Expansions and contractions of the FMR1 CGG repeat in 5,508 transmissions of normal,intermediate, and premutation alleles

Instability of the FMR1 repeat, commonly observed in transmissions of premutation alleles (55–200 repeats), is influenced by the size of the repeat, its internal structure and the sex of the transmitting parent. We assessed these three factors in unstable transmissions of 14/3,335 normal (~5 to 44 repeats), 54/293 intermediate (45–54 repeats), and 1561/1,880 premutation alleles. While most unstable transmissions led to expansions, contractions to smaller repeats were observed in all size classes. For normal alleles, instability was more frequent in paternal transmissions and in alleles with long 3′ uninterrupted repeat lengths. For premutation alleles, contractions also occurred more often in paternal than maternal transmissions and the frequency of paternal contractions increased linearly with repeat size. All paternal premutation allele contractions were transmitted as premutation alleles, but maternal premutation allele contractions were transmitted as premutation, intermediate, or normal alleles. The eight losses of AGG interruptions in the FMR1 repeat occurred exclusively in contractions of maternal premutation alleles. We propose a refined model of FMR1 repeat progression from normal to premutation size and suggest that most normal alleles without AGG interruptions are derived from contractions of maternal premutation alleles.     

Professionalism and the basic sciences: an untapped resource

CONTEXT: Medical, technological and societal developments influence doctors' professional responsibilities and present challenges to educating medical students about professionalism. Medical education about professionalism generally focuses on behaviours and competencies which are taught primarily by clinicians in clinical courses and settings. DISCUSSION: Many professional competencies in medicine parallel those in science. We consider here whether medical professionalism can also be taught through the basic science courses which often initiate medical education, and which are typically taught by scientists. CONCLUSIONS: Like doctors, basic science faculty staff can teach professional competencies to medical students. Science faculty are well situated to teach professional competencies and should do so. They can model how to pursue evidence and manage conflicting information. They can also provide explicit messages to students about professional competencies and their value, and create learning objectives that reinforce those messages.     

Identifying Smokers with a Medical Extraction System

The Clinical Language Understanding group at Nuance Communications has developed a medical information extraction system that combines a rule-based extraction engine with machine learning algorithms to identify and categorize references to patient smoking in clinical reports. The extraction engine identifies smoking references; documents that contain no smoking references are classified as UNKNOWN. For the remaining documents, the extraction engine uses linguistic analysis to associate features such as status and time to smoking mentions. Machine learning is used to classify the documents based on these features. This approach shows overall accuracy in the 90s on all data sets used. Classification using engine-generated and word-based features outperforms classification using only word-based features for all data sets, although the difference gets smaller as the data set size increases. These techniques could be applied to identify other risk factors, such as drug and alcohol use, or a family history of a disease.     

Rhino-orbital-cerebral mucormycosis--a clinico-pathological report of two cases

Rhino-orbital-cerebral mucormycosis is an acute fungal infection of the oropharynx, paranasal sinuses, orbit and intracranial structures. It is rare, occurring mainly in diabetics in ketoacidosis. The clinical presentation is highly suggestive of the diagnosis. Current treatment has resulted in a greatly improved prognosis for survival and clinical awareness of this disease is important for early initiation of treatment with optimal effect. A clinico-pathological report of two cases is presented.     

Intrahepatic encystment of umbilical vein catheter infusate

Massive hepatomegaly in a 2.1 kg female infant, with an indwelling umbilical vein catheter for total parenteral nutrition, occurred on the 10th day of life. Ultrasound and computed tomography studies revealed a large hepatic cyst filled with the catheter infusate. Percutaneous drainage brought about subsequent recovery. To our knowledge, this complication of umbilical vein catheter use has not been previously reported.     

Examining the sensitivity of an injury surveillance program using population-based estimates.

This study uses population-based estimates to assess the sensitivity and representativeness of an injury surveillance system using a 1-year population-based approach. Data from the Ottawa Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) site (Children's Hospital of Eastern Ontario) were compared with those from six expansion sites. The overall sensitivity of CHIRPP was 43% of all treated injuries and 57% of injuries treated at emergency departments. CHIRPP was less likely to be representative for older children and more likely to capture children with more severe injuries. The limitations related to using CHIRPP for representing population-based injury remain fairly stable over time. A one-time population-based sample can provide useful information to add to routinely collected injury surveillance.