The Angiotensin Converting Enzyme Insertion/Deletion polymorphism is not associated with an increased risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants

BACKGROUND: The ACE gene contains a polymorphism consisting of either the presence (insertion, I) or absence (deletion, D) of a 287 bp alu repeat in intron 16. The D allele is associated with increased ACE activity in both tissue and plasma. The DD genotype is associated with risk of developing ARDS and mortality. The frequency of the D allele is higher in patients with pulmonary fibrosis, sarcoidosis and berylliosis. The role of this polymorphism has not been studied in the development of BPD in the premature newborn. METHODS: ACE I/D genotype was determined in 245 (194 African-American, 47 Caucasian and 4 Hispanic) mechanically ventilated infants weighing less than 1250 grams at birth and compared to outcome (death and/or development of BPD). RESULTS: The incidence of the D allele in the study population was 0.58. Eighty-eight (35.9%) infants were homozygous DD, 107 (43.7%) were heterozygous ID and 50 (20.4%) were homozygous II. There were no significant differences between genotype groups with respect to ethnic origin, birth weight, gestation, or gender. There was no effect of the ACE I/D polymorphism on mortality or development of BPD (O(2 )on 28 days or 36 weeks PCA). Secondary outcomes (intraventricular hemorrhage and periventricular leukomalacia) similarly were not influenced by the ACE ID polymorphism. CONCLUSIONS: The ACE I/D polymorphism does not significantly influence the development of BPD in ventilated infants less than 1250 grams

Genetic Linkage and Association Analysis for Loneliness in Dutch Twin and Sibling Pairs Points to a Region on Chromosome 12q23–24

We obtained evidence from a large study in Dutch twins (N = 8387) and siblings (N = 2295) that variation in loneliness has a genetic component. The heritability estimate for loneliness, which was assessed as an ordinal trait, was 40% and did not differ between males and females. There were 682 sibling pairs with genotypic (around 400 microsatellite markers) data. We combined phenotypic and genotypic data to carry out a genome scan to localize QTLs for loneliness. One region on chromosome 12q23.3-24.3, showed near suggestive linkage. Genetic association tests within this region revealed significant association (p-value 0.009) with one of the alleles of marker D12S79 and with one of the alleles of neighbouring marker D12S395 (p-value 0.043). We review evidence for linkage in this region for psychiatric disorders and discuss our findings within this context. © 2006 Springer Science+Business Media, Inc

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine

Evaluation of peer teaching and deliberate practice to teach veterinary surgery

OBJECTIVE: To assess the impact of peer teaching and deliberate practice on surgical skills acquisition and retention in first- and second-year veterinary students. STUDY DESIGN: Randomized, prospective, comparative study. SAMPLE POPULATION: Eighteen first-year and 25 second-year students from 1 college of veterinary medicine who had previously demonstrated proficiency in basic surgical skills. METHODS: Forty-three participants were divided into 3 groups: the test group (group A, n = 15), who participated in a structured peer-assisted learning program using deliberate practice; the time-practice control group (group B, n = 15), who participated in an unstructured peer-supported environment; and the assessment-only control group (group C, n = 13), who participated in the assessments. Participants performed a subcutaneous mass removal on a cadaver model and were assessed via a global rating system. Three assessment points were evaluated: pretraining, immediate posttraining, and retention. RESULTS: The number of participants who achieved acceptable or excellent grand total scores in group A increased after training. Among all participants, 22% in group A, 35% in group B, and 38% in group C did not achieve an acceptable total score at the retention assessment. CONCLUSION: The study population improved in skill level and retention through the use of standardized video and peer instruction with attention to effective learning strategies, particularly deliberate practice. CLINICAL SIGNIFICANCE: Use and enhancement of the format introduced in this study could augment veterinary surgical education

A survey of risk factors for digit injuries among dogs training and competing in agility events.

OBJECTIVE To identify potential risk factors for digit injuries in dogs training and competing in agility events. DESIGN Internet-based, retrospective, cross-sectional survey. ANIMALS 1,081 dogs training or competing in agility events. PROCEDURES Data were collected for eligible animals via retrospective surveys distributed electronically to handlers of dogs participating in agility-related activities. Variables evaluated included demographic (handlers) and signalment (dogs) information, physical characteristics of dogs, and injury characteristics. A separate survey of dogs competing in similar agility-related activities but without digit injuries was also administered. Multivariable logistic regression was used to develop a model for assessment of risk factors. RESULTS Data were collected from 207 agility dogs with digit injuries and 874 agility dogs without digit injuries. Factors associated with significantly increased odds of injury included Border Collie breed (OR, 2.3; 95% confidence interval [CI], 1.5 to 3.3), long nails (OR, 2.4; 95% CI, 1.3 to 4.5), absence of front dewclaws (OR, 1.9; 95% CI, 1.3 to 2.6), and greater weight-to-height ratio (OR, 1.5; 95% CI, 1.1 to 2.0). Odds of injury decreased with increasing age of the dog (OR, 0.8; 95% CI, 0.76 to 0.86). CONCLUSIONS AND CLINICAL RELEVANCE Results should be cautiously interpreted because of potential respondent and recall bias and lack of review of medical records. Nevertheless, results suggested that retaining healthy dewclaws, maintaining lean body mass, and trimming nails short for training and competition may decrease the likelihood of digit injuries. Research to investigate training practices, obstacle construction specifcations, and surface considerations for dogs competing in agility activities is indicated

Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): An international, prospective, randomised, non-inferiority phase 3 trial

Background: After breast-conserving surgery, 90% of local recurrences occur within the index quadrant despite the presence of multicentric cancers elsewhere in the breast. Thus, restriction of radiation therapy to the tumour bed during surgery might be adequate for selected patients. We compared targeted intraoperative radiotherapy with the conventional policy of whole breast external beam radiotherapy. Methods: Having safely piloted the new technique of single-dose targeted intraoperative radiotherapy with Intrabeam, we launched the TARGIT-A trial on March 24, 2000. In this prospective, randomised, non-inferiority trial, women aged 45 years or older with invasive ductal breast carcinoma undergoing breast-conserving surgery were enrolled from 28 centres in nine countries. Patients were randomly assigned in a 1:1 ratio to receive targeted intraoperative radiotherapy or whole breast external beam radiotherapy, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy. Neither patients nor investigators or their teams were masked to treatment assignment. Postoperative discovery of predefined factors (eg, lobular carcinoma) could trigger addition of external beam radiotherapy to targeted intraoperative radiotherapy (in an expected 15% of patients). The primary outcome was local recurrence in the conserved breast. The predefined non-inferiority margin was an absolute difference of 2·5% in the primary endpoint. All randomised patients were included in the intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00983684. Findings: 1113 patients were randomly allocated to targeted intraoperative radiotherapy and 1119 were allocated to external beam radiotherapy. Of 996 patients who received the allocated treatment in the targeted intraoperative radiotherapy group, 854 (86%) received targeted intraoperative radiotherapy only and 142 (14%) received targeted intraoperative radiotherapy plus external beam radiotherapy. 1025 (92%) patients in the external beam radiotherapy group received the allocated treatment. At 4 years, there were six local recurrences in the intraoperative radiotherapy group and five in the external beam radiotherapy group. The Kaplan-Meier estimate of local recurrence in the conserved breast at 4 years was 1·20% (95% CI 0·53–2·71) in the targeted intraoperative radiotherapy and 0·95% (0·39–2·31) in the external beam radiotherapy group (difference between groups 0·25%, –1·04 to 1·54; p=0·41). The frequency of any complications and major toxicity was similar in the two groups (for major toxicity, targeted intraoperative radiotherapy, 37 [3·3%] of 1113 vs external beam radiotherapy, 44 [3·9%] of 1119; p=0·44). Radiotherapy toxicity (Radiation Therapy Oncology Group grade 3) was lower in the targeted intraoperative radiotherapy group (six patients [0·5%]) than in the external beam radiotherapy group (23 patients [2·1%]; p=0·002). Interpretation: For selected patients with early breast cancer, a single dose of radiotherapy delivered at the time of surgery by use of targeted intraoperative radiotherapy should be considered as an alternative to external beam radiotherapy delivered over several weeks