Adjuvant low-dose interferon α2a with or without dacarbazine compared with surgery alone: a prospective-randomized phase III DeCOG trial in melanoma patients with regional lymph node metastasis

Background: More than half of patients with melanoma that has spread to regional lymph nodes develop recurrent disease within the first 3 years after surgery. The aim of the study was to improve disease-free survival (DFS) and overall survival (OS) with interferon (IFN) α2a with or without dacarbazine (DTIC) compared with observation alone. Patients and methods: A total of 444 patients from 42 centers of the German Dermatologic Cooperative Oncology Group who had received a complete lymph node dissection for pathologically proven regional node involvement were randomized to receive either 3 MU s.c. of IFNα2a three times a week for 2 years (Arm A) or combined treatment with same doses of IFNα2a plus DTIC 850 mg/m2 every 4-8 weeks for 2 years (Arm B) or to observation alone (Arm C). Treatment was discontinued at first sign of relapse. Results: A total of 441 patients were eligible for intention-to-treat analysis. Kaplan-Meier 4-year OS rate of those who had received IFNα2a was 59%. For those with surgery alone, survival was 42% (A versus C, P = 0.0045). No improvement of survival was found for the combined treatment Arm B with 45% survival rate (B versus C, P = 0.76). Similarly, DFS rates showed significant benefit for Arm A, and not for Arm B. Multivariate Cox model confirmed that Arm A has an impact on OS (P = 0.005) but not Arm B (P = 0.34). Conclusions: 3 MU interferon α2a given s.c. three times a week for 2 years significantly improved OS and DFS in patients with melanoma that had spread to the regional lymph nodes. Interestingly, the addition of DTIC reversed the beneficial effect of adjuvant interferon α2a therap

Evolution of a Bridge Builder Outreach Activity

Many engineering outreach programs use building a bridge as a hands-on activity for multiple grade levels and audiences. South Dakota State University has used a bridge building activity, with slight modifications for grade level and time allowed, for over 10 years in outreach at schools and campus workshops. In recent years, it has been noted that the same level of students attending these outreach events are either performing the same or a similar activity at their school or another event outside of our outreach program which has adversely affected using this activity to stimulate interest in engineering. In the last two years, modifications have been made to create a bridge builder challenge that incorporates measurement, experimentation, simulation, design, and redesign for middle and high school students. Incorporation of design standards and performance as well as economic efficiency has been the key to linking science principles to engineering principles. Details of the activity and its implementation are discussed

Radiosensitization by BRAF inhibitor therapy—mechanism and frequency of toxicity in melanoma patients

This study shows radiosensitization by BRAF inhibitors in clinical practice and ex vivo by fluorescence in situ hybridization of chromosomal breaks. Nevertheless, radiotherapy with concomitant BRAF inhibitor therapy is feasible with an acceptable increase in toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib in both the patient study and the ex vivo experiment

Differential influence of vemurafenib and dabrafenib on patients' lymphocytes despite similar clinical efficacy in melanoma

In this study, we demonstrate that vemurafenib but not dabrafenib reduces peripheral lymphocyte counts in melanoma patients while both agents show similar clinical efficacy. Within the lymphocyte compartment, vemurafenib selectively decreases circulating CD4+ T cells and changes their phenotype and function. This indicates that selective BRAFi need to be assessed individually for immunomodulatory effects, especially, when planning combinations with immunotherapie

A Spectroscopic and Photometric Study of Short-Timescale Variability in NGC5548

Results of a ground-based optical monitoring campaign on NGC5548 in June 1998 are presented. The broad-band fluxes (U,B,V), and the spectrophotometric optical continuum flux F_lambda(5100 A) monotonically decreased in flux while the broad-band R and I fluxes and the integrated emission-line fluxes of Halpha and Hbeta remained constant to within 5%. On June 22, a short continuum flare was detected in the broad band fluxes. It had an amplitude of about ~18% and it lasted only ~90 min. The broad band fluxes and the optical continuum F_lambda(5100 A) appear to vary simultaneously with the EUV variations. No reliable delay was detected for the broad optical emission lines in response to the EUVE variations. Narrow Hbeta emission features predicted as a signature of an accretion disk were not detected during this campaign. However, there is marginal evidence for a faint feature at lambda = 4962 A with FWHM=~6 A redshifted by Delta v = 1100 km/s with respect to Hbeta_narrow.Comment: 12 pages, 7 figures, accepted for publishing in A&

Engineering the Future: A Workshop for High School Teachers

The framework guiding the development of Next Generation Science Standards (NGSS) identifies eight science and engineering principles essential for all students to learn. The Engineering the Future workshop, offered by South Dakota State University (SDSU) in the summer of 2012, focused on helping teachers better understand those principles and how to employ them effectively in their classrooms. Each day of the week-long workshop, teachers participated in a variety of engineering-related activities, accessed low and high-end instrumentation, took tours of engineering-related facilities in the region, and developed lesson plans to incorporate what they learned into their science classrooms. We used pre- and postworkshop surveys to assess the participants’ understanding and attitudes regarding science and engineering. Results of the survey showed participants had a narrow view of engineering prior to the workshop but by the end of the workshop, they were more aware of the nature of engineering, the various types of engineering, and they better understood how they could incorporate engineering principles into their current curriculum

Improving processing by adaption to conditional geostatistical simulation of block compositions

Exploitation of an ore deposit can be optimized by adapting the beneficiation processes to the properties of individual ore blocks. This can involve switching in and out certain treatment steps, or setting their controlling parameters. Optimizing this set of decisions requires the full conditional distribution of all relevant physical parameters and chemical attributes of the feed, including concentration of value elements and abundance of penalty elements. As a first step towards adaptive processing, the mapping of adaptive decisions is explored based on the composition, in value and penalty elements, of the selective mining units. Conditional distributions at block support are derived from cokriging and geostatistical simulation of log-ratios. A one-to-one log-ratio transformation is applied to the data, followed by modelling via classical multivariate geostatistical tools, and subsequent back-transforming of predictions and simulations. Back-transformed point-support simulations can then be averaged to obtain block averages that are fed into the process chain model. The approach is illustrated with a \u27toy\u27 example where a four-component system (a value element, two penalty elements, and some liberable material) is beneficiated through a chain of technical processes. The results show that a gain function based on full distributions outperforms the more traditional approach of using unbiased estimates

Allele frequencies of BRAFV600 mutations in primary melanomas and matched metastases and their relevance for BRAF inhibitor therapy in metastatic melanoma

Background: The detection of BRAFV600 mutations in patients with metastatic melanoma is important because of the availability of BRAF inhibitor therapy. However, the clinical relevance of the frequency of BRAFV600 mutant alleles is unclear. Patients and Methods: Allele frequencies of BRAFV600 mutations were analyzed byultra-deepnext-generation sequencing in formalin-fixed, paraffin-embedded melanoma tissue (75 primary melanomas and 88 matched metastases). In a second study, pretreatment specimens from 76 patients who received BRAF inhibitors were retrospectively analyzed, and BRAFV600 allele frequencies were correlated with therapeutic results. Results: Thirty-five patients had concordantly BRAF-positive and 36 (48%) patients had concordantly BRAF-negative primary melanomas and matched metastases, and four patients had discordant samples with low allele frequencies (3.4–5.2%). Twenty-six of 35 patients with concordant samples had BRAFV600E mutations, three of whom had additional mutations (V600K in two patients and V600R in one) and nine patients had exclusively non-V600E mutations (V600K in eight patients and V600E -c.1799_1800TG > AA- in one patient). The frequency of mutated BRAFV600 alleles was similar in the primary melanoma and matched metastasis in 27/35 patients, but differed by >3-fold in 8/35 of samples. BRAFV600E allele frequencies in pretreatment tumor specimens were not significantly correlated with treatment outcomes in 76 patients with metastatic melanoma who were treated with BRAF inhibitors. Conclusions: BRAFV600 mutation status and allele frequency is consistent in the majority of primary melanomas and matched metastases. A small subgroup of patients has double mutations. BRAFV600 allele frequencies are not correlated with the response to BRAF inhibitors