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

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

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

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

First-line, Fixed-Duration Nivolumab plus Ipilimumab Followed by Nivolumab in Clinically Diverse Patient Populations With Unresectable Stage III or IV Melanoma: CheckMate 401

PURPOSETo address the paucity of data in patients with historically poor outcomes, we conducted the single-arm phase IIIb CheckMate 401 study to evaluate the safety and efficacy of nivolumab plus ipilimumab followed by nivolumab monotherapy in clinically diverse patient populations with advanced melanoma.METHODSTreatment-naive patients with unresectable stage III-IV melanoma received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg (240 mg following a protocol amendment) once every 2 weeks for 24 months. The primary end point was the incidence of grade 3-5 select treatment-related adverse events (TRAEs). Overall survival (OS) was a secondary end point. Outcomes were evaluated in subgroups defined by Eastern Cooperative Oncology Group performance status (ECOG PS), brain metastasis status, and melanoma subtype.RESULTSIn total, 533 patients received at least one dose of study drug. Grade 3-5 select TRAEs affecting the GI (16%), hepatic (15%), endocrine (11%), skin (7%), renal (2%), and pulmonary (1%) systems occurred in the all-treated population; similar incidence rates were observed across all subgroups. At 21.6 months' median follow-up, 24-month OS rates were 63% in the all-treated population, 44% in the ECOG PS 2 subgroup (including patients with cutaneous melanoma only), 71% in the brain metastasis subgroup, 36% in the ocular/uveal melanoma subgroup, and 38% in the mucosal melanoma subgroup.CONCLUSIONNivolumab plus ipilimumab followed by nivolumab monotherapy was tolerable in patients with advanced melanoma and poor prognostic characteristics. Efficacy was similar between the all-treated population and patients with brain metastases. Reduced efficacy was observed in patients with ECOG PS 2, ocular/uveal melanoma, and/or mucosal melanoma, highlighting the continued need for novel treatment options for these difficult-to-treat patients