The effect of Parkinson’s disease subgroups on verbal and nonverbal fluency

BACKGROUND: Parkinson’s disease (PD) leads to deficits in executive function, including verbal and nonverbal fluency, as a result of compromised frontostriatal circuits. It is unknown whether deficits in verbal and nonverbal fluency in PD are driven by certain subgroups of patients, or how strategy use may facilitate performance. PARTICIPANTS: Sixty-five nondemented individuals with PD, including 36 with right-body onset (RPD; 20 with tremor as their initial symptom, 16 nontremor) and 29 with left-body onset (LPD; 14 with tremor as their initial symptom, 15 nontremor), and 52 normal control participants (NC) took part in the study. MEASUREMENTS: Verbal fluency was assessed using the FAS and Animals tests. Nonverbal fluency was assessed using the Ruff Figural Fluency Test. RESULTS: Both RPD and LPD were impaired in generating words and in using clustering and switching strategies on phonemic verbal fluency, whereas different patterns of impairment were found on nonverbal fluency depending on the interaction of side of onset and initial motor symptom (tremor vs. nontremor). Strategy use correlated with number of correct responses on verbal fluency in LPD, RPD, and NC. By contrast, on nonverbal fluency, strategy use correlated with correct responses for RPD and LPD, but not for NC. CONCLUSION: Our findings demonstrate the importance of considering subgroups in PD and analyzing subcomponents of verbal and nonverbal fluency (correct responses, errors, and strategies), which may depend differently on the integrity of dorsolateral prefrontal cortex, inferior frontal cortex, and anterior cingulate cortex.Published versio

Circadian rest-activity rhythms predict cognitive function in early Parkinson's disease independently of sleep

BACKGROUND: Cognitive impairment is a common and debilitating symptom of Parkinson's disease (PD), and its etiology is likely multifactorial. One candidate mechanism is circadian disruption. Although there is evidence of circadian abnormalities in PD, no studies have directly assessed their association with cognitive impairment. OBJECTIVES: Investigate whether circadian rest-activity rhythm is associated with cognitive function in PD independently of sleep. METHODS: Thirty-five participants with PD wore wrist actigraph monitors and completed sleep diaries for 7 to 10 days, then underwent neuropsychological testing. Rest-activity rhythm was characterized using nonparametric circadian rhythm analysis of actigraphy data. Objective sleep parameters were also estimated using actigraphy data. Hierarchical regression models assessed the independent contributions of sleep and rest-activity rhythm to cognitive performance. RESULTS: Less stable day-to-day rest-activity rhythm was associated with poorer executive, visuospatial, and psychomotor functioning, but not with memory. Hierarchical regressions showed that interdaily stability's contribution to cognitive performance was independent of sleep's contributions. Whereas sleep contributed to executive function, but not psychomotor or visuospatial performance, rest-activity rhythm stability significantly contributed to variance in all three of these domains, uniquely accounting for 14.4% to 17.6% of their performance variance. CONCLUSIONS: Our findings indicate that circadian rest-activity rhythm is associated with cognitive impairment independently of sleep. This suggests the possible utility of rest-activity rhythm as a biomarker for circadian function in PD. Future research should explore interventions to stabilize behavioral rhythms in order to strengthen circadian function, which, in turn, may reduce cognitive impairment in PD.R00 HL102241 - NHLBI NIH HHS; R01 AG048108 - NIA NIH HHSAccepted manuscrip

A nexus perspective on competing land demands: Wider lessons from a UK policy case study

As nations develop policies for low-carbon transitions, conflicts with existing policies and planning tools are leading to competing demands for land and other resources. This raises fundamental questions over how multiple demands can best be managed. Taking the UK as an empirical example, this paper critiques current policies and practices to explore the interdependencies at the water-energy-food nexus. It considers how current land uses and related policies affect the UK’s resilience to climate change, setting out an agenda for research and practice relevant to stakeholders in land-use management, policy and modelling. Despite recent progress in recognising such nexus challenges, most UK land-related policies and associated science continue to be compartmentalised by both scale and sector and seldom acknowledge nexus interconnections. On a temporal level, the absence of an over-arching strategy leaves inter-generational trade-offs poorly considered. Given the system lock-in and the lengthy policy-making process, it is essential to develop alternative ways of providing dynamic, flexible, practical and scientifically robust decision support for policy-makers. A range of ecosystem services need to be valued and integrated into a resilient land-use strategy, including the introduction of non-monetary, physical-unit constraints on the use of particular services

Real-time analysis of endogenous Wnt signalling in 3D mesenchymal stromal cells

Wnt signalling has been implicated in the regulation of stem cell self-renewal and differentiation; however, the majority of in vitro studies are carried out using monolayer 2D culture techniques. Here, we used mesenchymal stromal cell (MSC) EGFP reporter lines responsive to Wnt pathway activation in a 3D spheroid culture system to mimic better the in vivo environment. Endogenous Wnt signalling was then investigated under basal conditions and when MSCs were induced to undergo osteogenic and adipogenic differentiation. Interestingly, endogenous Wnt signalling was only active during 3D differentiation whereas 2D cultures showed no EGFP expression throughout an extended differentiation time-course. Furthermore, exogenous Wnt signalling in 3D adipogenic conditions inhibited differentiation compared to unstimulated controls. In addition, suppressing Wnt signalling by Dkk-1 restored and facilitated adipogenic differentiation in MSC spheroids. Our findings indicate that endogenous Wnt signalling is active and can be tracked in 3D MSC cultures where it may act as a molecular switch in adipogenesis. The identification of the signalling pathways that regulate MSCs in a 3D in vivo-like environment will advance our understanding of the molecular mechanisms that control MSC fate

How the augmented Lagrangian algorithm can deal with an infeasible convex quadratic optimization problem

International audienceThis paper analyses the behavior of the augmented Lagrangian algorithm when it deals with an infeasible convex quadratic optimization problem. It is shown that the algorithm finds a point that, on the one hand, satisfies the constraints shifted by the smallest possible shift that makes them feasible and, on the other hand, minimizes the objective on the corresponding shifted constrained set. The speed of convergence to such a point is globally linear, with a rate that is inversely proportional to the augmentation parameter. This suggests us a rule for determining the augmentation parameter that aims at controlling the speed of convergence of the shifted constraint norm to zero; this rule has the advantage of generating bounded augmentation parameters even when the problem is infeasible.\addtext{ Implications on an SQP algorithm using the AL algorithm for solving its osculating quadratic problems are discussedCet article analyse le comportement de l'algorithme du lagrangien augmenté lorsqu'il cherche à résoudre un problème d'optimisation quadratique convexe non réalisable. Nous montrons que l'algorithme trouve un point qui, d'une part, réalise les contraintes translatées par la plus petite translation qui les rend compatibles et, d'autre part, minimise l'objectif sur l'ensemble admissible ainsi transformé. La vitesse de convergence vers un tel point est globalement linéaire, avec un taux inversement proportionnel au paramètre d'augmentation. Ceci suggère une règle de mise à jour de ce paramètre, de manière à obtenir une vitesse de convergence donnée des contraintes translatées vers zéro; cette règle a l'avantage de générer des paramètres d'augmentation bornés, même lorsque le problème n'est pas réalisabl

Using environmental DNA for detection of Batrachochytrium salamandrivorans in natural water

Rapid, early, and reliable detection of invasive pathogenic microorganisms is essential in order to either predict or delineate an outbreak, and monitor appropriate mitigation measures. The chytrid fungus Batrachochytrium salamandrivorans is expanding in Europe, and infection with this fungus may cause massive mortality in urodelans (salamanders and newts). In this study, we designed and validated species‐specific primers and a probe for detection of B. salamandrivorans in water. In a garden pond in close proximity to the B. salamandrivorans index site in the Netherlands, B. salamandrivorans‐infected newts had been detected in 2015 and have been monitored since. In 2016 and 2017, no B. salamandrivorans was detected at this site, but in 2018 B. salamandrivorans flared up in this isolated pond which allowed validation of the technique in situ. We here present the development of an environmental DNA technique that successfully detects B. salamandrivorans DNA in natural waterbodies even at low concentrations. This technique may be further validated to play a role in B. salamandrivorans range delineation and surveillance in both natural waterbodies and in captive collections