Admissions and costs to acute hospitals resulting from road traffic crashes, 2005-2009

Road traffic crashes (RTCs) remain a leading cause of death and injury. The aim of this study was to explore the use of hospital data as a source of RTC-related injury data in Ireland, as current systems are believed to under-estimate the burden. Information on inpatient discharges for years 2005-2009, admitted with RTC-related injuries were extracted from HIPE. There were 14,861 discharges; 9,661 (65.0%) were male, with an average age of 33 years. The median length of stay was two days. The most common diagnosis was head injury (n = 4,644; 31.2%). The average inpatient hospital cost was Euro 6,395 per discharge. 1,498 (10.1%) were admitted to intensive care units. This study has identified 3.5 times more serious injuries (14,861) than identified in the Road Safety Authority (RSA) statistics (4,263) indicating that the extent of road injuries is greater than previously estimated. Hospital data could be used annually in conjunction with RSA and other data; ideally the data should be linked.     

Isolation and characterization of a mRNA encoding a novel insulin receptor (IR) subtype, IR2, from rainbow trout (Oncorhynchus mykiss) and patterns of expression of the four IR subtypes, IR1-IR4, in tissues and during embryonic development

Insulin (INS) plays a critical role in the growth, development, and metabolism of vertebrates. In this study, a cDNA encoding a novel insulin receptor (IR) subtype was isolated, cloned, and sequenced from the liver of rainbow trout. A 1525-bp cDNA encoding a partial amino acid sequence of the β-subunit including the transmembrane domain, the tyrosine kinase domain, and the 3′ untranslated region (UTR) was obtained and designated IR2 based on comparison with known IR subtypes, including the three previously reported IR subtypes of trout. Trout IR2 shares 90.0%, 82.8%, and 84.3% nucleotide identity with previously characterized trout IR1, IR3 and IR4, respectively. Quantitative real-time PCR revealed that the four IR mRNAs were differentially expressed, both in terms of distribution among tissues as well as in terms of abundance within selected tissues of juvenile trout. IR1 mRNA was most abundant in spleen, liver, kidney, and muscle (white, red and cardiac), but least abundant in adipose. IR3 mRNA was most abundant in liver, spleen, kidney, and pancreas; in other tissues, levels of IR3 mRNA were uniformly abundant. By contrast, levels of IR2 and IR4 mRNA were uniformly abundant in most tissues, except in spleen where levels of IR4 were significantly lower. All IR subtypes were detected over the course of embryonic development. In head and tail regions, levels of IR2 and IR3 mRNA declined from pre-hatch (29 days post-fertilization, dpf) to post-hatch (68-90 dpf), whereas levels of IR1 and IR4 remained relatively unchanged. These findings contribute to our understanding of the evolution, distribution, and function of insulin receptors.     

Telepathology for routine light microscopic and frozen section diagnosis

Telepathology (TP) uses telecommunication linkages to electronically capture, store, retrieve, and transmit images to distant sites. We assessed the feasibility of a dynamic real-time TP system for light microscopic (LM) diagnosis of anatomic pathology specimens, including frozen sections. Six pathologists, in 2 separate periods, read a set of 160 retrospectively retrieved slides (80 of which were frozen sections) by TP and LM. Reading times were recorded. Diagnoses were compared with the reference diagnosis (established by a group of 5 independent pathologists) and graded on a scale of 0 to 2 (2, correct; 1, incorrect but no clinical impact; 0, incorrect with clinical impact). Overall, LM was more accurate than TP compared with the reference diagnosis (score, 1.68 vs 1.54). There was no difference in accuracy between frozen section and paraffin-embedded tissue. Intraobserver agreement ranged from 82.5% to 88.2%. The average reading time was 6.0 minutes for TP and 1.4 minutes for LM. During the study, reading time decreased for TP but not for LM. These results show that despite marginally lower accuracy and longer reading times, TP isfeasible for routine light microscopic diagnosis, including frozen sections.     

Accurate assignment of disease liability to genetic variants using only population data

PurposeThe growing size of public variant repositories prompted us to test the accuracy of pathogenicity prediction of DNA variants using population data alone.MethodsUnder the a priori assumption that the ratio of the prevalence of variants in healthy population vs that in affected populations form 2 distinct distributions (pathogenic and benign), we used a Bayesian method to assign probability to a variant belonging to either distribution.ResultsThe approach, termed Bayesian prevalence ratio (BayPR), accurately parsed 300 of 313 expertly curated CFTR variants: 284 of 296 pathogenic/likely pathogenic variants in 1 distribution and 16 of 17 benign/likely benign variants in another. BayPR produced an area under the receiver operating characteristic curve of 0.99 for 103 functionally confirmed missense CFTR variants, which is equal to or exceeds 10 commonly used algorithms (area under the receiver operating characteristic curve range = 0.54-0.99). Application of BayPR to expertly curated variants in 8 genes associated with 7 Mendelian conditions led to the assignment of a disease-causing probability of ≥80% to 1350 of 1374 (98.3%) pathogenic/likely pathogenic variants and of ≤20% to 22 of 23 (95.7%) benign/likely benign variants.ConclusionIrrespective of the variant type or functional effect, the BayPR approach provides probabilities of pathogenicity for DNA variants responsible for Mendelian disorders using only the variant counts in affected and unaffected population samples.