Local dynamics of a randomly pinned crack front: A numerical study

We investigate numerically the dynamics of crack propagation along a weak plane using a model consisting of fibers connecting a soft and a hard clamp. This bottom-up model has previously been shown to contain the competition of two crack propagation mechanisms: coalescence of damage with the front on small scales and pinned elastic line motion on large scales. We investigate the dynamical scaling properties of the model, both on small and large scale. The model results compare favorable with experimental results

Onset of Localization in Heterogeneous Interfacial Failure

We study numerically the failure of an interface joining two elastic materials under load using a fiber bundle model connected to an elastic half space. We find that the breakdown process follows the equal load sharing fiber bundle model without any detectable spatial correlations between the positions of the failing fibers until localization sets in. The onset of localization is an instability, not a phase transition. Depending on the elastic constant describing the elastic half space, localization sets in before or after the critical load causing the interface to fail completely, is reached. There is a crossover between failure due to localization or failure without spatial correlations when tuning the elastic constant, not a phase transition. Contrary to earlier claims based on models different from ours, we find that a finite fraction of fibers must fail before the critical load is attained, even in the extreme localization regime, i.e.\ for very small elastic constant. We furthermore find that the critical load remains finite for all values of the elastic constant in the limit of an infinitely large system.Comment: 4 pages, 5 figure

25-Hydroxyvitamin D and Peripheral Immune Mediators:Results from Two Nationwide Danish Pediatric Cohorts

(1) Background: We aimed to examine if 25-hydroxyvitamin D (25(OH)D) was related to the peripheral immunological and inflammatory signature both at birth, and in newly diagnosed patients with childhood type 1 diabetes (T1D) and their healthy controls; (2) Methods: The birth cohort consisted of 470 patients and 500 healthy controls. Dried blood samples were collected from the neonates in the period 1981–1999. The newly diagnosed cohort consisted of 460 patients and 453 siblings. Serum samples were collected in the period 1997–2005. A variety of peripheral immune mediators were measured and compared to total 25(OH)D levels (25(OH)D2 + 25(OH)D3). For each immune mediator, the relative change (RC) in the mean level was modeled by robust log-normal regression and correction for multiple testing was performed; (3) Results: Two associations were identified; there was a negative association between 25(OH)D (10 nmol/L increase) and leptin (RC (95% confidence interval (CI)), 0.98 (0.96; 1.00)), and a positive association between 25(OH)D (10 nmol/L increase) and the chemokine, chemokine (c-x-c motif) ligand (CXCL) 8 (RC (95% CI), 1.07 (1.01; 1.13)); (4) Conclusion: CXCL8 and leptin have significant associations with levels of 25(OH)D in the newly diagnosed cohort. These results do not indicate a strong influence of 25(OH)D on the peripheral immunological or inflammatory signature

Systemic and local inflammatory response in women with preterm prelabor rupture of membranes

Objective:To evaluate the inflammatory pattern in maternal circulation, amniotic cavity, cervix and vagina from women with preterm prelabor rupture of membranes (PPROM) considering the occurrence of microbial invasion of the amniotic cavity (MIAC). Methodology: A prospective study was performed in 58 women with PPROM before 34+0 weeks of gestational age. Twenty-six proteins were analyzed by a multiple immunoassay in samples of amniotic fluid, serum, cervix and vagina. Association of an inflammatory response in the invasive and non-invasive samples with MIAC was investigated. Results: The rate of MIAC was 36.2% (21/58). Both amniotic fluid IL-6 and cervical C-reactive protein (CRP) showed to be independent predictors of MIAC. A cut-off level of cervical CRP≥1836 pg/mL showed a detection rate of 75%, false positive rate of 19% and positive and negative predictive values to predict MIAC of 67% and 87%, respectively. There were no independent biomarkers of MIAC either in the serum or vaginal compartment. Conclusion: A cervical inflammatory response mediated by CRP was observed in PPROM women with MIAC. Evaluation of serum or vaginal samples did not add valuable information regarding the outcome evaluated

Influences of the Common FTO rs9939609 Variant on Inflammatory Markers Throughout a Broad Range of Body Mass Index

A recent study reported that the fatness associated A-allele of FTO rs9939609 increased plasma high sensitivity C-reactive protein (hs-CRP) levels independent of fatness. We aimed to investigate if this gene variant had fatness-independent effects on plasma hs-CRP and 10 additional circulating obesity-related adipokines throughout a broad range of body mass index (BMI) among Danish men.In a population of 362,200 young men, examined for military service between 1943 and 1977, two groups were identified: 1) a random 1% sample and 2) all obese men (BMI = 31.0 kg/m(2), all of whom were above the 99(th) percentile of this population). At an average age of 49 years (range: 39 through 65 years), 551 men, hereof 231 of the obese, were re-examined, including genotyping and measurement of the fasting circulating inflammatory markers hs-CRP, IL-1β, IL-6, IL-10, IL-18, mip1α, mip1β, sTNFα-R1, TGF-β, TNF-α and leptin. Men with known disease were excluded from the examination. All the inflammatory markers were log-transformed to approximate a normal distribution. Genotype-phenotype relationships were studied using linear regression analyses with the inflammatory markers as the response variable. Significant positive associations between hs-CRP, leptin and a broad range of BMI were observed, but the associations did not significantly differ across FTO rs9939609 genotype. There were no significant associations between the other inflammatory markers, FTO rs9939609 genotype or BMI, respectively.No fatness-independent effects of the FTO rs9939609 A-allele on a series of inflammatory markers were observed in this cohort of healthy middle-aged men representing a broad range of fatness

Intra-amniotic inflammatory response in subgroups of women with preterm prelabor rupture of the membranes

Background To evaluate the influence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) on the magnitude of intra-amniotic inflammatory response in preterm prelabor rupture of membranes (PPROM). Methodology/Principal Finding A prospective cohort study was performed in 107 women with PPROM between 23.0 and 36.6 weeks of gestational age. Twenty-six proteins were assayed by multiple immunoassay in amniotic fluid. The policy for PPROM in Czech Republic is active, and 90% of the women were delivered within 96 hours of membrane rupture. Histopathological placental findings were evaluated based on the Salafia classification. Data were analyzed in four subgroups of population according to the presence of MIAC and/or HCA. Results were stratified by gestational age at PPROM (< or ≥34.0 weeks). The rates of MIAC and HCA were 44% and 57%, respectively. Regardless of gestational age at PPROM, intra-amniotic inflammatory response was higher when MIAC and HCA were both present. There were no differences in the intra-amniotic inflammatory response between women with MIAC or HCA alone and women without infection. Conclusion A higher intra-amniotic inflammatory response was identified when both HCA and MIAC were detected

The association between selected mid-trimester amniotic fluid candidate proteins and spontaneous preterm delivery

Objective: The aim of this study was to explore inflammatory response and identify early potential biomarkers in mid-trimester amniotic fluid associated with subsequent spontaneous preterm delivery (PTD). Methods: A cohort study was performed at Sahlgrenska University Hospital/ 6stra, Gothenburg, Sweden, between 2008 and 2010. Amniotic fluid was collected from consecutive women undergoing mid-trimester transabdominal genetic amniocentesis at 14–19 gestational weeks. Clinical data and delivery outcome variables were obtained from medical records. The analysis included 19 women with spontaneous PTD and 118 women who delivered at term. A panel of 26 candidate proteins was analyzed using Luminex xMAP technology. Candidate protein concentrations were analyzed with ANCOVA and adjusted for plate effects. Results: The median gestational age at delivery was 35 + 3 weeks in women with spontaneous PTD and 40 + 0 weeks in women who delivered at term. Nominally significantly lower amniotic fluid levels of adiponectin (PTD: median 130,695 pg/mL (IQR 71,852–199,414) vs term: median 185,329 pg/mL (IQR (135,815–290,532)), granulocyte-macrophage colony stimulating factor (PTD: median 137 pg/mL (IQR 74–156) vs term: median 176 pg/mL (IQR 111–262)), and macrophage migration inhibitory factor (PTD: median 3025 pg/mL (IQR 1885–3891) vs term: median 3400 pg/mL (IQR 2181–5231)) were observed in the spontaneous PTD group, compared with the term delivery group, after adjusting for plate effects. No significant differences remained after Bonferroni correction for multiple comparisons. Conclusions: Our results are important in the process of determining the etiology behind spontaneous PTD but due to the non-significance after Bonferroni correction, the results should be interpreted with caution. Further analyses of larger sample size will be required to determine whether these results are cogent and to examine whether microbial invasion of the amniotic cavity or intra-amniotic inflammation occurs in asymptomatic women in the mid-trimester with subsequent spontaneous PTD

Expanding the Utilization of Formalin-Fixed, Paraffin-Embedded Archives : Feasibility of miR-Seq for Disease Exploration and Biomarker Development from Biopsies with Clear Cell Renal Cell Carcinoma

Novel predictive tools for clear cell renal cell carcinoma (ccRCC) are urgently needed. MicroRNAs (miRNAs) have been increasingly investigated for their predictive value, and formalin-fixed paraffin-embedded biopsy archives may potentially be a valuable source of miRNA sequencing material, as they remain an underused resource. Core biopsies of both cancerous and adjacent normal tissues were obtained from patients (n = 12) undergoing nephrectomy. After small RNA-seq, several analyses were performed, including classifier evaluation, obesity-related inquiries, survival analysis using publicly available datasets, comparisons to the current literature and ingenuity pathway analyses. In a comparison of tumour vs. normal, 182 miRNAs were found with significant differential expression; miR-155 was of particular interest as it classified all ccRCC samples correctly and correlated well with tumour size (R-2 = 0.83); miR-155 also predicted poor survival with hazard ratios of 2.58 and 1.81 in two different TCGA (The Cancer Genome Atlas) datasets in a univariate model. However, in a multivariate Cox regression analysis including age, sex, cancer stage and histological grade, miR-155 was not a statistically significant survival predictor. In conclusion, formalin-fixed paraffin-embedded biopsy tissues are a viable source of miRNA-sequencing material. Our results further support a role for miR-155 as a promising cancer classifier and potentially as a therapeutic target in ccRCC that merits further investigation.Peer reviewe