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Our study goal was to characterize the relative frequencies of molecular and phenotypic traits of tuberous sclerosis complex (TSC) in a Canadian adult population. Previous studies have sought to identify TSC-related genotypic and phenotypic trends in pediatric cohorts, but little is known about clinical manifestations and severity when it presents in adults.
Methods:
We conducted a retrospective chart review of adult patients seen at the TSC clinic at the University Health Network genetics clinics (Toronto, Ontario) to compare trends in the relative frequency of TSC manifestations with genotype.
Results:
Fifty-one patients were eligible for this study. Eight patients had a pathogenic/likely pathogenic variant in the tuberous sclerosis complex 1 (TSC1) gene, 18 had a tuberous sclerosis complex 2 (TSC2) pathogenic/likely pathogenic variant, 6 patients had multiple variants identified in TSC1/TSC2 or TSC2/PKD1, 11 had no mutation identified (NMI) and 8 had no genetic testing done. Patients with a pathogenic/likely pathogenic variant in TSC2 presented with an increased involvement of multiple systems and a higher frequency of TSC-related manifestations relative to the other mutation groups.
Conclusion:
Previous studies comparing the wide phenotypic variability with TSC genotype have mainly comprised pediatric cohorts. With a focus on adults, we found trends to be similar across previous literature. An informed multidisciplinary approach should be taken to ensure proper surveillance and management of adults with TSC until a correlation between genotype and phenotype, especially past infancy, is better understood.
Body composition and phase angle (PhA) have been used to predict mortality in multiple diseases. However, little has been studied regarding segmental measurements, which could potentially help assess subtle changes in specific tissue segments. This study aimed to identify the total PhA cut-off point associated with mortality risk and changes in body composition within a week of hospitalisation in non-critical hospitalised patients with COVID-19. A cohort study was conducted where patients underwent to a complete nutritional assessment upon admission and after seven days, and followed up until hospital discharge or death. A receiver operating characteristic curve was constructed to determine the PhA cut-off point, and the Kaplan–Meier estimator was used to determine survival analysis. Segmental and complete body compositions on admission and after 7 d were compared. We included 110 patients (60 men) with a mean age of 50·5 ± 15·0 years and a median BMI of 28·5 (IQR, 25·6–33·5) kg/m2. The median length of hospital stay was 6 (IQR, 4–9) d, and the mortality rate was 13·6 %. The PhA cut-off point obtained was 4°, with significant differences in the survival rate (P < 0·001) and mortality (HR = 5·81, 95 % CI: 1·80, 18·67, P = 0·003). Segmental and whole-body compositions were negatively affected within one week of hospitalisation, with changes in the approach by the graphical method in both sexes. Nutritional status deteriorates within a week of hospitalisation. PhA < 4° is strongly associated with increased mortality in non-critical hospitalised patients with COVID-19.
A subset of positive integers F is a Schreier set if it is nonempty and $|F|\leqslant \min F$ (here $|F|$ is the cardinality of F). For each positive integer k, we define $k\mathcal {S}$ as the collection of all the unions of at most k Schreier sets. Also, for each positive integer n, let $(k\mathcal {S})^n$ be the collection of all sets in $k\mathcal {S}$ with maximum element equal to n. It is well known that the sequence $(|(1\mathcal {S})^n|)_{n=1}^\infty $ is the Fibonacci sequence. In particular, the sequence satisfies a linear recurrence. We show that the sequence $(|(k\mathcal {S})^n|)_{n=1}^\infty $ satisfies a linear recurrence for every positive k.
Existing theoretical analyses of Faraday waves in Hele-Shaw cells rely on the Darcy approximation and assume a parabolic flow profile in the narrow direction. However, Darcy's model is known to be inaccurate when convective or unsteady inertial effects are important. In this work, we propose a gap-averaged Floquet theory accounting for inertial effects induced by the unsteady terms in the Navier–Stokes equations, a scenario that corresponds to a pulsatile flow where the fluid motion reduces to a two-dimensional oscillating Poiseuille flow, similarly to the Womersley flow in arteries. When gap-averaging the linearised Navier–Stokes equation, this results in a modified damping coefficient, which is a function of the ratio between the Stokes boundary layer thickness and the cell's gap, and whose complex value depends on the frequency of the wave response specific to each unstable parametric region. We first revisit the standard case of horizontally infinite rectangular Hele-Shaw cells by also accounting for a dynamic contact angle model. A comparison with existing experiments shows the predictive improvement brought by the present theory and points out how the standard gap-averaged model often underestimates the Faraday threshold. The analysis is then extended to the less conventional case of thin annuli. A series of dedicated experiments for this configuration highlights how Darcy's thin-gap approximation overlooks a frequency detuning that is essential to correctly predict the locations of the Faraday tongues in the frequency–amplitude parameter plane. These findings are well rationalised and captured by the present model.
A new species of Oswaldocruzia Travassos, 1917 (Nematoda, Molineidae), parasite of Leptodactylus macrosternum Miranda-Ribeiro, 1926 (Anura: Leptodactylidae), from Caatinga morphoclimatic domain, Brazil, is described based on morphological and molecular data. Oswaldocruzia franciscoensis n. sp. is characterised by an anterior extremity with a cephalic vesicle divided into two portions, a body covered by cuticular longitudinal ridges, and cervical alae. Males of the new species have caudal bursa of type I with a 2-1-2 pattern, spicules divided into a shoe, bifurcated fork, and blade with two unequal branches, in which the longer branch bifurcates at its distal portion end and the smaller branch with three distal processes, each with distal bifurcations. Females have didelphic and amphidelphic uteri, an ovijector divided into vestibule, anterior and posterior sphincters, and anterior and posterior infundibula. The new species differs from its Neotropical congeners that have caudal bursa of type I, based on the presence of cervical alae and by having a spicular blade distally divided into two unequal branches, with the longer branch bifurcating at its distal portion and smaller branch with three distal processes, each distally bifurcated. The partial 18S rDNA sequence generated for Oswaldocruzia franciscoensis n. sp. is the first of a representative belonging to this genus in the Neotropical region.
This paper is concerned with the problem of collision-free path planning for manipulators in multi-obstacle scenarios. Aiming at overcoming the deficiencies of existing algorithms in excessive time consumption and poor expansion quality, a path planning algorithm named Fast Bi-directional Rapidly-exploring Random Tree (FBi-RRT) with novel heuristic node expansion is proposed, which includes a selective-expansion strategy and a vertical-exploration strategy. The selective-expansion strategy is designed to guide the selection of the nearest-neighbor node to avoid the repeated expansion failure, thereby shortening the overall planning time. Also, the vertical-exploration strategy is developed to regulate the expansion direction of the collision nodes to escape from the obstacle space with less blindness, thus improving the expansion quality and further reducing time cost. Compared with previous planning algorithms, FBi-RRT can generate a feasible path for manipulators in a drastically shorter time. To validate the effectiveness of the proposed heuristic node expansion, FBi-RRT is conducted on a 6-DOF manipulator and tested in five scenarios. The experimental results demonstrate that FBi-RRT outperforms the existing methods in time consumption and expansion quality.
We investigate how inhomogeneity influences the $k^{-5/3}$ inertial range scaling of turbulent kinetic energy spectra (with $k$ the wavenumber). For weak statistical inhomogeneity, the energy spectrum can be described as an equilibrium spectrum plus a perturbation. Theoretical arguments suggest that this latter contribution scales as $k^{-7/3}$. This prediction is assessed using direct numerical simulations of three-dimensional Kolmogorov flow.
Partially molten rock is a densely packed, melt-saturated, granular medium, but it has seldom been considered in these terms. In this paper we extend the continuum theory of partially molten rock to incorporate the physics of granular media. Our formulation includes dilatancy in a viscous constitutive law and introduces a non-local fluidity. We analyse the resulting poro-viscous–granular theory in terms of two modes of liquid–solid segregation that are observed in published torsion experiments: localisation of liquid into high-porosity sheets and radially inward liquid flow. We show that the newly incorporated granular physics brings the theory into agreement with experiments. We discuss these results in the context of grain-scale physics across the nominal jamming fraction at the high homologous temperatures relevant in geological systems.
The electoral base of the Democratic Party has been transformed over the past generation. Democrats have lost ground in rural America while adding strength in cities and, more recently, suburbs. A major consequence of this shift has been the creation of a “U-shaped” Democratic voting base, with both poorer metro voters and affluent suburbanites siding with the party. This spatial alliance overlays a multi-racial one, as Democrats rely more heavily on voters of color than any other major party in American history. Many analysts have argued that the Democratic Party has managed this sea change by shifting from economic to cultural and identity appeals. This claim is consistent with leading models of two-dimensional party competition, as well as a fair amount of cross-national research on parties of the left and center-left in contemporary knowledge economies. However, we find little evidence for this claim in national Democrats’ messaging (via party platforms and on Twitter), nor, more important, in their actual policy efforts. Instead, we show that even as Democrats have increasingly relied on affluent, educated voters, the party has embraced a more ambitious economic agenda. The national party has bridged the Blue Divide not by foreswearing redistribution or foregrounding cultural liberalism, but by formulating an increasingly bold economic program—albeit one that elides important inequalities within its metro-based multi-racial coalition. Understanding how and why Democrats have taken this path is central to understanding not just the party’s response to its shifting electorate, but the way parties manage coalitional change more broadly.
This study aims to gain a better understanding of the current scope of headache education received in Canadian medical schools. The Women’s College Hospital Centre for Headache at the University of Toronto, Canada, distributed a questionnaire to administrators and physicians involved in medical student education at Canadian medical schools and gathered information surrounding headache education. Overall, the degree of headache education varied between schools in regard to the hours of training that occurred and year the training took place. This survey provides an initial insight into the current standards of headache-specific education in Canadian medical schools.
While individuals’ proactive career behaviors (PCBs) are critical to sustainable career outcomes, knowledge of how and when PCBs translate into these outcomes is limited. Drawing upon the conservation of resources theory and the socially embedded model of thriving, this study examines the psychological process through which PCBs translate into two sustainable career outcomes (i.e., subjective career success and perceived employability). Based on data collected from 228 participants in a Chinese company, our findings reveal that PCBs positively predict subjective career success and perceived employability by fostering thriving at work. Furthermore, the indirect association between PCBs and perceived employability via thriving at work is strengthened when participants’ perception of humble leadership is high. This study extends our knowledge by identifying a psychological mechanism that explains how employees’ PCBs translate into sustainable career outcomes and enriches our understanding of the boundary conditions of PCBs by identifying humble leadership as an important factor.
We evaluated the effectiveness and tolerability of brivaracetam (BRV), an adjunctive antiseizure medication, as a treatment for focal epilepsy in adults. In this prospective study, we enrolled 51 participants from 3 sites across Canada. At 6 months, 68% (26/38) of participants were still taking BRV, among whom 35% (8/23) attained seizure freedom and 48% (11/23) saw their seizure frequency reduced by over 50%. We did not measure any significant change in irritability, quality of life, depression, and anxiety while treated with BRV. Our findings suggest BRV is effective in reducing seizure frequency among adults with focal epilepsy.
The adaptability of hexapods for various locomotion tasks, especially in rescue and exploration missions, drives their application. Unlike controlled environments, these robots need to navigate ever-changing terrains, where ground irregularities impact foothold positions and origin shifts in contact forces. This dynamic interaction leads to varying hexapod postures, affecting overall system stability. This study introduces a posture control approach that adjusts the hexapod’s main body orientation and height based on terrain topology. The strategy estimates ground slope using limb positions, thereby calculating novel limb trajectories to modify the hexapod’s angular position. Adjusting the hexapod’s height, based on the calculated slope, further enhances main body stability. The proposed methodology is implemented and evaluated on the ATHENA hexapod (All-Terrain Hexapod for Environment Adaptability). Control feasibility is assessed through dynamic analysis of the hexapod’s multibody model on irregular surfaces, using computational simulations in Gazebo software. Environmental complexity’s impact on hexapod stability is tested on both a ramp and uneven terrain. Independent analyses for each scenario evaluate the controller’s effect on roll and pitch angular velocities, as well as height variations. Results demonstrate the strategy’s suitability for both environments, significantly enhancing posture stability.
Prior studies have treated employees’ remedial voice as a single-stage phenomenon. However, it is problematic because, in reality, employees often respond to mistreatment in a sequence. This paper aims to add new insights by empirically testing a three-stage process model to explain employees’ remedial voice. Also, this study intends to test important factors in the employees’ remedial voice decision-making process. Based on data obtained by surveying 382 Chinese employees, we found that mistreatment severity, mistreatment source, and employees’ external job opportunities are related to employees’ remedial voice. Our data provides support for a three-stage-process model for remedial voice. We contribute to the gaps in the existing research which largely views employees’ remedial voice as a single ‘snapshot.’ The study also deepens understanding of what factors affect employees’ remedial voice.
A transcritical domain with a sharp two-phase interface may exist during the early times of liquid hydrocarbon fuel injection at supercritical pressure. Thus, two-phase dynamics are sustained before substantial heating of the liquid and drive the early three-dimensional deformation and atomisation. A recent study of a transcritical liquid jet showed distinct deformation features caused by interface thermodynamics, low surface tension and intraphase diffusive mixing. In the present work, the compressible vortex identification method $\lambda _\rho$ is used to study the vortex dynamics in a cool liquid n-decane transcritical jet surrounded by a hotter oxygen gaseous stream at supercritical pressures. The relationship between vortical structures and the liquid surface evolution is detailed, along with the vorticity generation mechanisms, including variable-density effects. The roles of hairpin and roller vortices in the early deformation of lobes, the layering and tearing of liquid sheets and the formation of fuel-rich gaseous blobs are analysed. At these high pressures, enhanced intraphase mixing and ambient gas dissolution affect the local liquid structures (i.e. lobes). Thus, liquid breakup differs from classical sub-critical atomisation. Near the interface, liquid density and viscosity drop by up to 10 % and 70 %, respectively, and the liquid is more easily affected by the vortical motion (e.g. liquid sheets wrap around vortices). Despite the variable density, compressible vorticity generation terms are smaller than the vortex stretching and tilting. Layering traps and aligns the vortices along the streamwise direction while mitigating the generation of new rollers.
The dynamics of the interaction of a system of two thin volatile liquid droplets resting on a soft viscoelastic solid substrate are investigated theoretically. The developed model fully considers the effect of evaporative cooling and the generated Marangoni stresses due to the induced thermal gradients, while also accounting for the effect of the gas phase composition and the diffusion of vapour in the atmosphere of the droplets. Using the framework of lubrication theory, we derive evolution equations for both the droplet profile and the displacement of the elastic solid, which are solved in combination with Laplace's equation for the vapour concentration in the gas phase. A disjoining-pressure/precursor-film approach is used to describe contact-line motion. The evolution equations are solved numerically, using the finite-element method, and we present a thorough parametric analysis to investigate the physical properties and mechanisms that affect the dynamics of droplet interactions. The results show that the droplets interact through both the soft substrate and the gas phase. In the absence of thermocapillary phenomena, the combined effect of non-uniform evaporation due to the increased vapour concentration between the two droplets and elastocapillary phenomena determines whether the drop–drop interaction is attractive or repulsive. The Marangoni stresses suppress droplet attraction at the early stages of the drying process and lead to longer droplet lifetimes. For substrates with intermediate stiffness, the emergence of spontaneous symmetry breaking at late stages of evaporation is found. The rich dynamics of this complex system is explored by constructing a detailed map of the dynamic regimes.
The gender and politics literature offers diverse views on the causes of gendered practices and the best methodologies for studying them. This article advances efforts to take stock of and systematize this diversity by grounding the feminist institutionalist perspective in critical realism. The article posits that gendered institutions are real entities with independent powers, while also emphasizing the crucial role that human ideas play in upholding and contesting gendered practices. To faithfully capture gendered institutions and their relationship with human agency, the article promotes the use of the abductive-retroductive research design. This approach allows feminist institutionalist scholars to construct and test multiple competing theories about gendered institutions, drawing from various empirical manifestations of institutional power. These expressions range from observable actions to codified rules, socially shared norms, and other subtle discourses. By shedding light on the principles at the heart of realist-oriented feminist research, this work paves the way for a more standardized and transparent approach to feminist inquiries.