ABSTRACT
Objective: Several studies have explored the relationship between intracranial aneurysms and psychiatric disorders; nevertheless, the causal connection remains ambiguous. This study aimed to evaluate the causal link between intracranial aneurysms and specific psychiatric disorders. Methods: A two-sample Mendelian randomization (MR) analysis was conducted utilizing aggregated genome-wide association study (GWAS) data from the International Stroke Genetics Association for Intracranial Aneurysms (IAs), unruptured Intracranial Aneurysm (uIA), and aneurysmal Subarachnoid Hemorrhage (aSAH). Psychiatric disorder data, encompassing Schizophrenia (SCZ), Bipolar Disorder (BD), and Panic Disorder (PD), were sourced from the Psychiatric Genomics Consortium (PGC), while Cognitive Impairment (CI) data, comprising Cognitive Function (CF) and Cognitive Performance (CP), were obtained from IEU OpenGWAS publications. Causal effects were evaluated using inverse variance weighted (IVW), MR-Egger, and weighted median methods, with the robustness of findings assessed via sensitivity analyses employing diverse methodological approaches. Results: Our MR analysis indicated no discernible causal link between intracranial aneurysm (IA) and an elevated susceptibility to psychiatric disorders. However, among individuals with genetically predisposed unruptured intracranial aneurysms (uIA), there was a modest reduction in the risk of SCZ (IVW odds ratio [OR] = 0.95, 95% confidence interval [CI] 0.92-0.98, p = 0.0002). Similarly, IAs also exhibited a moderate reduction in SCZ risk (OR = 0.92, 95% CI 0.86-0.99, p = 0.02). Nevertheless, limited evidence was found to support a causal association between intracranial aneurysms and the risk of the other three psychiatric disorders. Conclusion: Our findings furnish compelling evidence suggesting a causal influence of intracranial aneurysms on psychiatric disorders, specifically, both IAs and uIA exhibit a negative causal association with SCZ.
ABSTRACT
Exhaled breath volatilomics is a powerful non-invasive tool for biomarker discovery in medical applications, but compound annotation is essential for pathophysiological insights and technology transfer. This study was aimed at investigating the interest of a hybrid approach combining real-time proton transfer reaction-time-of-flight mass spectrometry (PTR-TOF-MS) with comprehensive thermal desorption-two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (TD-GCxGC-TOF-MS) to enhance the analysis and characterization of VOCs in clinical research, using COVID-19 as a use case. VOC biomarker candidates were selected from clinical research using PTR-TOF-MS fingerprinting in patients with COVID-19 and matched to the Human Breathomic Database. Corresponding analytical standards were analysed using both a liquid calibration unit coupled to PTR-TOF-MS and TD-GCxGC-TOF-MS, together with confirmation on new clinical samples with TD-GCxGC-TOF-MS. From 26 potential VOC biomarkers, 23 were successfully detected with PTR-TOF-MS. All VOCs were successfully detected using TD-GCxGC-TOF-MS, providing effective separation of highly chemically related compounds, including isomers, and enabling high-confidence annotation based on two-dimensional chromatographic separation and mass spectra. Four VOCs were identified with a level 1 annotation in the clinical samples. For future applications, the combination of real-time PTR-TOF-MS and comprehensive TD-GCxGC-TOF-MS, at least on a subset of samples from a whole study, would enhance the performance of VOC annotation, offering potential advancements in biomarker discovery for clinical research.
Subject(s)
Biomarkers , Breath Tests , COVID-19 , Volatile Organic Compounds , Humans , Breath Tests/methods , Biomarkers/analysis , Volatile Organic Compounds/analysis , COVID-19/diagnosis , Gas Chromatography-Mass Spectrometry/methods , Mass Spectrometry/methods , Exhalation , SARS-CoV-2ABSTRACT
The relevance of oxylipins as biomarkers of oxidative stress has been established in recent years. Phytoprostanes and phytofurans are plant metabolites derived from peroxidation of α-linolenic acid (ALA) induced by ROS. Previous findings have suggested new valuable biological properties for these new active compounds in the frame of diverse pathophysiological situations and health constraints. Lipidomic profiling of different aerial parts of the same Acacia cyanophylla Lindl. specimen, was evaluated for the first time here, using LC-MS/MS technology. Analysis revealed the existence of six PhytoPs and three PhytoFs. Stems have the highest amount of these metabolites with 179.35 ng/g and 320.79 ng/g respectively. This first complete profile paves the way to explore Acacia cyanophylla Lindl. as a source of plant oxylipins for therapeutic or pharmaceutical uses.
Subject(s)
Acacia , Oxylipins , Tandem Mass Spectrometry , Chromatography, Liquid , Molecular Structure , Plant Extracts , Plant Components, AerialABSTRACT
BACKGROUND AND AIMS: The oxidative metabolism of polyunsaturated fatty acids (PUFAs) leads to bioactive isoprostanoids. The aim was to establish the associations of a complete urinary isoprostanoid profiling in a cohort study of carefully phenotyped obese subjects to determine possible potential differential implications for omega-6 PUFA- and omega-3 PUFA-derived isoprostanoids for obesity, metabolic indicators, and inflammation. METHODS AND RESULTS: PUFA peroxidation compounds were determined in urine samples from obese human subjects (n = 46) by liquid chromatography coupled to tandem mass spectrometry. Increased omega-6 arachidonic acid (AA) oxidation, mainly represented by 5-F2c isoprostane (5-F2c-IsoP) and metabolites of 15-F2t-IsoP, was associated with body mass index, glycated hemoglobin (HbA1c) and mean arterial blood pressure. In addition, we identified the omega-3 PUFA-derived urinary metabolites 14-F4t-NeuroP from docosahexaenoic acid (DHA) and 5-F3t-IsoP from eicosapentaenoic acid (EPA), which declined with age. The omega-3 to omega-6 oxidation ratio was a significant predictor of inflammation in obesity. CONCLUSION: The findings point to full urinary isoprostanoid profiling as a more sensitive measure of PUFA oxidative stress in obesity-induced metabolic complications compared with individual isoprostanoid measures. Furthermore, the results suggest the balance between the omega-3 and omega-6 PUFA oxidation as determinative for the consequences of oxidative stress on inflammation in obesity.
Subject(s)
Fatty Acids, Omega-3 , Fatty Acids, Omega-6 , Humans , Cohort Studies , Fatty Acids, Unsaturated , Obesity/diagnosis , Inflammation/diagnosisABSTRACT
SCOPE: The purpose of the study is to characterize the chemical diversity in rice bran (RB) lipidome and determines whether daily RB consumption for 4 weeks may modulate plasma lipid profiles in children. METHODS AND RESULTS: Untargeted and targeted lipidomics via ultra-performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UPLC-MS/MS) are applied to identify bioactive RB lipids from a collection of 17 rice varieties. To determine the impact of RB (Calrose-USA variety) supplementation on plasma lipid profile, a secondary analysis of plasma lipidome is conducted on data recorded in a clinical study (NCT01911390, n = 18 moderately hypercholesterolemic children) before and after 4 weeks of dietary intervention with a control or RB supplemented (15 g day-1 ) snack. Untargeted lipidomic reveals 118 lipids as the core of lipidome across all varieties among which phospholipids are abundant and oxylipins present. Phytoprostanes and phytofurans are quantified and characterized. Lipidome analysis of the children plasma following RB consumption reveals the presence of polar lipids and oxylipins alongside putative modulations in endocannabinoids associated with RB consumption. CONCLUSION: The investigation of novel polar lipids, oxylipins, phytoprostanes, and phytofurans in RB extracts provides support for new health-promoting properties interesting for people at risk for cardiometabolic disease.
Subject(s)
Oryza , Phospholipids , Child , Humans , Chromatography, Liquid , Glycolipids , Lipid Metabolism , Lipidomics , Oxylipins , Phospholipids/analysis , Tandem Mass Spectrometry/methodsABSTRACT
Proinflammatory bioactive lipid mediators and oxidative stress are increased in coronavirus disease 2019 (COVID-19). The randomized controlled single-blind trial COVID-Omega-F showed that intravenous omega-3 polyunsaturated fatty acids (n-3 PUFA) shifted the plasma lipid signature of COVID-19 towards increased proresolving precursor levels and decreased leukotoxin diols, associated with a beneficial immunodulatory response. The present study aimed to determine the effects of n-3 PUFA on the urinary oxylipidome and oxidative stress in COVID-19. From the COVID-Omega-F trial, 20 patients hospitalized for COVID-19 had available serial urinary samples collected at baseline, after 24-48 h, and after completing 5 days treatment with one daily intravenous infusion (2 mL/kg) of either placebo (NaCl; n = 10) or a lipid emulsion containing 10 g of n-3 PUFA per 100 mL (n = 10). Urinary eicosanoids and isoprostanes were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Erythrocytes obtained at the different time-points from n = 10 patients (n = 5 placebo and n = 5 n-3 PUFA) were used for determination of reactive oxygen species. Intravenous n-3 PUFA emulsion administration altered eicosanoid metabolites towards decreased levels for mediators of inflammation and thrombosis, and increased levels of the endothelial function mediator prostacyclin. Furthermore, non-enzymatic metabolism was skewed towards n-3 PUFA-derived metabolites with potential anti-inflammatory and pro-resolving effects. The oxidative stress marker 15-F2t-isoprostane was significantly lower in patients receiving n-3 PUFA treatment, who also exhibited significantly decreased erythrocyte oxidative stress compared with placebo-treated patients. These findings point to additional beneficial effects of intravenous n-3 PUFA emulsion treatment through a beneficial oxylipin profile and decreased oxidative stress in COVID-19.
Subject(s)
COVID-19 , Fatty Acids, Omega-3 , Humans , Emulsions , Chromatography, Liquid , Single-Blind Method , Tandem Mass Spectrometry , Eicosanoids/metabolism , Oxidative StressABSTRACT
Background: Insulin resistance is associated with atrial remodeling as well as atrial fibrillation (AF). However, there was limited evidence on the relationship of triglyceride-glucose index (TyG) index, a simple, valuable marker of insulin resistance, with AF. Thus, we aimed to investigate the association between TyG index and AF among hospitalized patients. Methods: A retrospective observational study was conducted in Daping Hospital, which included 356 hospitalized patients from the Department of Cardiology. Clinical and biochemical parameters were collected from electronic medical records and AF was diagnosed from electrocardiogram (ECG) findings. Results: We found that the TyG index was significantly higher in the AF group than in the group without AF. Multivariate logistic regression revealed that hypertension (OR = 1.756, 95%CI 1.135-2.717, P = 0.011) and TyG index (OR = 2.092, 95%CI 1.412-3.100, P<0.001) were positively associated with AF. The analysis of the area under the ROC curve was performed and revealed that area under curve (AUC) of TyG index was 0.600 (95%CI, 0.542-0.659, P = 0.001), the optimal critical value was 8.35, the sensitivity was 65.4%, and the specificity was 52.0%. Additional subgroup analyses of diabetic and non-diabetic subjects were also performed and found the TyG index was increased in non-diabetic subjects with AF. Furthermore, a logistic regression analysis showed TyG index was associated with AF (OR = 3.065, 95% CI, 1.819-5.166, P<0.001) in non-diabetic subjects. However, TyG index was not associated with AF in diabetic subjects. Conclusion: Elevated TyG index is an independent risk factor for AF among non-diabetic hospitalized patients.
Subject(s)
Atrial Fibrillation , Insulin Resistance , Humans , Glucose , Triglycerides , Blood Glucose/analysis , Atrial Fibrillation/etiology , BiomarkersABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is an emerging driver of cardiac arrhythmias. However, the relationship between NAFLD and malignant arrhythmia in non-ST-segment elevation myocardial infarction (NSTEMI) patients is still unclear.In this study, 358 NSTEMI inpatients were enrolled. They all received 24-hour Holter monitoring after percutaneous coronary intervention. All inpatients were divided into two groups: the non-NAFLD group (236 cases, 65.9%) and the NAFLD group (122 cases, 34.1%). Compared with the non-NAFLD group, the NAFLD group had a significantly higher incidence of PVCs/hour > 5 (premature ventricular complexes, 32.0% versus 9.3%, P < 0.001), ventricular tachycardia (VT, 22.1% versus 5.9%, P < 0.001), and sinus arrest (SA, 7.4% versus 1.3%, P = 0.002). We found that NAFLD was closely associated with the occurrence of VT [unadjusted odds ratio (OR) 4.507, 95% confidence interval (CI) 2.263-8.974, P < 0.001] and SA (OR 6.186, 95%CI 1.643-23.291, P = 0.007). After adjusting for age, sex, body mass index, and other confounding factors, the above differences were still statistically significant (VT: OR 4.808, 95%CI 2.254-10.253, P < 0.001; SA: OR 9.589, 95%CI 2.027-45.367, P = 0.004).NAFLD is associated with the occurrence of VT and SA in NSTEMI patients. It indicates that NAFLD might be a risk factor for malignant arrhythmias in post-NSTEMI patients.
Subject(s)
Heart Arrest , Non-ST Elevated Myocardial Infarction , Non-alcoholic Fatty Liver Disease , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Tachycardia, Ventricular , Ventricular Premature Complexes , Heart Arrest/complications , Humans , Non-ST Elevated Myocardial Infarction/complications , Non-alcoholic Fatty Liver Disease/complications , Percutaneous Coronary Intervention/adverse effects , Risk Factors , ST Elevation Myocardial Infarction/complications , Tachycardia, Ventricular/complications , Tachycardia, Ventricular/etiology , Ventricular Premature Complexes/etiologyABSTRACT
Importance: Hypertension is a leading cause of end-stage renal disease (ESRD), but currently, those at risk are poorly identified. Objective: To develop and validate a prediction model for the development of hypertensive nephropathy (HN). Design Setting and Participants: Individual data of cohorts of hypertensive patients from Kailuan, China served to derive and validate a multivariable prediction model of HN from 12, 656 individuals enrolled from January 2006 to August 2007, with a median follow-up of 6.5 years. The developed model was subsequently tested in both derivation and external validation cohorts. Variables: Demographics, physical examination, laboratory, and comorbidity variables. Main Outcomes and Measures: Hypertensive nephropathy was defined as hypertension with an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 and/or proteinuria. Results: About 8.5% of patients in the derivation cohort developed HN after a median follow-up of 6.5 years that was similar in the validation cohort. Eight variables in the derivation cohort were found to contribute to the risk of HN: salt intake, diabetes mellitus, stroke, serum low-density lipoprotein, pulse pressure, age, hypertension duration, and serum uric acid. The discrimination by concordance statistics (C-statistics) was 0.785 (IQR, 0.770-0.800); the calibration slope was 1.129, the intercept was -0.117; and the overall accuracy by adjusted R 2 was 0.998 with similar results in the validation cohort. A simple points scale developed from these data (0, low to 40, high) detected a low morbidity of 7% in the low-risk group (0-10 points) compared with >40% in the high-risk group (>20 points). Conclusions and Relevance: A prediction model of HN over 8 years had high discrimination and calibration, but this model requires prospective evaluation in other cohorts, to confirm its potential to improve patient care.
ABSTRACT
Styrian pumpkin seed oil is a conditioned green-colored oil renowned for nutty smell and taste. Due to α-linolenic acid (ALA) contents below 1% of total fatty acids and the prospect of nutritional health claims based on its potential oxidation products, we investigated the fate of ALA and product oxylipins in the course of down-stream processing of seeds and in oils. Lipidomic analyses with Lipid Data Analyzer 2.8.1 revealed: Processing did not change (1) main fatty acid composition in the oils, (2) amounts of triacylglycerol species, (3) structures of triacylglycerol molecular species containing ALA. (4) Minor precursor ALA in fresh Styrian and normal pumpkins produced 6 product phytoprostanes in either cultivar, quantitatively more in the latter. (5) In oil samples 7 phytoprostanes and 2 phytofurans were detected. The latter two are specific for their presence in pumpkin seed oils, of note, quantitatively more in conditioned oils than in cold-pressed native oils.
Subject(s)
Cucurbita , Fatty Acids , Lipidomics , Molecular Structure , Oxylipins , Plant Oils , Seeds , Triglycerides , alpha-Linolenic AcidABSTRACT
Date palm fruit has been considered for centuries as an ancient nutritional constituent in the human diet. Recently, global trade in dates increased at an average that, simultaneously, will be accompanied by an increase in date palm byproducts. Supported by date phytochemicals and their health benefits, the aim of this work is to evaluate for the first time the presence of special metabolites of plant called phytoprostanes (PhytoPs) in five different varieties of the Phoenix dactylifera L. pulps and pits using a microLC-ESI-QTrap-MS/MS methodology. Results obtained showed the interest of using these matrices as potential sources of several PhytoPs (ent-16-B1-PhytoP; ent-9-L1-PhytoP; and epimers of ent-16-F1t-PhytoP and of 9-F1t-PhytoP). The variation in concentration between different varieties and different DPF parts was also evaluated. Results obtained will help to unravel the biological activities associated with DPF consumption that could be related to these bioactive metabolites.
Subject(s)
Phoeniceae , Tandem Mass Spectrometry , Humans , Phytochemicals , Plant ExtractsABSTRACT
A heterologous pathway for sucrose transport and metabolism was introduced into Clostridium beijerinckii to improve sucrose use for n-butanol production. The combined expression of StSUT1, encoding a sucrose transporter from potato (Solanum tuberosum), and SUC2, encoding a sucrose invertase from Saccharomyces cerevisiae, remarkably enhanced n-butanol production. With sucrose, sugarcane molasses and sugarcane juice as substrates, the C. beijerinckii strain harbouring StSUT1 and SUC2 increased acetone-butanol-ethanol production by 38.7%, 22.3% and 52.8%, respectively, compared with the wild-type strain. This is the first report to demonstrate enhanced sucrose fermentation due to the heterologous expression of a sucrose transporter and invertase in Clostridium. The metabolic engineering strategy used in this study can be widely applied in other microorganisms to enhance the production of high-value compounds from sucrose-based biomass.
ABSTRACT
The bovine hoof wall with an α-keratin structure protects the bovine foot from impact loads when the cattle are running. Reduced modulus, hardness and creep behavior of the bovine hoof wall have been investigated by a nanoindentation technique. The average reduced modulus of the Transverse Direction (TD) specimens from the outside to inside wall is 3.76 and 2.05 GPa, respectively, while the average reduced modulus of the Longitudinal Direction (LD) specimens from the outside to inside wall is 4.54 and 3.22 GPa, respectively. Obviously, the orientation and the position of the bovine hoof wall have a significant influence on its mechanical properties. The use of the generalized Voigt-Kelvin model can make a good prediction of creep stage. Mechanical properties of the LD specimens are stronger than those of the TD specimens. The bovine hoof wall has a layered structure, which can effectively absorb the energy released by the crack propagation and passivate the crack tip. Therefore, a kind of structural model was designed and fabricated by three-dimensional printing technology, which has a 55% performance improvement on fracture toughness. It is believed that the reported results can be useful in the design of new bionic structure materials which may be used in motorcycle helmets and athletes' protective equipment to achieve light weight and improved strength at the same time.
ABSTRACT
Brain functions are known to be mainly modulated by adequate dietary intake. Inadequate intake as can be an excess or significant deficiency affect cognitive processes, behavior, neuroendocrine functions and synaptic plasticity with protective or harmful effects on neuronal physiology. Lipids, in particular, ω-6 and ω-3 long chain polyunsaturated fatty acids (LC-PUFAs) play structural roles and govern the different functions of the brain. Hence, the goal of this study was to characterize the whole brain fatty acid composition (precursors, enzymatic and non-enzymatic oxidation metabolites) of fish model of rainbow trout fed with three experimental plant-based diet containing distinct levels of eicosapentaenoic acid (EPA, 20:5 ω-3) and docosahexaenoic acid (DHA, 22:6 ω-3) (0% for low, 15.7% for medium and 33.4% for high, total fatty acid content) during nine weeks. Trout fed with the diet devoid of DHA and EPA showed reduced brain content of total ω-3 LC-PUFAs, with diminution of EPA and DHA. Selected enzymatic (cyclooxygenases and lipoxygenases) oxidation metabolites of arachidonic acid (AA, 20:4 ω-6) decrease in medium and high ω-3 LC-PUFAs diets. On the contrary, total selected enzymatic oxidation metabolites of DHA and EPA increased in high ω-3 LC-PUFAs diet. Total selected non-enzymatic oxidation metabolites of DHA (not detected for EPA) increased in medium and high ω-3 LC-PUFAs diets. In conclusion, this work revealed for the first time in fish model the presence of some selected enzymatic and non-enzymatic oxidation metabolites in brain and the modulation of brain lipid content by dietary DHA and EPA levels.
Subject(s)
Brain Chemistry , Brain/metabolism , Docosahexaenoic Acids/metabolism , Docosahexaenoic Acids/pharmacology , Eicosapentaenoic Acid/metabolism , Eicosapentaenoic Acid/pharmacology , Oncorhynchus mykiss/metabolism , Animal Feed , Animals , Brain/drug effects , Dietary Fats, Unsaturated/metabolism , Dietary Fats, Unsaturated/pharmacology , Fatty Acids/chemistry , Fatty Acids/metabolism , Female , Lipid Metabolism , Oncorhynchus mykiss/growth & development , Plant Oils/metabolism , Plant Oils/pharmacologyABSTRACT
Algae result from a complex evolutionary history that shapes their metabolic network. For example, these organisms can synthesize different polyunsaturated fatty acids, such as those found in land plants and oily fish. Due to the presence of numerous double-bonds, such molecules can be oxidized nonenzymatically, and this results in the biosynthesis of high-value bioactive metabolites named isoprostanoids. So far, there have been only a few studies reporting isoprostanoid productions in algae. To fill this gap, the current investigation aimed at profiling isoprostanoids by liquid chromatography -mass spectrometry/mass spectrometry (LC-MS/MS) in four marine microalgae. A good correlation was observed between the most abundant polyunsaturated fatty acids (PUFAs) produced by the investigated microalgal species and their isoprostanoid profiles. No significant variations in the content of oxidized derivatives were observed for Rhodomonas salina and Chaetoceros gracilis under copper stress, whereas increases in the production of C18-, C20- and C22-derived isoprostanoids were monitored in Tisochrysis lutea and Phaeodactylum tricornutum. In the presence of hydrogen peroxide, no significant changes were observed for C. gracilis and for T. lutea, while variations were monitored for the other two algae. This study paves the way to further studying the physiological roles of isoprostanoids in marine microalgae and exploring these organisms as bioresources for isoprostanoid production.
Subject(s)
Fatty Acids, Unsaturated/analysis , Microalgae/chemistry , Prostaglandins/analysis , Chromatography, Liquid , Lipidomics , Tandem Mass SpectrometryABSTRACT
The area under the blood pressure curve is associated with target organ damage, but accurately estimating its value is challenging. This study aimed to improve the utility of the area under the blood pressure curve to predict hypertensive target organ damage. This retrospective cohort study comprised of 634 consecutive patients with essential hypertension for >1 year. Target organ damage was defined as the presence of left ventricular hypertrophy and/or carotid artery plaques. We evaluated the associations between the cumulative blood pressure load, which was derived from ambulatory blood pressure monitoring data, and target organ damage. The predictive value of the cumulative blood pressure load for target organ damage was assessed using receiver operating characteristic curves. Left ventricular hypertrophy and carotid artery plaques were present in 392 (61.8%) and 316 (49.8%) patients, respectively. Patients with left ventricular hypertrophy and/or carotid artery plaques had higher 24-hour blood pressure, nocturnal cumulative systolic blood pressure, and nocturnal cumulative pulse pressure load. The nocturnal cumulative systolic blood pressure load was an independent predictor of left ventricular hypertrophy (odds ratio = 1.002, 95% confidence interval: 1.001-1.004; P = .000) and carotid artery plaques (odds ratio = 1.003, 95% confidence interval: 1.002-1.007; P = .007). The nocturnal cumulative systolic blood pressure and cumulative pulse pressure load, relative to mean blood pressure, were superior in predicting hypertensive target organ damage. Hence, the cumulative blood pressure load is a better indicator of blood pressure consequences, and the nocturnal cumulative systolic blood pressure and cumulative pulse pressure loads could predict target organ damage.
Subject(s)
Diabetes Mellitus, Type 2 , Essential Hypertension , Aged , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Diabetes Mellitus, Type 2/physiopathology , Essential Hypertension/physiopathology , Female , Humans , Hypertrophy, Left Ventricular/diagnosis , Hypertrophy, Left Ventricular/epidemiology , Male , Middle Aged , Retrospective StudiesABSTRACT
Bovine hoof wall with an alpha keratin structure, as the interface between the ground and the body, can protect the bony skeleton from the impact and the destruction. Microstructure and mechanical properties of the bovine hoof wall are investigated by scanning electron microscope (SEM), transmission electron microscope (TEM) and quasi-static mechanical tests. Mechanical results show that the mean J-integral values of the LD specimens parallel to the tubular axis are higher than those of the TD specimens normal to the tubular axis, and the fracture toughness reaches the peak values (21 kJ/m2, 33 kJ/m2 for the TD and the LD specimens, respectively) at 16.5% moisture content. The morphology results show that the laminated keratin structure can form the extensive strain-transition interfaces and the tubules played an important role in twisting crack propagation. Angles of the laminated structures within the inter-tubular materials are not a uniform distribution varying from 0° to 90° against to the tubular axis. The interlocking interface in the tubular structure can provide increased the contact area and contribute to the bonding strength between the layers. We also propose models to illustrate the morphological structure and the crack propagation mechanism of the bovine hoof wall. This structure with the strong fracture resistance ability will provide a new inspiration for design of structural materials and architectures.
Subject(s)
Fractures, Bone , Hoof and Claw , Animals , Cattle , Keratins , Stress, Mechanical , Tensile StrengthABSTRACT
Recommendations for the analysis of competing risks in the context of randomized clinical trials are well established. Meta-analysis of individual patient data (IPD) is the gold standard for synthesizing evidence for clinical interpretation based on multiple studies. Surprisingly, no formal guidelines have been yet proposed to conduct an IPD meta-analysis with competing risk endpoints. To fill this gap, this work details (i) how to handle the heterogeneity between trials via a stratified regression model for competing risks and (ii) that the usual metrics of inconsistency to assess heterogeneity can readily be employed. Our proposal is illustrated by the re-analysis of a recently published meta-analysis in nasopharyngeal carcinoma, aiming at quantifying the benefit of the addition of chemotherapy to radiotherapy on each competing endpoint.
Subject(s)
Clinical Trials as Topic , Endpoint Determination , Meta-Analysis as Topic , Biometry , Humans , Linear Models , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/radiotherapy , RiskABSTRACT
Penalized variable selection methods have been extensively studied for standard time-to-event data. Such methods cannot be directly applied when subjects are at risk of multiple mutually exclusive events, known as competing risks. The proportional subdistribution hazard (PSH) model proposed by Fine and Gray (J Am Stat Assoc 94:496-509, 1999) has become a popular semi-parametric model for time-to-event data with competing risks. It allows for direct assessment of covariate effects on the cumulative incidence function. In this paper, we propose a general penalized variable selection strategy that simultaneously handles variable selection and parameter estimation in the PSH model. We rigorously establish the asymptotic properties of the proposed penalized estimators and modify the coordinate descent algorithm for implementation. Simulation studies are conducted to demonstrate the good performance of the proposed method. Data from deceased donor kidney transplants from the United Network of Organ Sharing illustrate the utility of the proposed method.
Subject(s)
Proportional Hazards Models , Risk , Data Interpretation, Statistical , Humans , IncidenceABSTRACT
High hydrogenated silicon-rich silicon nitride(SiNxâ¶H)thin films are deposited on the glass and monocrystalline silicon(110) substrates by plasma enhanced chemical vapor deposition using SiH4 and H2 as the main reaction gas with doping the N2. The ultraviolet-visible absorption spectrum, Fourier transform infrared absorption spectroscopy, Raman spectroscopy and photoluminescence spectrum are applied to characterize the changes of the band gap, the microstructure and related photoluminescence properties of the nitrogen-doped silicon film. It shows that hydrogen atoms can suppress the defects in the film and make film present silicon-rich under the low SiH4/H2 flow ratio, but they are not beneficial to the formation of silicon clusters in a hydrogen atmosphere. With the incorporation of nitrogen atoms, all the content of Si-N bonds, band gap and the degree of disorder in the microstructure of the films increase, films produce light emission related to the defect states. While the content of doped nitrogen atoms are further increased, it appears the band tail emission. Then the relationships between several light emissions and microstructure to be discussed. These results are useful for the optimization of light emission and microstructure for the silicon-rich silicon nitride film material prepared by PECVD.