An unknown absorber near the cloud-top level of Venus generates a broad absorption feature from the ultraviolet (UV) to visible, peaking around 360 nm, and therefore plays a critical role in the ...solar energy absorption. We present a quantitative study of the variability of the cloud albedo at 365 nm and its impact on Venus's solar heating rates based on an analysis of Venus Express and Akatsuki UV images and Hubble Space Telescope and MESSENGER UV spectral data; in this analysis, the calibration correction factor of the UV images of Venus Express (Venus Monitoring Camera) is updated relative to the Hubble and MESSENGER albedo measurements. Our results indicate that the 365 nm albedo varied by a factor of 2 from 2006 to 2017 over the entire planet, producing a 25%-40% change in the low-latitude solar heating rate according to our radiative transfer calculations. Thus, the cloud-top level atmosphere should have experienced considerable solar heating variations over this period. Our global circulation model calculations show that this variable solar heating rate may explain the observed variations of zonal wind from 2006 to 2017. Overlaps in the timescale of the long-term UV albedo and the solar activity variations make it plausible that solar extreme UV intensity and cosmic-ray variations influenced the observed albedo trends. The albedo variations might also be linked with temporal variations of the upper cloud SO2 gas abundance, which affects the H2SO4-H2O aerosol formation.
Objective
This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age.
Methods
A ...phase IIb multicenter randomized double‐blind placebo‐controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley‐III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug‐resistant epilepsy, additional developmental outcomes, and safety of vigabatrin.
Results
Of 84 infants enrolled, 12 were screen failures, 4 went straight to open label vigabatrin, and 12 were not randomized (normal EEG throughout). Fifty‐six were randomized to early vigabatrin (n = 29) or placebo (n = 27). Nineteen of 27 in the placebo arm transitioned to open label vigabatrin, with a median delay of 44 days after randomization. Bayley‐III cognitive composite scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug‐resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes. Incidence of infantile spasms was lower and time to spasms after randomization was later in the vigabatrin group. Adverse events were similar across groups.
Interpretation
Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children, nor does it delay onset or lower the incidence of focal seizures and drug‐resistant epilepsy at 24 months. Preventative vigabatrin was associated with later time to onset and lower incidence of infantile spasms. ANN NEUROL 2024;95:15–26
X-ray free-electron lasers (XFELs) provide very intense X-ray pulses suitable for macromolecular crystallography. Each X-ray pulse typically lasts for tens of femtoseconds and the interval between ...pulses is many orders of magnitude longer. Here we describe two novel acoustic injection systems that use focused sound waves to eject picoliter to nanoliter crystal-containing droplets out of microplates and into the X-ray pulse from which diffraction data are collected. The on-demand droplet delivery is synchronized to the XFEL pulse scheme, resulting in X-ray pulses intersecting up to 88% of the droplets. We tested several types of samples in a range of crystallization conditions, wherein the overall crystal hit ratio (e.g., fraction of images with observable diffraction patterns) is a function of the microcrystal slurry concentration. We report crystal structures from lysozyme, thermolysin, and stachydrine demethylase (Stc2). Additional samples were screened to demonstrate that these methods can be applied to rare samples.
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•Acoustic methods inject crystal-containing droplets directly from microplate wells•On-demand acoustic injection uses crystals efficiently without orifices or clogging•Diffraction patterns from crystals measuring several tens of μm are of high quality•Complete datasets can be obtained from fewer than 50,000 crystals
Acoustic droplet ejection provides an automated tool for efficient use of protein crystals in SFX experiments. Roessler et al. used this method to deliver crystal-containing droplets into the XFEL beam to coincide with each X-ray pulse.
Abstract
Objective
The objective of this study is to document pain scores during withdrawal of abortive medication in patients diagnosed with medication overuse headache.
Design
Cross-sectional ...study.
Setting
Children’s National Hospital’s Headache Program.
Subjects
Patients 6–18 years of age who presented to the Headache Clinic at Children’s National Hospital with presumed medication overuse headache between March 2017 and March 2019 were invited to participate.
Methods
Patients were instructed to abruptly discontinue overused medications and record their headache characteristics daily in a diary for 8 weeks.
Results
Fourteen diaries were returned and analyzed at a 4-week follow-up visit. Ninety-three percent of the patients were females, with a median age of 14.9 years (standard deviation SD = 2.0). The average headache intensity upon study entry was 4.7 out of 10 (SD = 2.5), and the average headache intensity upon study completion was 3.1 (SD = 2.5). Of the patients, 57% had daily headaches upon study entry, 71% had improved pain intensity from the first diary entry to the last diary entry, and 57% had complete headache resolution at an average of 7.6 days from medication discontinuation (SD = 5.1). Ibuprofen was the most overused medication (71%).
Conclusions
Our findings suggest that medication overuse headache will improve in the majority of pediatric patients who abruptly stop the offending medication(s) in an average of 8 days from withdrawal. Average pain intensity was reduced by more than one point among all patients who stopped taking abortive medications. Further larger-scale studies on medication withdrawal in pediatric patients with medication overuse headache could help us better understand whether this management strategy is effective.
Summary
Purpose: Investigate whether patients on vigabatrin demonstrated new‐onset and reversible T2‐weighted magnetic resonance imaging (MRI) abnormalities.
Methods: MRI of patients treated during ...vigabatrin therapy was reviewed, following detection of new basal ganglia, thalamus, and corpus callosum hyperintensities in an infant treated for infantile spasms. Patients were assessed for age at time of MRI, diagnosis, duration, and dose, MRI findings pre‐, on, and postvigabatrin, concomitant medications, and clinical correlation. These findings were compared to MRI in patients with infantile spasms who did not receive vigabatrin.
Results: Twenty‐three patients were identified as having MRI during the course of vigabatrin therapy. After excluding the index case, we detected new and reversible basal ganglia, thalamic, brainstem, or dentate nucleus abnormalities in 7 of 22 (32%) patients treated with vigabatrin. All findings were reversible following discontinuation of therapy. Diffusion‐weighted imaging (DWI) was positive with apparent diffusion coefficient (ADC) maps demonstrating restricted diffusion. Affected versus unaffected patients, respectively, had a median age of 11 months versus 5 years, therapy duration 3 months versus 12 months, and dosage 170 mg/kg/day versus 87 mg/kg/day. All affected patients were treated for infantile spasms; none of 56 patients with infantile spasms who were not treated with vigabatrin showed the same abnormalities.
Discussion: MRI abnormalities attributable to vigabatrin, characterized by new‐onset and reversible T2‐weighted hyperintensities and restricted diffusion in thalami, globus pallidus, dentate nuclei, brainstem, or corpus callosum were identified in 8 of 23 patients. Young age and relatively high dose appear to be risk factors.
Tuberous sclerosis complex (TSC) is a multiorgan disorder that primarily affects the brain, skin, and kidneys. Recent advances have elucidated the genetics of this complex, which has helped lead to ...an increased understanding of the basic neurobiology of this disorder. There is both phenotypic and geneotypic heterogeneity. The treatment of epilepsy remains a major challenge in these patients, and there is an increasing role for epileptic surgery. Many patients with TSC continue to have intractable seizures. Early identification to ensure proper monitoring and genetic counseling continue to be important clinically. The neurologist must be aware of other organ involvement, particularly the kidneys, and the lungs in female patients, to ensure appropriate monitoring for complications. It is also important to be aware of the marked variability of expression in all the clinical features of TSC.
X-ray free-electron lasers (XFELs) provide very intense X-ray pulses suitable for macromolecular crystallography. Each X-ray pulse typically lasts for tens of femtoseconds and the interval between ...pulses is many orders of magnitude longer. Here we describe two novel acoustic injection systems that use focused sound waves to eject picoliter to nanoliter crystal-containing droplets out of microplates and into the X-ray pulse from which diffraction data are collected. The on-demand droplet delivery is synchronized to the XFEL pulse scheme, resulting in X-ray pulses intersecting up to 88% of the droplets. We tested several types of samples in a range of crystallization conditions, wherein the overall crystal hit ratio (e.g., fraction of images with observable diffraction patterns) is a function of the microcrystal slurry concentration. Lastly, we report crystal structures from lysozyme, thermolysin, and stachydrine demethylase (Stc2). In addition, samples were screened to demonstrate that these methods can be applied to rare samples
Purpose The antiepileptic drug vigabatrin is known to cause permanent loss of vision. Both visual field testing and electroretinogram are used to detect retinal damage. Adult data on optical ...coherence tomography (OCT) shows that retinal nerve fiber layer (RNFL) thinning may be an early indicator of vigabatrin-induced retinal toxicity. The purpose of this study was to investigate whether OCT can detect early vigabatrin-induced retinal toxicity in children. Methods Pediatric patients (≤18 years of age) requiring vigabatrin for seizure control who were followed at our institution were invited to participate. Patients were examined according to manufacturer guidelines, with most examinations taking place under general anesthesia. RNFL thickness was measured by OCT (Stratus Model 3000, Zeiss) and compared to total cumulative dose of vigabatrin. In most cases, indirect ophthalmoscopy, fundus photography, and electroretinography were also performed. Results OCT and complete dosing data was available for 19 patients. Patients with tuberous sclerosis (TS, n = 12) received higher cumulative doses (mean, 1463 g) than non-TS patients (mean, 351 g, P = 0.044). RNFL thinning was detected in the nasal ( P < 0.01), superior ( P < 0.01), and inferior ( P < 0.05) quadrants in patients with TS, particularly once cumulative dose exceeded 1500 g. Conclusions In our study population of patients with TS, higher cumulative doses of vigabatrin were associated with RNFL thinning in the nasal, superior, and inferior quadrants. These findings were pronounced once cumulative dose exceeded 1500 g. This pattern of RNFL thinning is similar to what has been shown in adult patients taking vigabatrin.
An unknown absorber near the cloud top level of Venus generates a broad absorption feature from the ultraviolet (UV) to visible, peaking around 360 nm, and therefore plays a critical role in the ...solar energy absorption. We present a quantitative study on the variability of the cloud albedo at 365 nm and its impact on Venus' solar heating rates based on an analysis of Venus Express and Akatsuki's UV images, and Hubble Space Telescope and MESSENGER's UV spectral data; in this analysis the calibration correction factor of the UV images of Venus Express (VMC) is updated relative to the Hubble and MESSENGER albedo measurements. Our results indicate that the 365-nm albedo varied by a factor of 2 from 2006 to 2017 over the entire planet, producing a 25-40% change in the low latitude solar heating rate according to our radiative transfer calculations. Thus, the cloud top level atmosphere should have experienced considerable solar heating variations over this period. Our global circulation model calculations show that this variable solar heating rate may explain the observed variations of zonal wind from 2006 to 2017. Overlaps in the timescale of the long-term UV albedo and the solar activity variations make it plausible that solar extreme UV intensity and cosmic-ray variations influenced the observed albedo trends. The albedo variations might also be linked with temporal variations of the upper cloud SO2 gas abundance, which affects the H2SO4-H2O aerosol formation.
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