Pilot, randomized, placebo-controlled clinical field study to evaluate the effectiveness of bupivacaine liposome injectable suspension for the provision of post-surgical analgesia in dogs undergoing stifle surgery

Abstract Background Local anesthetics are an important component of perioperative pain management, but the duration of action of available products is limited. We hypothesized that a single local infiltration of a novel bupivacaine liposome injectable suspension (AT-003) would provide clinically effective analgesia over a 72-h period. In a masked, randomized, placebo-controlled, multi-center pilot field study, dogs undergoing lateral retinacular suture placement for cranial cruciate insufficiency were randomly assigned to surgical site infiltration with AT-003 (5.3 mg/kg) or an equivalent volume of saline. Infiltration of the surgical site was done prior to closure. Primary outcome measure was the Glasgow Composite Measure Pain Scale (CMPS-SF) assessed prior to surgery and at 2, 4, 8, 12, 24, 30, 36, 48, 54, 60 and 72 h following surgery by trained individuals. Provision for rescue analgesia was employed. Repeated measures analysis of variance were utilized to test for possible differences between treatment groups and a success/failure analysis was also employed, based on the need for rescue analgesia. Results Forty-six dogs were enrolled and evaluated. For CMPS-SF scores there was a significant overall treatment effect (p = 0.0027) in favor of AT-003. There were significantly more successes in the AT-003 group compared to placebo over each time period (p = 0.0001 for 0–24 h, p = 0.0349 for 0–48 h, and p = 0.0240 for 0-72 h). No significant adverse events were seen. Conclusions AT-003 (bupivacaine liposome injectable suspension) provided measurable local analgesia over a 72-h period following post-stifle surgery surgical site tissue infiltration. Further work is indicated to develop this product for clinical use

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Ten-Year Outcomes of High-Dose, Intensity-Modulated Radiotherapy for Localized Prostate Cancer

BACKGROUND. The authors investigated long-term tumor control and toxicity outcomes after high-dose, intensity-modulated radiation therapy (IMRT) in patients who had clinically localized prostate cancer. METHODS. Between April 1996 and January 1998, 170 patients received 81 gray (Gy) using a 5-field IMRT technique. Patients were classified according to the National Comprehensive Cancer Network-defined risk groups. Toxicity data were scored according to the Common Terminology Criteria for Adverse Events Version 3.0. Freedom from biochemical relapse, distant metastases, and cause-specific survival outcomes were calculated. The median follow-up was 99 months. RESULTS. The 10-year actuarial prostate-specific antigen relapse-free survival rates were 81% for the low-risk group, 78% for the intermediate-risk group, and 62% for the high-risk group; the 10-year distant metastases-free rates were 100%, 94%, and 90%, respectively; and the 10-year cause-specific mortality rates were 0%, 3%, and 14%, respectively. The 10-year likelihood of developing grade 2 and 3 late genitourinary toxicity was 11% and 5%, respectively; and the 10-year likelihood of developing grade 2 and 3 late gastrointestinal toxicity was 2% and 1%, respectively. No grade 4 toxicities were observed. CONCLUSIONS. To the authors' knowledge, this report represents the longest followed cohort of patients who received high-dose radiation levels of 81 Gy using IMRT for localized prostate cancer. The findings indicated that high-dose IMRT is well tolerated and is associated with excellent long-term tumor-control outcomes in patients with localized prostate cancer Cancer 2011; 117: 1429-37. (C) 2010 American Cancer Society