Milwaukie Downtown Revitalization Project: The Milwaukie Storefront (Final Report)

The Milwaukie Storefront was a one year program intended as a catalyst for the downtown and to focus attention on the potential for improved business activity. The Storefront, initiated in September of 1983, served as a technical resource, and as a coordinator and facilitator of promotional events in downtown Milwaukie. This report describes the Storefront as an organization, looking at its structure and original purpose. A review of the individual projects is presented to demonstrate the range of Storefront activities. In drawing conclusions, the report looks at whether the Storefront was able to meet its expectations and cites the accomplishments and problems that were experienced. The report finally looks at the Storefront\u27s activities and applies them in a broader perspective to small town or neighborhood commercial revitalization programs

Business Liaison Collaboration: A Case Study

The academic library has always been known as a place to go for a book, journal article, or item on reserve. During the past decade the format of these sources has changed from primarily print resources to a mix of print and electronic. Traditional resources and services have expanded to become electronically available from one’s desktop. Accessing online scholarly materials is challenging for both the librarian and faculty member. But while the tools of scholarly research have changed, the need for library instruction remains: “Since most faculty find it difficult to keep up with the rapid growth in electronic information sources, instructional librarians need to instruct both students and faculty about these new sources.” [1] Just as the tools have changed, instruction has expanded to include collaboration between librarians and faculty. As the role of the librarian has evolved to support the learning environment, collaboration has emerged as a key element in liaison relationships with faculty. The Business Liaison Team at the University of Louisville Libraries collaborated with College of Business and Public Administration faculty to offer a new series of workshops called Research Refreshers, designed to highlight specific electronic resources and demonstrate how to effectively use them

Prevention and Management of Bone Metastases in Lung Cancer: A Review

Abstract:Approximately 30 to 40% of patients with advanced lung cancer will develop bone metastases in the course of their disease, resulting in a significant negative impact on both morbidity and survival. Skeletal complications of bone metastases include pain, pathologic fractures, spinal cord compression, and hypercalcemia. Total medical care costs are greater among patients with bone metastases who develop skeletal complications. A randomized phase III trial of the third generation bisphosphonate zoledronic acid has shown clinical benefit in the management of a subgroup of patients with bone metastases from lung cancer. Zoledronic acid treatment was associated with a reduction in both the risk of, and time to, a skeletal-related event. One of the markers of bone resorption, N-telopeptide, is both prognositic for development of skeletal-related events and predictive for benefit from zoledronic acid. In preclinical models, bisphosphonates have also demonstrated antitumor activity and are therefore currently being evaluated in adjuvant trials. Inhibition of the receptor activator of nuclear factor kappa B ligand-RANK pathway can reduce osteoclast-mediated bone resorption, and trials comparing receptor activator of nuclear factor kappa B ligand inhibitors with bisphosphonates are ongoing, including patients with lung cancer. In this article, we review the management of bone metastases and hypercalcemia as well as potential future directions for bone directed therapies in patients with lung cancer

Correlation of baseline biomarkers with clinical outcomes and response to fulvestrant with vandetanib or placebo in patients with bone predominant metastatic breast cancer: An OCOG ZAMBONEY sub-study

AbstractBackgroundBone metastases are common in women with breast cancer and often result in skeletal related events (SREs). As the angiogenic factor vascular endothelial growth factor (VEGF) regulates osteoclast activity and is associated with more extensive bone metastases and SRE risk in metastatic breast cancer, we hypothesized that blockade of VEGF signaling could be a therapeutic strategy for inhibiting bone metastases progression and possibly prolonging overall (OS) or progression-free survival (PFS). The Zamboney trial was a randomized placebo-controlled study designed to assess whether patients with bone predominant metastatic breast cancer benefited from addition of the VEGF receptor (VEGFR) targeting agent, vandetanib, to endocrine therapy with fulvestrant. As a companion study, evaluation of biomarkers and their potential association with response to vandetanib or SRE risk was performed.MethodsBaseline overnight fasted serum from enrolled patients was analyzed for levels of various putative biomarkers including; VEGF-A, soluble (s)VEGFR2, sVEGFR3, transforming growth factor (TGF)-β1 and activinA by ELISA. Spearman correlation coefficients and Wilcoxon rank sum tests were used to investigate potential relationships between biomarker values and baseline clinical parameters. Prognostic and predictive ability of each marker was investigated using Cox proportional hazards regression with adjustments for treatment and baseline strata of serum CTx (<400 versus ≥400ng/L).ResultsOf 129 enrolled patients, serum was available for analysis in 101; 51 in vandetanib and 50 in placebo arm. Mean age amongst consenting patients was 59.8 years. Clinical characteristics were not significantly different between patients with or without serum biomarker data and serum markers were similar for patients by treatment arm. Baseline sVEGFR2 was prognostic for OS (HR=0.77, 95% CI=0.61–0.96, p=0.020), and although a modest association was observed, it was not significant for PFS (HR=0.90, 95% CI=0.80–1.01, p=0.085) nor time to first SRE (HR=0.82, 95% CI=0.66–1.02, p=0.079). When interaction terms were evaluated, sVEGFR2 was not found to be predictive of response to vandetanib, although a modest association remained with respect to PFS (interaction p=0.085). No other marker showed any significant prognostic or predictive ability with any measured outcome.ConclusionsIn this clinical trial, sVEGFR2 appeared prognostic for OS, hence validation of sVEGFR2 should be conducted. Moreover, the role of sVEGFR2 in breast cancer bone metastasis progression should be elucidated

Patient perceptions and expectations regarding imaging for metastatic disease in early stage breast cancer

Abstract Purpose The probability of detecting radiologically evident metastatic disease in asymptomatic women with newly diagnosed operable breast cancer is low. Despite the recommendations of most practice guidelines imaging is still frequently performed. Relatively little is known about what patients believe is important when it comes to radiologic staging. Methods Patients with early stage breast cancer who had completed their definitive breast surgery were surveyed about their personal experiences, perceptions, and expectations on the issue of perioperative imaging for distant metastatic disease. Results Over a 3 month period, 245 women with primary operable breast cancer completed the questionnaire (87.0% response rate) and 80.8% indicated having had at least one imaging test for distant metastatic disease. These were either of the thorax (72.2%), abdomen (55.9%) or skeleton (65.3%) with a total of 701 imaging tests (average of 3.5 tests per patient imaged) performed. Overall, 57.1% indicated that they would want imaging done if the chance of detecting metastases was ≤10%. Although 80.0% of patients indicated that, “doing whatever their doctor recommended” was important to them, 70.4% also noted that they would be uncomfortable if their physician did not order imaging, even if this was in keeping with practice guidelines. Conclusions Most patients with early stage breast cancer recall having imaging tests for distant metastases. Given the choice, most would prefer having imaging performed, even if this is not in line with current guidelines. If patient expectations are, in part, driving excessive imaging, new strategies addressing this are required

ABCC5 supports osteoclast formation and promotes breast cancer metastasis to bone

INTRODUCTION: Bone is the most common site of breast cancer metastasis, and complications associated with bone metastases can lead to a significantly decreased patient quality of life. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases. METHODS: To search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene-expression profiles from laser-capture microdissected trephine biopsies of both breast cancer bone metastases and independent primary breast tumors that metastasized to bone. Bioinformatics analysis identified genes that are differentially expressed in breast cancer bone metastases compared with primary, bone-metastatic breast tumors. RESULTS: ABCC5, an ATP-dependent transporter, was found to be overexpressed in breast cancer osseous metastases relative to primary breast tumors. In addition, ABCC5 was significantly upregulated in human and mouse breast cancer cell lines with high bone-metastatic potential. Stable knockdown of ABCC5 substantially reduced bone metastatic burden and osteolytic bone destruction in mice. The decrease in osteolysis was further associated with diminished osteoclast numbers in vivo. Finally, conditioned media from breast cancer cells with reduced ABCC5 expression failed to induce in vitro osteoclastogenesis to the same extent as conditioned media from breast cancer cells expressing ABCC5. CONCLUSIONS: Our data suggest that ABCC5 functions as a mediator of breast cancer skeletal metastasis. ABCC5 expression in breast cancer cells is important for efficient osteoclast-mediated bone resorption. Hence, ABCC5 may be a potential therapeutic target for breast cancer bone metastasis

Using technology to develop transferable skills and enhance the laboratory experience in first year chemistry

Background The laboratory has the potential to be a rich learning environment for students in any science discipline. (Hofstein and Lunetta 2004) The evolving nature of the job market in the 21st century has demanded that graduates leave university equipped with a broad range of generalised attributes. From an early stage in tertiary education, laboratory classes must reflect this need by actively highlighting skills such as: communication, problem solving, critical thinking and teamwork as well as practical competency. Herein lies the problem for educators in that these skills are inherently logistically difficult to assess and require a degree of self-reflection in order to be properly developed. Thus laboratory classes, associated assessments and learning resources must be adapted to provide students with tangible evidence of their development of these skills and to provide opportunities for institutional and self-directed feedback. (Galloway and Bretz 2015) Aims This project aims to develop technology-enhanced methods to highlight and enable students to receive automatic feedback on a particular generic skill that is being assessed in a laboratory. We have two objectives in this project: • To develop pre-laboratory activities which enhance problem solving and critical thinking skills. • To develop a usable, motivating online feedback system to assist students to develop and track practical skills attainment over the course of their unit. Design and methods To evaluate the impact of the pre-laboratory activity students were asked to complete a survey, which aimed to answer the following research questions: • Did the pre laboratory activity prepare students for the laboratory practical? • Did the pre laboratory activity stimulate the students’ curiosity for the laboratory practical? To evaluate the impact of an online feedback system to develop and track practical skills we asked students to complete a survey, which aimed to answer the following research question: • Are the practical laboratory skills (and in-situ recall of practical theory) of students performing recrystallisation experiments improved by providing feedback in the form of online self-directed development exercises before subsequent attempts of those skills? We will also administer interviews with lab demonstrators about the techniques they use to teach and give feedback on practical skills as well as how they perceive students to perform specific tasks and their knowledge of specific practical theory. Results and Conclusion Preliminary data will be presented on two surveys given in semester 1 2016. Results from the first survey indicate that while students feel well prepared for the laboratory, more work is needed to stimulate their curiosity about the experimental procedure. Initial results of the second survey will provide the baseline of knowledge that students have of the recrystallisation laboratory skills in the current format. We will also gain insight from the demonstrators on how they perceive student development of practical skills. We will discuss the direction and approach we are taking in semester 2 2016 based on the preliminary data to improve and integrate feedback and assessment of practical, problem solving and critical thinking skills in the first year chemistry laboratory. References Galloway, K. R. and S. L. Bretz (2015). "Development of an Assessment Tool To Measure Students' Meaningful Learning in the Undergraduate Chemistry Laboratory." Journal of Chemical Education 92(7): 1149-1158. Hofstein, A. and V. N. Lunetta (2004). "The laboratory in science education: Foundations for the twenty-first century." Science Education 88(1): 28-54

Topical Application of an Irreversible Small Molecule Inhibitor of Lysyl Oxidases Ameliorates Skin Scarring and Fibrosis

Scarring is a lifelong consequence of skin injury, with scar stiffness and poor appearance presenting physical and psychological barriers to a return to normal life. Lysyl oxidases are a family of enzymes that play a critical role in scar formation and maintenance. Lysyl oxidases stabilize the main component of scar tissue, collagen, and drive scar stiffness and appearance. Here we describe the development and characterisation of an irreversible lysyl oxidase inhibitor, PXS-6302. PXS-6302 is ideally suited for skin treatment, readily penetrating the skin when applied as a cream and abolishing lysyl oxidase activity. In murine models of injury and fibrosis, topical application reduces collagen deposition and cross-linking. Topical application of PXS-6302 after injury also significantly improves scar appearance without reducing tissue strength in porcine injury models. PXS-6302 therefore represents a promising therapeutic to ameliorate scar formation, with potentially broader applications in other fibrotic diseases

A Phase II Randomized Double Blinded Trial Evaluating the Efficacy of Curcumin With Pre-operative Chemoradiation for Rectal Cancer

Background In vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome. Methods From 2008–2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. Blood samples taken pre- and 1-hour post-ingestion and tissue biopsies (both collected at CRT week 2) were analyzed for pharmacokinetics. The primary outcome was surgical pCR rate. Results Of 22 enrolled patients, 15 received curcumin. Median age was 61 years and the majority were male (n=13; 59%). The median serum curcumin concentrations before (3.04 ng/mL; range, 1.24–18.88 ng/mL) and 1 hour after (3.32 ng/mL; range, 0.84–5.36 ng/mL) curcumin intake did not differ significantly (P=0.33). Serum curcumin concentrations both increased and decreased 1-hour post-administration (range as percentage of baseline: 8.8–258.1%). Twelve curcumin patient tissue biopsies had median curcumin concentration of 33.7 ng/mg tissue (range, 0.1–4,765.7 ng/mg). Two placebo and 1 curcumin patient achieved pCRs (P=0.18). One grade 3 toxicity (infection) was experienced. Conclusions The addition of curcumin to CRT did not increase pCR rates for LARC patients. The unpredictable bioavailability of curcumin contributes to continued uncertainties regarding curcumin efficacy

The use of complementary and alternative medicines among patients with locally advanced breast cancer – a descriptive study

BACKGROUND: Complementary and alternative medicine (CAM) use is common among cancer patients. This paper reviews the use of CAM in a series of patients with locally advanced breast cancer (LABC). METHODS: Women with LABC attending a specialist clinic at a single Canadian cancer centre were identified and approached. Participants completed a self-administered survey regarding CAM usage, beliefs associated with CAM usage, views of their risks of developing recurrent cancer and of dying of breast cancer. Responses were scored and compared between CAM users and non-users. RESULTS: Thirty-six patients were approached, 32 completed the questionnaire (response rate 89%). Forty-seven percent of LABC patients were identified as CAM users. CAM users were more likely to be younger, married, in a higher socioeconomic class and of Asian ethnicity than non-users. CAM users were likely to use multiple modalities simultaneously (median 4) with vitamins being the most popular (60%). Motivation for CAM therapy was described as, "assisting their body to heal" (75%), to 'boost the immune system' (56%) and to "give a feeling of control with respect to their treatment" (56%). CAM therapy was used concurrently with conventional treatment in 88% of cases, however, 12% of patients felt that CAM could replace their conventional therapy. Psychological evaluation suggests CAM users perceived their risk of dying of breast cancer was similar to that of the non-Cam group (33% vs. 35%), however the CAM group had less severe anxiety and depression. CONCLUSION: The motivation, objectives and benefits of CAM therapy in a selected population of women with LABC are similar to those reported for women diagnosed with early stage breast cancer. CAM users display less anxiety and depression and are less likely to believe they will die of their breast cancer. However the actual benefit to overall and disease free survival has yet to be demonstrated, as well as the possible interactions with conventional therapy. Consequently more research is needed in this ever-growing field