Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is inversely associated with type 2 diabetes mellitus (T2DM) risk. Metabolic changes due to DASH adherence and their potential relationship with incident T2DM have not been described. The objective is to determine metabolite clusters associated with adherence to a DASH-like diet in the Insulin Resistance Atherosclerosis Study cohort and explore if the clusters predicted 5-year incidence of T2DM. The current study included 570 non-diabetic multi-ethnic participants aged 40–69 years. Adherence to a DASH-like diet was determined a priori through an eighty-point scale for absolute intakes of the eight DASH food groups. Quantitative measurements of eighty-seven metabolites (acylcarnitines, amino acids, bile acids, sterols and fatty acids) were obtained at baseline. Metabolite clusters related to DASH adherence were determined through partial least squares (PLS) analysis using R. Multivariable-adjusted logistic regression was used to explore the associations between metabolite clusters and incident T2DM. A group of acylcarnitines and fatty acids loaded strongly on the two components retained under PLS. Among strongly loading metabolites, a select group of acylcarnitines had over 50 % of their individual variance explained by the PLS model. Component 2 was inversely associated with incident T2DM (OR: 0·89; (95 % CI 0·80, 0·99), P-value = 0·043) after adjustment for demographic and metabolic covariates. Component 1 was not associated with T2DM risk (OR: 1·02; (95 % CI 0·88, 1·19), P-value = 0·74). Adherence to a DASH-type diet may contribute to reduced T2DM risk in part through modulations in acylcarnitine and fatty acid physiology.

Pompe disease results from lysosomal acid α-glucosidase deficiency, which leads to cardiomyopathy in all infantile-onset and occasional late-onset patients. Cardiac assessment is important for its diagnosis and management. This article presents unpublished cardiac findings, concomitant medications, and cardiac efficacy and safety outcomes from the ADVANCE study; trajectories of patients with abnormal left ventricular mass z score at enrolment; and post hoc analyses of on-treatment left ventricular mass and systolic blood pressure z scores by disease phenotype, GAA genotype, and “fraction of life” (defined as the fraction of life on pre-study 160 L production-scale alglucosidase alfa). ADVANCE evaluated 52 weeks’ treatment with 4000 L production-scale alglucosidase alfa in ≥1-year-old United States of America patients with Pompe disease previously receiving 160 L production-scale alglucosidase alfa. M-mode echocardiography and 12-lead electrocardiography were performed at enrolment and Week 52. Sixty-seven patients had complete left ventricular mass z scores, decreasing at Week 52 (infantile-onset patients, change −0.8 ± 1.83; 95% confidence interval −1.3 to −0.2; all patients, change −0.5 ± 1.71; 95% confidence interval −1.0 to −0.1). Patients with “fraction of life” <0.79 had left ventricular mass z score decreasing (enrolment: +0.1 ± 3.0; Week 52: −1.1 ± 2.0); those with “fraction of life” ≥0.79 remained stable (enrolment: −0.9 ± 1.5; Week 52: −0.9 ± 1.4). Systolic blood pressure z scores were stable from enrolment to Week 52, and no cohort developed systemic hypertension. Eight patients had Wolff–Parkinson–White syndrome. Cardiac hypertrophy and dysrhythmia in ADVANCE patients at or before enrolment were typical of Pompe disease. Four-thousand L alglucosidase alfa therapy maintained fractional shortening, left ventricular posterior and septal end-diastolic thicknesses, and improved left ventricular mass z score.

Trial registry: ClinicalTrials.gov Identifier: NCT01526785 https://clinicaltrials.gov/ct2/show/NCT01526785.

Social Media Statement: Post hoc analyses of the ADVANCE study cohort of 113 children support ongoing cardiac monitoring and concomitant management of children with Pompe disease on long-term alglucosidase alfa to functionally improve cardiomyopathy and/or dysrhythmia.

Mass asymptomatic SARS-CoV-2 nucleic acid amplified testing of healthcare personnel (HCP) was performed at a large tertiary health system. A low period-prevalence of positive HCP was observed. Of those who tested positive, half had mild symptoms in retrospect. HCP with even mild symptoms should be isolated and tested.

We investigate the large-scale circulation (LSC) of turbulent Rayleigh–Bénard convection in a large box of aspect ratio $\varGamma =32$ for Rayleigh numbers up to $Ra=10^9$ and at a fixed Prandtl number $Pr=1$. A conditional averaging technique allows us to extract statistics of the LSC even though the number and the orientation of the structures vary throughout the domain. We find that various properties of the LSC obtained here, such as the wall-shear stress distribution, the boundary layer thicknesses and the wind Reynolds number, do not differ significantly from results in confined domains ($\varGamma \approx 1$). This is remarkable given that the size of the structures (as measured by the width of a single convection roll) more than doubles at the highest $Ra$ as the confinement is removed. An extrapolation towards the critical shear Reynolds number of $Re_s^{{crit}} \approx 420$, at which the boundary layer (BL) typically becomes turbulent, predicts that the transition to the ultimate regime is expected at $Ra_{{crit}} \approx {O}(10^{15})$ in unconfined geometries. This result is in line with the Göttingen experimental observations (He et al., Phys. Rev. Lett., vol. 108, 2012, 024502; New J. Phys., vol. 17, 2015, 063028). Furthermore, we confirm that the local heat transport close to the wall is highest in the plume impacting region, where the thermal BL is thinnest, and lowest in the plume emitting region, where the thermal BL is thickest. This trend, however, weakens with increasing $Ra$.

Rayleigh–Bénard (RB) convection with free-slip plates and horizontally periodic boundary conditions is investigated using direct numerical simulations. Two configurations are considered, one is two-dimensional (2-D) RB convection and the other one three-dimensional (3-D) RB convection with a rotating axis parallel to the plate, which for strong rotation mimics 2-D RB convection. For the 2-D simulations, we explore the parameter range of Rayleigh numbers $Ra$ from $10^{7}$ to $10^{9}$ and Prandtl numbers $Pr$ from $1$ to $100$. The effect of the width-to-height aspect ratio $\varGamma$ is investigated for $1\leqslant \varGamma \leqslant 128$. We show that zonal flow, which was observed, for example, by Goluskin et al. (J. Fluid. Mech., vol. 759, 2014, pp. 360–385) for $\varGamma =2$, is only stable when $\varGamma$ is smaller than a critical value, which depends on $Ra$ and $Pr$. The regime in which only zonal flow can exist is called the first regime in this study. With increasing $\varGamma$, we find a second regime in which both zonal flow and different convection roll states can be statistically stable. For even larger $\varGamma$, in a third regime, only convection roll states are statistically stable and zonal flow is not sustained. How many convection rolls form (or in other words, what the mean aspect ratio of an individual roll is), depends on the initial conditions and on $Ra$ and $Pr$. For instance, for $Ra=10^{8}$ and $Pr=10$, the aspect ratio $\varGamma _r$ of an individual, statistically stable convection roll can vary in a large range between $16/11$ and $64$. A convection roll with a large aspect ratio of $\varGamma _r = 64$, or more generally already with $\varGamma _r \gg 10$, can be seen as ‘localized’ zonal flow, and indeed carries over various properties of the global zonal flow. For the 3-D simulations, we fix $Ra=10^{7}$ and $Pr=0.71$, and compare the flow for $\varGamma =8$ and $\varGamma = 16$. We first show that with increasing rotation rate both the flow structures and global quantities like the Nusselt number $Nu$ and the Reynolds number $Re$ increasingly behave like in the 2-D case. We then demonstrate that with increasing aspect ratio $\varGamma$, zonal flow, which was observed for small $\varGamma =2{\rm \pi}$ by von Hardenberg et al. (Phys. Rev. Lett., vol. 15, 2015, 134501), completely disappears for $\varGamma =16$. For such large $\varGamma$, only convection roll states are statistically stable. In-between, here for medium aspect ratio $\varGamma = 8$, the convection roll state and the zonal flow state are both statistically stable. What state is taken depends on the initial conditions, similarly as we found for the 2-D case.

Taylor–Couette (TC) flow is the shear-driven flow between two coaxial independently rotating cylinders. In recent years, high-fidelity simulations and experiments revealed the shape of the streamwise and angular velocity profiles up to very high Reynolds numbers. However, due to curvature effects, so far no theory has been able to correctly describe the turbulent streamwise velocity profile for a given radius ratio, as the classical Prandtl–von Kármán logarithmic law for turbulent boundary layers over a flat surface at most fits in a limited spatial region. Here, we address this deficiency by applying the idea of a Monin–Obukhov curvature length to turbulent TC flow. This length separates the flow regions where the production of turbulent kinetic energy is governed by pure shear from that where it acts in combination with the curvature of the streamlines. We demonstrate that for all Reynolds numbers and radius ratios, the mean streamwise and angular velocity profiles collapse according to this separation. We then develop the functional form of the velocity profile. Finally, using the newly developed angular velocity profiles, we show that these lead to an alternative constant in the model proposed by Cheng et al. (J. Fluid Mech., vol. 890, 2020, A17) for the dependence of the torque on the Reynolds number, or, in other words, of the generalized Nusselt number (i.e. the dimensionless angular velocity transport) on the Taylor number.

We perform direct numerical simulations of wall sheared Rayleigh–Bénard convection for Rayleigh numbers up to $Ra=10^{8}$, Prandtl number unity and wall shear Reynolds numbers up to $Re_{w}=10\,000$. Using the Monin–Obukhov length $L_{MO}$ we observe the presence of three different flow states, a buoyancy dominated regime ($L_{MO}\lesssim \unicode[STIX]{x1D706}_{\unicode[STIX]{x1D703}}$; with $\unicode[STIX]{x1D706}_{\unicode[STIX]{x1D703}}$ the thermal boundary layer thickness), a transitional regime ($0.5H\gtrsim L_{MO}\gtrsim \unicode[STIX]{x1D706}_{\unicode[STIX]{x1D703}}$; with $H$ the height of the domain) and a shear dominated regime ($L_{MO}\gtrsim 0.5H$). In the buoyancy dominated regime, the flow dynamics is similar to that of turbulent thermal convection. The transitional regime is characterized by rolls that are increasingly elongated with increasing shear. The flow in the shear dominated regime consists of very large-scale meandering rolls, similar to the ones found in conventional Couette flow. As a consequence of these different flow regimes, for fixed $Ra$ and with increasing shear, the heat transfer first decreases, due to the breakup of the thermal rolls, and then increases at the beginning of the shear dominated regime. In the shear dominated regime the Nusselt number $Nu$ effectively scales as $Nu\sim Ra^{\unicode[STIX]{x1D6FC}}$ with $\unicode[STIX]{x1D6FC}\ll 1/3$, while we find $\unicode[STIX]{x1D6FC}\simeq 0.30$ in the buoyancy dominated regime. In the transitional regime, the effective scaling exponent is $\unicode[STIX]{x1D6FC}>1/3$, but the temperature and velocity profiles in this regime are not logarithmic yet, thus indicating transient dynamics and not the ultimate regime of thermal convection.

We perform a numerical study of the heat transfer and flow structure of Rayleigh–Bénard (RB) convection in (in most cases regular) porous media, which are comprised of circular, solid obstacles located on a square lattice. This study is focused on the role of porosity $\unicode[STIX]{x1D719}$ in the flow properties during the transition process from the traditional RB convection with $\unicode[STIX]{x1D719}=1$ (so no obstacles included) to Darcy-type porous-media convection with $\unicode[STIX]{x1D719}$ approaching 0. Simulations are carried out in a cell with unity aspect ratio, for Rayleigh number $Ra$ from $10^{5}$ to $10^{10}$ and varying porosities $\unicode[STIX]{x1D719}$, at a fixed Prandtl number $Pr=4.3$, and we restrict ourselves to the two-dimensional case. For fixed $Ra$, the Nusselt number $Nu$ is found to vary non-monotonically as a function of $\unicode[STIX]{x1D719}$; namely, with decreasing $\unicode[STIX]{x1D719}$, it first increases, before it decreases for $\unicode[STIX]{x1D719}$ approaching 0. The non-monotonic behaviour of $Nu(\unicode[STIX]{x1D719})$ originates from two competing effects of the porous structure on the heat transfer. On the one hand, the flow coherence is enhanced in the porous media, which is beneficial for the heat transfer. On the other hand, the convection is slowed down by the enhanced resistance due to the porous structure, leading to heat transfer reduction. For fixed $\unicode[STIX]{x1D719}$, depending on $Ra$, two different heat transfer regimes are identified, with different effective power-law behaviours of $Nu$ versus $Ra$, namely a steep one for low $Ra$ when viscosity dominates, and the standard classical one for large $Ra$. The scaling crossover occurs when the thermal boundary layer thickness and the pore scale are comparable. The influences of the porous structure on the temperature and velocity fluctuations, convective heat flux and energy dissipation rates are analysed, further demonstrating the competing effects of the porous structure to enhance or reduce the heat transfer.

We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from $z = 0.35$ to 3; and a deep, high-redshift HI IM survey over 100 deg2 from $z = 3$ to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to $z \sim 3$ with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to $z = 6$ . These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.

We perform direct numerical simulations of spiral turbulent Taylor–Couette (TC) flow for $400\leqslant Re_{i}\leqslant 1200$ and $-2000\leqslant Re_{o}\leqslant -1000$, i.e. counter-rotation. The aspect ratio $\unicode[STIX]{x1D6E4}=\text{height}/\text{gap width}$ of the domain is $42\leqslant \unicode[STIX]{x1D6E4}\leqslant 125$, with periodic boundary conditions in the axial direction, and the radius ratio $\unicode[STIX]{x1D702}=r_{i}/r_{o}=0.91$. We show that, with decreasing $Re_{i}$ or with decreasing $Re_{o}$, the formation of a turbulent spiral from an initially ‘featureless turbulent’ flow can be described by the phenomenology of the Ginzburg–Landau equations, similar as seen in the experimental findings of Prigent et al. (Phys. Rev. Lett., vol. 89, 2002, 014501) for TC flow at $\unicode[STIX]{x1D702}=0.98$ an $\unicode[STIX]{x1D6E4}=430$ and in numerical simulations of oblique turbulent bands in plane Couette flow by Rolland & Manneville (Eur. Phys. J., vol. 80, 2011, pp. 529–544). We therefore conclude that the Ginzburg–Landau description also holds when curvature effects play a role, and that the finite-wavelength instability is not a consequence of the no-slip boundary conditions at the upper and lower plates in the experiments. The most unstable axial wavelength $\unicode[STIX]{x1D706}_{z,c}/d\approx 41$ in our simulations differs from findings in Prigent et al., where $\unicode[STIX]{x1D706}_{z,c}/d\approx 32$, and so we conclude that $\unicode[STIX]{x1D706}_{z,c}$ depends on the radius ratio $\unicode[STIX]{x1D702}$. Furthermore, we find that the turbulent spiral is stationary in the reference frame of the mean velocity in the gap, rather than the mean velocity of the two rotating cylinders.

We investigate the interplay between large-scale patterns, so-called superstructures, in the fluctuation fields of temperature $\unicode[STIX]{x1D703}$ and vertical velocity $w$ in turbulent Rayleigh–Bénard convection at large aspect ratios. Earlier studies suggested that velocity superstructures were smaller than their thermal counterparts in the centre of the domain. However, a scale-by-scale analysis of the correlation between the two fields employing the linear coherence spectrum reveals that superstructures of the same size exist in both fields, which are almost perfectly correlated. The issue is further clarified by the observation that, in contrast to the temperature, and unlike assumed previously, superstructures in the vertical-velocity field do not result in a peak in the power spectrum of $w$. The origin of this difference is traced back to the production terms of the $\unicode[STIX]{x1D703}$ and $w$ variance. These results are confirmed for a range of Rayleigh numbers $Ra=10^{5}{-}10^{9}$; the superstructure size is seen to increase monotonically with $Ra$. Furthermore, the scale distribution of the temperature fluctuations in particular is pronouncedly bimodal. In addition to the large-scale peak caused by the superstructures, there exists a strong small-scale peak. This ‘inner peak’ is most intense at a distance of $\unicode[STIX]{x1D6FF}_{\unicode[STIX]{x1D703}}$ from the wall and is associated with structures of size ${\approx}10\unicode[STIX]{x1D6FF}_{\unicode[STIX]{x1D703}}$, where $\unicode[STIX]{x1D6FF}_{\unicode[STIX]{x1D703}}$ is the thermal boundary layer thickness. Finally, based on the vertical coherence relative to a reference height of $\unicode[STIX]{x1D6FF}_{\unicode[STIX]{x1D703}}$, a self-similar structure is identified in the velocity field (vertical and horizontal components) but not in the temperature.

In Rayleigh–Bénard convection experiments, the thermal coupling between the sidewall and fluid is unavoidable. As a result, the thermal properties of the sidewall can influence the flow structure that develops. To get a better understanding of the influence of the sidewall, we performed a one-to-one comparison between experiments and direct numerical simulations (DNS) in aspect ratio (diameter over height) $\unicode[STIX]{x1D6E4}=1.00$ samples. We focus on the global heat transport, i.e. the Nusselt number $Nu$, and the local vertical temperature gradients near the horizontal mid-plane on the cylinder axis and close to the sidewall. The data cover the range $10^{5}\lesssim Ra\lesssim 10^{10}$ where $Ra$ is the Rayleigh number. The $Nu$ number obtained from experimental measurements and DNS, in which we use an adiabatic sidewall, agree well. The experiments are performed with several gases, which have widely varying thermal conductivities, but all have a Prandtl number $Pr\approx 0.7$. For $Ra\gtrsim 10^{7}$, both experiments and DNS reveal a stabilizing (positive) temperature gradient at the cylinder axis. This phenomenon was known for high $Pr$, but had not been observed for small $Pr\approx 0.7$ before. The experiments reveal that the temperature gradient decreases with decreasing $Ra$ and eventually becomes destabilizing (negative). The decrease appears at a higher $Ra$ when the sidewall admittance, which measures how easily the heat transfers from the fluid to the wall, is smaller. However, the simulations with an adiabatic sidewall do not reproduce the destabilizing temperature gradient at the cylinder axis in the low $Ra$ number regime. Instead, these simulations show that the temperature gradient increases with decreasing $Ra$. We find that the simulations can reproduce the experimental findings on the temperature gradient at the cylinder axis qualitatively when we consider the physical properties of the sidewall and the thermal shields. However, the temperature gradients obtained from experiments and simulations do not agree quantitatively. The reason is that it is incredibly complicated to reproduce all experimental details accurately due to which it is impossible to reproduce all experimental measurement details. The simulations show, in agreement with the models of Ahlers (Phys. Rev. E, vol. 63 (1), 2000, 015303) and Roche et al. (Eur. Phys. J. B, vol. 24 (3), 2001, pp. 405–408), that the sidewall can act as an extra heat conductor, which absorbs heat from the fluid near the bottom plate and releases it into the fluid near the top plate. The importance of this effect decreases with increasing $Ra$. A crucial finding of the simulations is that the thermal coupling between the sidewall and fluid can strongly influence the flow structure, which can result in significant changes in heat transport. Since this effect goes beyond a simple short circuit of the heat transfer through the sidewall, it is impossible to correct experimental measurements for this effect. Therefore, careful design of experimental set-ups is required to minimize the thermal interaction between the fluid and sidewall.

Progress in roughness research, mapping any given roughness geometry to its fluid dynamic behaviour, has been hampered by the lack of accurate and direct measurements of skin-friction drag, especially in open systems. The Taylor–Couette (TC) system has the benefit of being a closed system, but its potential for characterizing irregular, realistic, three-dimensional (3-D) roughness has not been previously considered in depth. Here, we present direct numerical simulations (DNSs) of TC turbulence with sand grain roughness mounted on the inner cylinder. The model proposed by Scotti (Phys. Fluids, vol. 18, 031701, 2006) has been modified to simulate a random rough surface of monodisperse sand grains. Taylor numbers range from $Ta=1.0\times 10^{7}$(corresponding to $Re_{\unicode[STIX]{x1D70F}}=82$) to $Ta=1.0\times 10^{9}$ ($Re_{\unicode[STIX]{x1D70F}}=635$). We focus on the influence of the roughness height $k_{s}^{+}$ in the transitionally rough regime, through simulations of TC with rough surfaces, ranging from $k_{s}^{+}=5$ up to $k_{s}^{+}=92$. We analyse the global response of the system, expressed both by the dimensionless angular velocity transport $Nu_{\unicode[STIX]{x1D714}}$ and by the friction factor $C_{f}$. An increase in friction with increasing roughness height is accompanied with enhanced plume ejection from the inner cylinder. Subsequently, we investigate the local response of the fluid flow over the rough surface. The equivalent sand grain roughness $k_{s}^{+}$ is calculated to be $1.33k$, where $k$ is the size of the sand grains. We find that the downwards shift of the logarithmic layer, due to transitionally rough sand grains exhibits remarkably similar behaviour to that of the Nikuradse (VDI-Forsch., vol. 361, 1933) data of sand grain roughness in pipe flow, regardless of the Taylor number dependent constants of the logarithmic layer. Furthermore, we find that the dynamical effects of the sand grains are contained to the roughness sublayer $h_{r}$ with $h_{r}=2.78k_{s}$.

In turbulent Rayleigh–Bénard (RB) convection with regular, mono-scale, surface roughness, the scaling exponent $\unicode[STIX]{x1D6FD}$ in the relationship between the Nusselt number $Nu$ and the Rayleigh number $Ra$, $Nu\sim Ra^{\unicode[STIX]{x1D6FD}}$ can be ${\approx}1/2$ locally, provided that $Ra$ is large enough to ensure that the thermal boundary layer thickness $\unicode[STIX]{x1D706}_{\unicode[STIX]{x1D703}}$ is comparable to the roughness height. However, at even larger $Ra$, $\unicode[STIX]{x1D706}_{\unicode[STIX]{x1D703}}$ becomes thin enough to follow the irregular surface and $\unicode[STIX]{x1D6FD}$ saturates back to the value for smooth walls (Zhu et al., Phys. Rev. Lett., vol. 119, 2017, 154501). In this paper, we prevent this saturation by employing multiscale roughness. We perform direct numerical simulations of two-dimensional RB convection using an immersed boundary method to capture the rough plates. We find that, for rough boundaries that contain three distinct length scales, a scaling exponent of $\unicode[STIX]{x1D6FD}=0.49\pm 0.02$ can be sustained for at least three decades of $Ra$. The physical reason is that the threshold $Ra$ at which the scaling exponent $\unicode[STIX]{x1D6FD}$ saturates back to the smooth wall value is pushed to larger $Ra$, when the smaller roughness elements fully protrude through the thermal boundary layer. The multiscale roughness employed here may better resemble the irregular surfaces that are encountered in geophysical flows and in some industrial applications.