To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid ...tic disorders.
Study subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for ADHD, and had concurrent Tourette syndrome or chronic motor tic disorder. Patients were randomly assigned to double-blind treatment with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18 weeks.
Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo, approaching significance on the Yale Global Tic Severity Scale total score (-5.5 +/- 6.9 vs -3.0 +/- 8.7, p = 0.063) and Tic Symptom Self-Report total score (-4.7 +/- 6.5 vs -2.9 +/- 5.2, p = 0.095) and achieving significance on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (-0.7 +/- 1.2 vs -0.1 +/- 1.0, p = 0.002). Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score (-10.9 +/- 10.9 vs -4.9 +/- 10.3, p < 0.001) and CGI severity of ADHD/psychiatric symptoms scale score (-0.8 +/- 1.1 vs -0.3 +/- 1.0, p = 0.015). Discontinuation rates were not significantly different between treatment groups. Atomoxetine patients had greater increases in heart rate and decreases of body weight, and rates of treatment-emergent decreased appetite and nausea were higher. No other clinically relevant treatment differences were seen in any other vital sign, adverse event, or electrocardiographic or laboratory measures.
Atomoxetine did not exacerbate tic symptoms. Rather, there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and well tolerated.
This large, prospective, community-based study characterized neuropsychological functioning and academic achievement at the time of the first recognized seizure and identified risk factors for ...cognitive deficits.
We compared 282 children (ages 6-14 years, IQ > or =70) with a first recognized seizure to 147 healthy siblings on a battery of well-standardized and widely used neuropsychological and academic achievement tests and examined relationships with demographic and clinical variables.
In this intellectually normal cohort, 27% with just one seizure and up to 40% of those with risk factors exhibited neuropsychological deficits at or near onset. Risk factors associated with neuropsychological deficits included multiple seizures (i.e., second unprovoked seizure; odds ratio OR = 1.96), use of antiepileptic drugs (OR = 2.27), symptomatic/cryptogenic etiology (OR = 2.15), and epileptiform activity on the initial EEG (OR = 1.90); a child with all 4 risks is 3.00 times more likely than healthy siblings to experience neuropsychological deficits by the first clinic visit. Absence epilepsy carried increased odds for neuropsychological impairment (OR = 2.00).
A subgroup of intellectually normal children with seizures showed neuropsychological deficits at onset. Academic achievement was unaffected, suggesting that there is a window early in the disorder for intervention to ameliorate the impact on school performance. Therefore, the risk factors identified here (especially if multiple risks are present) warrant swift referral for neuropsychological evaluation early in the course of the condition.
The Jovian magnetosphere is highly dynamic, influenced by both solar wind and internal processes associated with the rapid planetary rotation and Io's volcanic activities. Accompanying the mass and ...energy circulations driven by the magnetospheric dynamics, the magnetic configuration also changes dramatically. One of the crucial parameters to characterize the magnetic configuration is magnetic field line curvature (FLC), which generally describes how stretched the field line is. The curvature is pivotal to influence particle behaviors, for example, pitch angle scattering which may lead to auroral particle precipitation. In this work, a method is proposed to investigate the real‐time magnetic FLC in Jovian current sheet using the magnetic field data from the Juno spacecraft. The results indicate that the FLC scattering of ions and relativistic electrons are common in Jovian magnetosphere, providing a crucial insight to understand the particle behaviors.
Plain Language Summary
Both the Earth and the Jupiter have intrinsic magnetic field. When the planetary magnetic field interacts with the solar wind, a region called magnetosphere is formed. Particle behaviors in different planetary systems are different, due to the different magnetospheric dynamics. The curvature of magnetic field, describing the stretch level of a magnetic field line, is a basic parameter to describe a planetary space system, and it can significantly influence particle behaviors, for example, to scatter the magnetospheric particles to planetary atmosphere, causing auroral emissions. In this work, we proposed a method to calculate the magnetic field line curvature (FLC) near the equatorial plane inside the Jupiter's magnetosphere using Juno data set, for the first time to provide a global picture on the magnetic FLC. By comparing with the radius of particles' gyration motions, we suggest that ions and electrons can be strongly scattered by the magnetic FLC. We believe that the results in this study provide useful information on the different particle behaviors between the terrestrial system and the Jovian system.
Key Points
We proposed a method to investigate the magnetic field line curvature (FLC) in Jupiter's current sheet using data from Juno data set
50 events are selected by specific criteria. The magnetic FLC and different particles' Larmor radius are investigated
The FLC will scatter ions and relativistic electrons as a potential cause of auroral precipitation
Extracellular ATP plays a role in nociceptive signalling and sensory regulation of visceral function through ionotropic receptors
variably composed of P2X 2 and P2X 3 subunits. P2X 2 and P2X 3 ...subunits can form homomultimeric P2X 2 , homomultimeric P2X 3 , or heteromultimeric P2X 2/3 receptors. However, the relative contribution of these receptor subtypes to afferent functions of ATP in vivo is poorly understood. Here we describe null mutant mice lacking the P2X 2 receptor subunit (P2X 2 â/â ) and double mutant mice lacking both P2X 2 and P2X 3 subunits (P2X 2 /P2X 3 Dblâ/â ), and compare these with previously characterized P2X 3 â/â mice. In patch-clamp studies, nodose, coeliac and superior cervical ganglia (SCG) neurones from wild-type mice responded
to ATP with sustained inward currents, while dorsal root ganglia (DRG) neurones gave predominantly transient currents. Sensory
neurones from P2X 2 â/â mice responded to ATP with only transient inward currents, while sympathetic neurones had barely detectable responses. Neurones
from P2X 2 /P2X 3 Dblâ/â mice had minimal to no response to ATP. These data indicate that P2X receptors on sensory and sympathetic ganglion neurones
involve almost exclusively P2X 2 and P2X 3 subunits. P2X 2 â/â and P2X 2 /P2X 3 Dblâ/â mice had reduced pain-related behaviours in response to intraplantar injection of formalin. Significantly, P2X 3 â/â , P2X 2 â/â , and P2X 2 /P2X 3 Dblâ/â mice had reduced urinary bladder reflexes and decreased pelvic afferent nerve activity in response to bladder distension.
No deficits in a wide variety of CNS behavioural tests were observed in P2X 2 â/â mice. Taken together, these data extend our findings for P2X 3 â/â mice, and reveal an important contribution of heteromeric P2X 2/3 receptors to nociceptive responses and mechanosensory transduction within the urinary bladder.
The ultimate goal of clinical transplantation is for the recipients to achieve long‐term survival, with continuing graft function, that is equivalent to that of the age‐matched general population. We ...studied subsequent outcome in kidney transplant recipients with 10 years of graft function. In all, 2202 kidney transplant recipients survived with graft function >10 years. For 10‐year survivors, the actuarial 25‐year patient survival rate for primary transplant living donor (LD) recipients was 57%; graft survival, 43%. For primary transplant deceased donor (DD) recipients, the actuarial 25‐year patient survival rate was 39%; graft survival, 27%. The two major causes of late graft loss were death (with graft function) and chronic allograft nephropathy (tubular atrophy and interstitial fibrosis). The two major causes of death with function were cardiovascular disease (CVD) and malignancy. For nondiabetic recipients, the mean age at death with function from CVD was 54 ± 13 years; for diabetic recipients, 53 ± 7 years. By 20 years posttransplant, morbidity was common: >40% recipients had skin cancer (mean age for nondiabetic recipients, 53 ± 13 years; for diabetics, 49 ± 8 years), >10% had non‐skin cancer (mean age for nondiabetic recipients, 53 ± 16 years; for diabetics, 46 ± 9 years), and >30% had CVD (mean age for nondiabetic recipients, 53 ± 15 years; for diabetics, 47 ± 9 years). We conclude that long‐term transplant recipients have a high rate of morbidity and early mortality. As short‐term results have improved, more focus is needed on long‐term outcome.
This retrospective study of long‐term outcome for kidney transplants recipients with 10 years of graft function found a high rate of morbidity and early mortality.
Aminoacyl transfer RNA (tRNA) synthetases (aaRSs) are attractive drug targets, and we present class I and II aaRSs as previously unrecognized targets for adenosine 5'-monophosphate-mimicking ...nucleoside sulfamates. The target enzyme catalyzes the formation of an inhibitory amino acid-sulfamate conjugate through a reaction-hijacking mechanism. We identified adenosine 5'-sulfamate as a broad-specificity compound that hijacks a range of aaRSs and ML901 as a specific reagent a specific reagent that hijacks a single aaRS in the malaria parasite
, namely tyrosine RS (
YRS). ML901 exerts whole-life-cycle-killing activity with low nanomolar potency and single-dose efficacy in a mouse model of malaria. X-ray crystallographic studies of plasmodium and human YRSs reveal differential flexibility of a loop over the catalytic site that underpins differential susceptibility to reaction hijacking by ML901.
The Moderate Resolution Imaging Radiometer (MODIS) is the primary instrument in the NASA Earth Observing System for monitoring the seasonality of global terrestrial vegetation. Estimates of 8-day ...mean daily gross primary production (GPP) at the 1 km spatial resolution are now operationally produced by the MODIS Land Science Team for the global terrestrial surface using a production efficiency approach. In this study, the 2001 MODIS GPP product was compared with scaled GPP estimates (25 km
2) based on ground measurements at two forested sites. The ground-based GPP scaling approach relied on a carbon cycle process model run in a spatially distributed mode. Land cover classification and maximum annual leaf area index, as derived from Landsat ETM+ imagery, were used in model initiation. The model was driven by daily meteorological observations from an eddy covariance flux tower situated at the center of each site. Model simulated GPPs were corroborated with daily GPP estimates from the flux tower. At the hardwood forest site, the MODIS GPP phenology started earlier than was indicated by the scaled GPP, and the summertime GPP from MODIS was generally lower than the scaled GPP values. The fall-off in production at the end of the growing season was similar to the validation data. At the boreal forest site, the GPP phenologies generally agreed because both responded to the strong signal associated with minimum temperature. The midsummer MODIS GPP there was generally higher than the ground-based GPP. The differences between the MODIS GPP products and the ground-based GPPs were driven by differences in the timing of FPAR and the magnitude of light use efficiency as well as by differences in other inputs to the MODIS GPP algorithm—daily incident PAR, minimum temperature, and vapor pressure deficit. Ground-based scaling of GPP has the potential to improve the parameterization of light use efficiency in satellite-based GPP monitoring algorithms.
The
Interface Region Imaging Spectrograph
(IRIS) small explorer spacecraft provides simultaneous spectra and images of the photosphere, chromosphere, transition region, and corona with 0.33 – ...0.4 arcsec spatial resolution, two-second temporal resolution, and 1 km s
−1
velocity resolution over a field-of-view of up to 175 arcsec × 175 arcsec. IRIS was launched into a Sun-synchronous orbit on 27 June 2013 using a Pegasus-XL rocket and consists of a 19-cm UV telescope that feeds a slit-based dual-bandpass imaging spectrograph. IRIS obtains spectra in passbands from 1332 – 1358 Å, 1389 – 1407 Å, and 2783 – 2834 Å, including bright spectral lines formed in the chromosphere (Mg
ii
h 2803 Å and Mg
ii
k 2796 Å) and transition region (C
ii
1334/1335 Å and Si
iv
1394/1403 Å). Slit-jaw images in four different passbands (C
ii
1330, Si
iv
1400, Mg
ii
k 2796, and Mg
ii
wing 2830 Å) can be taken simultaneously with spectral rasters that sample regions up to 130 arcsec × 175 arcsec at a variety of spatial samplings (from 0.33 arcsec and up). IRIS is sensitive to emission from plasma at temperatures between 5000 K and 10 MK and will advance our understanding of the flow of mass and energy through an
interface region
, formed by the chromosphere and transition region, between the photosphere and corona. This highly structured and dynamic region not only acts as the conduit of all mass and energy feeding into the corona and solar wind, it also requires an order of magnitude more energy to heat than the corona and solar wind combined. The IRIS investigation includes a strong numerical modeling component based on advanced radiative–MHD codes to facilitate interpretation of observations of this complex region. Approximately eight Gbytes of data (after compression) are acquired by IRIS each day and made available for unrestricted use within a few days of the observation.
Rapid discontinuation of prednisone (RDP) has minimized steroid‐related complications following kidney transplant (KT). This trial compares long‐term (10‐year) outcomes with three different ...maintenance immunosuppressive protocols following RDP in adult KT. Recipients (n = 440; 73% living donor) from March 2001 to April 2006 were randomized into one of three arms: cyclosporine (CSA) and mycophenolate mofetil (MMF) (CSA/MMF, n = 151); high‐level tacrolimus (TAC, 8–12 μg/L) and low‐level sirolimus (SIR, 3–7 μg/L) (TACH/SIRL, n = 149) or low‐level TAC (3–7 μg/L) and high‐level SIR (8–12 μg/L) (TACL/SIRH, n = 140). Median follow‐up was ∼7 years. There were no differences between arms in 10‐year actuarial patient, graft and death‐censored graft survival or in allograft function. There were no differences in the 10‐year actuarial rates of biopsy‐proven acute rejection (30%, 26% and 20% in CSA/MMF, TACH/SIRL and TACL/SIRH) and chronic rejection (38%, 35% and 31% in CSA/MMF, TACH/SIRL and TACL/SIRH). Rates of new‐onset diabetes mellitus were higher with TACH/SIRL (p = 0.04), and rates of anemia were higher with TACH/SIRL and TACL/SIRH (p = 0.04). No differences were found in the overall rates of 16 other post‐KT complications. These data indicate that RDP‐based protocol yield acceptable 10‐year outcomes, but side effects differ based on the maintenance regimen used and should be considered when optimizing immunosuppression following RDP.
A prospective randomized trial comparing three different maintenance immunosuppressive regimens following rapid discontinuation of prednisone reports no differences in recipient and graft survival outcomes or graft function up to 10 years after kidney transplant, but reports differences in rates of drug‐related complications such as new‐onset diabetes and anemia.
Hypogonadism is a prominent risk factor for osteoporosis in older men. However, bone loss during androgen ablation therapy for prostate cancer has rarely been quantitated.
Femoral neck bone mineral ...density was determined in 26 men before orchiectomy or chemical castration as initial hormone therapy for prostate cancer and at 6-month intervals thereafter for 6 to 42 months. Measurements were made in 16 other men at 12 to 24 months beginning 3 to 8 years after the onset of castration. Baseline and post-castration bone loss was related to several host and tumor characteristics, and compared to similar measurements in 12 control subjects.
Average age corrected baseline femoral neck bone mineral density was higher in controls than in treated men and remained essentially unchanged for 2 years. Following orchiectomy average bone mineral density decreased 2.4% and 7.6%, respectively, during years 1 and 2 (2-year loss 2.5% to 17.0%), with similar losses documented in men undergoing chemical castration. Average bone mineral density decreased 1.4% to 2.6% per year 3 to 8 years after uninterrupted androgen deprivation. Age corrected baseline bone mineral density was greater in men who were obese, younger than 75 years or participated in regular exercise but the influence of each characteristic could not be isolated. Post-castration bone loss was greater in men who were obese, younger than 75 years without regular exercise.
Chemical or surgical castration in men with prostate cancer is usually followed by greatly accelerated bone loss which may be superimposed on a bone mass already depleted before hormonal therapy. Baseline bone mass and subsequent bone loss may be influenced by host obesity, age and exercise habits.
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