Ultra-high strength steels employed in safety-critical applications, such as AerMet®100 used in aircraft landing gear structures, are managed on very conservative rejection criteria for small defects ...and repair options are limited. A novel repair technique using laser cladding has recently been developed. In the present paper we report a study of the fatigue endurance of AerMet®100 steel components repaired by the laser cladding process, and a fracture mechanics based model to predict the fatigue endurance of repaired components. Three different types of samples were tested; baseline AerMet®100 sample with a small electro-discharge machining notch to initiate a crack, as-clad repaired, and as-clad repaired followed by heat treatment to relieve residual stresses. The specimens were subjected to cyclic loading under a special sequence consisting of constant amplitude segments at two different stress-ratios (ratio of minimum to maximum cyclic stress). The test results showed that the crack propagation lives from a common initial depth of 0.25mm for the as-clad samples were significantly longer than the baseline samples by a factor of three to four. The longer life is attributed to the beneficial compressive residual stresses resulting from the repair process. The model predictions are found to correlate well with the results of quantitative fractography measurements from samples tested under variable amplitude cyclic loads.
•We study the association of long-term air pollution exposure with Parkinson’s Disease (PD)•Our study among 271,720 ELAPSE cohort participants noted 381 deaths from PD.•We find that long-term ...exposure to PM2.5, NO2 and BC are associated with risk of PD death.•Associations persist at low levels of pollutant concentration, below current EU standards.•Our study adds strong evidence in support of an association between air pollution and PD.
The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson’s Disease (PD) remains limited.
We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts.
Within the project ‘Effects of Low-Level Air Pollution: A Study in Europe’ (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders.
Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01–1.55), NO2 (1.13; 0.95–1.34 per 10 µg/m3), and BC (1.12; 0.94–1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58–0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95–1.62) or BC (1.28; 0.96–1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5.
Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality.
The association among body mass index (BMI), height, and the risk of lymphatic malignancies was investigated in the Netherlands Cohort Study. The participants (n = 120,852), Dutch men and women aged ...55–69 years, completed a self-administered questionnaire at baseline in 1986. After 13.3 years of follow-up, data on 1,042 lymphatic malignancy cases (including diffuse large-cell lymphoma, chronic lymphocytic leukemia, multiple myeloma, and other subtypes) and 4,588 subcohort members were available. Incidence rate ratios were estimated by using Cox regression models. BMI at baseline and BMI change since the age of 20 years were not associated with lymphatic malignancy risk. However, the rate ratio of lymphatic malignancies per 4-unit increase in BMI at 20 years of age was 1.13 (95% confidence interval (CI): 1.01, 1.25). The rate ratio of lymphatic malignancies per 5-cm increase in height was 1.08 (95% CI: 1.02, 1.15). For diffuse large-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia, the relative risks were 1.19 (95% CI: 1.07, 1.33), 1.15 (95% CI: 0.95, 1.40), and 1.09 (95% CI: 0.95, 1.26), respectively, for each 5-cm increase in height. The positive associations among BMI at 20 years of age, height, and the risk of lymphatic malignancies suggest that exposures during early life play a role in the etiology of lymphatic malignancies.
Abstract Objective Follistatin-like 3 (fstl3), a natural inhibitor of members of the TGF-β family, increases during resistance training in human plasma. Fstl3 primarily binds myostatin and activin A, ...and thereby inhibits their functions. We hypothesize that blocking myostatin and activin A signalling through systemic fstl3 over-expression protects against diet-induced obesity and insulin resistance. Methods Fstl3 was over-expressed by DNA electrotransfer in tibialis anterior, quadriceps and gastrocnemius muscles in female C57BL/C mice, and the mice were subsequently randomized to chow or high-fat feeding. Body weight, food intake, fat accumulation by MR scanning, and glucose, insulin and glucagon tolerance were evaluated, as was the response in body weight and metabolic parameters to 24 h fasting. Effects of fstl3 on pancreatic insulin and glucagon content, and pancreatic islet morphology were determined. Results Fstl3 over-expression reduced fat accumulation during high-fat feeding by 16%, and liver fat by 50%, as determined by MRI. No changes in body weight were observed, while the weight of the transfected muscles increased by 10%. No transcriptional changes were found in the subcutaneous adipose tissue. Fstl3 mice displayed improved insulin sensitivity and muscle insulin signalling. In contrast, glucose tolerance was impaired in high-fat fed fstl3 mice, which was explained by increased hepatic glucagon sensitivity and glucose output, as well as a decrease in the pancreatic insulin/glucagon ratio. Accordingly, fstl3 transfection improved counter-regulation to 24 h fasting. Conclusion Fstl3 over-expression regulates insulin and glucagon sensitivities through increased muscular insulin action, as well as increased hepatic glucagon sensitivity and pancreatic glucagon content.
We study the relationship between the structure and star formation rate (SFR) of X-ray selected low and moderate luminosity active galactic nuclei (AGNs) in the two Chandra Deep Fields, using Hubble ...Space Telescope imaging from the Cosmic Assembly Near Infrared Extragalactic Legacy Survey (CANDELS) and deep far-infrared maps from the PEP+GOODS-Herschel survey. We derive detailed distributions of structural parameters and FIR luminosities from carefully constructed control samples of galaxies, which we then compare to those of the AGNs. At z ~ 1, AGNs show slightly diskier light profiles than massive inactive (non-AGN) galaxies, as well as modestly higher levels of gross galaxy disturbance (as measured by visual signatures of interactions and clumpy structure). In contrast, at z ~ 2, AGNs show similar levels of galaxy disturbance as inactive galaxies, but display a red central light enhancement, which may arise from a more pronounced bulge in AGN hosts or extinguished nuclear light. We undertake a number of tests of both these alternatives, but our results do not strongly favor one interpretation over the other. The mean SFR and its distribution among AGNs and inactive galaxies are similar at z> 1.5. At z< 1, however, clear and significant enhancements are seen in the SFRs of AGNs with bulge-dominated light profiles. These trends suggest an evolution in the relation between nuclear activity and host properties with redshift, towards a minor role for mergers and interactions at z> 1.5.
Cervical Artery Dissection and Sports Engelter, Stefan T.; Traenka, Christopher; Grond-Ginsbach, Caspar ...
Frontiers in neurology,
05/2021, Volume:
12
Journal Article
Peer reviewed
Open access
Cervical artery dissection (CeAD) occurring in the context of sports is a matter of concern for CeAD patients. They seek advice on the role of sports in CeAD and on the safety of resuming sports ...after CeAD. The scarcity of studies and guidelines addressing these issues poses a challenge. We aimed at summarizing the current knowledge about CeAD and sports in order to provide an informed, comprehensive opinion for counseling CeAD patients. We took into account pathophysiological considerations, observations of cases reports, series, and registries, and conclusions by analogy from aortic dissection or inherited connective tissue syndromes. In summary, practicing active sports as the cause of CeAD seems uncommon. It seems recommendable to refrain from any kind of sports activities for at least 1 month, which can be extended in case of an unfavorable clinical or neurovascular course. We recommend starting with sport activities at low intensity—preferably with types of endurance sports—and to gradually increase the pace in an individually tailored manner, taking into circumstances of the occurrences of the CeAD in the individual patient (particularly in relation to sports), the meaning of sports activities for the individual well-being, the presence or absence of comorbidities and of neurological sequela, neurovascular findings, and whether there are signs of an underlying connective tissue alteration. Major limitations and several forms of bias are acknowledged. Still, in the absence of any better data, the summarized observations and considerations might help clinicians in advising and counseling patients with CeAD in clinical practice.
Comprehensively mapping the genetic basis of human disease across diverse individuals is a long-standing goal for the field of human genetics
. The All of Us Research Program is a longitudinal cohort ...study aiming to enrol a diverse group of at least one million individuals across the USA to accelerate biomedical research and improve human health
. Here we describe the programme's genomics data release of 245,388 clinical-grade genome sequences. This resource is unique in its diversity as 77% of participants are from communities that are historically under-represented in biomedical research and 46% are individuals from under-represented racial and ethnic minorities. All of Us identified more than 1 billion genetic variants, including more than 275 million previously unreported genetic variants, more than 3.9 million of which had coding consequences. Leveraging linkage between genomic data and the longitudinal electronic health record, we evaluated 3,724 genetic variants associated with 117 diseases and found high replication rates across both participants of European ancestry and participants of African ancestry. Summary-level data are publicly available, and individual-level data can be accessed by researchers through the All of Us Researcher Workbench using a unique data passport model with a median time from initial researcher registration to data access of 29 hours. We anticipate that this diverse dataset will advance the promise of genomic medicine for all.
Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL ...susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P=1.22×10(-14)), 18q21.33 (BCL2, P=7.76×10(-11)), 11p15.5 (C11orf21, P=2.15×10(-10)), 4q25 (LEF1, P=4.24×10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50×10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27×10(-8)), 18q21.32 (PMAIP1, P=2.51×10(-8)), 15q15.1 (BMF, P=2.71×10(-10)) and 2p22.2 (QPCT, P=1.68×10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08×10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
Intraoperative adverse events (iAEs) are frequent in visceral surgery, but severity and related postoperative outcome are poorly investigated. A novel classification of intraoperative adverse events, ...ClassIntra, includes surgical and anesthesiologic intraoperative adverse events using 5 severity grades and showed a high criterion and construct validity across all surgical disciplines. ClassIntra was studied for reproducibility in a prespecified group of patients undergoing visceral surgery.
iAEs were recorded in all patients enrolled in the ClassIntra validation study (NCT03009929). Postoperative complications were assessed daily according to the Clavien-Dindo classification. Results of the visceral group were compared with those of the non-visceral group and the full cohort. The risk-adjusted association between most severe intra and postoperative complications was investigated in a multivariable proportional odds model. Second, risk-adjusted association between ClassIntra grade and Comprehensive Complication Index, and postoperative length of stay was investigated.
In total, 1,270 out of 2,520 patients (50%) underwent visceral surgery. Compared with the nonvisceral group and full cohort, more intraoperative (337/1270 27% vs 273/1250 22% vs 610/2520 24% patients) and postoperative complications (457/1270 36% vs 381/1250 30% vs 838/2520 33% patients) occurred. The risk for a more severe postoperative complication increased with each ClassIntra grade (odds ratio 95% confidence interval I vs 0 1.10 0.73 to 1.66, II vs 0 1.69 1.10 to 2.60, III vs 0 2.31 1.21 to 4.41, IV vs 0 2.35 0.69 to 8.06). Accordingly, CCI and postoperative length of stay increased with each ClassIntra grade in the visceral group, comparable with the nonvisceral and full cohort.
Consistent results for the association of intraoperative adverse events and patient outcomes render ClassIntra a valuable instrument in visceral surgery.
Malformations of the index nails Hussein, T. P.; Brandt, H. R. C.; Gabbi, T. V. B. ...
Clinical and experimental dermatology,
December 2009, Volume:
34, Issue:
8
Journal Article
Peer reviewed
Summary
We report a 52‐year‐old woman with micronychia of the index fingers. Radiographic examination revealed a Y‐shaped bifurcation of the distal phalanx of both index fingers. She was diagnosed ...with congenital onychodysplasia of the index fingers (COIF) or Iso–Kikuchi syndrome. COIF is a rare condition characterized by a variety of nail dysplasia of the index fingers. Five criteria characterize COIF: congenital occurrence, unilateral or bilateral index finger involvement, variability in nail appearance, hereditary involvement and frequently associated bone abnormalities. Micronychia, polyonychia, anonychia, hemionychrogryphosis and malalignment are the observed index finger defects. Most cases have been described in Japan, and to our knowledge, this is the first case of COIF reported in South America.
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