Recently, suction buckets have become a very prominent foundation for bottom fixed and floating offshore wind turbines. They are embedded with an installation force that stems from water evacuation ...inside the bucket. This internal negative pressure leads to a high risk of structural buckling. The buckling strength is significantly reduced by geometric imperfections. In previous work, equivalent geometric imperfection forms were introduced and the lower bound was evaluated. However, it has not yet been possible to identify a generally appropriate imperfection form. A probabilistic design approach based on realistic imperfections was not yet considered for suction buckets. Therefore, in this work, a stochastic modeling approach is introduced, which bases on measured data. The imperfection is decomposed to the half-wave cosine Fourier representation. Realizations of the imperfection pattern are generated by filtering white noise with the amplitude spectrum. They are then applied as out of plane deviations on a geometrically and materially nonlinear finite element model and evaluated. The resulting buckling pressure distribution can then be evaluated for different reliability levels. By considering more realistic imperfections and a plastic soil model, the buckling pressure increases by up to a factor of two compared to the conservative stress-based buckling approach.
Carbonation caused by atmospheric carbon dioxide is one of the major physicochemical processes which can compromise the service life of reinforced concrete structures. While the bulk of the ...carbonation reaction is that of calcium hydroxide, other constituents of the porous matrix can also carbonate and compete with calcium hydroxide for carbon dioxide. Particularly the carbonation of calcium–silicate hydrates and unhydrated constituents are neglected by most authors in carbonation prediction models. In this paper, a mathematical model of carbonation is extended to include additional carbonation and hydration reactions. The competition of the several reactions and their effect on the carbonation depth is investigated by dimensional analysis and numerical simulations. A parameter study emphasises that multiple internal reaction layers appear. Their position and speed essentially depend on the strength of the different reactions. It is also observed that, for a wide range of parameters, the effect of some of the additional reactions on the carbonation depth is small. In particular, a comparison with data from laboratory experiments justifies the neglect of the carbonation of the unhydrated constituents in prediction models.
Strict emission limits have forced the automotive industry to reduce the carbon dioxide emissions produced by internal combustion engines. Emissions can also be reduced by increasing the efficiency ...of internal combustion engines by implementing technologies such as cylinder deactivation, the main benefit of which is a reduction in fuel consumption. However, there are some negative effects associated with this technology. There are two approaches to cylinder deactivation – selective and rolling. This paper focuses on the constraints of the technology and compares the two methods of cylinder deactivation in terms of torsional vibration, friction losses and load on the main bearings. The results for the selective and rolling cylinder deactivation are obtained from a verified multibody simulation of a four-cylinder engine.
•Cylinder deactivation (CDA) decreases CO2 emissions, especially for SI engines.•CDA also has negative effects, such as worse NVH and higher friction losses.•Selective cylinder deactivation produces a high level of torsional vibration.•Using rolling CDA leads to higher friction losses and load on the main bearings.
Current data on the use of irreversible electroporation (IRE) in the treatment of prostate cancer (PCa) is limited. We aim to evaluate the safety, short-term functional and oncological outcomes of ...focal IRE in low-intermediate risk PCa.
Between February 2013 and May 2014, 32 consecutive men underwent IRE at a single centre. Patients with low-intermediate risk PCa who had not received previous PCa treatment were included for analysis. The tumour was ablated using 3-6 electrodes, ensuring a minimum 5-mm safety margin around the visible magnetic resonance imaging (MRI) lesion. Follow-up included recording Clavien complications, Expanded Prostate Cancer Index Composite (EPIC) questionnaires (baseline, 1.5, 3, 6 months), 6-month multi-parametric MRI (mp-MRI) and 7-month biopsy. Findings on mp-MRI and biopsy were sub-divided into infield, adjacent or outfield of the treatment zone.
Twenty-five men were included for final analysis. Safety follow-up revealed one Clavien Grade 3 complication and five Grade 1 complications. Functional follow-up confirmed no significant change in American Urological Association urinary symptom score, sexual or bowel function. Infield, there were no suspicious findings on mp-MRI (n=24) or biopsy (n=21) in all patients. Adjacent to the treatment zone, five (21%) had suspicious findings on mp-MRI with four (19%) proving to be significant on biopsy. Outfield, there were two (8%) with suspicious findings on mp-MRI and one (5%) significant finding on biopsy. For the five patients with significant findings on follow-up biopsy, one is awaiting repeat IRE, one had radical prostatectomy and three remained on active surveillance.
In selected patients with low-intermediate risk PCa, focal IRE appears to be safe with minimal morbidity. There were no infield recurrences and 76% of patients were histologically free of significant cancer at 8 months. Almost all recurrences were adjacent to the treatment zone, and this was addressed by widening the treatment margins.
Purpose We assess the accuracy of multiparametric magnetic resonance imaging for significant prostate cancer detection before diagnostic biopsy in men with an abnormal prostate specific ...antigen/digital rectal examination. Materials and Methods A total of 388 men underwent multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted and dynamic contrast enhanced imaging before biopsy. Two radiologists used PI-RADS to allocate a score of 1 to 5 for suspicion of significant prostate cancer (Gleason 7 with more than 5% grade 4). PI-RADS 3 to 5 was considered positive. Transperineal template guided mapping biopsy of 18 regions (median 30 cores) was performed with additional manually directed cores from magnetic resonance imaging positive regions. The anatomical location, size and grade of individual cancer areas in the biopsy regions (18) as the primary outcome and in prostatectomy specimens (117) as the secondary outcome were correlated to the magnetic resonance imaging positive regions. Results Of the 388 men who were enrolled in the study 344 were analyzed. Multiparametric magnetic resonance imaging was positive in 77.0% of patients, 62.5% had prostate cancer and 41.6% had significant prostate cancer. The detection of significant prostate cancer by multiparametric magnetic resonance imaging had a sensitivity of 96%, specificity of 36%, negative predictive value of 92% and positive predictive value of 52%. Adding PI-RADS to the multivariate model, including prostate specific antigen, digital rectal examination, prostate volume and age, improved the AUC from 0.776 to 0.879 (p <0.001). Anatomical concordance analysis showed a low mismatch between the magnetic resonance imaging positive regions and biopsy positive regions (4 2.9%), and the significant prostate cancer area in the radical prostatectomy specimen (3 3.3%). Conclusions In men with an abnormal prostate specific antigen/digital rectal examination, multiparametric magnetic resonance imaging detected significant prostate cancer with an excellent negative predictive value and moderate positive predictive value. The use of multiparametric magnetic resonance imaging to diagnose significant prostate cancer may result in a substantial number of unnecessary biopsies while missing a minimum of significant prostate cancers.
Abstract
Since the publication of the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines for the Management of Arterial Hypertension, several high-quality ...studies, including randomised, sham-controlled trials on catheter-based renal denervation (RDN) were published, confirming both the blood pressure (BP)-lowering efficacy and safety of radiofrequency and ultrasound RDN in a broad range of patients with hypertension, including resistant hypertension. A clinical consensus document by the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on RDN in the management of hypertension was considered necessary to inform clinical practice. This expert group proposes that RDN is an adjunct treatment option in uncontrolled resistant hypertension, confirmed by ambulatory BP measurements, despite best efforts at lifestyle and pharmacological interventions. RDN may also be used in patients who are unable to tolerate antihypertensive medications in the long term. A shared decision-making process is a key feature and preferably includes a patient who is well informed on the benefits and limitations of the procedure. The decision-making process should take (i) the patient’s global cardiovascular (CV) risk and/or (ii) the presence of hypertension-mediated organ damage or CV complications into account. Multidisciplinary hypertension teams involving hypertension experts and interventionalists evaluate the indication and facilitate the RDN procedure. Interventionalists require expertise in renal interventions and specific training in RDN procedures. Centres performing these procedures require the skills and resources to deal with potential complications. Future research is needed to address open questions and investigate the impact of BP-lowering with RDN on clinical outcomes and potential clinical indications beyond hypertension.
Abstract The melanocortin‐1 receptor (MC1R) is a G protein‐coupled receptor that plays a pivotal role in human skin pigmentation, melanin synthesis, redox homeostasis and inflammation. ...Loss‐of‐function MC1R variants suppress G protein‐coupled receptor coupling or cell surface expression leading to a decrease in adenyl cyclase activation and intracellular levels of cyclic adenosine monophosphate. Chronic activation of MC1R can occur in certain medical conditions such as Addison's disease and physiologic states such as pregnancy melasma. MC1R activation is more commonly caused by environmental exposure to ultraviolet (UV) radiation. Approved pharmacologic melanocortin agonists that activate MC1R signalling in a targeted manner or as a bystander effect have recently become available for erythropoietic protoporphyria, sexual desire disorders, monogenic obesity and syndromic obesity. Further, small peptide analogues of α–melanocortin‐stimulating hormone, human MC1R selective agonists, are photoprotective, decreasing the adverse impact of UV radiation (a primary risk factor for skin cancer) and are being investigated as potential chemoprevention strategies. MC1R activation through induction of UV‐protective skin pigmentation increased DNA repair, and control of aberrant cell growth may reduce the risk of melanoma but importantly does not prevent melanoma particularly in individuals with risk factors and regular skin examination remains critical in high‐risk individuals.
Understanding the dynamics of correlated many-body quantum systems is a challenge for modern physics. Owing to the simplicity of their Hamiltonians, (4)He (bosons) and (3)He (fermions) have served as ...model systems for strongly interacting quantum fluids, with substantial efforts devoted to their understanding. An important milestone was the direct observation of the collective phonon-roton mode in liquid (4)He by neutron scattering, verifying Landau's prediction and his fruitful concept of elementary excitations. In a Fermi system, collective density fluctuations (known as 'zero-sound' in (3)He, and 'plasmons' in charged systems) and incoherent particle-hole excitations are observed. At small wavevectors and energies, both types of excitation are described by Landau's theory of Fermi liquids. At higher wavevectors, the collective mode enters the particle-hole band, where it is strongly damped. The dynamics of Fermi liquids at high wavevectors was thus believed to be essentially incoherent. Here we report inelastic neutron scattering measurements of a monolayer of liquid (3)He, observing a roton-like excitation. We find that the collective density mode reappears as a well defined excitation at momentum transfers larger than twice the Fermi momentum. We thus observe unexpected collective behaviour of a Fermi many-body system in the regime beyond the scope of Landau's theory. A satisfactory interpretation of the measured spectra is obtained using a dynamic many-body theory.
Abstract Type 2 diabetes is associated with an increased risk of cardiac complications. Inhibitors of dipeptidylpeptidase 4 (DPP-4) are novel drugs for the treatment of patients with type 2 diabetes. ...The effect of DPP-4 inhibitors on myocardial metabolism has not been studied in detail. In wild-type C57Bl6-mice, 3 weeks of treatment with sitagliptin had no effect on body weight and glucose tolerance nor on phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoAcarboxylase (ACC), phosphofructokinase-2 (PFK2) or tuberin-2 (TSC2) in the left ventricular myocardium. However, in 10 week old db/db−/− mice, a model of diabetes and obesity, sitagliptin potently reduced plasma glucose rise in peritoneal glucose tolerance tests and reduced weight increase. The myocardium of untreated db/db−/− mice exhibited a marked increase of the phosphorylation of AMPK, ACC, TSC2, expression of p53 and fatty acid translocase (FAT/CD36) membrane expression. These changes were reduced by DPP-4 inhibition. Sitagliptin showed no effect on cardiomyocyte size but prevented myocardial fibrosis in the 10 week old db/db−/− mice and reduced expression of TGF-β1, markers of oxidative stress and the accumulation of advanced glycation end products in cardiomyocytes. Working heart analyses did not show an effect of sitagliptin on parameters of systolic cardiac function. In animals with diabetes and obesity, sitagliptin improved glucose tolerance, reduced weight gain, myocardial fibrosis and oxidative stress. Furthermore the study provides evidence that treatment with sitagliptin decreases elevated myocardial fatty acid uptake and oxidation in the diabetic heart. These observations show beneficial myocardial metabolic effect of DPP-4 inhibition in this mouse model of diabetes and obesity.
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