In this paper the authors draw on three sequential keynote addresses that they gave at Active Learning in Engineering Education (ALE) workshops in Copenhagen (2012), Caxias do Sol (2014) and San ...Sebastian (2015). Active Learning in Engineering Education is an informal international network of engineering educators dedicated to improving engineering education through active learning (
http://www.ale-net.org/
). The paper reiterates themes from those keynotes, namely, the philosophical and pedagogical underpinnings of Active Learning in Engineering Education, the scholarly questions that inspire engineering educators to go on improving their practice and exemplary models designed to activate the learning of engineering students. This paper aims to uncover the bedrock of established educational philosophies and theories that define and support active learning. The paper does not claim to present any new or innovative educational theory. There is already a surfeit of them. Rather, the aim is to assist Engineering Educators who wish to research how they can best activate the learning of their students by providing a readable, reasonable and solid underpinning for best practice in this field.
The presence of autoantibodies to multiple-islet autoantigens confers high risk for the development of type 1 diabetes. Four major autoantigens are established (insulin, glutamate decarboxylase, IA2, ...and zinc transporter-8), but the molecular identity of a fifth, a 38-kDa membrane glycoprotein (Glima), is unknown. Glima antibodies have been detectable only by immunoprecipitation from extracts of radiolabeled islet or neuronal cells. We sought to identify Glima to enable efficient assay of these autoantibodies. Mouse brain and lung were shown to express Glima. Membrane glycoproteins from extracts of these organs were enriched by detergent phase separation, lectin affinity chromatography, and SDS-PAGE. Proteins were also immunoaffinity purified from brain extracts using autoantibodies from the sera of patients with diabetes before SDS-PAGE. Eluates from gel regions equivalent to 38 kDa were analyzed by liquid chromatography-tandem mass spectrometry for protein identification. Three proteins were detected in samples from the brain and lung extracts, and in the immunoaffinity-purified sample, but not in the negative control. Only tetraspanin-7, a multipass transmembrane glycoprotein with neuroendocrine expression, had physical characteristics expected of Glima. Tetraspanin-7 was confirmed as an autoantigen by demonstrating binding to autoantibodies in type 1 diabetes. We identify tetraspanin-7 as a target of autoimmunity in diabetes, allowing its exploitation for diabetes prediction and immunotherapy.
Monetary valuation of ecosystem services enables more accurate accounting of the environmental costs and benefits of policies, but this has rarely been applied in developing countries. In such ...contexts, there are particular methodological and epistemological challenges that require novel valuation methodologies. This paper introduces a new participatory, deliberative choice experiment approach conducted in the Solomon Islands. The research aimed to determine the value people placed on ecosystem services and whether participatory interventions to elicit deeper held values influenced the preferences expressed. Results found that the initial willingness to pay for a number of tropical forest ecosystem services amounted to 30% of household income. Following deliberative intervention exercises, key ecosystem services effectively became priceless as participants were unwilling to trade them off in the choice experiment scenarios, regardless of financial cost. The group based deliberative approach, combined with participatory interventions, also resulted in significant learning for participants. This included a more sophisticated view of ecological-cultural linkages, greater recognition of deeper held values, and greater awareness of the consequences of human actions for the environment. The use of a group-based participatory approach instead of a conventional individual survey helped to overcome many of the practical difficulties associated with valuation in developing countries. Given the impact of learning on valuation outcomes, participation and deliberation should be integrated into valuation of any complex good, both in developing and developed economies. However, such a methodology raises questions about how valuation can deal with unwillingness to trade-off key ecosystem services, which results in the breakdown of monetary valuation methods. Evaluation of the appropriateness of valuation processes and methodologies for assessing deeper held values and use of mixed-method approaches will be essential to ensure policies take into account the extent to which human life is dependent on ecosystem services.
Bivalve shellfish aquaculture provides many benefits to society, beyond their traditional market value. This study collates the evidence available on the provisioning, regulating and cultural ...ecosystem services provided by the bivalve species commonly used in aquaculture. For the first time, it synthesises this evidence to provide a global assessment of the potential market and non‐market economic value of bivalve aquaculture. Bivalves are filter feeders, filtering water and particulates, creating substrates which provide habitat to act as nursery grounds for other species. Goods from provisioning services include meat, worth an estimated $23.9 billion as well as, pearls, shell and poultry grit, with oyster shell being the most important, with a global potential worth of $5.2 billion. The most important regulating services are nutrient remediation. Cultivated bivalves remove 49,000 tonnes of nitrogen and 6,000 tonnes of phosphorus, worth a potential $1.20 billion. Currently, there is little evidence on the cultural services per year of bivalve aquaculture, but we argue that these cultural values are broad ranging, although difficult to quantify. Our assessment indicates that the global, non‐food bivalve aquaculture services are worth $6.47 billion ($2.95 billion–9.99 billion) per annum. However, this is likely to be an underestimate of the true value of bivalve aquaculture as there are significant gaps in evidence of the value for a number of key services. The analysis presented here can be used to indicate the likely scale of payments for ecosystem services provided by bivalve aquaculture, prior to more detailed assessments.
Background
Pelvic discontinuity is an increasingly common complication of THA. Treatments of this complex situation are varied, including cup-cage constructs, acetabular allografts with plating, ...pelvic distraction technique, and custom triflange acetabular components. It is unclear whether any of these offer substantial advantages.
Questions/purposes
We therefore determined (1) revision and overall survival rates, (2) discontinuity healing rate, and (3) Harris hip score (HHS) after treatment of pelvic discontinuity with a custom triflange acetabular component and (4) the cost of this reconstructive operation compared to other constructs.
Methods
We retrospectively reviewed 57 patients with pelvic discontinuity treated with revision THA using a custom triflange acetabular component. We reviewed operative reports, radiographs, and clinical data for clinical and radiographic results. We also performed a cost comparison with utilization of other techniques. Minimum followup was 24 months (average, 65 months; range, 24–215 months).
Results
Fifty-six of 57 (98%) were free of revision for aseptic loosening at latest followup. Fifty-four (95%) were free of revision of the triflange component for any reason. Thirty-seven (65%) were free of revision for any reason. Twenty-eight (49%) were free of revision for any reason and free of any component migration and had a healed discontinuity. Forty-six (81%) had a stable triflange component with a healed pelvic discontinuity. Average HHS was 74.8. The costs of the custom triflange implants and a Trabecular Metal
®
cup-cage construct were equivalent: $12,500 and $11,250, respectively.
Conclusions
In this group of patients with osteolytic pelvic discontinuity, triflange implants provided predictable mid-term fixation at a cost equivalent to other treatment methods.
Level of Evidence
Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
Mucinous ovarian carcinoma (MOC) is a unique subtype of ovarian cancer with an uncertain etiology, including whether it genuinely arises at the ovary or is metastatic disease from other organs. In ...addition, the molecular drivers of invasive progression, high-grade and metastatic disease are poorly defined. We perform genetic analysis of MOC across all histological grades, including benign and borderline mucinous ovarian tumors, and compare these to tumors from other potential extra-ovarian sites of origin. Here we show that MOC is distinct from tumors from other sites and supports a progressive model of evolution from borderline precursors to high-grade invasive MOC. Key drivers of progression identified are TP53 mutation and copy number aberrations, including a notable amplicon on 9p13. High copy number aberration burden is associated with worse prognosis in MOC. Our data conclusively demonstrate that MOC arise from benign and borderline precursors at the ovary and are not extra-ovarian metastases.
Massive acetabular bone loss, encountered complex primary or revision total hip arthroplasty, remains a reconstructive challenge. The custom triflange cup reliably achieves both early fixation and ...longer-term stability. This study presents the 10-year minimum three-surgeon follow-up of acetabular defects managed with a custom triflange component.
All patients who underwent a custom triflange acetabular component implantation from January 1992 to December 2009 were identified. Demographics, implant data, outcomes, and reoperations were collected and analyzed. Bone defects in all cases were Paprosky type IIIA, IIIB, or IV. A total of 233 patients (241 hips) underwent implantation of a custom triflange during the study period. There were 81 patients (83 hips) who died prior to minimum follow-up and 84 patients (88 hips) had minimum follow-up of 10 years (mean 15.2; range, 10 to 28), or failure prior to 10 years.
Complications requiring additional surgery occurred in 43 hips (49%). There were 10 revisions for failure (11.4%); four were due to recurrent infection, three for aseptic loosening, and one for recurrent infection with all revised to a new triflange. There was one patient who was resected to a Girdlestone for infection and one patient was revised for infection to a bipolar hemiprosthesis due to a healed discontinuity.
To our knowledge, this study represents the largest cohort and longest follow-up in the current literature and demonstrates excellent survivorship and clinical results at an average of 15 years follow-up. The component was retained in 89% of cases.
In patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA ...(ctDNA) analysis, as a marker of minimal residual disease, is a powerful prognostic factor in patients with nonmetastatic colorectal cancer (CRC). Serial analysis of ctDNA in patients with resectable CRLM could inform the optimal use of perioperative chemotherapy. Here, we performed a validation study to confirm the prognostic impact of postoperative ctDNA in resectable CRLM observed in a previous discovery study.
We prospectively collected plasma samples from patients with resectable CRLM, including presurgical and postsurgical samples, serial samples during any pre- or postoperative chemotherapy, and serial samples in follow-up. Via targeted sequencing of 15 genes commonly mutated in CRC, we identified at least 1 somatic mutation in each patient's tumor. We then designed a personalized assay to assess 1 mutation in plasma samples using the Safe-SeqS assay. A total of 380 plasma samples from 54 patients recruited from July 2011 to Dec 2014 were included in our analysis. Twenty-three (43%) patients received neoadjuvant chemotherapy, and 42 patients (78%) received adjuvant chemotherapy after surgery. Median follow-up was 51 months (interquartile range, 31 to 60 months). At least 1 somatic mutation was identified in all patients' tumor tissue. ctDNA was detectable in 46/54 (85%) patients prior to any treatment and 12/49 (24%) patients after surgery. There was a median 40.93-fold (19.10 to 87.73, P < 0.001) decrease in ctDNA mutant allele fraction with neoadjuvant chemotherapy, but ctDNA clearance during neoadjuvant chemotherapy was not associated with a better recurrence-free survival (RFS). Patients with detectable postoperative ctDNA experienced a significantly lower RFS (HR 6.3; 95% CI 2.58 to 15.2; P < 0.001) and overall survival (HR 4.2; 95% CI 1.5 to 11.8; P < 0.001) compared to patients with undetectable ctDNA. For the 11 patients with detectable postoperative ctDNA who had serial ctDNA sampling during adjuvant chemotherapy, ctDNA clearance was observed in 3 patients, 2 of whom remained disease-free. All 8 patients with persistently detectable ctDNA after adjuvant chemotherapy have recurred. End-of-treatment (surgery +/- adjuvant chemotherapy) ctDNA detection was associated with a 5-year RFS of 0% compared to 75.6% for patients with an undetectable end-of-treatment ctDNA (HR 14.9; 95% CI 4.94 to 44.7; P < 0.001). Key limitations of the study include the small sample size and the potential for false-positive findings with multiple hypothesis testing.
We confirmed the prognostic impact of postsurgery and posttreatment ctDNA in patients with resected CRLM. The potential utility of serial ctDNA analysis during adjuvant chemotherapy as an early marker of treatment efficacy was also demonstrated. Further studies are required to define how to optimally integrate ctDNA analyses into decision-making regarding the use and timing of adjuvant therapy for resectable CRLM.
ACTRN12612000345886.
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