The nematode (worm) C. elegans is a leading multicellular animal model to study neuronal-basis of behavior. Worms respond to a wide range of stimuli and exhibit characteristic movement patterns. Here we describe the use of a microfluidics setup to probe neuronal activity that relies on the innate response of C. elegans to swim toward the cathode in the presence of a DC electric field (termed “electrotaxis”). Using this setup, we examined mutants affecting sensory and dopaminergic neurons and found that their electrotactic responses were defective. Such animals moved with reduced speed (35–80% slower than controls) with intermittent pauses, abnormal turning and slower body bends. A similar phenotype was observed in worms treated with neurotoxins 6-OHDA (6- hydroxy dopamine), MPTP (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine) and rotenone (20–60% slower). We also found that neurotoxin effects could be suppressed by pre-exposing worms to a known neuroprotective compound acetaminophen. Collectively, these results show that microfluidic electrotaxis can identify alterations in dopamine and amphid neuronal signaling based on swimming responses of C. elegans. Further characterization has revealed that the electrotactic swimming response is highly sensitive and reliable in detecting neuronal abnormalities. Thus, our microfluidics setup could be used to dissect neuronal function and toxin-induced neurodegeneration. Among other applications, the setup promises to facilitate genetic and chemical screenings to identify factors that mediate neuronal signaling and neuroprotection.
36 Background: The medical specialty of oncology relies heavily on clinical trials to advance policies and practices related to cancer care. However, oncology clinical trial accrual in Ontario has dropped from 12.4% in 2007, to 8.5% in 2009. The objective of this study was to determine barriers experienced by Oncologists and Clinical Research Personnel (CRP) in recruiting patients to oncology trials in Ontario. Methods: In June 2012, an electronic survey was emailed to about 400 oncologists and CRP across Ontario. Variables of interest included demographic data, clinical trial involvement, and perceived barriers to participation in clinical trials amongst three previously identified barrier domains. Barriers were ranked, from 1 (least significant) to 5 (most significant). Statistics were compiled using Graphpad Prism software. Differences in responses were analyzed using the Kruskal – Wallis test and Dunn’s Multiple Comparison Test. Results: Of the 400 emails sent, there were 126 respondents (32%). Of the 126 respondents, 82 fully completed the survey (64.6% useable response rate). Amongst system related barriers, “time related” (Median Agreement (M): 4, Inter Quartile Range (IQR): 3-5), and “resource related” barriers (M: 4, IQR: 3-5) had the most negative effect on accrual (p<0.05). Amongst trial design barriers, “Relevance to patient population” (M: 3, IQR: 3-5), “Deviation from Standard of Care” (M: 3, IQR: 3-5) and “Complexity of Trial Protocol” (M: 4, IQR: 3-5) were the most significant barriers (p<0.05). Lastly, amongst personal barriers, “Commitment of the Principal Investigator/Research Staff” (M: 4, IQR: 3-5) and Drug Safety (M: 4, IQR: 2-4) were the most significant barriers to recruitment (p<0.05). Conclusions: Multiple barriers were identified as having a significant impact on patient accrual in clinical trials. Addressing these barriers prospectively in clinical trial design may benefit future studies to successfully accrue cancer patients. Also, creating clinical trial collaboration vehicles amongst sites in similar geographical areas may contribute to improving patient accrual to clinical trials.
527 Background: Cancer Care Ontario (CCO) guidelines advise that colorectal cancer (CRC) patients receive their first adjuvant chemotherapy (AC) no later than 8 weeks after surgical resection, with new data suggesting optimal treatment to commence between 4 and 6 weeks. This retrospective study was performed to determine treatment timelines and identify barriers at St. Michael’s Hospital (SMH). Methods: Of the 507 patients diagnosed with CRC between Jan 1, 2005 and May 1, 2012 at SMH, 304 patients had stage II or III CRC. Our sample population of 159 patients received both surgical resection and AC at SMH. Data collected included: time between surgery and first AC, patient demographics, systemic/clinical barriers and recurrence-free survival. Data was analyzed using SAS statistical software assuming p-values <0.05 as significant. Results: Of our 159 patients, mean age was 61.3 years (range 28 – 91); 54% male and 70% had stage III disease; colon cancer (64%) and mean follow-up was 2.2 years (range 0.1 – 5.7). Mean time from surgery to first AC was 50.4 days (sd = 15.8) or 7.2 weeks ranging from 3 to almost 17 weeks. Medical complications affected 21.4% of patients. The presence of a complication was associated with delay in AC (9.5 days, p=0.001). Moreover, 11.1% of patients were excluded from sample, since complications exceeded treatment past 12 weeks, equating to no AC. Referral from surgeon averaged 21 days (sd=12.0), 10 days awaiting pathology. Medical Oncology consult to first AC averaged 19 days (sd=12.7), 12 days awaiting port-a-cath insertion. Each part of referral process was correlated with delay to AC. Only 18.9% of patients recurred. While trends were identified, association between delay and recurrence was weak (p=0.1457). Medical complication correlated strongly with recurrence (p=0.0472). Patients with complications had a higher rate of recurrence (32.4% vs 15.2%). Conclusions: Compliance to current CCO guidelines can be optimized in CRC patients at SMH. Barriers to timely treatment include patient age, timely referral and presence of a medical complication. Quality improvement rapid cycling of confounding barriers will be used prospectively to lower variance and achieve greater consistency in treatment.
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