Prostate-specific membrane antigen (PSMA) is overexpressed in most prostate adenocarcinoma (AdPC) cells and acts as a target for molecular imaging. However, some case reports indicate that PSMA-targeted imaging could be ineffectual for delineation of neuroendocrine (NE) prostate cancer (NEPC) lesions due to the suppression of the PSMA gene (FOLH1). These same reports suggest that targeting somatostatin receptor type 2 (SSTR2) could be an alternative diagnostic target for NEPC patients. This study evaluates the correlation between expression of FOLH1, NEPC marker genes and SSTR2. We evaluated the transcript abundance for FOLH1 and SSTR2 genes as well as NE markers across 909 tumors. A significant suppression of FOLH1 in NEPC patient samples and AdPC samples with high expression of NE marker genes was observed. We also investigated protein alterations of PSMA and SSTR2 in an NE-induced cell line derived by hormone depletion and lineage plasticity by loss of p53. PSMA is suppressed following NE induction and cellular plasticity in p53-deficient NEPC model. The PSMA-suppressed cells have more colony formation ability and resistance to enzalutamide treatment. Conversely, SSTR2 was only elevated following hormone depletion. In 18 NEPC patient-derived xenograft (PDX) models we find a significant suppression of FOLH1 and amplification of SSTR2 expression. Due to the observed FOLH1-supressed signature of NEPC, this study cautions on the reliability of using PMSA as a target for molecular imaging of NEPC. The observed elevation of SSTR2 in NEPC supports the possible ability of SSTR2-targeted imaging for follow-up imaging of low PSMA patients and monitoring for NEPC development.

No abstract

This study examines safety seat use among Canadian children and evaluates child safety seat use relative to the national policy for child occupant safety, Road Safety Vision 2010. Using a probability sample, roadside observations of car safety seat use were collected from May to October of 2006 for 13,500 children aged from birth to 9 years in 10,084 vehicles at 182 sites in nine Canadian provinces and one territory. Observations revealed that 89.9% of Canadian children were restrained in some type of restraint. However, only 60.5% of these children were restrained in the correct safety seat. When comparing rates of correct use across provinces, results were not significantly different in provinces with booster seat legislation and those without this legislation. This data may be useful for healthcare practitioners and policy makers to develop interventions aimed at increasing appropriate car safety seat use for children in Canada.

This is the first Canadian national study using direct observation to determine the effect of legislation on booster seat use. Provinces with legislation had higher booster seat use, but overall rates were still disappointingly low. Ongoing surveillance of child safety seat use and evaluation of effective adjuncts to legislation is required in order to see collision-related child deaths and injuries drop in the future.

Monitoring binary outcomes when evaluating health care performance has recently become common. Classical statistical methodologies such as cumulative sum (CUSUM) charts have been refined and used for this purpose. For instance, the risk-adjusted CUSUM chart (RA-CUSUM) for monitoring binary outcomes was proposed for monitoring 30-day mortality following cardiac surgery. The RA-CUSUM inherits optimality properties of the original CUSUM charts in the sense of signaling early when there is change. However, although the RA-CUSUM is a powerful monitoring tool, it will always eventually signal a change with probability 1 even when there is no real change. In other words, the probability of a type I error for the RA-CUSUM is 1. It also turns out that, because of the skewed distribution of the run lengths of the RA-CUSUM, the median is often well below the mean, and as a consequence more than half of all its false alarms occur before the designed average run length. In addition, when the change to be detected occurs at a later time in the series of observations being monitored, the rate of false alarms increases, and the RA-CUSUM may not be appropriate. Therefore, if the price of false alarms is high, it is preferable to use methods that control the rate of false alarms. In this paper, we propose alternative sequential curtailed and risk-adjusted charts that control the type I error rate in the context of monitoring 30-day mortality following cardiac surgery. We explore the merits of each of these methodologies in terms of average run lengths as well as in terms of type I error probabilities, and we compare them to the RA-CUSUM chart. We illustrate the methodologies by using data on monitoring performance of seven surgeons from a medical center.

This pilot study compared a novel electronic Montreal Cognitive Assessment (eMoCA) tool to the original paper-based MoCA. Potential participants were approached at primary care practices, a geriatric day hospital, and a university campus. Each of the 401 participants were randomly assigned to either the eMoCA (N=182) or MoCA (N=219). Scores were adjusted by self-reported demographic and health information using regression analysis. The difference in average scores (26.21±3.11 for the MoCA group and 24.84±4.21 for the eMoCA group) was found to be statistically significant. Controlling for the effect of potential covariate factors with regression analyses, the adjusted difference is -0.90 (95% confidence interval, -1.45 to -0.35). This difference may be due to factors related to use of the electronic device or software usability. However, the standardized, self-administered eMoCA may offer an opportunity for health systems to screen for early changes in cognitive function in primary care settings and offer greater access to assessment for rural or remote communities. Population-level research may be required to identify whether the score difference between test versions requires a downward adjustment to the eMoCA score taken as indicative of cognitive impairment.

The findings from this study suggest that child safety seat legislation has an impact on restraint use in Canada. Despite the increase in rates of child safety seat use in provinces with new legislation and stable rates in provinces with old legislation, use rates remain low. Injury prevention strategies including further surveillance, interventions, and enforcement of restraint use in children are important to decrease motor vehicle related injury and death.

No abstract