Citations

This paper describes the sentiment classification system developed by the Mayo Clinic team for the 2011 I2B2/VA/Cincinnati Natural Language Processing (NLP) Challenge. The sentiment classification task is to assign any pertinent emotion to each sentence in suicide notes. We have implemented three systems that have been trained on suicide notes provided by the I2B2 challenge organizer–-a machine learning system, a rule-based system, and a system consisting of a combination of both. Our machine learning system was trained on re-annotated data in which apparently inconsistent emotion assignment was adjusted. Then, the machine learning methods by RIPPER and multinomial Naïve Bayes classifiers, manual pattern matching rules, and the combination of the two systems were tested to determine the emotions within sentences. The combination of the machine learning and rule-based system performed best and produced a micro-average F-score of 0.5640.

Background— Prior studies have demonstrated low use of implantable cardioverter defibrillators (ICDs) as primary prevention, particularly among women and blacks. The degree to which the overall use of ICD therapy and disparities in use have changed is unclear. Methods and Results— We examined 11 880 unique patients with a history of heart failure and left ventricular ejection fraction ≤35% who were ≥65 years old and enrolled in the Get With the Guidelines–Heart Failure (GWTG-HF) program from January 2005 through December 2009. We determined the rate of ICD use by year for the overall population and for sex and race groups. From 2005 to 2007, overall ICD use increased from 30.2% to 42.4% and then remained unchanged in 2008 to 2009. After adjustment for potential confounders, ICD use increased significantly in the overall study population during 2005 to 2007 (odds ratio, 1.28; 95% confidence interval, 1.11–1.48 per year; P =0.0008) and in black women (odds ratio, 1.82; 95% confidence interval, 1.28–2.58 per year; P =0.0008), white women (odds ratio, 1.30; 95% confidence interval, 1.06–1.59 per year; P =0.010), black men (odds ratio, 1.54; 95% confidence interval, 1.19–1.99 per year; P =0.0009), and white men (odds ratio, 1.25; 95% confidence interval, 1.06–1.48 per year; P =0.0072). The increase in ICD use was greatest among blacks. Conclusions— In the GWTG-HF quality improvement program, a significant increase in ICD therapy use was observed over time in all sex and race groups. The previously described racial disparities in ICD use were no longer present by the end of the study period; however, sex differences persisted.

The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood. We molecularly and functionally characterized one member of an evolutionarily dynamic gene family, plac8 onzin related protein 1 (ponzr1), in the zebrafish. ponzr1 mRNA is expressed early in the developing kidney and pharyngeal arches. Using ponzr1-targeting morpholinos, we show that ponzr1 is required for formation of the glomerulus. Loss of ponzr1 results in a nonfunctional glomerulus but retention of a functional pronephros, an arrangement similar to the aglomerular kidneys found in a subset of marine fish. ponzr1 is integrated into the pax2a pathway, with ponzr1 expression requiring pax2a gene function, and proper pax2a expression requiring normal ponzr1 expression. In addition to pronephric function, ponzr1 is required for pharyngeal arch formation. We functionally demonstrate that ponzr1 can act as a transcription factor or co-factor, providing the first molecular mode of action for this newly described gene family. Together, this work provides experimental evidence of an additional mechanism that incorporates evolutionarily dynamic, lineage-specific gene families into conserved regulatory gene networks to create functional organ diversity.

Purpose To identify clinical variables that affect a surgeon's decision to recommend arthroscopic partial meniscectomy (APM). Methods Members of 2 orthopaedic specialty societies were invited to participate in an online survey by e‐mail. The survey consisted of surgeon demographics and case scenarios to evaluate clinical decision making for APM. Posterior probabilities were calculated to determine the effect of clinical factors on the likelihood of recommending APM. Results Of the respondents with valid e‐mail addresses, 733 (19.3%) returned a completed survey, but only 533 (14.1%) met the eligibility criteria (treated or referred an APM candidate within the past year). Respondents were aged 46.7 ± 9.4 and had performed a mean of 115 APMs in the previous year. Posterior probabilities for a combination of 6 clinical indicators identified 3 factors that most influenced a surgeon's decision to recommend APM: radiographic findings, McMurray test, and failure of nonoperative management. Conclusions Significant variation exists among practicing orthopaedic surgeons with regard to decision making for APM. The 3 clinical factors that most influenced a surgeon's decision to recommend APM were normal radiographic findings, failed nonoperative treatment, and the presence of positive physical examination findings (i.e., positive McMurray test, joint line tenderness, and effusion). Level of Evidence Level III, decision analysis.

Abstract Routine incorporation of FISH into multiple myeloma (MM) diagnostic testing has led to a better appreciation of the heterogeneity of genetic abnormalities associated with this disease. We studied a group of 484 patients with newly diagnosed symptomatic MM to better understand the prevalence of the various abnormalities and the prognostic significance of the overlapping abnormalities. A translocation involving the IgH locus and 1 of the 5 recurrent partner chromosomes was seen in 161 (33%) patients, and 275 (57%) had trisomy of at least 1 odd-numbered chromosome. High-risk FISH, defined as the presence of t(4;14), t(14;16), t(14;20), or loss of P53, was seen in 115 (24%) patients; the median overall survival for this group was 3.9 years, compared with “not reached” for standard-risk patients (P < .001). Among the patients with high-risk FISH, 49 patients who also had at least 1 trisomy had a median overall survival that was not reached, compared with 3 years for high-risk patients without a concurrent trisomy (P = .01). Based on the current findings, we conclude that the presence of trisomies in patients with t(4;14), t(14;16), t(14;20), or p53 deletion abnormalities in MM ameliorates the usual adverse impact associated with these prognostic markers.

Dietary sodium and blood pressure regulation differs between normotensive men and women, an effect which may involve endothelial production of nitric oxide (NO). Therefore, we tested the hypothesis that differences in the NO component of endothelium-dependent vasodilation between low and high dietary sodium intake depend on sex. For 5 days prior to study, healthy adults consumed a controlled low-sodium diet (10 mmol/day, n = 30, mean age ± SE: 30 ± 1 yr, 16 men) or high-sodium diet (400 mmol/day, n = 36, age 23 ± 1 yr, 13 men). Forearm blood flow (FBF, plethysmography) responses to brachial artery administration of acetylcholine (ACh, 4 μg·100 ml tissue−1·min−1) were measured before and after endothelial NO synthase inhibition with NG-monomethyl-l-arginine (l-NMMA, 50 mg bolus + 1 mg/min infusion). The NO component of endothelium-dependent dilation was calculated as the response to ACh before and after l-NMMA accounting for changes in baseline FBF: [(FBF ACh − FBF baseline) − (FBF AChL-NMMA − FBF baselineL-NMMA)]. This value was 5.7 ± 1.3 and 2.5 ± 0.8 ml·100 ml forearm tissue−1·min−1 for the low- and high-sodium diets, respectively (main effect of sodium, P = 0.019). The sodium effect was larger for the men, with values of 7.9 ± 2.0 and 2.2 ± 1.4 for men vs. 3.1 ± 1.3 and 2.7 ± 1.0 ml·100 ml forearm tissue−1·min−1 for the women ( P = 0.034, sex-by-sodium interaction). We conclude that the NO component of endothelium-dependent vasodilation is altered by dietary sodium intake based on sex, suggesting that endothelial NO production is sensitive to dietary sodium in healthy young men but not women.

Purpose A phase I/II study of cixutumumab (IMC-A12) in children with refractory solid tumors was conducted. This study was designed to assess the toxicities, pharmacokinetics, and pharmacodynamics of cixutumumab in children to determine a recommended phase II dose and to assess antitumor activity in Ewing sarcoma (ES). Patients and Methods Pediatric patients with relapsed or refractory solid tumors were treated with cixutumumab as a 1-hour intravenous infusion once per week. Two dose levels—6 and 9 mg/kg—were evaluated using a standard three-plus-three cohort design. Patients with refractory ES were treated in an expanded phase II cohort at each dose level. Results Forty-seven eligible patients with a median age of 15 years (range, 4 to 28 years) were enrolled. Twelve patients were treated in the dose-finding phase. Hematologic and nonhematologic toxicities were generally mild and infrequent. Dose-limiting toxicities included grade 4 thrombocytopenia at 6 mg/kg and grade 3 dehydration at 9 mg/kg. Mean trough concentration (± standard deviation) at 9 mg/kg was 106 ± 57 μg/mL, which exceeded the effective trough concentration of 60 μg/mL observed in xenograft models. Three patients with ES had confirmed partial responses: one of 10 at 6 mg/kg and two of 20 at 9 mg/kg. Serum insulin-like growth factor I (IGF-I) levels consistently increased after one dose of cixutumumab. Tumor IGF-I receptor expression by immunohistochemistry did not correlate with response in patients with ES. Conclusion Cixutumumab is well tolerated in children with refractory solid tumors. The recommended phase II dose is 9 mg/kg. Limited single-agent activity of cixutumumab was seen in ES.