Boundary element method for resonances in dielectric microcavities

A boundary element method based on a Green's function technique is introduced to compute resonances with intermediate lifetimes in quasi-two-dimensional dielectric cavities. It can be applied to single or several optical resonators of arbitrary shape, including corners, for both TM and TE polarization. For cavities with symmetries a symmetry reduction is described. The existence of spurious solutions is discussed. The efficiency of the method is demonstrated by calculating resonances in two coupled hexagonal cavities.Comment: 9 pages, 7 figures (quality reduced

KAI407, a potent non-8-aminoquinoline compound that kills Plasmodium cynomolgi early dormant liver stage parasites in vitro.

Preventing relapses of Plasmodium vivax malaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. For future malaria eradication strategies, new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. A new compound with potential radical cure activity was identified using a low-throughput assay of in vitro-cultured hypnozoite forms of Plasmodium cynomolgi (an excellent and accessible model for Plasmodium vivax). In this assay, primary rhesus hepatocytes are infected with P. cynomolgi sporozoites, and exoerythrocytic development is monitored in the presence of compounds. Liver stage cultures are fixed after 6 days and stained with anti-Hsp70 antibodies, and the relative proportions of small (hypnozoite) and large (schizont) forms relative to the untreated controls are determined. This assay was used to screen a series of 18 known antimalarials and 14 new non-8-aminoquinolines (preselected for blood and/or liver stage activity) in three-point 10-fold dilutions (0.1, 1, and 10 μM final concentrations). A novel compound, designated KAI407 showed an activity profile similar to that of primaquine (PQ), efficiently killing the earliest stages of the parasites that become either primary hepatic schizonts or hypnozoites (50% inhibitory concentration [IC50] for hypnozoites, KAI407, 0.69 μM, and PQ, 0.84 μM; for developing liver stages, KAI407, 0.64 μM, and PQ, 0.37 μM). When given as causal prophylaxis, a single oral dose of 100 mg/kg of body weight prevented blood stage parasitemia in mice. From these results, we conclude that KAI407 may represent a new compound class for P. vivax malaria prophylaxis and potentially a radical cure

Self-reported quantity and quality of sleep in children and adolescents with a chronic condition compared to healthy controls

To assess self-reported quantity and quality of sleep in Dutch children with a chronic condition compared to healthy controls and to the recommended hours of sleep for youth. Sleep quantity and quality were analyzed in children with a chronic condition (cystic fibrosis, chronic kidney disease, congenital heart disease, (auto-)immune disease, and medically unexplained symptoms (MUS); n = 291; 15 ± 3.1 years, 63% female. A subset of 171 children with a chronic condition were matched to healthy controls using Propensity Score matching, based on age and sex, ratio 1:4. Self-reported sleep quantity and quality were assessed with established questionnaires. Children with MUS were analyzed separately to distinguish between chronic conditions with and without an identified pathophysiological cause. Generally, children with a chronic condition met the recommended amount of sleep, however 22% reported poor sleep quality. No significant differences in sleep quantity and quality were found between the diagnosis groups. Children with a chronic condition and with MUS slept significantly more than healthy controls at ages 13, 15, and 16. Both at primary and secondary school, poor sleep quality was least frequent reported in children with a chronic condition and most often reported in children with MUS. Conclusion: Overall, children with chronic conditions, including MUS, met the recommended hours of sleep for youth, and slept more than healthy controls. However, it is important to obtain a better understanding of why a substantial subset of children with chronic conditions, mostly children with MUS, still perceived their sleep quality as poor.What is Known:• According to the Consensus statement of the American Academy of Sleep medicine, typically developing children (6 to 12 years) should sleep 9 to 12 h per night, and adolescents (13 to 18 years) should sleep 8 to 10 h per night.• Literature on the optimal quantity and quality of sleep in children with a chronic condition is very limited.What is New:• In general, children with a chronic condition sleep according to the recommended hours of sleep.• A substantial subset of children with chronic conditions, perceived their sleep quality as poor. Although this was reported mostly by children with medically unexplained symptoms (MUS), the found poor sleep quality was independent of specific diagnosis

Self-reported quantity and quality of sleep in children and adolescents with a chronic condition compared to healthy controls

To assess self-reported quantity and quality of sleep in Dutch children with a chronic condition compared to healthy controls and to the recommended hours of sleep for youth. Sleep quantity and quality were analyzed in children with a chronic condition (cystic fibrosis, chronic kidney disease, congenital heart disease, (auto-)immune disease, and medically unexplained symptoms (MUS); n = 291; 15 ± 3.1 years, 63% female. A subset of 171 children with a chronic condition were matched to healthy controls using Propensity Score matching, based on age and sex, ratio 1:4. Self-reported sleep quantity and quality were assessed with established questionnaires. Children with MUS were analyzed separately to distinguish between chronic conditions with and without an identified pathophysiological cause. Generally, children with a chronic condition met the recommended amount of sleep, however 22% reported poor sleep quality. No significant differences in sleep quantity and quality were found between the diagnosis groups. Children with a chronic condition and with MUS slept significantly more than healthy controls at ages 13, 15, and 16. Both at primary and secondary school, poor sleep quality was least frequent reported in children with a chronic condition and most often reported in children with MUS. Conclusion: Overall, children with chronic conditions, including MUS, met the recommended hours of sleep for youth, and slept more than healthy controls. However, it is important to obtain a better understanding of why a substantial subset of children with chronic conditions, mostly children with MUS, still perceived their sleep quality as poor.What is Known:• According to the Consensus statement of the American Academy of Sleep medicine, typically developing children (6 to 12 years) should sleep 9 to 12 h per night, and adolescents (13 to 18 years) should sleep 8 to 10 h per night.• Literature on the optimal quantity and quality of sleep in children with a chronic condition is very limited.What is New:• In general, children with a chronic condition sleep according to the recommended hours of sleep.• A substantial subset of children with chronic conditions, perceived their sleep quality as poor. Although this was reported mostly by children with medically unexplained symptoms (MUS), the found poor sleep quality was independent of specific diagnosis

Central Adrenal Insufficiency Is Rare in Adults With Prader-Willi Syndrome

CONTEXT: Prader-Willi syndrome (PWS) is associated with several hypothalamic-pituitary hormone deficiencies. There is no agreement on the prevalence of central adrenal insufficiency (CAI) in adults with PWS. In some countries, it is general practice to prescribe stress-dose hydrocortisone during physical or psychological stress in patients with PWS. Side effects of frequent hydrocortisone use are weight gain, osteoporosis, diabetes mellitus, and hypertension-already major problems in adults with PWS. However, undertreatment of CAI can cause significant morbidity-or even mortality. OBJECTIVE: To prevent both over- and undertreatment with hydrocortisone, we assessed the prevalence of CAI in a large international cohort of adults with PWS. As the synacthen test shows variable results in PWS, we only use the metyrapone test (MTP) and insulin tolerance test (ITT). DESIGN: Metyrapone test or ITT in adults with PWS (N = 82) and review of medical files for symptoms of hypocortisolism related to surgery (N = 645). SETTING: Outpatient clinic. PATIENTS OR OTHER PARTICIPANTS: Eighty-two adults with genetically confirmed PWS. MAIN OUTCOME MEASURE: For MTP, 11-deoxycortisol > 230 nmol/L was considered sufficient. For ITT, cortisol > 500 nmol/L (Dutch, French, and Swedish patients) or > 450 nmol/L (British patients) was considered sufficient. RESULTS: Central adrenal insufficiency was excluded in 81 of 82 patients. Among the 645 patients whose medical files were reviewed, 200 had undergone surgery without perioperative hydrocortisone treatment. None of them had displayed any features of hypocortisolism. CONCLUSIONS: Central adrenal insufficiency is rare (1.2%) in adults with PWS. Based on these results, we recommend against routinely prescribing hydrocortisone stress-doses in adults with PWS

Membrane curvature during peroxisome fission requires Pex11

Pex11p is required for peroxisome proliferation. This study demonstrates that the N-terminus of Pex11p forms an amphipathic helix that generates membrane curvature required for peroxisome fission

Direct measurements of meltwater runoff on the Greenland ice sheet surface

Meltwater runoff from the Greenland ice sheet surface influences surface mass balance (SMB), ice dynamics, and global sea level rise, but is estimated with climate models and thus difficult to validate. We present a way to measure ice surface runoff directly, from hourly in situ supraglacial river discharge measurements and simultaneous high-resolution satellite/drone remote sensing of upstream fluvial catchment area. A first 72-h trial for a 63.1-km2 moulin-terminating internally drained catchment (IDC) on Greenland?s midelevation (1,207?1,381 m above sea level) ablation zone is compared with melt and runoff simulations from HIRHAM5, MAR3.6, RACMO2.3, MERRA-2, and SEB climate/SMB models. Current models cannot reproduce peak discharges or timing of runoff entering moulins but are improved using synthetic unit hydrograph (SUH) theory. Retroactive SUH applications to two older field studies reproduce their findings, signifying that remotely sensed IDC area, shape, and supraglacial river length are useful for predicting delays in peak runoff delivery to moulins. Applying SUH to HIRHAM5, MAR3.6, and RACMO2.3 gridded melt products for 799 surrounding IDCs suggests their terminal moulins receive lower peak discharges, less diurnal variability, and asynchronous runoff timing relative to climate/SMB model output alone. Conversely, large IDCs produce high moulin discharges, even at high elevations where melt rates are low. During this particular field experiment, models overestimated runoff by +21 to +58%, linked to overestimated surface ablation and possible meltwater retention in bare, porous, low-density ice. Direct measurements of ice surface runoff will improve climate/SMB models, and incorporating remotely sensed IDCs will aid coupling of SMB with ice dynamics and subglacial systemspublishersversionPeer reviewe

Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN): Design and statistical analysis plan of the extended follow-up study

Background: MR CLEAN was the first randomized trial to demonstrate the short-term clinical effectiveness of endovascular treatment in patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation. Several other trials confirmed that endovascular treatment improves clinical outcome at three months. However, limited data are available on long-term clinical outcome. We aimed to estimate the effect of endovascular treatment on functional outcome at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed to assess the effect of endovascular treatment on major vascular events and mortality during two years of follow-up. Methods: MR CLEAN is a multicenter clinical trial with randomized treatment allocation, open-label treatment, and blinded endpoint evaluation. Patients included were 18 years or older with acute ischemic stroke caused by a proven anterior proximal artery occlusion who could be treated within six hours after stroke onset. The intervention contrast was endovascular treatment and usual care versus no endovascular treatment and usual care. The current study extended the follow-up duration from three months to two years. The primary outcome is the score on the modified Rankin scale at two years. Secondary outcomes include all-cause mortality and the occurrence of major vascular events within two years of follow-up. Discussion: The results of our study provide information on the long-term clinical effectiveness of endovascular treatment, which may have implications for individual treatment decisions and estimates of cost-effectiveness. Trial registration:NTR1804. Registered on 7 May 2009; ISRCTN10888758. Registered on 24 July 2012 (main MR CLEAN trial); NTR5073. Registered on 26 February 2015 (extended follow-up study)

Prognostication using SpO(2)/FiO(2) in invasively ventilated ICU patients with ARDS due to COVID-19-Insights from the PRoVENT-COVID study

Background: The SpO(2)/FiO(2) is a useful oxygenation parameter with prognostic capacity in patients with ARDS. We investigated the prognostic capacity of SpO(2)/FiO(2) for mortality in patients with ARDS due to COVID-19. Methods: This was a post-hoc analysis of a national multicenter cohort study in invasively ventilated patients with ARDS due to COVID-19. The primary endpoint was 28-day mortality. Results: In 869 invasively ventilated patients, 28-day mortality was 30.1%. The SpO(2)/FiO(2) on day 1 had no prognostic value. The SpO(2)/FiO(2) on day 2 and day 3 had prognostic capacity for death, with the best cut-offs being 179 and 199, respectively. Both SpO(2)/FiO(2) on day 2 (OR, 0.66 [95%-CI 0.46-0.96]) and on day 3 (OR, 0.70 [95%-CI 0.51-0.96]) were associated with 28-day mortality in a model corrected for age, pH, lactate levels and kidney dysfunction (AUROC 0.78 [0.76-0.79]). The measured PaO2/FiO(2) and the PaO2/FiO(2) calculated from SpO(2)/FiO(2) were strongly correlated (Spearman's r = 0.79). Conclusions: In this cohort of patients with ARDS due to COVID-19, the SpO(2)/FiO(2) on day 2 and day 3 are independently associated with and have prognostic capacity for 28-day mortality. The SpO(2)/FiO(2) is a useful metric for risk stratification in invasively ventilated COVID-19 patients. (C) 2021 The Authors. Published by Elsevier Inc

Neuropsychological intervention in kindergarten children with subtyped risks of reading retardation

Kindergarten children at risk of developing language problems were administered the Florida Kindergarten Screening Battery. A principal components analysis revealed a verbal and a visual-spatial component and subsequent discriminant function analyses a high verbal/low visual-spatial group (LAL: Latent L) and a high visual-spatial/low verbal group (LAP: Latent P). LAL- and LAP-children were considered at risk for developing an L- or P-type of dyslexia, respectively. As is common practice with children suffering from manifest L- or Pdyslexia, the LAL- and LAP-kindergartners received right and left hemisphere stimulation, respectively. The outcomes were compared with those of bilateral hemispheric stimulation and no intervention. Reading tests were administered in primary school Grades 1 and 5/6; teachers' evaluation of reading took place in Grade 5/6. Overall, the LAL- and LAP- groups showed significant backwardness in word and text reading, both at early and late primary school. Types of intervention made a difference though: not significantly backward in early word, late word, and late text reading were the LAL-children who had received right hemisphere stimulation. Nonintervened LAP-children did not show significant backwardness in early word reading and late text reading, nor did LAP-children who had received left hemisphere or bilateral stimulation. Early text reading was not affected by any treatment. Teacher's evaluations were in support of these findings. Copyright © 2005 by The International Dyslexia Association®