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Background & Aim: To assess consonant proficiency and velopharyngeal function in 10-year-old children born with unilateral cleft lip and palate (UCLP) within the Scandcleft project.Methods & Procedures: Three parallel group, randomized, clinical trials were undertaken as an international multicentre study by nine cleft teams in five countries. Three different surgical protocols for primary palate repair (Arm B–Lip and soft palate closure at 3–4 months, hard palate closure at 36 months, Arm C–Lip closure at 3–4 months, hard and soft palate closure at 12 months, and Arm D–Lip closure at 3–4 months combined with a single-layer closure of the hard palate using a vomer flap, soft palate closure at 12 months) were tested against a common procedure (Arm A–Lip and soft palate closure at 3–4 months followed by hard palate closure at 12 months) in the total cohort of 431 children born with a non-syndromic UCLP. Speech audio and video recordings of 399 children were available and perceptually analysed. Percentage of consonants correct (PCC) from a naming test, an overall rating of velopharyngeal competence (VPC) (VPC-Rate), and a composite measure (VPC-Sum) were reported.Outcomes & Results: The mean levels of consonant proficiency (PCC score) in the trial arms were 86–92% and between 58% and 83% of the children had VPC (VPC-Sum). Only 50–73% of the participants had a consonant proficiency level with their peers. Girls performed better throughout. Long delay of the hard palate repair (Arm B) indicated lower PCC and simultaneous hard and soft palate closure higher (Arm C). However, the proportion of participants with primary VPC (not including velopharyngeal surgeries) was highest in Arm B (68%) and lowest in Arm C (47%).Conclusions & Implications: The speech outcome in terms of PCC and VPC was low across the trials. The different protocols had their pros and cons and there is no obvious evidence to recommend any of the protocols as superior. Aspects other than primary surgical method, such as time after velopharyngeal surgery, surgical experience, hearing level, language difficulties and speech therapy, need to be thoroughly reviewed for a better understanding of what has affected speech outcome at 10 years.

Genetic polymorphisms at the IFNL4 loci are known to influence the clinical outcome of several different infectious diseases. Best described is the association between the IFNL4 genotype and hepatitis C virus clearance. However, an influence of the IFNL4 genotype on the adaptive immune system was suggested by several studies but never investigated in humans. In this cross-sectional study, we have genotyped 201 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive participants for 3 IFNL4 polymorphisms (rs368234815, rs12979860, and rs117648444) and stratified them according to the IFNλ4 activity. Based on this stratification, we investigated the association between the IFNL4 genotype and the antibody as well as the CD8+ T cell response in the acute phase of the SARS-CoV-2 infection. We observed no differences in the genotype distribution compared with a Danish reference cohort or the 1,000 Genome Project, and we were not able to link the IFNL4 genotype to changes in either the antibody or CD8+ T cell responses of these patients.

Background: The SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search and evaluation of new treatment modalities and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed.Methods: We included 203 recovered SARS-CoV-2 infected patients in Denmark between April 3rd and July 9th 2020, at least 14 days after COVID-19 symptom recovery. The participants had experienced a range of disease severities from asymptomatic to severe. We collected plasma, serum and PBMC's for analysis of SARS-CoV-2 specific antibody response by Meso Scale analysis including other coronavirus strains, ACE2 competition, IgA ELISA, pseudovirus neutralization capacity, and dextramer flow cytometry analysis of CD8+ T cells. The immunological outcomes were compared amongst severity groups within the cohort, and 10 pre-pandemic SARS-CoV-2 negative controls.Findings: We report broad serological profiles within the cohort, detecting antibody binding to other human coronaviruses. 202(>99%) participants had SARS-CoV-2 specific antibodies, with SARS-CoV-2 neutralization and spike-ACE2 receptor interaction blocking observed in 193(95%) individuals. A significant positive correlation (r=0.7804) between spike-ACE2 blocking antibody titers and neutralization potency was observed. Further, SARS-CoV-2 specific CD8+ T-cell responses were clear and quantifiable in 95 of 106(90%) HLA-A2+ individuals.Interpretation: The viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8+ T-cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of their disease severity.Funding: This study was supported by the Danish Ministry for Research and Education (grant# 0238-00001B) and The Danish Innovation Fund (grant# 0208-00018B)

The SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search for treatments and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed. We investigated the breadth and potency of antibody-, and T-cell immune responses, in 203 recovered SARS-CoV-2 infected patients who presented with asymptomatic to severe infections. We report very broad serological profiles with cross-reactivity to other human coronaviruses. Further, >99% had SARS-CoV-2 epitope specific antibodies, with SARS-CoV-2 neutralization and spike-ACE2 receptor interaction blocking observed in 95% of individuals. A significant positive correlation between spike-ACE2 blocking antibody titers and neutralization potency was observed. SARS-CoV-2 specific CD8+T-cell responses were clear and quantifiable in 90% of HLA-A2+individuals. The viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8+T cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of disease severity.Author summarySARS-CoV-2 can cause severe and deadly infections. However, the immunological understanding of this viral infection is limited. Currently, several vaccines are being developed to help limit transmission and prevent the current pandemic. However, basic understanding of the adaptive immune response developed during SARS-CoV-2 infections is needed to inform further vaccine development and to understand the protective properties of the developed immune response. We investigated, the adaptive immune response developed during SARS-CoV-2 infections in recovered patients experiencing a full spectrum of disease severity, from asymptomatic infections to severe cases requiring hospitalization. We used a novel multiplex serological platform, cell-based neutralization assays and dextramer flow cytometry assays to characterize a broad and robust humoral and cellular immune response towards SARS-CoV-2. We found that the vast majority of recovered individuals have clear detectable and functional SARS-CoV-2 spike specific adaptive immune responses, despite diverse disease severities. The detection of both a humoral and cellular functional spike specific immune response in the vast majority of the individuals, irrespective of asymptomatic manifestations, supports vaccine designs currently underway, and encourages further exploration of whether primary infections provide protection to reinfection.

Humanized mice provide a sophisticated platform to study human immunodeficiency virus (HIV) virology and to test antiviral drugs. This protocol describes the establishment of a human immune system in adult NOG mice. Here, we explain all the practical steps from isolation of umbilical cord blood derived human CD34+ cells and their subsequent intravenous transplantation into the mice, to the manipulation of the model through HIV infection, combination antiretroviral therapy (cART), and blood sampling. Approximately 75,000 hCD34+ cells are injected intravenously into the mice and the level of human chimerism, also known as humanization, in the peripheral blood is estimated longitudinally for months by flow cytometry. A total of 75,000 hCD34+ cells yields 20%–50% human CD45+ cells in the peripheral blood. The mice are susceptible to intravaginal infection with HIV and blood can be sampled once weekly for analysis, and twice monthly for extended periods. This protocol describes an assay for quantification of plasma viral load using droplet digital PCR (ddPCR). We show how the mice can be effectively treated with a standard-of-care cART regimen in the diet. The delivery of cART in the form of regular mouse chow is a significant refinement of the experimental model. This model can be used for preclinical analysis of both systemic and topical pre-exposure prophylaxis compounds as well as for testing of novel treatments and HIV cure strategies.

Thin films of fullerenes (C60) were deposited onto silicon using matrix-assisted pulsed laser evaporation (MAPLE). The deposition was carried out from a frozen homogeneous dilute solution of C60 in anisole (0.67 wt%), and over a broad range of laser fluences, from 0.15 J/cm2 up to 3.9 J/cm2. MAPLE has been applied for deposition of fullerenes for the first time and we have studied the growth of thin films of solid C60. The fragmentation of C60 fullerene molecules induced by ns ablation in vacuum of a frozen anisole target with C60 was investigated by matrix-assisted laser desorption/ionization (MALDI). Our findings show that intact fullerene films can be produced with laser fluences ranging from 0.15 J/cm2 up to 1.5 J/cm2.

For the realization of fusion as an energy source, the development of suitable materials is one of the most critical issues. The required material properties are in many aspects unique compared to the existing solutions, particularly the need for necessary resistance to irradiation with neutrons having energies up to 14 MeV. In addition to withstanding the effects of neutrons, the mechanical stability of structural materials has to be maintained up to high temperatures. Plasma-exposed materials must be compatible with the fusion plasma, both with regard to the generation of impurities injected into the plasma and resistance to erosion and hydrogen isotope retention. The development of materials fulfilling these and other criteria is a large-scale and long-term activity which involves basic materials science, materials development, characterization under both loading conditions and off-line, as well as testing under neutron flux-induced conditions. For the realization of a DEMO power plant, the materials solutions must be available in time. The European initiative FEMaS-CA-Fusion Energy Materials Science - Coordination Action - aims at accelerating materials development by integrating advanced materials characterization techniques, among them the efficient use of neutron and synchrotron-based techniques, into the fusion materials community. Further, high-end transmission electron microscopy and mechanical characterization (also on a microscopic level in order to facilitate tests of small material volumes, such as from neutron irradiation campaigns) are to be more extensively applied in fusion materials research. Finally, irradiation facilities for neutron damage benchmarking are contributing to the understanding of radiation effects. This overview demonstrates by means of a few examples the recent advancements in fusion materials research, e. g. by applying synchrotron X-ray and neutron tomography to novel materials and components. Deeper understanding of radiation effects is achieved by in situ TEM of materials under irradiation. Modeling of irradiation effects is closely linked to activities at irradiation facilities. Finally, new developments in mechanical testing on micro-and nano-scales are addressed. (C) 2013 Elsevier B.V. All rights reserved.

A series of novel macrocyclic multidentate crown compounds have been prepared from a series of dioxodioic acids. The dioxodioic acids were prepared by treating various oligoethylene glycols or amines with maleic, succinic, citraconic, and glutaric anhydrides. The crown compounds were then synthesized from the dioxodioic acid chlorides obtained from the diacids and various oligoethylene glycols or ethylene diamine. The following macrocyclic compounds have been prepared: 1,4,9,12-tetraoxacyclohexadecane-5,8,13,16-tetrone (1); 1,4,7,10,15,18-hexaoxacyclodocosane-11,14,19,22-tetrone (2); 1,4-dioxa-9,12-diazacyclohexadecane-5,8,13,16-tetrone (3); 1,4,7-trioxa-12,15-diazacyclonoadecane-8,11,16,19-tetrone (4); 1,4,7,10-tetraoxa-15,18-diazacyclodocosane-11,14,19,22-tetrone (5); 4-benzyl-1,7,12,15-tetraoxa-4-azacyclonona-decane-8,11,16,19-tetrone (6); 1,4,7,12,15,18-hexaoxacyclodocosa-9,20-diene-8,11,19,22-tetrone(7); and 9,21-dimethyl-1,4,7,12,15,18-hexaoxacyclodocosa-9,20-diene-8,11,19,22-tetrone (8) (Figure 1).

A series of macrocyclic ether–esters, thioether–esters, and ether–thiolesters [(1)–(10)] have been prepared by treating various oligo-ethylene glycols and sulphur-containing oligo-ethylene glycols with malonyl, succinyl, and glutaryl chlorides.

A new series of macrocyclic polyether-diesler compounds (3-12) have been prepared by treating various oligoethylene glyeols or mercaplans with oxalyl chloride. The compounds prepared were: 1,4,7,10,13-pentaoxacyclopentadecane-2,3-dione (3), 1,4,7,1 3-tetraoxa-10-thiacyclopenta-decane-2,3-dione (4), 1,4,10-lrioxa-7,13-dithiacyclopenladecane-2,3-dione (5), 1,4,7,10,13,16-hexaoxacyclooctadecane-2,3-dione (6), 1,4,7,10,13, 16-hexaoxacyclooctadecane-2,3,11,12-tetra-one (7), 1,4,10,13-tetraoxa-7,16-dithiacyclooctadecane-2,3,11,12-tetraone (8), 7,16-dioxa-1,4, 10,13-letralhiacyclooctadecane-2,3,11,12-tctraone (9), 1,4,7,10,13,16-hexathiacyclooctadecane-2,3,11,12-tetraone (10), 1,4,7,10,13,16,19-heptaoxacyclohencicosane-2,3-dione (11), and 1,4,7, 10,13,16,19,22-octaoxacyclolelracosane-2,3,14,15-letraone (12).

(1931). Watertests in otology. Experiments with water-chargeing. (Reports from the ear department of the Copenhagen Commune Hospital. Leader. Dr. S. H. Mygind) Acta Oto-Laryngologica: Vol. 16, No. 2-3, pp. 415-429.

Ten subjects volunteered to inhale a test gas containing 0, 10, 20 and 30% nitrous oxide. After equilibration at each nitrous oxide concentration, the reaction time was measured using both the single-hand and the double-hand methods, and then the critical flicker fusion frequency was measured. Using the flicker funsion frequency test, significant changes from the normal range were found at 20 and 30% nitrous oxide in the test gas, whereas no significant changes were found with the fusion flicker frequency test. No significant prolongation was found with either double-hand or single-hand reaction time measurements until 30% nitrous oxide in the test gas was reached. It is concluded that critical flicker fusion frequency measurement is a simpler, more time-saving and more sensitive method for the estimation of the changes which nitrous oxide produces in healthy subjects than reaction time measurement, and that critical flicker fusion frequency measurement will presumably be a useful supplement to clinical examination as an objective method for the estimation of postanaesthetic recovery in patients.

A series of macrocyclic ether-esters has been prepared by treating various glycols with adipoyl chloride and various substituted malonyl, succinyl and glutaryl chlorides. The prepared compounds include: 15-ethyl- and 15-phenyl-1,4,7,10,13-pentaoxacyclohexadecane-14,16-dione ( 5 and 6 ); 15-methyl-, 15-phenyl-, cis -cyclohexo-[o]-and benzo-[o]-1,4,7,10,13-pentaoxacycloheptadecane-14,17-dione ( 7–10 ); trans,trans -1,4,7,10,13,18,21,24,27,30-de-caoxacyclotetratriacontane-15, 32-diene-14,17,31,34-tetraone ( 11 ); 1,4,7,10,13-pentaoxacyclooctadecane-14,18-dione ( 12 ); 15,15,16,16,17,17-hexafluoro- and 16-methyl-1,4,7,10,13-pentaoxacyclooctadecane-14,18-dione ( 13 and 14 ); 1,4,7,10-tetraoxacyclohexadecane-11,16-dione ( 15 ); and 1,4,7,10,13-pentaoxacyclononadecane-14,19-dione ( 16 ).

Three new crown ether-esters have been prepared, 2,4-diketo(13-crown-4)(I), 2,4-diketo(16-crown-5)(II), and 2,4-diketo(19-crown-6)(III); (II) and (III) complex with alkaline-earth-metal ions.