Misunderstanding the Match: Do Students Create Rank Lists Based on True Preferences?

INTRODUCTION: The "stable marriage" algorithm underlying the National Residency Match Program (NRMP) has been shown to create optimal outcomes when students submit true preference lists. Previous research has shown students may allow external information to affect their rank lists. The objective of this study was to determine whether medical students consistently make rank lists that reflect their true preferences. METHODS: A voluntary online survey was sent to third-year students at a single midwestern medical school. Students were given hypothetical scenarios that either should or should not affect their true residency preferences and rated the importance of six factors to their final rank list. The survey was edited by a group of education scholars and revised based on feedback from a pilot with current postgraduate year 1 residents. RESULTS: Of 175 students surveyed, 140 (80%) responded; 63% (88/140) reported that their "perceived competitiveness" would influence their rank list at least a "moderate amount. Of 135 students, 31 (23%) moved a program lower on their list if they learned they were ranked "low" by that program, while 6% (8/135) of respondents moved a program higher if they learned they were ranked "at the top of the list." Participants responded similarly (κ = 0.71) when presented with scenarios asking what they would do vs what a classmate should do. CONCLUSION: Students' hypothetical rank lists did not consistently match their true residency preferences. These results may stem from a misunderstanding of the Match algorithm. Medical schools should consider augmenting explicit education related to the NRMP Match algorithm to ensure optimal outcomes for students.

Sedimentation Velocity Analysis with Fluorescence Detection of Mutant Huntingtin Exon 1 Aggregation in Drosophila melanogaster and Caenorhabditis elegans.

At least nine neurodegenerative diseases that are caused by the aggregation induced by long tracts of glutamine sequences have been identified. One such polyglutamine-containing protein is huntingtin, which is the primary factor responsible for Huntington's disease. Sedimentation velocity with fluorescence detection is applied to perform a comparative study of the aggregation of the huntingtin exon 1 protein fragment upon transgenic expression in Drosophila melanogaster and Caenorhabditis elegans. This approach allows the detection of aggregation in complex mixtures under physiologically relevant conditions. Complementary methods used to support this biophysical approach included fluorescence microscopy and semidenaturing detergent agarose gel electrophoresis, as a point of comparison with earlier studies. New analysis tools developed for the analytical ultracentrifuge have made it possible to readily identify a wide range of aggregating species, including the monomer, a set of intermediate aggregates, and insoluble inclusion bodies. Differences in aggregation in the two animal model systems are noted, possibly because of differences in levels of expression of glutamine-rich sequences. An increased level of aggregation is shown to correlate with increased toxicity for both animal models. Co-expression of the human Hsp70 in D. melanogaster showed some mitigation of aggregation and toxicity, correlating best with inclusion body formation. The comparative study emphasizes the value of the analytical ultracentrifuge equipped with fluorescence detection as a useful and rigorous tool for in situ aggregation analysis to assess commonalities in aggregation across animal model systems.

Studying polyglutamine aggregation in Caenorhabditis elegans using an analytical ultracentrifuge equipped with fluorescence detection.

This work explores the heterogeneity of aggregation of polyglutamine fusion constructs in crude extracts of transgenic Caenorhabditis elegans animals. The work takes advantage of the recent technical advances in fluorescence detection for the analytical ultracentrifuge. Further, new sedimentation velocity methods, such as the multi-speed method for data capture and wide distribution analysis for data analysis, are applied to improve the resolution of the measures of heterogeneity over a wide range of sizes. The focus here is to test the ability to measure sedimentation of polyglutamine aggregates in complex mixtures as a prelude to future studies that will explore the effects of genetic manipulation and environment on aggregation and toxicity. Using sedimentation velocity methods, we can detect a wide range of aggregates, ranging from robust analysis of the monomer species through an intermediate and quite heterogeneous population of oligomeric species, and all the way up to detecting species that likely represent intact inclusion bodies based on comparison to an analysis of fluorescent puncta in living worms by confocal microscopy. Our results support the hypothesis that misfolding of expanded polyglutamine tracts into insoluble aggregates involves transitions through a number of stable intermediate structures, a model that accounts for how an aggregation pathway can lead to intermediates that can have varying toxic or protective attributes. An understanding of the details of intermediate and large-scale aggregation for polyglutamine sequences, as found in neurodegenerative diseases such as Huntington's Disease, will help to more precisely identify which aggregated species may be involved in toxicity and disease.

Clinical implications of alpha-fetoprotein expression in gastric adenocarcinoma.

BACKGROUND: Alpha-fetoprotein (AFP)-producing gastric adenocarcinoma has an extremely poor prognosis. Few cases have been reported in Germany until now. Here we report on a patient with an AFP-producing gastric cancer and a subsequent analysis of AFP expression in a more extended series of gastric cancer patients. MATERIAL AND METHODS: A 62-year-old man was referred to our hospital with suspected gastric cancer. Gastroscopy, ultrasound, and CT scans of the abdomen showed a gastric tumour. Serological and histopathological investigations led to the diagnosis of a poorly differentiated adenocarcinoma expressing AFP. Following diagnosis, a short-term response was achieved by palliative chemotherapy. Expression of AFP and albumin was then investigated on an extended series of 25 patients with gastric cancer and four gastric cancer cell lines using immunohistochemistry and RT-PCR. No patient had suffered from hepatocellular carcinoma or germ cell tumor. RESULTS: Using paraffin-embedded gastric cancer specimens, we found AFP immunohistochemically in 2 of 25 (8%) patients. AFP-mRNA was expressed in 3 (12%) patients and a single gastric cancer cell line (AGS). Albumin-mRNA was not found in any gastric cancer sample or gastric cancer cell line. CONCLUSIONS: Our study shows that AFP-producing gastric adenocarcinomas are an important clinical entity with a frequency that has been underestimated in the past. In the absence of a primary liver tumor, clinicians have to consider a primary gastric cancer, which has a poor prognosis, and merits a more aggressive therapy.