Summary: Cre-expressing mouse lines constitute an important asset to mammalian genetics, allowing the deletion of genes in a spatio-temporal specific manner. Our study on Hox gene function in lung development has led us to use a lung endoderm-specific deletion with the Sftpc-cre mouse line expressing the Cre recombinase gene under the control of human surfactant protein C regulatory sequences. In control experiments, the Cre recombinase faithfully activated the Rosa26-lacZ reporter gene in lung epithelium. However as early as e15.5, lungs from Sftp-Cre 1 embryos showed abnormal dilated cysts. This unexpected phenotype was also observed in mice carrying the conditional lung epithelial Hoxa5 deletion, indicating some bias due to Cre deleterious effects. Excessive apoptosis, likely due to Cre toxicity, could explain the abnormal cysts. Our findings illustrate the need for appropriate control experiments and careful interpretation of data to discriminate between the phenotype due to the targeted mutation and the confounding effects of the Cre recombinase. genesis 49:152-159, 2011. V V C 2011 Wiley-Liss, Inc.

BACKGROUND:The drug approval timeline is a lengthy process that often varies between countries. The objective of this study was to delineate the Canadian drug approval timeline for oncology drugs and to compare the time to drug approval between Health Canada (HC) and the US Food and Drug Administration (FDA). METHODS: In total, 54 antineoplastic drugs that were approved by the FDA between 1989 and 2012 were reviewed. For each drug, the following milestones were determined: the dates of submission and approval for both the FDA and HC and the dates of availability on provincial drug formularies in Canadian provinces and territories. The time intervals between the aforementioned milestones were calculated. RESULTS: Of 54 FDA-approved drugs, 49 drugs were approved by HC at the time of the current study. The median time from submission to approval was 9 months (interquartile range [IQR], 6-14.5 months) for the FDA and 12 months (IQR, 10-21.1 months) for HC (P <.0006). The time from HC approval to the placement of a drug on a provincial drug formulary was a median of 16.7 months (IQR, 5.9-27.2 months), and there was no interprovincial variability among the 5 Canadian provinces that were analyzed (P 5.5). CONCLUSIONS: The time from HC submission to HC approval takes 3 months longer than the same time interval for the FDA. To the authors' knowledge, this is the first documentation of the time required to bring an oncology drug from HC submission to placement on a provincial drug formulary. Cancer 2015;121:1688-93. In the United States, drugs are generally available to all states after FDA approval. In Canada, the drug approval process begins after HC receives a new drug submission application by the drug company. Subsequently, drug safety, efficacy, and quality data are evaluated to assess the potential risks and benefits of the drug. After HC approval, provincial health ministries make independent decisions regarding funding for HC-approved drugs. After approval by the provincial health ministry, a drug is placed on the provincial formulary and is routinely available for patients who meet prespecified indications. This introduces interprovincial variability with respect to which drugs are approved for funding and the length of time required for final approval.The objective of the current study was to delineate the Canadian drug approval timeline for anticancer drugs and to compare the time to drug approval between HC and the FDA. Milestones in the process were determined, including the date of submission to the regulatory authority, the date of regulatory approval, and the date of placement on a provincial formulary. In light of the increasing use of targeted anticancer therapy, comparison was made between these novel agents and traditional cytotoxic agents.

IntroductionTo alleviate some of the burden associated with the development of novel quality questions on a regular basis, medical education programs may favour the use of item banks. This practice answers the real pragmatic need of having to create exams de novo at each administration while benefiting from using psychometrically sound questions to assess students. Unfortunately, programs cannot prevent trainees from engaging in cheating behaviours such as content sharing, and little is known about the impact of re-using items.MethodsWe conducted an exploratory descriptive study to assess the effect of repeated use of banked items within an in-house assessment context. The difficulty and discrimination coefficients for the 16-unit exams of the past 5 years (1,629 questions) were analyzed using repeated measure ANOVAs.ResultsDifficulty coefficients increased significantly (M = 79.8% for the first use of an item, to a mean difficulty coefficient of 85.2% for the fourth use) and discrimination coefficients decreased significantly with repeated uses (M = 0.17, 0.16, 0.14, 0.14 for the first, second, third and fourth uses respectively).DiscussionThe results from our study suggest that using an item three times or more within a short time span may cause a significant risk to its psychometric properties and consequently to the quality of the examination. Pooling items from different institutions or the recourse to automatic generated items could offer a greater pool of questions to administrators and faculty members while limiting the re-use of questions within a short time span.