The dynamically tunable terahertz (THz) waves and electromagnetically induced transparency (EIT) in coupled hybrid superconducting niobium-graphene split-ring resonator arrays are investigated. ...Active modulation of THz waves is studied through two different approaches. Thermal tuning of THz amplitude and group delay is observed due to the temperature sensitivity of the niobium superconductor. Stronger photoresponses are observed when niobium is superconducting. The electrical tuning of the integrated hybrid device is accomplished through the integration of graphene patches with the superconducting circuit. The modulation of resonance strength and group delay is observed due to damping of the dark mode resonance in coupled split-ring resonator arrays. The proposed chip-scale device provides a route toward the implementation of active cryogenic THz devices.
The purpose of this study was to use spectral domain-optical coherence tomography in imaging retina and vitreoretinal relationship in healed cytomegalovirus (CMV) retinitis.
Patients with a history ...of confirmed CMV retinitis and a healed CMV scar on clinical examination underwent spectral domain-optical coherence tomography examinations using a Spectralis Heidelberg retinal angiograph/optical coherence tomography instrument (Heidelberg Engineering, Heidelberg, Germany). Horizontal and vertical cross-sectional B-scans 6 mm x 6 mm passing through the center and margins of healed CMV scars and adjacent retina were obtained. We analyzed the integrity of retinal layers in the area of the CMV scar, integrity of retinal layers at the margins of the CMV scar, margins of the scar and adjacent nonaffected retina, and any structural alterations in the retina or vitreous.
Eleven eyes (50%) had vitreous detached, and 11 eyes attached over the area of healed retinitis. Nineteen eyes (86%) had an epiretinal membrane, and 12 eyes (54%) had vitreoretinal gliosis present over the healed retinitis or in its vicinity. The epiretinal membrane and vitreoretinal gliosis occurred concomitantly in 10 eyes and could be well differentiated on scans. None of these were found in control eyes.
This first in vivo study of vitreoretinal interface in inactive CMV retinitis shows that the vitreoretinal interface in healed CMV is pathologically changed. The presence of epiretinal membranes, vitreoretinal gliosis, and traction may help explain the higher incidence of retinal elevation, retinal breaks, and retinal detachment in these eyes.
MRC CRASH is a randomised controlled trial (ISRCTN74459797) of the effect of corticosteroids on death and disability after head injury. We randomly allocated 10 008 adults with head injury and a ...Glasgow Coma Scale score of 14 or less, within 8 h of injury, to a 48-h infusion of corticosteroid (methylprednisolone) or placebo. Data at 6 months were obtained for 9673 (96·7%) patients. The risk of death was higher in the corticosteroid group than in the placebo group (1248 25·7%
vs 1075 22·3% deaths; relative risk 1·15, 95% CI 1·07–1·24; p=0·0001), as was the risk of death or severe disability (1828 38·1%
vs 1728 36·3% dead or severely disabled; 1·05, 0·99–1·10; p=0·079). There was no evidence that the effect of corticosteroids differed by injury severity or time since injury. These results lend support to our earlier conclusion that corticosteroids should not be used routinely in the treatment of head injury.
Marine spatial planning is emerging as an integrated, resource management-led approach to governing the use of the seas. Recent initiatives include those of some north European countries, including ...Germany, which has now completed a plan for its federal offshore territory. In this article, an analysis is presented of this pioneering plan and the consultation process behind its production, with a particular emphasis on the treatment of different sectoral interests around which the plan was structured. This revealed the attempts to coordinate not only the different demands at sea by means of allocation of areas and cross-sectoral considerations, but also the uneven representation of activities with certain interests gaining strongly and others effectively marginalized. This study provides early empirical evidence of the tensions involved in the attempt to adopt a spatial approach to marine governance. This new domain for planning is situated in the overlapping, but distinct domains of marine management and spatial planning. The conceptual backgrounds of both are drawn upon in assessing the strengths and weaknesses of the plan and in suggesting how marine plans might gain by giving close attention to the broader principles of marine and strategic planning.
Cataract is the leading cause of blindness in the world, and in the United States accounts for approximately 60% of Medicare costs related to vision. The purpose of this study was to identify genetic ...markers for age-related cataract through a genome-wide association study (GWAS).
In the electronic medical records and genomics (eMERGE) network, we ran an electronic phenotyping algorithm on individuals in each of five sites with electronic medical records linked to DNA biobanks. We performed a GWAS using 530,101 SNPs from the Illumina 660W-Quad in a total of 7,397 individuals (5,503 cases and 1,894 controls). We also performed an age-at-diagnosis case-only analysis.
We identified several statistically significant associations with age-related cataract (45 SNPs) as well as age at diagnosis (44 SNPs). The 45 SNPs associated with cataract at p<1×10(-5) are in several interesting genes, including ALDOB, MAP3K1, and MEF2C. All have potential biologic relationships with cataracts.
This is the first genome-wide association study of age-related cataract, and several regions of interest have been identified. The eMERGE network has pioneered the exploration of genomic associations in biobanks linked to electronic health records, and this study is another example of the utility of such resources. Explorations of age-related cataract including validation and replication of the association results identified herein are needed in future studies.
Tafenoquine is a promising new 8-aminoquinoline drug that may be useful for malaria prophylaxis in non-pregnant persons with normal glucose-6-phosphate dehydrogenase (G6PD) function. A randomized, ...double-blind, placebo-controlled chemoprophylaxis trial was conducted with adult residents of northern Ghana to determine the minimum effective weekly dose of tafenoquine for the prevention of infection by Plasmodium falciparum. The primary end point was a positive malaria blood smear result during the 13 weeks of study drug coverage. Relative to the placebo, all 4 tafenoquine dosages demonstrated significant protection against P. falciparum infection: for 25 mg/week, protective efficacy was 32% (95% confidence interval CI, 20%–43%); for 50 mg/week, 84% (95% CI, 75%–91%); for 100 mg/week, 87% (95% CI, 78%–93%); and for 200 mg/week, 86% (95% CI, 76%–92%). The mefloquine dosage of 250 mg/week also demonstrated significant protection against P. falciparum infection (protective efficacy, 86%; 95% CI, 72%–93%). There was little difference between study groups in the adverse events reported, and there was no evidence of a relationship between tafenoquine dosage and reports of physical complaints or the occurrence of abnormal laboratory parameters. Tafenoquine dosages of 50, 100, and 200 mg/week were safe, well tolerated, and effective against P. falciparum infection in this study population.
Background
In TRAILBLAZER‐ALZ, donanemab cleared brain amyloid plaques and significantly slowed disease progression in early symptomatic Alzheimer’s disease (AD).
Methods
TRAILBLAZER‐ALZ 2 ...(NCT04437511), a multicenter, randomized, double‐blind, placebo‐controlled trial, enrolled participants with early symptomatic AD and amyloid and tau pathology by positron‐emission tomography. The study randomized participants with low/medium‐tau (n = 1182) and high‐tau (n = 552) pathology (missing tau category, n = 2). Participants (randomized 1:1) received donanemab (n = 860) or placebo (n = 876) intravenously every 4 weeks (w) for 72w. Donanemab participants meeting amyloid clearance treatment completion criteria at 24w or 52w were switched to placebo in a blinded procedure.
The primary outcomes were change in Integrated AD Rating Scale (iADRS) score from baseline at 76w in either the low/medium‐tau or combined (low/medium‐tau and high‐tau) populations. Statistical testing allocated most power (80% alpha spend) to low/medium‐tau population outcomes, with the remainder for combined population outcomes, which included clinical and biomarker assessments.
Results
In the low/medium‐tau population, change in iADRS score at 76w was ‐6.02 with donanemab and ‐9.27 with placebo (difference, 3.25; 95% CI, 1.88 to 4.62; P<0.001), representing a 35.1% slowing of disease progression. Change in Clinical Dementia Rating Scale (CDR) – Sum of Boxes, the key secondary outcome, was 1.20 with donanemab and 1.88 with placebo (difference, ‐0.67; 95% CI ‐0.95 to ‐0.40; P<0.001), representing a 36.0% slowing. Participants receiving donanemab experienced a 38.6% lower risk of progressing to the next disease stage versus placebo over 76w (CDR‐Global score, Hazard Ratio = 0.61; P<0.001). Amyloid clearance at 24w, 52w and 76w was achieved in 34.2%, 71.3% and 80.1% of donanemab‐treated participants, respectively. Plasma P‐tau217 was significantly reduced by 39.3% from baseline with donanemab and increased by 8.4% with placebo at 76w (P<0.001). Significant, positive results across all clinical endpoints were also observed in the combined population. The incidence of serious adverse events was 17.4% (donanemab) and 15.8% (placebo), with three deaths among patients treated with donanemab who experienced serious ARIA. Adverse events with donanemab included amyloid‐related imaging abnormalities (ARIA)‐E (24.0%, 6.1% symptomatic); ARIA‐H (31.4%); and infusion‐related reactions (8.7%).
Conclusion
Donanemab treatment significantly slowed clinical progression at 76w and had a safety profile consistent with earlier studies.
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