Challenges of transformation:Innovation, re-bundling and traditional manufacturing in Canada’s Technology Triangle

This is an Accepted Manuscript of an article published by Taylor & Francis in Regional Studies on Oct 2011, available online: http://www.tandfonline.com/10.1080/00343404.2011.602058This paper develops a perspective of regional re-bundling in overcoming economic crises. It does this by focusing on the effects of the recent global financial crisis on traditional manufacturing. It analyses the structure of innovation processes and their development over time in Canada's Technology Triangle – a region known for university-related spin-off processes and successful modernization. What is less well known is that this region has been strongly influenced by traditional manufacturing industries. It is shown that these industries have been well prepared to deal with the effects of the crisis due to ongoing innovation and diversification stimulated by prior economic crises

Eutrophication processes regulated by a plunging river inflow

Abstract Lake Rotoiti (North Island, New Zealand) is a deep mesotrophic lake that has declined in water quality over the last 30 years. The main river entering the lake was identified as the primary enrichment source, but its interaction with the surrounding lakewater varied with season and time of day. During winter the river was colder than the lake and penetrated 6-8 km into the main basin as an underflow. In summer the river often entered as a plunging inflow during the early morning, but it warmed during the day, and in the afternoon entered the lake as a buoyant jet that flowed directly to a nearby outlet river. From continuous temperature measurements in the inflow and lake surface it was estimated that the river plunged and penetrated the lake as an interflow or underflow for 60.2 % of the year. This translated into 31 % of the N and 64% of the P loading on the lake. The river also injected phytoplankton into the main basin of Lake Rotoiti, including populations of bloom-forming cyanobacteria. The underflow was the dominant term in calculating the hydraulic flushing time of the main basin, and also made a large contribution of dissolved oxygen to the subsurface waters. These complex interactions between Lake Rotoiti and its inflowing river were controlled by small temperature differences (<3 C), and had wide-ranging implications in the eutrophication process

Targeted therapy for advanced salivary gland carcinoma based on molecular profiling: Results from MyPathway, a phase IIa multiple basket study

BACKGROUND: Systemic therapy options for salivary cancers are limited. MyPathway (NCT02091141), a phase IIa study, evaluates targeted therapies in non-indicated tumor types with actionable molecular alterations. Here, we present the efficacy and safety results for a subgroup of MyPathway patients with advanced salivary gland cancer (SGC) matched to targeted therapies based on tumor molecular characteristics. PATIENTS AND METHODS: MyPathway is an ongoing, multiple basket, open-label, non-randomized, multi-center study. Patients with advanced SGC received pertuzumab + trastuzumab (HER2 alteration), vismodegib (PTCH-1/SMO mutation), vemurafenib (BRAF V600 mutation), or atezolizumab [high tumor mutational burden (TMB)]. The primary endpoint is the objective response rate (ORR). RESULTS: As of January 15, 2018, 19 patients with SGC were enrolled and treated in MyPathway (15 with HER2 amplification and/or overexpression and one each with a HER2 mutation without amplification or overexpression, PTCH-1 mutation, BRAF mutation, and high TMB). In the 15 patients with HER2 amplification/overexpression (with or without mutations) who were treated with pertuzumab + trastuzumab, 9 had an objective response (1 complete response, 8 partial responses) for an ORR of 60% (9.2 months median response duration). The clinical benefit rate (defined by patients with objective responses or stable disease \u3e4 months) was 67% (10/15), median progression-free survival (PFS) was 8.6 months, and median overall survival was 20.4 months. Stable disease was observed in the patient with a HER2 mutation (pertuzumab + trastuzumab, n = 1/1, PFS 11.0 months), and partial responses in patients with the PTCH-1 mutation (vismodegib, n = 1/1, PFS 14.3 months), BRAF mutation (vemurafenib, n = 1/1, PFS 18.5 months), and high TMB (atezolizumab, n = 1/1, PFS 5.5+ months). No unexpected toxicity occurred. CONCLUSIONS: Overall, 12 of 19 patients (63%) with advanced SGC, treated with chemotherapy-free regimens matched to specific molecular alterations, experienced an objective response. Data from MyPathway suggest that matched targeted therapy for SGC has promising efficacy, supporting molecular profiling in treatment determination

Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study.

BACKGROUND: Therapies targeting HER2 have improved clinical outcomes in HER2-positive breast and gastric cancers, and are emerging as potential treatments for HER2-positive metastatic colorectal cancer. MyPathway evaluates the activity of targeted therapies in non-indicated tumour types with potentially predictive molecular alterations. We aimed to assess the activity of pertuzumab and trastuzumab in patients with HER2-amplified metastatic colorectal cancer. METHODS: MyPathway is an ongoing, phase 2a, multiple basket study. Patients in this subset analysis were aged 18 years or older and had treatment-refractory, histologically confirmed HER2-amplified metastatic colorectal cancer with measurable or evaluable disease and an Eastern Cooperative Oncology Group performance status score of 2 or less, enrolled from 25 hospitals or clinics in 16 states of the USA. Patients received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks, intravenously) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks, intravenously). The primary endpoint was the proportion of patients who achieved an objective response based on investigator-reported tumour responses. Analyses were done per protocol. This ongoing trial is registered with ClinicalTrials.gov, number NCT02091141. FINDINGS: Between Oct 20, 2014, and June 22, 2017, 57 patients with HER2-amplified metastatic colorectal cancer were enrolled in the MyPathway study and deemed eligible for inclusionin this cohort analysis. Among these 57 evaluable patients, as of Aug 1, 2017, one (2%) patient had a complete response and 17 (30%) had partial responses; thus overall 18 of 57 patients achieved an objective response (32%, 95% CI 20-45). The most common treatment-emergent adverse events were diarrhoea (19 [33%] of 57 patients), fatigue (18 [32%] patients), and nausea (17 [30%] patients). Grade 3-4 treatment-emergent adverse events were recorded in 21 (37%) of 57 patients, most commonly hypokalaemia and abdominal pain (each three [5%] patients). Serious treatment-emergent adverse events were reported in ten (18%) patients and two (4%) of these adverse events (ie, chills and infusion-related reaction) were considered treatment related. There were no treatment-related deaths. INTERPRETATION: Dual HER2-targeted therapy with pertuzumab plus trastuzumab is well tolerated and could represent a therapeutic opportunity for patients with heavily pretreated, HER2-amplified metastatic colorectal cancer. FUNDING: F Hoffmann-La Roche/Genentech

Questioning cultural narratives of economic development—an investigation of Kitchener-Waterloo

The version of record [Spigel, B. & Bathelt, H. (2019). Questioning cultural narratives of economic development - An investigation of Kitchener-Waterloo. Canadian Geographer, 63(2), 267-283.] is available online at: https://onlinelibrary.wiley.com/doi/abs/10.1111/cag.12512This paper investigates the relationship between culture and economy and scrutinizes cultural narratives of economic development in Kitchener-Waterloo, southern Ontario. It argues for the need to carefully conceptualize the link between culture and economic development to avoid boosting deterministic stereotypes. In the case of Kitchener-Waterloo, a notable hub of high-technology firms and technology development, a link is frequently drawn between the German community and culture and the region’s technology economy and entrepreneurial culture. A social capital analysis, however, reveals that the German ethnic community neither has the strong professional internal ties nor the external social ties to other regional communities that could constitute a lead role in economic development. Rather, the legacy of Kitchener-Waterloo’s ethnic German population has been absorbed into the region’s self-image and creates a feeling of belonging and common reference points for joint social and economic initiatives in the region

Triple malignancy in a single patient including a cervical carcinoma, a basal cell carcinoma of the skin and a neuroendocrine carcinoma from an unknown primary site: A case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>The occurrence of multiple primary cancers is rare. Only a few cases and patient reviews of an association of triple malignancy have been reported.</p> <p>Case presentation</p> <p>We report here a case of a 78-year-old Moroccan woman presenting initially with a synchronous double malignancy, the first in her cervix and the second in her skin. Our patient was treated with radiation therapy for both tumors and remained in good control for 17 years, when she developed a metastatic disease from a neuroendocrine carcinoma of an unknown primary site.</p> <p>Conclusions</p> <p>Although the association of multiple primary cancers can be considered a rare occurrence, improving survival in cancer patients has made this situation more frequent.</p

Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study

PURPOSE: Detection of specific molecular alterations in tumors guides the selection of effective targeted treatment of patients with several types of cancer. These molecular alterations may occur in other tumor types for which the efficacy of targeted therapy remains unclear. The MyPathway study evaluates the efficacy and safety of selected targeted therapies in tumor types that harbor relevant genetic alterations but are outside of current labeling for these treatments. METHODS: MyPathway (ClinicalTrials.gov identifier: NCT02091141) is a multicenter, nonrandomized, phase IIa multiple basket study. Patients with advanced refractory solid tumors harboring molecular alterations in human epidermal growth factor receptor-2, epidermal growth factor receptor, v-raf murine sarcoma viral oncogene homolog B1, or the Hedgehog pathway are treated with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. The primary end point is investigator-assessed objective response rate within each tumor-pathway cohort. \ud RESULTS: Between April 1, 2014 and November 1, 2016, 251 patients with 35 different tumor types received study treatment. The efficacy population contains 230 treated patients who were evaluated for response or discontinued treatment before evaluation. Fifty-two patients (23%) with 14 different tumor types had objective responses (complete, n = 4; partial, n = 48). Tumor-pathway cohorts with notable objective response rates included human epidermal growth factor receptor-2–amplified/overexpressing colorectal (38% [14 of 37]; 95% CI, 23% to 55%) and v-raf murine sarcoma viral oncogene homolog B1 V600-mutated non–small-cell lung cancer (43% [six of 14]; 95% CI, 18% to 71%). CONCLUSIONS: The four currently approved targeted therapy regimens in the MyPathway study produced meaningful responses when administered without chemotherapy in several refractory solid tumor types not currently labeled for these agents