•3D CFD modelling of buoyancy-driven convection flow resolved on full-geometry vehicle.•Convective heat transfer coefficients characterised during natural soak environment.•Coupled transient CFD - ...heat transfer modelling analysis was demonstrated.•9 h cool-down behaviours of the key engine fluids were resolved.•A CAE tool developed enabling evaluations of heat retention and encapsulation design.
This paper investigates transient heat transfer processes of a vehicle under-bonnet region during natural soak condition using computer aided engineering (CAE). Heat reserved within the engine bay is beneficial to the engine cold-start for potentially reductions in friction losses, CO2 emissions and fuel consumption. Buoyancy-driven convection, thermal radiation and conduction are key contributors to heat transfer processes of engine compartments during soak. In this study, a coupled transient 3D computational fluids dynamics (CFD) – heat transfer modelling method was studied in a passenger vehicle to simulate its 9 h cool-down behaviours. The developed CAE method was able to predict the temperature cool-down of the key fluids of good agreement with experiments. Potential air and heat leakage paths around the engine bay were identified. The flow development during the early stage (0–2 h) of the soak was vital to accurate prediction of the heat transfer coefficients for the heat retention modelling, where convection and radiation have played important parts. Optimum simulation strategy was obtained with reduced simulation time and good prediction accuracy. This further allows the integration of engine encapsulation design for optimising fuel consumption and emissions in a timely and robust manner, aiding the development of low-carbon transport technologies.
•Substantial reduction in organs at risk doses were achieved in radiotherapy over period 2000–2016.•Despite improvements in radiotherapy treatment planning, global quality of life did not improve ...significantly.•Small but significant improvements in dry mouth were seen over 2000–2016.
Technical improvements in head and neck cancer radiotherapy over the last decade have resulted in substantial reductions in dose to organs-at-risk. For a mix of tumors, we saw less xerostomia moving from 3D-conformal to more advanced techniques. For oropharynx-only there were additional improvements, including in global quality-of-life and sticky saliva.
Ectopic bone deposition plays an important role in osteoarthritis (OA) and in arterial wall disease. We aimed to investigate the prevalence and progression of arterial calcifications on whole-body ...computed tomography (CT) in persons with knee OA.
We included 118 (36 male) participants who satisfied the clinical American College of Rheumatology classification criteria for knee OA. Baseline investigations included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Kellgren-Lawrence grading. At baseline and after two years, a whole-body CT was performed using the same scanner and protocol. Calcifications were quantified in the carotid, brachiocephalic, coronary, thoracic aortic, abdominal aortic, iliac, femoropopliteal and crural arteries. Multivariable linear and logistic regression modeling was used for analyses.
At baseline males were 66.9 ± 7.7 and females were 68.0 ± 5.6 years old. Calcifications were common, all participants except two females had some calcification, and prevalence ranged between 41.8% and 94.4% for various arterial beds. Baseline femoropopliteal calcifications were associated with a higher Kellgren-Lawrence grade (more severe knee OA). Median annual progression rate was 13.1% in males and 15.7% in females. Structural OA severity was not associated with progression, but a five points lower (worse) WOMAC was associated with 1% faster progression of arterial calcifications (p= 0.008).
Around age 70 nearly all persons with knee OA have arterial calcifications, which progress substantially. For further investigation into shared causality intervention studies are needed.
Recent molecular profiling studies reported a new class of ultramutated colorectal cancers (CRCs), which are caused by exonuclease domain mutations (EDMs) in DNA polymerase ϵ (POLE). Data on the ...clinical implications of these findings as to whether these mutations define a unique CRC entity with distinct clinical outcome are lacking. We performed Sanger sequencing of the POLE exonuclease domain in 431 well‐characterized patients with microsatellite stable (MSS) CRCs of a population‐based patient cohort. Mutation data were analyzed for associations with major epidemiological, clinical, genetic, and pathological parameters including overall survival (OS) and disease‐specific survival (DSS). In 373 of 431 MSS CRC, all exons of the exonuclease domain were analyzable. Fifty‐four mutations were identified in 46 of these samples (12.3%). Besides already reported EDMs, we detected many new mutations in exons 13 and 14 (corresponding to amino acids 410–491) as well as in exon 9 and exon 11 (corresponding to aa 268–303 and aa 341–369). However, we did not see any significant associations of EDMs with clinicopathological parameters, including sex, age, tumor location and tumor stage, CIMP, KRAS, and BRAF mutations. While with a median follow‐up time of 5.0 years, survival analysis of the whole cohort revealed nonsignificantly different adjusted hazard ratios (HRs) of 1.35 (95% CI: 0.82–2.25) and 1.44 (0.81–2.58) for OS and DSS indicating slightly impaired survival of patients with EDMs, subgroup analysis for patients with stage III/IV disease receiving chemotherapy revealed a statistically significantly increased adjusted HR (1.87; 95%CI: 1.02–3.44). In conclusion, POLE EDMs do not appear to define an entirely new clinically distinct disease entity in CRC but may have prognostic or predictive implications in CRC subgroups, whose significance remains to be investigated in future studies.
It is currently unclear whether polymerase ɛ (POLE)‐mutated colorectal cancers (CRC) define a specific clinical subtype which is associated with a particular outcome. We found (i) that exonuclease domain mutations (EDMs) are more frequent than described previously, (ii) novel POLE EDMs, (iii) POLE EDMs per se do not correlate with BRAF‐, KRAS‐ or CIMP‐status or a distinct clinical phenotype including outcome, and (iv) subgroup analysis for patients with POLE mutations in stage III/IV tumors treated with chemotherapy revealed increased mortality. The findings translate pure genetic data in the clinic and suggest that POLE mutations do not define an entirely new clinical CRC‐subtype but may have a prognostic or predictive impact whose significance remains to be investigated in future studies.
Objectives/Hypothesis
To evaluate the influence of the introduction of newborn hearing screening programs on the age at cochlear implantation in children.
Study Design
Retrospective, multicenter ...cohort study.
Methods
All 1,299 pediatric cochlear implant users who received their implants before the age of 5 years between 1995 and 2011 in the Medical University Hannover, Germany and University Medical Center Utrecht, the Netherlands were enrolled in this study. Age at implantation and the number of children implanted within the first year of life was assessed for each center.
Results
Age at cochlear implantation gradually declined over the years in both centers. The introduction of the screening resulted in significant decline in the age at implantation in the Netherlands; simultaneously, the number of children implanted within their first year of life increased significantly. Comparing 4‐year epochs immediately before and after introduction of the screening, the mean age decreased from 2.4 to 1.2 years, and the percentage of early implanted children increased from 9% to 37%. In the German population, a similar effect of the introduction of the hearing screening program was absent.
Conclusions
The introduction of the national newborn hearing screening program has reduced the age at cochlear implantation in young children in the Netherlands but not in Germany. Correspondingly, it resulted in an increase in the number of children implanted early in life. The difference between the Dutch and German population might be due to differences in the follow‐up and referral after the hearing screening.
Level of Evidence
2b Laryngoscope, 125:985–990, 2015
Atrial fibrillation (AF) is the most frequent arrhythmic disease in humans, which leads to thrombus formation in the left atrial appendage and stroke through peripheral embolization. Depending on ...their origin, large extracellular vesicles (lEVs) can exert pro-coagulant functions. In the present study, we investigated how different types of AF influence the levels of large EV subtypes in three distinct atrial localizations. Blood samples were collected from the right and left atrium and the left atrial appendage of 58 patients. 49% of the patients had permanent AF, 34% had non-permanent AF, and 17% had no history of AF. Flow cytometric analysis of the origin of the lEVs showed that the proportion of platelet-derived lEVs in the left atrial appendage was significantly higher in permanent AF patients compared to non-permanent AF. When we grouped patients according to their current heart rhythm, we also detected significantly higher levels of platelet-derived lEVs in the left atrial appendage (LAA) in patients with atrial fibrillation. In vitro studies revealed, that platelet activation with lipopolysaccharide (LPS) leads to higher levels of miR-222-3p and miR-223-3p in platelet-derived lEVs. Treatment with lEVs from LPS- or thrombin-activated platelets reduces the migration of endothelial cells in vitro. These results suggest that permanent atrial fibrillation is associated with increased levels of platelet-derived lEVs in the LAA, which are potentially involved in LAA thrombus formation.
Deafness induction in mice Jansen, Thijs T G; Bremer, Hendrik G; Topsakal, Vedat ...
Otology & neurotology
34, Številka:
8
Journal Article
Recenzirano
How to induce most efficiently severe sensorineural hearing loss in mice using a single coadministration of an aminoglycoside antibiotic and a loop diuretic?
The coadministration of aminoglycosides ...and a loop diuretic has been widely used to induce hair cell and spiral ganglion cell loss in guinea pigs. However, the development of new treatment strategies against sensorineural hearing loss, such as tissue engineering techniques, requires the use of mouse models. Previous attempts to induce hearing loss in mice have rendered inconsistent results because of resistance to aminoglycoside-induced ototoxicity. Especially inner hair cells seem to be resistant to aminoglycoside-induced ototoxicity.
In the present study, we aim to optimize hearing loss in mice, using a single high-dose kanamycin (700 and 1,000 mg/kg) injection followed by a furosemide (100 mg/kg) administration. Although previous studies used intraperitoneal furosemide injections 30 minutes after kanamycin administration, we used intravenous furosemide injections administered within 5 minutes after kanamycin treatment.
Auditory brain stem responses illustrated severe threshold shifts, and histologic analysis showed marked outer hair cell destruction as well as spiral ganglion cell loss. The present protocol results in more severe inner hair cell loss when compared with the results of previous researches.
We conclude that severe sensorineural hearing loss can be induced in mice. Moreover, we found that this mouse model can be augmented via the use of rapid intravenous furosemide administrations to maximize inner hair cell loss.
Obesity is a major risk factor for the development of hypertension. Because the prevalence of obesity is increasing worldwide, the prevalence of obesity hypertension is also increasing. Importantly, ...hypertension in obesity is commonly complicated by dyslipidemia and type 2 diabetes mellitus and hence imposes a high cardiovascular disease risk. Furthermore, obesity is strongly associated with resistant hypertension. Activation of the sympathetic nervous system and the renin-angiotensin system, leading to renal sodium and water retention, links obesity with hypertension. There is also evidence for the release of factors by visceral adipose tissue promoting excessive aldosterone production, and a more central role of aldosterone in obesity hypertension is emerging. Randomized studies evaluating the effect of different classes of antihypertensive agents in obesity hypertension are scarce, short-lasting, and small. Considering the emerging role of aldosterone in the pathogenesis of obesity hypertension, mineralocorticoid receptor antagonism may play a more central role in the pharmacologic treatment of obesity hypertension in the near future.
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