Aripiprazole in children and adolescents with Tourette's disorder: an open-label safety and tolerability study

The aim of this study was to conduct a prospective safety and tolerability study of aripiprazole for the treatment of tics in children and adolescents with Tourette's disorder (TD).Eleven subjects (10 males) with TD (age 9-19 years, mean 13.36, standard deviation [SD] 3.33) who did not respond or were unable to tolerate previous tic medication were treated with aripiprazole in an open-label, flexible-dosing study over 10 weeks. Tic severity was rated using the Yale Global Tic Severity Scale (YGTSS) and the Clinical Global Impressions Scale for tics (CGI-Tics) at baseline and at follow-up.The mean (+/-SD) daily dose for aripiprazole was 4.5 +/- 3.0 mg. Mean (+/-SD) YGTSS Global Severity scores reduced from 61.82 +/- 13.49 at baseline to 33.73 +/- 15.18 at end point; mean YGTSS total tic scores reduced from 28.18 +/- 7.74 at baseline to 16.73 +/- 7.54 at end point. Mean (+/-SD) CGI-Tic severity scores reduced from 4.45 +/- 0.52 (moderate-marked) at baseline to 3.18 +/- 0.60 (mild) at end point. On the CGI-Tic improvement scale, 10 (91%) subjects achieved 1 ("very much improved") or 2 ("much improved") at end point. Most common adverse effects included appetite increase and weight gain in 5 subjects, mild extrapyramidal effects in 7 subjects, and headaches and tiredness/fatigue in 7 subjects; 1 subject experienced akathisia and muscle cramps.Aripiprazole appears to be a safe and tolerable treatment in children and adolescents with TD that appears to reduce tics; it should be further investigated as a treatment option in controlled trials

Vascular changes in diabetic retinopathy-a longitudinal study in the Nile rat.

Diabetic retinopathy is the most common microvascular complication of diabetes and is a major cause of blindness, but an understanding of the pathogenesis of the disease has been hampered by a lack of accurate animal models. Here, we explore the dynamics of retinal cellular changes in the Nile rat (Arvicanthis niloticus), a carbohydrate-sensitive model for type 2 diabetes. The early retinal changes in diabetic Nile rats included increased acellular capillaries and loss of pericytes that correlated linearly with the duration of diabetes. These vascular changes occurred in the presence of microglial infiltration but in the absence of retinal ganglion cell loss. After a prolonged duration of diabetes, the Nile rat also exhibits a spectrum of retinal lesions commonly seen in the human condition including vascular leakage, capillary non-perfusion, and neovascularization. Our longitudinal study documents a range and progression of retinal lesions in the diabetic Nile rat remarkably similar to those observed in human diabetic retinopathy, and suggests that this model will be valuable in identifying new therapeutic strategies

Tic disorders in children and adolescents:does the clinical presentation differ in males and females? A report by the EMTICS group

Tic disorders have a strong male predominance, with a male-to-female ratio of 4:1 in Tourette syndrome (TS) and 2:1 in persistent tic disorders. In other neurodevelopmental conditions, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), the disparity in sex distribution has been partially related to differences in symptom presentation between males and females. In tic disorders, however, little research has been conducted on this topic, probably due to the limited access to large samples with a significant proportion of females. The aim of this study was to describe sex differences in the clinical presentation of tic disorders in children and adolescents in one of the largest pediatric samples with TS/persistent tic disorders (n = 709, 23.3% females) recruited as part of the European Multicenter Tics in Children Study (EMTICS). Validated measures assessed the severity of tics and comorbid psychiatric symptoms. Using mixed-effect models, we found that sex had a significant influence on the severity of tics, ADHD symptoms, ASD symptoms, and emotional problems. Males had more severe symptoms than females, except for emotional problems. We also observed a statistically significant interaction between sex and age on the severity of tics and compulsions, with females showing higher symptom severity with increasing age than males. These findings indicate that the clinical presentation of TS/persistent tic disorders varies with sex. Males seem to exhibit a more noticeable pattern of clinical symptoms at a younger age that may contribute to their earlier detection in comparison to females

Diagnosis and management of functional tic-like phenomena

Over the past 3 years, a global phenomenon has emerged characterized by the sudden onset and frequently rapid escalation of tics and tic-like movements and phonations. These symptoms have occurred not only in youth known to have tics or Tourette syndrome (TS), but also, and more notably, in youth with no prior history of tics. The Tourette Association of America (TAA) convened an international, multidisciplinary working group to better understand this apparent presentation of functional neurological disorder (FND) and its relationship to TS. Here, we review and summarize the literature relevant to distinguish the two, with recommendations to clinicians for diagnosis and management. Finally, we highlight areas for future emphasis and research

Enhancement of the magnetic anisotropy of nanometer-sized Co clusters: influence of the surface and of the inter-particle interactions

We study the magnetic properties of spherical Co clusters with diameters between 0.8 nm and 5.4 nm (25 to 7500$ atoms) prepared by sequential sputtering of Co and Al2O3. The particle size distribution has been determined from the equilibrium susceptibility and magnetization data and it is compared to previous structural characterizations. The distribution of activation energies was independently obtained from a scaling plot of the ac susceptibility. Combining these two distributions we have accurately determined the effective anisotropy constant Keff. We find that Keff is enhanced with respect to the bulk value and that it is dominated by a strong anisotropy induced at the surface of the clusters. Interactions between the magnetic moments of adjacent layers are shown to increase the effective activation energy barrier for the reversal of the magnetic moments. Finally, this reversal is shown to proceed classically down to the lowest temperature investigated (1.8 K).Comment: 13 figures submitted to Phys. Rev.

Properties, Propagation, and Excitation of EMIC Waves Properties, Propagation, and Excitation of EMIC Waves

Electromagnetic ion cyclotron (EMIC) waves (0.1-5 Hz) play an important role in particle dynamics in the Earth's magnetosphere. EMIC waves are preferentially excited in regions where hot anisotropic ions and cold dense plasma populations spatially overlap. While the generation region of EMIC waves is usually on or near the magnetic equatorial plane in the inner magnetosphere, EMIC waves have both equatorial and off-equator source regions on the dayside in the compressed outer magnetosphere. Using field and plasma measurements from the Magnetospheric Multiscale (MMS) mission, we perform a case study of EMIC waves and associated local plasma conditions observed on 19 October 2015. From 0315 to 0810 UT, before crossing the magnetopause into the magnetosheath, all four MMS spacecraft detected long-lasting He(exp +)-band EMIC wave emissions around local noon (MLT = 12.7 - 14.0) at high L-shells (L = 8.8 - 15.2) and low magnetic latitudes (MLAT = -21.8deg - -30.3deg). Energetic (greater than 1 keV) and anisotropic ions were present throughout this event that was in the recovery phase of a weak geomagnetic storm (min. Dst = -48 nT at 1000 UT on 18 October 2015). The testing of linear theory suggests that the EMIC waves were excited locally. Although the wave event is dominated by small normal angles, its polarization is mixed with right- and left-handedness and its propagation is bi-directional with regard to the background magnetic field. The short inter-spacecraft distances (as low as ~15 km) of the MMS mission make it possible to accurately determine the k vector of the waves using the phase difference technique. Preliminary analysis finds that the k vector magnitude, phase speed, and wavelength of the 0.3-Hz wave packet at 0453:55 UT are 0.005 km(exp -1), 372.9 km/s, and 1242.9 km, respectively

Wave-particle energy exchange directly observed in a kinetic Alfvén-branch wave

Alfvén waves are fundamental plasma wave modes that permeate the universe. At small kinetic scales, they provide a critical mechanism for the transfer of energy between electromagnetic fields and charged particles. These waves are important not only in planetary magnetospheres, heliospheres and astrophysical systems but also in laboratory plasma experiments and fusion reactors. Through measurement of charged particles and electromagnetic fields with NASA’s Magnetospheric Multiscale (MMS) mission, we utilize Earth’s magnetosphere as a plasma physics laboratory. Here we confirm the conservative energy exchange between the electromagnetic field fluctuations and the charged particles that comprise an undamped kinetic Alfvén wave. Electrons confined between adjacent wave peaks may have contributed to saturation of damping effects via nonlinear particle trapping. The investigation of these detailed wave dynamics has been unexplored territory in experimental plasma physics and is only recently enabled by high-resolution MMS observations

Quantum-Classical Transition of the Escape Rate of a Uniaxial Spin System in an Arbitrarily Directed Field

The escape rate \Gamma of the large-spin model described by the Hamiltonian H = -DS_z^2 - H_zS_z - H_xS_x is investigated with the help of the mapping onto a particle moving in a double-well potential U(x). The transition-state method yields $\Gamma$ in the moderate-damping case as a Boltzmann average of the quantum transition probabilities. We have shown that the transition from the classical to quantum regimes with lowering temperature is of the first order (d\Gamma/dT discontinuous at the transition temperature T_0) for h_x below the phase boundary line h_x=h_{xc}(h_z), where h_{x,z}\equiv H_{x,z}/(2SD), and of the second order above this line. In the unbiased case (H_z=0) the result is h_{xc}(0)=1/4, i.e., one fourth of the metastability boundary h_{xm}=1, at which the barrier disappears. In the strongly biased limit \delta\equiv 1-h_z << 1, one has h_{xc} \cong (2/3)^{3/4}(\sqrt{3}-\sqrt{2})\delta^{3/2}\cong 0.2345 \delta^{3/2}, which is about one half of the boundary value h_{xm} \cong (2\delta/3)^{3/2} \cong 0.5443 \delta^{3/2}.The latter case is relevant for experiments on small magnetic particles, where the barrier should be lowered to achieve measurable quantum escape rates.Comment: 17 PR pages, 16 figures; published versio