Identification and Interpretation of Longitudinal Gene Expression Changes in Trauma

The relationship between leukocyte gene expression and recovery of respiratory function after injury may provide information on the etiology of multiple organ dysfunction.To find a list of genes for which expression after injury predicts respiratory recovery, and to identify which networks and pathways characterize these genes.Blood was sampled at 12 hours and at 1, 4, 7, 21 and 28 days from 147 patients who had been admitted to the hospital after blunt trauma. Leukocyte gene expression was measured using Affymetrix oligonucleotide arrays. A linear model, fit to each probe-set expression value, was used to impute the gene expression trajectory over the entire follow-up period. The proportional hazards model score test was used to calculate the statistical significance of each probe-set trajectory in predicting respiratory recovery. A list of genes was determined such that the expected proportion of false positive results was less than 10%. These genes were compared to the Gene Ontology for 'response to stimulus' and, using Ingenuity software, were mapped into networks and pathways.The median time to respiratory recovery was 6 days. There were 170 probe-sets representing 135 genes that were found to be related to respiratory recovery. These genes could be mapped to nine networks. Two known pathways that were activated were antigen processing and presentation and JAK-signaling.The examination of the relationship of gene expression over time with a patient's clinical course can provide information which may be useful in determining the mechanism of recovery or lack of recovery after severe injury

Reproducible radiomics through automated machine learning validated on twelve clinical applications

Radiomics uses quantitative medical imaging features to predict clinical outcomes. Currently, in a new clinical application, findingthe optimal radiomics method out of the wide range of available options has to be done manually through a heuristic trial-anderror process. In this study we propose a framework for automatically optimizing the construction of radiomics workflows perapplication. To this end, we formulate radiomics as a modular workflow and include a large collection of common algorithms foreach component. To optimize the workflow per application, we employ automated machine learning using a random search andensembling. We evaluate our method in twelve different clinical applications, resulting in the following area under the curves: 1)liposarcoma (0.83); 2) desmoid-type fibromatosis (0.82); 3) primary liver tumors (0.80); 4) gastrointestinal stromal tumors (0.77);5) colorectal liver metastases (0.61); 6) melanoma metastases (0.45); 7) hepatocellular carcinoma (0.75); 8) mesenteric fibrosis(0.80); 9) prostate cancer (0.72); 10) glioma (0.71); 11) Alzheimer’s disease (0.87); and 12) head and neck cancer (0.84). Weshow that our framework has a competitive performance compared human experts, outperforms a radiomics baseline, and performssimilar or superior to Bayesian optimization and more advanced ensemble approaches. Concluding, our method fully automaticallyoptimizes the construction of radiomics workflows, thereby streamlining the search for radiomics biomarkers in new applications.To facilitate reproducibility and future research, we publicly release six datasets, the software implementation of our framework,and the code to reproduce this study

GENETIC TYPE AND GROWTH INFLUENCE ON THE PRODUCTION CHARACTERISTICS OF LIGHT LINE HEN HYBRIDS**

Apstract: The aim of this work was parallel investigation of the producting characteristics of light line hen hybrids. Investigation enclosed two hen proveniences: Hisex Brown and Shawer 579. Within the period of 19 up to 63 weeks we followed next parameters: egg-laying hen body mass, mortality, food consumption and egg-laying capacity. Hens body mass on the begining of the examination, within the 19 weeks of growth was, for Hisex Brown provenience 1607g, and for Shawer 579 provenience 1563g. Hisex Brown provenience acchieved about 250 g higher body mass on the end of investigation. During the experiment, mortality at Hisex Brown egg-laying hen was a little bit smaller (5,40%), while the Shawer 579 had 5,56 % of dead hens. Globaly, the mortality at both hen hybrids was in the range of technologycal normative. The average consumption of the food at Hisex Brown provenience was higher and it was 127,28g, and at Shawer 579 provenience 125,14g. The average consumption of the nutrition for egg production at both provenience was the same (150g). Key words: egg-laying,, nutrition consumption, body mass, mortalit

Comparison of pegvisomant and long-acting octreotide in patients with acromegaly naïve to radiation and medical therapy.

BACKGROUND: Normalization of IGF-I in patients with acromegaly is associated with a decrease in mortality. Pegvisomant may be more effective in lowering IGF-I than octreotide. SUBJECTS AND METHODS: The efficacy and safety of pegvisomant and octreotide long-acting release (LAR) were compared in 118 patients with acromegaly in this 52-week, multicenter, open-label, randomized study. The primary endpoint was IGF-I normalization at week 52. Secondary endpoints included mean changes from baseline in IGF-I, IGF binding protein 3, acromegaly signs and symptom scores, ring size, acromegaly quality of life questionnaire scores, and safety. RESULTS: Fifty-six patients received pegvisomant and 57 received octreotide LAR. IGF-I normalized in 51% of pegvisomant patients and 34% treated with octreotide LAR (p=0.09, ns). Patients with baseline IGF-I > or = 2x upper limit of normal had a higher rate of IGF-I normalization with pegvisomant vs octreotide LAR (p=0.05). Among the patients who did not achieve a normalized IGF-I, pegvisomant-treated patients were more likely to be receiving < 30 mg of study drug (71% vs 16%). Treatment-related adverse events were mild-to-moderate in both groups. Mean fasting glucose decreased in diabetic and non-diabetic patients on pegvisomant whereas octreotide LAR was associated with an increase at week 52 (p=0.005 and p=0.003 between groups, respectively). Mean change in tumor volume during treatment was similar between groups. CONCLUSIONS: Pegvisomant and octreotide LAR were equally effective in normalizing IGF-I in the overall population, and pegvisomant was more effective in patients with higher baseline IGF-I levels. Pegvisomant had a more favorable effect on parameters of glycemic control

Comparison of pegvisomant and long-acting octreotide in patients with acromegaly naïve to radiation and medical therapy

Background: Normalization of IGF-I in patients with acromegaly is associated with a decrease in mortality. Pegvisomant may be more effective in lowering IGF-I than octreotide. Subjects and methods: The efficacy and safety of pegvisomant and octreotide long-acting release (LAR) were compared in 118 patients with acromegaly in this 52-week, multicenter, open-label, randomized study. The primary endpoint was IGF-I normalization at week 52. Secondary endpoints included mean changes from baseline in IGF-I, IGF binding protein 3, acromegaly signs and symptom scores, ring size, acromegaly quality of life questionnaire scores, and safety. Results: Fifty-six patients received pegvisomant and 57 received octreotide LAR. IGF-I normalized in 51% of pegvisomant patients and 34% treated with octreotide LAR (p=0.09, ns). Patients with baseline IGF-I ≥2×upper limit of normal had a higher rate of IGF-I normalization with pegvisomant vs octreotide LAR (p=0.05). Among the patients who did not achieve a normalized IGF-I, pegvisomant-treated patients were more likely to be receiving <30 mg of study drug (71% vs 16%). Treatment-related adverse events were mild-to-moderate in both groups. Mean fasting glucose decreased in diabetic and non-diabetic patients on pegvisomant whereas octreotide LAR was associated with an increase at week 52 (p=0.005 and p=0.003 between groups, respectively). Mean change in tumor volume during treatment was similar between groups. Conclusions: Pegvisomant and octreotide LAR were equally effective in normalizing IGF-I in the overall population, and pegvisomant was more effective in patients with higher baseline IGF-I levels. Pegvisomant had a more favorable effect on parameters of glycemic control. ©2009, Editrice Kurtis

A novel programme to evaluate and communicate 10-year risk of CHD reduces predicted risk and improves patients' modifiable risk factor profile

Aims: We assessed whether a novel programme to evaluate/communicate predicted coronary heart disease (CHD) risk could lower patients' predicted Framingham CHD risk vs. usual care. Methods: The Risk Evaluation and Communication Health Outcomes and Utilization Trial was a prospective, controlled, cluster-randomised trial in nine European countries, among patients at moderate cardiovascular risk. Following baseline assessments, physicians in the intervention group calculated patients' predicted CHD risk and were instructed to advise patients according to a risk evaluation/communication programme. Usual care physicians did not calculate patients' risk and provided usual care only. The primary end-point was Framingham 10-year CHD risk at 6 months with intervention vs. usual care. Results: Of 1103 patients across 100 sites, 524 patients receiving intervention, and 461 receiving usual care, were analysed for efficacy. After 6 months, mean predicted risks were 12.5% with intervention, and 13.7% with usual care [odds ratio = 0.896; p = 0.001, adjusted for risk at baseline (17.2% intervention; 16.9% usual care) and other covariates]. The proportion of patients achieving both blood pressure and low-density lipoprotein cholesterol targets was significantly higher with intervention (25.4%) than usual care (14.1%; p < 0.001), and 29.3% of smokers in the intervention group quit smoking vs. 21.4% of those receiving usual care (p = 0.04). Conclusions: A physician-implemented CHD risk evaluation/communication programme improved patients' modifiable risk factor profile, and lowered predicted CHD risk compared with usual care. By combining this strategy with more intensive treatment to reduce residual modifiable risk, we believe that substantial improvements in cardiovascular disease prevention could be achieved in clinical practice