During embryogenesis, the XIST RNA is expressed from and localizes to one X chromosome in females and induces chromosomewide silencing. Although many changes to inactive X heterochromatin are known, the functional relationships between different modifications are not well understood, and studies of the initiation of X-inactivation have been largely confined to mouse. We now present a model system for human XIST RNA function in which induction of an XIST cDNA in somatic cells results in localized XIST RNA and transcriptional silencing. Chromatin immunoprecipitation and immunohistochemistry shows that this silencing need only be accompanied by a subset of heterochromatic marks and that these can differ between integration sites. Surprisingly, silencing is XIST-dependent, remaining reversible over extended periods. Deletion analysis demonstrates that the first exon of human XIST is sufficient for both transcript localization and the induction of silencing and that, unlike the situation in mice, the conserved repeat region is essential for both functions. In addition to providing mechanistic insights into chromosome regulation and formation of facultative heterochromatin, this work provides a tractable model system for the study of chromosome silencing and suggests key differences from mouse embryonic X-inactivation.dosage compensation ͉ heterochromatin ͉ histone modification ͉ X-chromosome inactivation ͉ DNA methylation

Mammalian X-chromosome inactivation is an impressive example of epigenetic gene regulation, whereby the majority of genes on the approximately 160 Mb X chromosome are silenced in a strictly cis-limited fashion. In this review we will discuss the important players involved in the silencing process. The process is initiated by transcription and cis-localization of the non-coding XIST RNA, which then recruits many of the epigenetic features generally associated with heterochromatin, including histone modifications, histone variants and DNA methylation.

Study Design: Observational cohort comparison. Objectives: To compare the previously validated Spine Adverse Events Severity system (SAVES) with International Classification of Diseases, Tenth Revision codes (ICD-10) codes for identifying adverse events (AEs) in patients with traumatic spinal cord injury (TSCI). Setting: Quaternary Care Spine Program. Methods: Patients discharged between 2006 and 2010 were identified from our prospective registry. Two consecutive cohorts were created based on the system used to record acute care AEs; one used ICD-10 coding by hospital coders and the other used SAVES data prospectively collected by a multidisciplinary clinical team. The ICD-10 codes were appropriately mapped to the SAVES. There were 212 patients in the ICD-10 cohort and 173 patients in the SAVES cohort. Analyses were adjusted to account for the different sample sizes, and the two cohorts were comparable based on age, gender and motor score. Results: The SAVES system identified twice as many AEs per person as ICD-10 coding. Fifteen unique AEs were more reliably identified using SAVES, including neuropathic pain (32 Â more; Po0.001), urinary tract infections (1.4 Â ; Po0.05), pressure sores (2.9 Â ; Po0.001) and intra-operative AEs (2.3 Â ; Po0.05). Eight of these 15 AEs more frequently identified by SAVES significantly impacted length of stay (Po0.05). Risk factors such as patient age and severity of paralysis were more reliably correlated to AEs collected through SAVES than ICD-10. Conclusion: Implementation of the SAVES system for patients with TSCI captured more individuals experiencing AEs and more AEs per person compared with ICD-10 codes. This study demonstrates the utility of prospectively collecting AE data using validated tools.

,5 and the SCIRE Research TeamObjective: To conduct a systematic review examining the effectiveness of knowledge translation (KT) interventions in changing clinical practice and patient outcomes. Methods: MEDLINE/PubMed, CINAHL, EMBASE and PsycINFO were searched for studies published from January 1980 to July 2012 that reported and evaluated an implemented KT intervention in spinal cord injury (SCI) care. We reviewed and summarized results from studies that documented the implemented KT intervention, its impact on changing clinician behavior and patient outcomes as well as the facilitators and barriers encountered during the implementation. Results: A total of 13 articles featuring 10 studies were selected and abstracted from 4650 identified articles. KT interventions included developing and implementing patient care protocols, providing clinician education and incorporating outcome measures into clinical practice. The methods (or drivers) to facilitate the implementation included organizing training sessions for clinical staff, introducing computerized reminders and involving organizational leaders. The methodological quality of studies was mostly poor. Only 3 out of 10 studies evaluated the success of the implementation using statistical analyses, and all 3 reported significant behavior change. Out of the 10 studies, 6 evaluated the effect of the implementation on patient outcomes using statistical analyses, with 4 reporting significant improvements. The commonly cited facilitators and barriers were communication and resources, respectively. Conclusion: The field of KT in SCI is in its infancy with only a few relevant publications. However, there is some evidence that KT interventions may change clinician behavior and improve patient outcomes. Future studies should ensure rigorous study methods are used to evaluate KT interventions.

International Classification of Diseases (ICD) codes are used to document patient morbidity in administrative databases. Although administrative data are used for research purposes, the validity of the data to accurately describe clinical diagnostic information is uncertain. We compared the clinical diagnoses for spinal cord and column injuries from a longitudinal patient registry, the Rick Hansen Spinal Cord Injury Registry (RHSCIR), to the ICD-10 spinal injury codes from the Discharge Abstract Database (DAD) at one institution. There were 603 RHSCIR participants with data describing the spinal cord injury, and 341 had data on the spinal column injury. The validity of DAD data to describe spinal injuries was evaluated using the sensitivity and positive predictive values of specific ICD-10 codes; 5.3% of the spinal column injuries and 10.9% of the spinal cord injuries documented in RHSCIR were missed in data from the DAD using ICD-10 codes. The most problematic spinal column ICD-10 code was the dislocation of the cervical vertebra (S13.1); only 14.0% of the dislocations of the cervical vertebrae in RHSCIR were correctly coded in the DAD. The most problematic spinal cord injury ICD-10 code was the incomplete lesion of the lumbar spinal cord (S34.1X); 66.7% of incomplete lesions of the lumbar spinal cord in RHSCIR were correctly coded in the DAD. The validity of DAD data to code spinal injuries is variable, and cannot be reliably used to classify all types of spinal injuries. Patient registries, such as RHSCIR, should be used if accurate detailed diagnostic data are required.