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Parkinson’s disease (PD) is characterized by motor and non-motor symptoms (NMS) due to alpha-synuclein aggregation in the central and peripheral nervous system. There is limited data on the temporal evolution of NMS in patients with long-standing PD.
Objective:
To elucidate the chronology of the evolution of NMS in patients with long-standing PD.
Methods:
This single-centre cross-sectional study was conducted at a tertiary care centre from May 2023 to December 2024. Patients with clinically diagnosed idiopathic PD of at least 10 years” duration were recruited, and the chronology of the evolution of NMS was characterized.
Results:
One hundred patients with PD (68% male) were recruited, with a mean age at assessment of 58.8 ± 9.7 years, an age at onset of 45.7 ± 10.1 years and a disease duration of 13.2 ± 3.3 years. Six percent of the patients did not develop any NMS despite the long duration of the illness. Rapid eye movement sleep behavioural disorder (RBD) (63%) was the most frequent NMS, followed by constipation (59%) and urinary dysfunction (55%). Pre-motor onset of NMS was present in 24% of the patients, with RBD (8%) and constipation (8%) being the most frequent. Post-motor onset was observed in 70% of cases. Based on the pre- or post-motor onset of RBD, patients were classified into two subtypes: body-first (8%) and brain-first (84%) PD subtypes.
Conclusion:
This study highlights the distinct trajectories of NMS evolution in PD. While the majority developed at least one NMS, the occurrence of pre-motor NMS was present in about one-fourth. The body-first subtype, characterized by pre-motor RBD, was distinctly uncommon.
We establish new uncertainty bounds for commutators and anti-commutators of observables in both finite- and infinite-dimensional quantum systems. Beginning with a short, elementary proof of Robertson’s standard uncertainty principle, we then derive inequalities whose lower bounds remain nonzero, regardless of the number of observables. The main result is a novel trace inequality comparing the block matrices of commutators and anti-commutators of several observables.
Subjective cognitive decline (SCD) may represent the earliest observable stage of Alzheimer’s disease (AD), yet identifying individuals at risk of progressing remains challenging. Cognitive dispersion, or intra-individual variability (IIV-D), may serve as a sensitive early marker. This study examined IIV-D across diagnostic groups, focusing on SCD and amnestic mild cognitive impairment (aMCI) progressors (SCD-p, aMCI-p; progressing to a more advanced disease stage) versus non-progressors (SCD-np, aMCI-np; not progressing to a more advanced stage). We expected greater IIV-D across groups (AD > aMCI > SCD > controls) and in progressors.
Methods:
A total of 308 participants aged 65–94 (67 healthy controls [HC], 126 SCD, 79 aMCI, 36 AD) from the Consortium for the Early Identification of Alzheimer’s Disease – Quebec (CIMA-Q) were included. SCD and aMCI participants were followed for up to eight years (34 SCD-p, 92 SCD-np; 29 aMCI-p, 50 aMCI-np). Analyses of covariance assessed baseline across- and verbal memory within-domain IIV-D, maximum discrepancy (MD), and domain-specific deviation.
Results:
IIV-D increased with disease severity (HC = SCD < aMCI < AD). Among SCD participants, progressors showed greater episodic memory deviation than non-progressors, primarily driven by poorer Logical Memory delayed recall. In aMCI, progressors showed higher IIV-D across all indices (across- and within-domain, IIV-D and MD), with domain-specific differences limited to episodic memory.
Conclusions:
These findings indicate that IIV-D measures distinguish aMCI progressors from non-progressors, although they do not appear to enhance predictive accuracy for progression to AD and may not yet be a reliable marker at the SCD stage.
It is a well-established fact that at a fixed angle of attack, with increasing Reynolds number, ${\textit{Re}}$, a laminar separation bubble (LSB) will shrink and eventually cease to exist, due to increase in the growth rate of hydrodynamic instability modes. However, during this wind tunnel test campaign, we observed that paradoxically the LSB increased in length from ${\textit{Re}}=2\times 10^5$ to ${\textit{Re}}=2.5\times 10^5$. Further diagnostics showed that this was due to a modification of the background forcing environment, often neglected in the literature. The perturbation generated from potential aero–vibroacoustic interaction unexpectedly boosted Tollmien–Schlichting modes and their faster amplification even upstream of the LSB drove the rapid secondary growth and breakdown at ${\textit{Re}}=2\times 10^5$. At ${\textit{Re}}=2.5\times 10^5$, when the lock-in with background forcing modes was not significant, a well-behaved LSB was observed with spatially amplifying Kelvin–Helmhotz modes. This finding raises important questions on the mechanisms entailing the dynamics and instability of LSBs proposed from not only experiments in similar facilities in the literature, but also in other scenarios where background perturbation due vibration, noise and confinement are non-negligible.
‘Teaching about Transatlantic Slavery’ was a three-year professional development project for teachers centring on the Historic Collections of Balliol College, University of Oxford, and the Museum of the American Revolution (MOAR) in Philadelphia. The project grew out of Balliol’s 2021 exhibition, ‘Slavery in the Age of Revolution’, which was inspired by the work of Fellows Sudhir Hazareesingh, Black Spartacus: the epic life of Toussaint Louverture (2020) and Marisa J. Fuentes, Dispossessed Lives: enslaved women, violence and the archive (2016). This paper discusses how we approached the aims of the project, telling a fuller history by foregrounding the role of Black people in the struggle for abolition and increasing awareness of the lasting impact of transatlantic slavery on the way we live and think today. We will address how some of the challenges of working with the material in Balliol’s collections became project strengths when we learnt to navigate bias and acknowledge and elaborate on the gaps and erasures in the historical record. We also acknowledge the diverse range of people who contributed and their importance to the consequent depth and effectiveness of the project. ‘Teaching about Transatlantic Slavery’ reached forty teachers and educators from the USA and the UK and has had lasting impact. The programme allowed teachers to practise teaching with objects, artwork, and primary source documents, deepen their subject knowledge, and develop skills for engaging in sensitive and difficult conversations around complex topics.
In this paper, we analyze the potential harms of everyday self-help discourse, particularly in contexts of systemic oppression. After analyzing the core principles of self-help, such as the power of positive thinking, eliminating negative thinking, gratitude, self-knowledge for self-improvement, and individual choice and responsibility, we argue that self-help discourse is likely to perpetuate different forms of harm in conditions of oppression. First, we argue that, when used in contexts of systemic oppression, self-help discourse contributes to victim-blaming. Secondly, we highlight that the harms of self-help discourse include epistemic and affective dimensions. On the epistemic front, self-help discourse carries epistemic risks, including testimonial smothering and hermeneutical injustice, by discouraging the expression of certain perspectives and lived experiences. On the affective front, self-help discourse reinforces oppression by adding emotional burdens to the oppressed, dismissing their emotional experiences, and imposing the emotional norms of the dominant group. Finally, we revisit the principles of self-help, and show how they contribute to the highlighted harms, particularly by reinforcing victim-blaming, and epistemic and affective forms of injustice.
In this study, experimental deep reinforcement learning (DRL) control of aerofoil flow separation is conducted at a chord-based Reynolds number of ${\textit{Re}}_c=1.5\times 10^5$. A dielectric barrier discharge plasma actuator mounted at the leading edge and a hotwire placed in the separated shear layer act as the flow disturber and the state monitor, respectively. The closed-loop control law is parameterised by a radial basis function network and executed in real time on a field-programmable gate array at 1 kHz. With the aid of a deep deterministic policy gradient algorithm, a satisfying closed-loop control strategy can be derived in less than one minute, and the resulting lift coefficient increment (21 %) is similar to that achieved by the best open-loop control. For stable and effective DRL control, the sensor should be placed at the position with strongest velocity fluctuation, and both time delay and cashing period should be accounted in the reward design. Incorporating historical sensor measurements are beneficial to DRL control, and the optimal history length is approximately equal to the ratio of the local Taylor microscale to the control period. The final control law sought by DRL dictates that strong plasma actuation should only be applied when the flow separation region contracts to a minimum. Statistically, control benefits can be ascribed to both the increase of average reward at each cluster and the elevation of occurrence probabilities of high-reward clusters. Physically, suppression of the aerofoil flow separation is attributed to the excitation of large-scale shear layer vortices, which promotes the momentum exchange between the free stream and the reverse flow.
We introduce and study Liouville number groups, namely additive subgroups of the real numbers in which every nonzero element is a Liouville number. Using continued-fraction methods and linear independence over the field of algebraic numbers, we establish the existence of large families of such groups with rich algebraic and topological structure. We prove that there exist $(2^{\mathfrak {c}}) $ pairwise distinct Liouville number groups generated by strong Liouville numbers and that, among these, there are $(2^{\mathfrak {c}})$ pairwise nonhomeomorphic groups. We further show that there exist continuum many countable Liouville number groups, each generated by countably many strong Liouville numbers and homeomorphic, as topological spaces, to the rational numbers. In addition, we prove that no subgroup of the real numbers is homeomorphic to the space of Liouville numbers, thereby highlighting a strong topological distinction between the space of Liouville numbers and Liouville number groups.
Historically, investigations on gust encounters have been limited to thin airfoils. In this work, we examine vortex-gust encounters by a family of airfoils at a chord-based Reynolds number ${\textit{Re}}_c=100$, which includes variations in the gust ratio, initial gust position, gust radius, angle of attack, airfoil thickness and airfoil camber. We examine differences in the flow fields, lift-element distributions and aerodynamic responses across several airfoil–gust interactions. We observe a large deviation of the flow fields and aerodynamic responses with respect to the baseline flows for increasing gust ratios and gust sizes. The initial position of the vortex gust influences the magnitude of the velocity gradients observed near the leading edge, effectively heightening or mitigating the amplitude of the lift response. Moreover, the lift fluctuation increases with the angle of attack until it flattens around $10^\circ$, reminiscent of an unsteady stall-like regime. Furthermore, we report a decrease in the amplitude of the gust-induced lift fluctuations for thicker airfoils, which we attribute to a decrease in the vorticity production levels from the leading edge, as well as a spatial redirection of the transient aerodynamic forces, which shifts the response in favour of drag fluctuations. The exploration of a sensitive subset of the parameter space uncovers relevant trends, shedding light on regions that have received limited attention in past studies, with special focus on the influence of airfoil geometry.
Spherical robots can conduct surveillance in hostile, cluttered environments without being damaged. Their protective shell can safely house sensors and sensitive components. The pendulum-based spherical robot provides a platform (yoke) for a camera to be housed inside the protective hull. However, lateral oscillations, also known as wobble, become prominent when operated at low speeds, leading to shaky camera feedback. These oscillations are caused by the coupling between the forward and steering motions due to nonholonomic constraints. Designing a controller to limit wobbling in these robots is challenging due to their underactuated nature. In this paper, we propose a model-based (wobble-free) controller to navigate a pendulum-steered spherical robot to perform wobble-free turning maneuvers consisting of circular arcs and straight lines. The model is developed using Lagrange-D’Alembert equations and accounts for the coupled forward and steering motions. Furthermore, we also propose quantifiable metrics for wobble by deriving expressions for radius of curvature, precession rate, wobble amplitude, and wobble frequency during circular motions and designed an input–output feedback linearization-based controller to control the robot’s heading direction and wobble. Additionally, we extend the controller’s capabilities to handle point-to-point navigation, enabling the robot to execute more complex and goal-oriented trajectories. This research ensures the robot maintains wobble-free motion across diverse paths, enhancing its navigational autonomy and the quality of camera feedback. Overall, the proposed controller enables a teleoperator to command a specific forward velocity and pendulum angle as per the desired turning radius or destination while effectively limiting the robot’s lateral oscillations.
We consider the down-slope propagation of a compositional inertial Boussinesq gravity current released from a lock into a linearly stratified ambient fluid. We present a novel shallow-water formulation, which takes into account the stratification, slope, entrainment and drag. The solution of the resulting hyperbolic system of equations provides clear-cut predictions of realistic physical systems and insights into the influence of the governing parameters. Comparisons with previously published experimental data show fair agreement and the reasons for the discrepancies are elucidated. Directions for further work needed for the extension (in particular to particle-driven flows) and improvement of the model are outlined.
This article explores the evolution of school dress code policies in the United States as a critical lens into the workings of public education, authority, and exclusion. Focusing on metropolitan Seattle as a case study, the research traces the shift from informal appearance norms to formalized and punitive dress code enforcement from the 1950s to the present. Rather than functioning as neutral guidelines, dress codes have historically reinforced gendered, racialized, and class-based hierarchies under the guise of order and safety. By situating dress policies within broader political and social transformations—including student rights movements, the rise of zero-tolerance policies, and recent federal investigations—this article demonstrates how dress codes have become tools of gatekeeping that shape access to learning and belonging in public schools. In highlighting moments of resistance and change, this study interrogates the role of schools in regulating identity and offers a historical foundation to understand contemporary inequities in educational discipline and policy.
Prospective audit and feedback (PAF) is a core antimicrobial stewardship strategy. Discontinuing PAF in favor of alternative interventions has not been previously evaluated.
Methods:
This descriptive study assessed changes in antimicrobial days of therapy per 1,000 patient days (DOTs/1,000 PD) following PAF removal at two urban hospitals. Preintervention PAF included daily review of broad-spectrum antibiotics and oral therapy transitions. Postintervention efforts emphasized system standardization, education, guideline optimization, and electronic medical record enhancements. Secondary outcomes included trends in antibiotics previously reviewed under PAF: antibiotics targeting methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa, carbapenems, and oral antibiotics.
Results:
Hospital A demonstrated a change in the trend of DOTs/1,000 PD with a significant downward slope after PAF removal (−5.994; 95% CI −8.072 to −3.929; P < .001). Hospital B continued to down-trend postintervention. At hospital A, carbapenem use decreased significantly postintervention (slope change −0.117; 95% CI −0.198 to −0.036; P = .007), with no changes in anti-MRSA or anti-pseudomonal agents. Hospital B demonstrated increasing use of anti-MRSA (slope change + 0.394; 95% CI 0.198 to 0.589; P < .001), anti-pseudomonal (slope change + 0.378; 95% CI 0.075 to 0.681; P = .016), and carbapenem agents (slope change + 0.124; 95% CI 0.020 to 0.228; P = .021). No changes were observed in oral antibiotic use or C. difficile rates.
Conclusion:
Shifting stewardship resources away from PAF did not increase total antibiotic use trends. Broad-spectrum antibiotics increased modestly with unclear clinical significance (≤1.3 DOT/1,000 PD). Antimicrobial stewardship strategies, beyond PAF, should continue to be assessed to maximize effectiveness relative to effort.
Let K be a number field with ring of integers $\mathcal {O}_K$, and let $f(x)\in \mathcal {O}_K[x]$ be a monic, irreducible polynomial. We establish necessary and sufficient conditions in terms of the critical points of $f(x)$ for the iterates of $f(x)$ to be monogenic polynomials. More generally, we give necessary and sufficient conditions for the backward orbits of elements of $\mathcal {O}_K$ under $f(x)$ to be monogenerators. We apply our criteria to construct novel examples of dynamically monogenic polynomials, yielding infinite towers of monogenic number fields with the backward orbit of one monogenerator giving a monogenerator at the next level.