Abnormal connectivity between the default mode and the visual system underlies the manifestation of visual hallucinations in Parkinson’s disease:A task-based fMRI study

Background: The neural substrates of visual hallucinations remain an enigma, due primarily to the difficulties associated with directly interrogating the brain during hallucinatory episodes. Aims: To delineate the functional patterns of brain network activity and connectivity underlying visual hallucinations in Parkinson’s disease. Methods: In this study, we combined functional magnetic resonance imaging (MRI) with a behavioral task capable of eliciting visual misperceptions, a confirmed surrogate for visual hallucinations, in 35 patients with idiopathic Parkinson’s disease. We then applied an independent component analysis to extract time series information for large-scale neuronal networks that have been previously implicated in the pathophysiology of visual hallucinations. These data were subjected to a task-based functional connectivity analysis, thus providing the first objective description of the neural activity and connectivity during visual hallucinations in patients with Parkinson’s disease. Results: Correct performance of the task was associated with increased activity in primary visual regions; however, during visual misperceptions, this same visual network became actively coupled with the default mode network (DMN). Further, the frequency of misperception errors on the task was positively correlated with the strength of connectivity between these two systems, as well as with decreased activity in the dorsal attention network (DAN), and with impaired connectivity between the DAN and the DMNs, and ventral attention networks. Finally, each of the network abnormalities identified in our analysis were significantly correlated with two independent clinical measures of hallucination severity. Conclusions: Together, these results provide evidence that visual hallucinations are due to increased engagement of the DMN with the primary visual system, and emphasize the role of dysfunctional engagement of attentional networks in the pathophysiology of hallucinations

A perspective on the ultrafast photochemistry of solution-phase sunscreen molecules

Sunscreens are one of the most common ways of providing on-demand additional photoprotection to the skin. Ultrafast transient absorption spectroscopy has recently proven to be an invaluable tool in understanding how the components of commercial sunscreen products display efficient photoprotection. Important examples of how this technique has unravelled the photodynamics of common components are given in this Perspective, and some of the remaining unanswered questions are discussed

Further investigations into the single metal deposition (SMD II) technique for the detection of latent fingermarks

Single metal deposition (SMD II), a recently proposed method for the development of latent fingermarks, was investigated by systematically altering aspects of the procedure to assess their effect on the level of development and contrast achieved. Gold nanoparticle size, temperature of the deposition solution bath, and orbital shaking during detection were shown to affect the levels of development and contrast obtained. Gold nanoparticles of diameter 15–21 nm were found to be most effective for satisfactory visualisation of latent fingermarks, while solutions that were applied at room temperature were found to adequately balance the ratio between the contrast of the fingermark ridge detail and the level of background staining achieved. Finally, optimum levels of development and contrast were obtained through constant agitation of both solution baths at approximately 50 RPM throughout the submersion time. SMD II was also tested on a large variety of substrate types and shown to be effective on a range of porous, non-porous, and semi-porous surfaces; however, the detection quality can be significantly influenced by the substrate nature. This resulted in the production of dark grey, white, or gold coloured fingermarks on different surfaces, as well as reversed detection on certain types of plastic, similarly seen through the use of vacuum metal deposition. © 2016 Elsevier Ireland Lt

Sex differences in plasma clozapine and norclozapine concentrations in clinical practice and in relation to body mass index and plasma glucose concentrations: a retrospective survey

Background Clozapine is widely prescribed and, although effective, can cause weight gain and dysglycemia. The dysmetabolic effects of clozapine are thought to be more prevalent in women with this gender on average attaining 17 % higher plasma clozapine concentrations than men. Methods We investigated the relationship between dose, body mass index (BMI), plasma glucose concentration, and plasma clozapine and N-desmethylclozapine (norclozapine) concentrations in 100 individuals with a severe enduring mental illness. Results Mean (10th/90th percentile) plasma clozapine concentrations were higher for women [0.49 (0.27–0.79) mg/L] compared with men [0.44 (0.26–0.70) mg/L] (F = 2.2; p = 0.035). There was no significant gender difference in the prescribed clozapine dose. BMI was significantly higher in women [mean (95 % CI) = 34.5 (26.0–45.3)] for females compared with 32.5 (25.2–41.0) for males. Overall, BMI increased by 0.7 kg/m 2 over a mean follow-up period of 210 days. A lower proportion, 41 % of women had a fasting blood glucose ≤6.0 mmol/L (<6.0 mmol/L is defined by the International Diabetes Federation as normal glucose handling), compared with 88 % of men (χ2  = 18.6, p < 0.0001). Conclusions We have shown that mean BMI and blood glucose concentrations are higher in women prescribed clozapine than in men. Women also tended to attain higher plasma clozapine concentrations than men. The higher BMI and blood glucose in women may relate to higher tissue exposure to clozapine, as a consequence of sex differences in drug metabolism

Measuring Anxiety in Lewy Body Disease – Which Scale to Choose?

Background: Anxiety is among the most prevalent mood disorders in Lewy Body Disease (LBD) (i.e., Parkinson’s disease (PD), Dementia with Lewy bodies DLB), and those at-risk for developing LBD (e.g. isolated REM Sleep Behaviour Disorder (iRBD)). Yet, there is little consensus on which clinical scale best evaluates anxiety across synuclein-based diseases. Objective: This study compared the convergent validity of commonly used anxiety scales across PD, DLB and iRBD patients. Methods: Anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS-A), State-Trait Anxiety Inventory (STAI), MDS-UPDRS Anxiety item, and the Parkinson Anxiety Scale (PAS) in 57 participants (17 PD, 16 DLB, and 23 iRBD). Results: Across all groups, PAS total score was significantly associated with trait anxiety (STAI-Y2), whilst HADS-A was associated with PAS total score in the PD and iRBD group. In DLB patients, HADS-A was weakly associated with PAS total score, and significantly correlated with PAS episodic anxiety. Notably, the anxiety item from the MDS-UPDRS did not correlate with any of the other anxiety outcome measures in any group. Conclusions: PAS and STAI-Y2 are the most suitable scales to assess anxiety in synuclein-based diseases. HADS-A showed strong convergent validity in PD and iRBD, it had weaker convergent validity in DLB. The UPDRS anxiety item did not correlate with any of the other anxiety measures, and thus may not be sensitive at detecting anxiety symptoms. Future work should validate anxiety scales in all Lewy Body Disease groups if they are to be implemented in prospective longitudinal cohorts

Fluid/solid transition in a hard-core system

We prove that a system of particles in the plane, interacting only with a certain hard-core constraint, undergoes a fluid/solid phase transition

Association of Cumulative Lead Exposure with Parkinson's Disease

BACKGROUND. Research using reconstructed exposure histories has suggested an association between heavy metal exposures, including lead, and Parkinson's disease (PD), but the only study that used bone lead, a biomarker of cumulative lead exposure, found a nonsignificant increase in risk of PD with increasing bone lead. OBJECTIVES. We sought to assess the association between bone lead and PD. METHODS. Bone lead concentrations were measured using 109Cd excited K-shell X-ray fluorescence from 330 PD patients (216 men, 114 women) and 308 controls (172 men, 136 women) recruited from four clinics for movement disorders and general-community cohorts. Adjusted odds ratios (ORs) for PD were calculated using logistic regression. RESULTS. The average age of cases and controls at bone lead measurement was 67 (SD = 10) and 69 (SD = 9) years of age, respectively. In primary analyses of cases and controls recruited from the same groups, compared with the lowest quartile of tibia lead, the OR for PD in the highest quartile was 3.21 [95% confidence interval (CI), 1.17-8.83]. Results were similar but slightly weaker in analyses restricted to cases and controls recruited from the movement disorders clinics only (fourth-quartile OR = 2.57; 95% CI, 1.11-5.93) or when we included controls recruited from sites that did not also contribute cases (fourth-quartile OR = 1.91; 95% CI, 1.01-3.60). We found no association with patella bone lead. CONCLUSIONS. These findings, using an objective biological marker of cumulative lead exposure among typical PD patients seen in our movement disorders clinics, strengthen the evidence that cumulative exposure to lead increases the risk of PD.National Institutes of Health (R01-ES010798, K01-ES01265

The need for speed : escape velocity and dynamical mass measurements of the Andromeda galaxy

Our nearest large cosmological neighbour, the Andromeda galaxy (M31), is a dynamical system, and an accurate measurement of its total mass is central to our understanding of its assembly history, the life-cycles of its satellite galaxies, and its role in shaping the Local Group environment. Here, we apply a novel approach to determine the dynamical mass of M31 using high velocity Planetary Nebulae (PNe), establishing a hierarchical Bayesian model united with a scheme to capture potential outliers and marginalize over tracers unknown distances. With this, we derive the escape velocity run of M31 as a function of galacto-centric distance, with both parametric and non-parametric approaches. We determine the escape velocity of M31 to be 470 ± 40  km s−1 at a galacto-centric distance of 15  kpc, and also, derive the total potential of M31, estimating the virial mass and radius of the galaxy to be 0.8±0.1×1012M⊙ and 240 ± 10  kpc, respectively. Our M31 mass is on the low-side of the measured range, this supports the lower expected mass of the M31-Milky Way system from the timing and momentum arguments, satisfying the H i constraint on circular velocity between 10 ≲ R/ kpc < 35, and agreeing with the stellar mass Tully-Fisher relation. To place these results in a broader context, we compare them to the key predictions of the ΛCDM cosmological paradigm, including the stellar-mass–halo-mass and the dark matter halo concentration–virial mass correlation, and finding it to be an outlier to this relation.PostprintPeer reviewe