Degradability of cross-linked polyurethanes based on synthetic polyhydroxybutyrate and modified with polylactide

In many areas of application of conventional non-degradable cross-linked polyurethanes (PUR), there is a need for their degradation under the influence of specific environmental factors. It is practiced by incorporation of sensitive to degradation compounds (usually of natural origin) into the polyurethane structure, or by mixing them with polyurethanes. Cross-linked polyurethanes (with 10 and 30%wt amount of synthetic poly([R,S]-3-hydroxybutyrate) (R,S-PHB) in soft segments) and their physical blends with poly([d,l]-lactide) (PDLLA) were investigated and then degraded under hydrolytic (phosphate buffer solution) and oxidative (CoCl2/H2O2) conditions. The rate of degradation was monitored by changes of samples mass, morphology of surface and their thermal properties. Despite the small weight losses of samples, the changes of thermal properties of polymers and topography of their surface indicated that they were susceptible to gradual degradation under oxidative and hydrolytic conditions. Blends of PDLLA and polyurethane with 30 wt% of R,S-PHB in soft segments and PUR/PDLLA blends absorbed more water and degraded faster than polyurethane with low amount of R,S-PHB

Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts.

OBJECTIVES: To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age. DESIGN: Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa. SETTING: Multiple institutions that were members of international PRACTICAL consortium. PARTICIPANTS: All consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men. MAIN OUTCOME MEASURES: Prediction with hazard score of age of onset of aggressive cancer in validation set. RESULTS: In the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score. CONCLUSIONS: Polygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa

Polygenic hazard score to guide screening for aggressive - prostate cancer: development and validation in large scale - cohorts

OBJECTIVESTo develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age.DESIGNAnalysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score >= 7, stage T3-T4, PSA (prostate specific antigen) concentration >= 10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa.SETTINGMultiple institutions that were members of international PRACTICAL consortium.PARTICIPANTSAll consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men.MAIN OUTCOME MEASURESPrediction with hazard score of age of onset of aggressive cancer in validation set.RESULTSIn the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z= 11.2, P98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P= 0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score.CONCLUSIONSPolygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa

Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts.

ObjectivesTo develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age.DesignAnalysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa.SettingMultiple institutions that were members of international PRACTICAL consortium.ParticipantsAll consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men.Main outcome measuresPrediction with hazard score of age of onset of aggressive cancer in validation set.ResultsIn the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P<10-16). When men in the validation set with high scores (>98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score.ConclusionsPolygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes