte Azoarcus sp. Strain BH72

gene encoding the structural protein of type IV pili that are essential for plant colonization appears to be regulated in a population density-dependent manner.. The expression of one of them was shown to be induced in plant roots. sp. to analyze mechanisms and molecules involved in the population-dependent gene expression in this endophyte in future

Compilation of a hydropower development assistance tool for evaluating hydropower resources in South Africa

A nation’s industrial growth as well as the quality of life is dependent on energy supply and demand. With the current situation of the supply of energy not matching the growing demand, small-scale hydropower projects could play an important role, especially in providing electricity to remote areas. Even though the experts classify South Africa as a water-scarce country, there is still abundant water for small-scale hydropower schemes which could help with the sustainable energy supply for the future (Banks & Schäffler, 2006). There are numerous small-scale hydropower plants which played an important role in providing both urban and rural areas of South Africa with energy, even though not well documented. Both Pretoria’s and Cape Town’s initial electricity was provided by small scale hydropower stations, however these stations were decommissioned due to the national electricity grid expansions (Jonker Klunne, 2009). Approximately 188 hydropower sites are currently in South Africa, which are either potential (54 sites), under construction (21 sites), operational (91 sites) or have been decommissioned (22 sites), excluding privately owned sites (Jonker Klunne, 2016). It was hypothesised that a user-friendly framework in conjunction with a Hydropower Development Assistance Tool (HDAT) could be compiled. The designed framework and the HDAT could guide the potential power producers through the process of developing new or upgrading existing hydropower facilities in South Africa. The objective of this study was to develop a framework which is designed to guide users through a decision analysis procedure regarding the refurbishment, renewal or replacement of existing hydropower sites in South Africa, as well as providing guidance for the development of these identified sites. Using a visual representation with the necessary economic evaluation to determine feasibility using an Excel-based assistance tool. The Hydropower Development Assistance Tool was tested on the Aliwal North decommissioned hydropower site. This site was chosen by the Water Research Commission (WRC) to be recommissioned. The result was a practical decision support system for the evaluation of existing or decommissioned hydropower sites in South Africa.Dissertation (MEng)--University of Pretoria, 2018.Civil EngineeringMEngUnrestricte

Expression of a transcriptional <i>azo2876::gfp</i> fusion in pure culture or during interaction with rice roots.

<p>Phase contrast (A–C) and corresponding fluorescence micrographs (E–G), of strain <i>Azoarcus</i> sp. BH<i>azo2876</i> expressing a transcriptional <i>2876::gfp</i> fusion in pure culture, or in infected rice roots (fluorescence micrographs D, H). Cells grown in VM-ethanol medium at exponential (A, E) or stationary growth phase (C, G), or in conditioned supernatant for 4 h (B, F); all fluorescence images taken with the same setting of the video camera. (D, H) Roots of rice seedlings 13 d after inoculation; bacterial GFP fluorescence at emergence points of lateral roots (D, with close-up in right corner, and in epidermal root cell (H). Bars correspond to 7 µm (A–C, E–G), 10 µm (D) and 20 µM (H).</p

Expression of transcriptional gene fusions in conditioned supernatant.

<p>(A–F) Gene expression determined by ß-glucuronidase activities from respective transcriptional reporter gene fusions with <i>uidA</i>, in VM-ethanol medium. (A) Induction of <i>pilAB</i> gene expression in BHΔ<i>pilS</i>::pJBLP14 by supernatants of <i>Azoarcus</i> sp. BH72, <i>Azoarcus communis</i>, <i>Chromobacterium violaceum</i>, <i>Pseudomonas stutzeri</i> and <i>Azospirillum brasilense</i> obtained by supernatant bioassays after four hours of incubation. (B, C, D, E) Induction of <i>azo1544</i> (B), <i>azo1684</i> (C), <i>azo2876</i> (D) and <i>azo3874</i> (E) gene expression in the respective strains by supernatants of <i>Azoarcus</i> sp. BH72, <i>Azoarcus communis</i> and <i>Azospirillum brasilense</i> obtained by supernatant bioassays after four hours of incubation. (F) Fold changes of induction for all tested genes (<i>pilAB</i>, <i>azo1544</i>, <i>azo1684</i>, <i>azo2876</i> and <i>azo3874</i>) in comparison to each other. For all experiments, fresh medium was used instead of supernatant as negative control, and the values were set to one for calculation of fold changes. Standard deviation was calculated from at least three independent experiments. Stars indicate significance (at least <i>P<0.05</i>) as determined by unpaired t-test analyses.</p

Population density-dependent expression of <i>pilAB</i> of <i>Azoarcus</i> sp.

<p>(A) Population density-dependent induction of <i>pilAB</i> gene expression in <i>Azoarcus</i> sp. BH72 wild type background and BHΔ<i>pilS</i> mutant background. Cultures were grown in liquid aerobic culture (VM-Ethanol), and samples were taken at certain time points to measure β-glucuronidase activity (<i>pilAB</i>::<i>uidA</i>-fusion, left axis). The optical densities at these time points are shown in the inlay. The results are representative of three independent experiments. Error bars indicate standard deviations. Increase of the expression levels at exponential in comparison to stationary growth phase (last time point) was significant for wild type (BH72::pJBLP14, black triangles, <i>P</i><0.001), and highly significant for <i>pilS</i> mutant cells (BHD<i>pilS</i>::pJBLP14, black squares, <i>P</i><0.0001, unpaired t-test). (B) PilA protein abundance in <i>Azoarcus</i> sp. BH72 wild type and mutant background. Stationary phase cultures (OD 2.5) of <i>Azoarcus</i> wild type (wt) and Δ<i>pilS</i> mutant cells were compared. Western blot of whole-cell protein extracts with antiserum against PilA. Equal amounts of protein were loaded (8 µg).</p

Safety and efficacy of intravenous thrombolysis in stroke patients on prior antiplatelet therapy in the WAKE-UP trial.

One quarter to one third of patients eligible for systemic thrombolysis are on antiplatelet therapy at presentation. In this study, we aimed to assess the safety and efficacy of intravenous thrombolysis in stroke patients on prescribed antiplatelet therapy in the WAKE-UP trial. WAKE-UP was a multicenter, randomized, double-blind, placebo-controlled clinical trial to study the efficacy and safety of MRI-guided intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time. The medication history of all patients randomized in the WAKE-UP trial was documented. The primary safety outcome was any sign of hemorrhagic transformation on follow-up MRI. The primary efficacy outcome was favorable functional outcome defined by a score of 0-1 on the modified Rankin scale at 90 days after stroke, adjusted for age and baseline stroke severity. Logistic regression models were fitted to study the association of prior antiplatelet treatment with outcome and treatment effect of intravenous alteplase. Of 503 randomized patients, 164 (32.6%) were on antiplatelet treatment. Patients on antiplatelet treatment were older (70.3 vs. 62.8 years,  <  0.001), and more frequently had a history of hypertension, atrial fibrillation, diabetes, hypercholesterolemia, and previous stroke or transient ischaemic attack. Rates of symptomatic intracranial hemorrhage and hemorrhagic transformation on follow-up imaging did not differ between patients with and without antiplatelet treatment. Patients on prior antiplatelet treatment were less likely to achieve a favorable outcome (37.3% vs. 52.6%,  = 0.014), but there was no interaction of prior antiplatelet treatment with intravenous alteplase concerning favorable outcome ( = 0.355). Intravenous alteplase was associated with higher rates of favorable outcome in patients on prior antiplatelet treatment with an adjusted odds ratio of 2.106 (95% CI 1.047-4.236). Treatment benefit of intravenous alteplase and rates of post-treatment hemorrhagic transformation were not modified by prior antiplatelet intake among MRI-selected patients with unknown onset stroke. Worse functional outcome in patients on antiplatelets may result from a higher load of cardiovascular co-morbidities in these patients