Concert recording 2014-03-11a

[Track 01]. No. 4 Susse stille from Neun deutsche arien / George Frideric Handel -- [Track 02]. Si mes vers avaient des ailes / Reynaldo Hahn -- La diva de l\u27empire / Erik Satie -- [Track 03]. Er der Herrlichste von allen ; Du Ring an meinem Finger from Frauenliebe und leben / Robert Schumann -- [Track 04]. My name is Barbara ; A big Indian and a little Indian ; I\u27m a person too from I hate music!: A cycle of five kid songs / Leonard Bernstein -- [Track 05]. Deh vieni, non tardar o goija bella from Le Nozze di Figaro / Wolfgang Amadeus Mozart -- Je veux vivre from Romeo et Juliette / Charles Gounod

Vermonters’ Opinions on Low-Dose CT Lung Cancer Screening

Introduction: Lung cancer is the number one cause of cancer death among men and women in Vermont and the United States. Smoking increases the risk of lung cancer—nearly 90% of lung cancer is due to smoking. Frequently, lung cancers do not present clinically until they are advanced stage and therefore prognosis is poor. However, if detected early lung cancers are more operable and patients have better outcomes. In December 2013 the US Preventive Services Task Force released new guidelines for lung cancer screening among current and former smokers ages 55 to 80. It is recommended that current and former (within 15 years of quitting) smokers of 30 pack years receive an annual low-dose CT scan. The objective of this project was to assess the level of knowledge and attitudes towards lung cancer screening with low-dose CT scanning among Vermonters in the Burlington area.https://scholarworks.uvm.edu/comphp_gallery/1205/thumbnail.jp

A new framework for global data regulation

Under the current regulatory framework for data protections, the protection of human rights writ large and the corresponding outcomes are regulated largely independently from the data and tools that both threaten those rights and are needed to protect them. This separation between tools and the outcomes they generate risks overregulation of the data and tools themselves when not linked to sensitive use cases. In parallel, separation risks under-regulation if the data can be collected and processed under a less-restrictive framework, but used to drive an outcome that requires additional sensitivity and restrictions. A new approach is needed to support differential protections based on the genuinely high-risk use cases within each sector. Here, we propose a regulatory framework designed to apply not to specific data or tools themselves, but to the outcomes and rights that are linked to the use of these data and tools in context. This framework is designed to recognize, address, and protect a broad range of human rights, including privacy, and suggests a more flexible approach to policy making that is aligned with current engineering tools and practices. We test this framework in the context of open banking and describe how current privacy-enhancing technologies and other engineering strategies can be applied in this context and that of contract tracing applications. This approach for data protection regulations more effectively builds on existing engineering tools and protects the wide range of human rights defined by legislation and constitutions around the globe.Comment: 15 pages, 2 figure

Concert recording 2013-12-05a

[Track 01]. Introduction -- [Track 02]. Papageno\u27s aria, Die Zauberflote / Wolfgang Amadeus Mozart -- [Track 03]. Canzonetta sull\u27aria, Le nozze di Figaro / Wolfgang Amadeus Mozart -- [Track 04]. Tutto e diposto...Aprite un po\u27 quegl\u27occhi, Le nozze di Figaro / Wolfgang Amadeus Mozart -- [Track 05]. Oh goodness me, what misery, Die Fledermaus / Johann Strauss -- [Track 06]. Parle-moi de ma mere, Carmen / Georges Bizet -- [Track 07]. Nous avons en tete une affaire, Carmen / Georges Bizet -- [Track 08]. Melons, coupons, Carmen / Georges Bizet -- [Track 09]. You are not rich, La Perichole / Jacques Offenbach -- [Track 10]. Alla bella despinetta, Cosi fan tutte / Wolfgang Amadeus Mozart -- [Track 11]. When I lay me down to sleep, Hansel and Gretel / Engelbert Humperdinck

Concert recording 2013-11-15

[Track 01]. Amarilli, mia bella / Guilio Caccini ; [Track 02]. Dein blaues auge / Johannes Brahms -- [Track 03]. Come raggio di sol / Antonio Caldara -- [Track 04]. Come ready and see me / Richard Hundley -- [Track 05]. La promessa / Giacchino Rossini -- [Track 06]. Se tu m\u27ami / Giovanni Pergolesi -- [Track 07]. Sonntag / Johannes Brahms -- [Track 08]. Le colibri / Ernest Chausson -- [Track 09]. Paulus. Jerusalem! / Felix Mendelssohn -- [Track 10]. Gia il sole dal Gange / Alessandro Scarlatti -- [Track 11]. Go, lovely Rose / Roger Quilter -- [Track 12]. Si mes vers avaient des ailes / Raynaldo Hahn -- [Track 13]. I\u27m a person too / Leonard Bernstein -- [Track 14]. Les chemins de l\u27amour / Francis Poulenc -- [Track 15]. La Boheme. Donde lieta usci al tuo... / Giacomo Puccini -- [Track 16]. Plum pudding / Leonard Bernstein -- [Track 17]. Queues de boeuf / Leonard Bernstein -- [Track 18]. Tavouk gueunksis / Leonard Bernstein -- [Track 19]. Civet a toute vitesse / Leonard Bernstein -- [Track 20]. When I have sung my songs to you / Ernest Charles -- [Track 21]. Linda di chamournix. Ah! Tardai troppo...o luce di quest\u27anima / Gaetano Donizetti

Depletion of key protein components of the RISC pathway impairs pre-ribosomal RNA processing

Little is known about whether components of the RNA-induced silencing complex (RISC) mediate the biogenesis of RNAs other than miRNA. Here, we show that depletion of key proteins of the RISC pathway by antisense oligonucleotides significantly impairs pre-rRNA processing in human cells. In cells depleted of Drosha or Dicer, different precursors to 5.8S rRNA strongly accumulated, without affecting normal endonucleolytic cleavages. Moderate yet distinct processing defects were also observed in Ago2-depleted cells. Physical links between pre-rRNA and these proteins were identified by co-immunoprecipitation analyses. Interestingly, simultaneous depletion of Dicer and Drosha led to a different processing defect, causing slower production of 28S rRNA and its precursor. Both Dicer and Ago2 were detected in the nuclear fraction, and reduction of Dicer altered the structure of the nucleolus, where pre-rRNA processing occurs. Together, these results suggest that Drosha and Dicer are implicated in rRNA biogenesis

Insulin Degrading Enzyme Induces a Conformational Change in Varicella-Zoster Virus gE, and Enhances Virus Infectivity and Stability

Varicella-zoster virus (VZV) glycoprotein E (gE) is essential for virus infectivity and binds to a cellular receptor, insulin-degrading enzyme (IDE), through its unique amino terminal extracellular domain. Previous work has shown IDE plays an important role in VZV infection and virus cell-to-cell spread, which is the sole route for VZV spread in vitro. Here we report that a recombinant soluble IDE (rIDE) enhances VZV infectivity at an early step of infection associated with an increase in virus internalization, and increases cell-to-cell spread. VZV mutants lacking the IDE binding domain of gE were impaired for syncytia formation and membrane fusion. Pre-treatment of cell-free VZV with rIDE markedly enhanced the stability of the virus over a range of conditions. rIDE interacted with gE to elicit a conformational change in gE and rendered it more susceptible to proteolysis. Co-incubation of rIDE with gE modified the size of gE. We propose that the conformational change in gE elicited by IDE enhances infectivity and stability of the virus and leads to increased fusogenicity during VZV infection. The ability of rIDE to enhance infectivity of cell-free VZV over a wide range of incubation times and temperatures suggests that rIDE may be useful for increasing the stability of varicella or zoster vaccines

Safety, efficacy, and immunogenicity of the NVX-CoV2373 vaccine.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in significant morbidity and mortality worldwide. As SARS-CoV-2 moves into endemic status, vaccination remains a key element in protecting the health of individuals, societies, and economies worldwide. AREAS COVERED: NVX-CoV2373 (Novavax, Gaithersburg, MD) is a recombinant protein vaccine composed of SARS-CoV-2 spike trimer nanoparticles formulated with saponin-based Matrix-M™ adjuvant (Novavax, Gaithersburg, MD). NVX-CoV2373 is authorized for emergency use in adults and adolescents aged ≥12 years in the United States and numerous other countries. EXPERT OPINION: In clinical trials, NVX-CoV2373 showed tolerable reactogenicity and favorable safety profiles characterized by mostly mild-to-moderate adverse events of short duration and by low rates of severe and serious adverse events comparable to those seen with placebo. The two-dose primary vaccination series resulted in robust increases in anti-spike protein immunoglobulin G, neutralizing antibody titers, and cellular immune responses. NVX-CoV2373 vaccination was associated with complete protection against severe disease and a high (90%) rate of protection against symptomatic disease in adults, including symptomatic disease caused by SARS-CoV-2 variants. Additionally, the NVX-CoV2373 adjuvanted recombinant protein platform offers a means to address issues of COVID-19 vaccination hesitancy and global vaccine equity

Characterizing Long COVID: Deep Phenotype of a Complex Condition.

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or long COVID ), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. FINDINGS: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411

Extended optical treatment versus early patching with an intensive patching regimen in children with amblyopia in Europe (EuPatch): a multicentre, randomised controlled trial

Background Amblyopia, the most common visual impairment of childhood, is a public health concern. An extended period of optical treatment before patching is recommended by the clinical guidelines of several countries. The aim of this study was to compare an intensive patching regimen, with and without extended optical treatment (EOT), in a randomised controlled trial. Methods EuPatch was a randomised controlled trial conducted in 30 hospitals in the UK, Greece, Austria, Germany, and Switzerland. Children aged 3–8 years with newly detected, untreated amblyopia (defined as an interocular difference ≥0·30 logarithm of the minimum angle of resolution [logMAR] best corrected visual acuity [BCVA]) due to anisometropia, strabismus, or both were eligible. Participants were randomly assigned (1:1) via a computer-generated sequence to either the EOT group (18 weeks of glasses use before patching) or to the early patching group (3 weeks of glasses use before patching), stratified for type and severity of amblyopia. All participants were initially prescribed an intensive patching regimen (10 h/day, 6 days per week), supplemented with motivational materials. The patching period was up to 24 weeks. Participants, parents or guardians, assessors, and the trial statistician were not masked to treatment allocation. The primary outcome was successful treatment (ie, ≤0·20 logMAR interocular difference in BCVA) after 12 weeks of patching. Two primary analyses were conducted: the main analysis included all participants, including those who dropped out, but excluded those who did not provide outcome data at week 12 and remained on the study; the other analysis imputed this missing data. All eligible and randomly assigned participants were assessed for adverse events. This study is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN51712593) and is no longer recruiting. Findings Between June 20, 2013, and March 12, 2020, after exclusion of eight participants found ineligible after detailed screening, we randomly assigned 334 participants (170 to the EOT group and 164 to the early patching group), including 188 (56%) boys, 146 (44%) girls, and two (1%) participants whose sex was not recorded. 317 participants (158 in the EOT group and 159 in the early patching group) were analysed for the primary outcome without imputation of missing data (median follow-up time 42 weeks [IQR 42] in the EOT group vs 27 weeks [27] in the early patching group). 24 (14%) of 170 participants in the EOT group and ten (6%) of 164 in the early patching group were excluded or dropped out of the study, mostly due to loss to follow-up and withdrawal of consent; ten (6%) in the EOT group and three (2%) in the early patching group missed the 12 week visit but remained on the study. A higher proportion of participants in the early patching group had successful treatment (107 [67%] of 159) than those in the EOT group (86 [54%] of 158; 13% difference; p=0·019) after 12 weeks of patching. No serious adverse events related to the interventions occurred. Interpretation The results from this trial indicate that early patching is more effective than EOT for the treatment of most children with amblyopia. Our findings also provide data for the personalisation of amblyopia treatments. Funding Action Medical Research, NIHR Clinical Research Network, and Ulverscroft Foundation