Increased markers of cardiac vagal activity in leucine-rich repeat kinase 2-associated Parkinson's disease.

PurposeCardiac autonomic dysfunction manifests as reduced heart rate variability (HRV) in idiopathic Parkinson's disease (PD), but no significant reduction has been found in PD patients who carry the LRRK2 mutation. Novel HRV features have not been investigated in these individuals. We aimed to assess cardiac autonomic modulation through standard and novel approaches to HRV analysis in individuals who carry the LRRK2 G2019S mutation.MethodsShort-term electrocardiograms were recorded in 14 LRRK2-associated PD patients, 25 LRRK2-non-manifesting carriers, 32 related non-carriers, 20 idiopathic PD patients, and 27 healthy controls. HRV measures were compared using regression modeling, controlling for age, sex, mean heart rate, and disease duration. Discriminant analysis highlighted the feature combination that best distinguished LRRK2-associated PD from controls.ResultsBeat-to-beat and global HRV measures were significantly increased in LRRK2-associated PD patients compared with controls (e.g., deceleration capacity of heart rate: p = 0.006) and idiopathic PD patients (e.g., 8th standardized moment of the interbeat interval distribution: p = 0.0003), respectively. LRRK2-associated PD patients also showed significantly increased irregularity of heart rate dynamics, as quantified by Rényi entropy, when compared with controls (p = 0.002) and idiopathic PD patients (p = 0.0004). Ordinal pattern statistics permitted the identification of LRRK2-associated PD individuals with 93% sensitivity and 93% specificity. Consistent results were found in a subgroup of LRRK2-non-manifesting carriers when compared with controls.ConclusionsIncreased beat-to-beat HRV in LRRK2 G2019S mutation carriers compared with controls and idiopathic PD patients may indicate augmented cardiac autonomic cholinergic activity, suggesting early impairment of central vagal feedback loops in LRRK2-associated PD

Topological phases of shaken quantum Ising lattices

The quantum compass model consists of a two-dimensional square spin lattice where the orientation of the spin-spin interactions depends on the spatial direction of the bonds. It has remarkable symmetry properties and the ground state shows topological degeneracy. The implementation of the quantum compass model in quantum simulation setups like ultracold atoms and trapped ions is far from trivial, since spin interactions in those systems typically are independent of the spatial direction. Ising spin interactions, on the contrary, can be induced and controlled in atomic setups with state-of-the art experimental techniques. In this work, we show how the quantum compass model on a rectangular lattice can be simulated by the use of the photon-assisted tunneling induced by periodic drivings on a quantum Ising spin model. We describe a procedure to adiabatically prepare one of the doubly-degenerate ground states of this model by adiabatically ramping down a transverse magnetic field, with surprising differences depending on the parity of the lattice size. Exact diagonalizations confirm the validity of this approach for small lattices. Specific implementations of this scheme are presented with ultracold atoms in optical lattices in the Mott insulator regime, as well as with Rydberg atoms

Cervical dystonia incidence and diagnostic delay in a multiethnic population.

BackgroundCurrent cervical dystonia (CD) incidence estimates are based on small numbers in relatively ethnically homogenous populations. The frequency and consequences of delayed CD diagnosis is poorly characterized.ObjectivesTo determine CD incidence and characterize CD diagnostic delay within a large, multiethnic integrated health maintenance organization.MethodsWe identified incident CD cases using electronic medical records and multistage screening of more than 3 million Kaiser Permanente Northern California members from January 1, 2003, to December 31, 2007. A final diagnosis was made by movement disorders specialist consensus. Diagnostic delay was measured by questionnaire and health utilization data. Incidence rates were estimated assuming a Poisson distribution of cases and directly standardized to the 2000 U.S. census. Multivariate logistic regression models were employed to assess diagnoses and behaviors preceding CD compared with matched controls, adjusting for age, sex, and membership duration.ResultsCD incidence was 1.18/100,000 person-years (95% confidence interval [CI], 0.35-2.0; women, 1.81; men, 0.52) based on 200 cases over 15.4 million person-years. Incidence increased with age. Half of the CD patients interviewed reported diagnostic delay. Diagnoses more common in CD patients before the index date included essential tremor (odds ratio [OR] 68.1; 95% CI, 28.2-164.5), cervical disc disease (OR 3.83; 95% CI, 2.8-5.2), neck sprain/strain (OR 2.77; 95% CI, 1.99-3.62), anxiety (OR 2.24; 95% CI, 1.63-3.11) and depression (OR 1.94; 95% CI, 1.4-2.68).ConclusionsCD incidence is greater in women and increases with age. Diagnostic delay is common and associated with adverse effects. © 2019 International Parkinson and Movement Disorder Society

Enhanced Interleukin (IL)-13 Responses in Mice Lacking IL-13 Receptor α 2

Interleukin (IL)-13 has recently been shown to play important and unique roles in asthma, parasite immunity, and tumor recurrence. At least two distinct receptor components, IL-4 receptor (R)α and IL-13Rα1, mediate the diverse actions of IL-13. We have recently described an additional high affinity receptor for IL-13, IL-13Rα2, whose function in IL-13 signaling is unknown. To better appreciate the functional importance of IL-13Rα2, mice deficient in IL-13Rα2 were generated by gene targeting. Serum immunoglobulin E levels were increased in IL-13Rα2−/− mice despite the fact that serum IL-13 was absent and immune interferon γ production increased compared with wild-type mice. IL-13Rα2–deficient mice display increased bone marrow macrophage progenitor frequency and decreased tissue macrophage nitric oxide and IL-12 production in response to lipopolysaccharide. These results are consistent with a phenotype of enhanced IL-13 responsiveness and demonstrate a role for endogenous IL-13 and IL-13Rα2 in regulating immune responses in wild-type mice

Moving in extreme environments:extreme loading; carriage versus distance

This review addresses human capacity for movement in the context of extreme loading and with it the combined effects of metabolic, biomechanical and gravitational stress on the human body. This topic encompasses extreme duration, as occurs in ultra-endurance competitions (e.g. adventure racing and transcontinental races) and expeditions (e.g. polar crossings), to the more gravitationally limited load carriage (e.g. in the military context). Juxtaposed to these circumstances is the extreme metabolic and mechanical unloading associated with space travel, prolonged bedrest and sedentary lifestyle, which may be at least as problematic, and are therefore included as a reference, e.g. when considering exposure, dangers and (mal)adaptations. As per the other reviews in this series, we describe the nature of the stress and the associated consequences; illustrate relevant regulations, including why and how they are set; present the pros and cons for self versus prescribed acute and chronic exposure; describe humans’ (mal)adaptations; and finally suggest future directions for practice and research. In summary, we describe adaptation patterns that are often U or J shaped and that over time minimal or no load carriage decreases the global load carrying capacity and eventually leads to severe adverse effects and manifest disease under minimal absolute but high relative loads. We advocate that further understanding of load carrying capacity and the inherent mechanisms leading to adverse effects may advantageously be studied in this perspective. With improved access to insightful and portable technologies, there are some exciting possibilities to explore these questions in this context

Web-Based Genome-Wide Association Study Identifies Two Novel Loci and a Substantial Genetic Component for Parkinson's Disease

Although the causes of Parkinson's disease (PD) are thought to be primarily environmental, recent studies suggest that a number of genes influence susceptibility. Using targeted case recruitment and online survey instruments, we conducted the largest case-control genome-wide association study (GWAS) of PD based on a single collection of individuals to date (3,426 cases and 29,624 controls). We discovered two novel, genome-wide significant associations with PD–rs6812193 near SCARB2 (, ) and rs11868035 near SREBF1/RAI1 (, )—both replicated in an independent cohort. We also replicated 20 previously discovered genetic associations (including LRRK2, GBA, SNCA, MAPT, GAK, and the HLA region), providing support for our novel study design. Relying on a recently proposed method based on genome-wide sharing estimates between distantly related individuals, we estimated the heritability of PD to be at least 0.27. Finally, using sparse regression techniques, we constructed predictive models that account for 6%–7% of the total variance in liability and that suggest the presence of true associations just beyond genome-wide significance, as confirmed through both internal and external cross-validation. These results indicate a substantial, but by no means total, contribution of genetics underlying susceptibility to both early-onset and late-onset PD, suggesting that, despite the novel associations discovered here and elsewhere, the majority of the genetic component for Parkinson's disease remains to be discovered

Determining how internal and external process connectivity affect supply chain agility: a life-cycle theory perspective

This paper examines how organizations connect internal and external processes to enable an agile response to continuous change. Drawing on life cycle theory, a hypothetical model is developed regarding the independent and combinative effects of internal and external process connectivity on supply chain agility and the moderating effect of product and supply complexity. The model is tested using hierarchical regression analysis based on survey data from 143 managers at German manufacturing firms. Our findings suggest that internal and external process connectivity have a positive effect on supply chain agility independently and collectively, with complexity having a moderating effect in particular instances. The findings build on prior research regarding the process-related enablers of supply chain agility; research that has yet to clearly differentiate between internal and external processes or uses the terms interchangeably. The theoretical contribution of the paper rests on its extension of life cycle theory to the supply chain