Work-in-Progress: Rapid Development of Advanced Virtual Labs for In-Person and Online Education

During the closure of K-12 schools and universities thanks to the COVID-19 pandemic, many educators turned to web conferencing tools such as Zoom and WebEx to deliver online lectures. For courses with labs, some teachers provide recorded videos of real labs. Watching recorded lab videos is a passive experience, as the procedures and point of view are fixed, and students do not have any control of the lab and thus miss the opportunity to explore different options, including making mistakes that is important part of the learning process. One approach that holds great potential to enhance laboratory experience for online education is the use of computer-based modeling and simulation tools. Simulation based virtual laboratories emulate lab equipment and configurations in highly realistic 3D environments and can provide very effective learning experiences. While there exist limited interactive lab computer simulations for various subjects, their presentations are still very primitive and often lack realism and complexity. This paper presents methodologies and preliminary findings on rapid development of advanced virtual labs using modeling and simulation for in-person and online education. The importance of modeling and simulation has long been recognized by the scientific community and agencies such as DoD and NSF. However, high-quality simulations are not commonplace, and simulations have not been widely employed in education. Existing simulations for education lack interoperability and compatibility. While there are sporadic uses of computer-based simulations in education that were developed in a piecemeal fashion, there was never systematic development at an industry level for such purposes. Virtual lab development usually require substantial amount of effort and lack of systematic research on rapid virtual lab development hinders their wide use in education. This paper proposes a wholistic and systematic approach for addressing the issues in rapid lab simulation development from several perspectives, including rapid generation of virtual environment, integration of state-of-the-art industry leading software tools, advanced software design techniques that enables large scale software reuse, and innovative user interface design that facilitate the configuration and use of virtual labs by instructors and students. This paper will implement a virtual circuit lab that emulates a circuit lab for the course XXX offered at XXX University and will be used to elucidate the crucial methodologies for rapid virtual lab development. The virtual lab contains highly realistic visual renderings and accurate functional representations of sophisticated equipment, such as digital oscilloscopes, function generator, and digital multimeters, and authentic rendition of the lab space. The virtual lab allows advanced analog and digital circuit simulation by integrating the de-facto industry standard circuit simulation engine SPICE and Xspice, supporting the circuit labs in the course XXX. The Unity game engine is used to develop the front end of the virtual lab. Advanced software development methodologies will be investigated to facilitate software reuse and rapid development, e.g., the same simulation code can be used to support equipment manufactured by different vendors. The paper will also investigate the impact of fidelity of the virtual lab, e.g., equipment and lab room, on student learning outcomes and efficacy

Updated guidance on the management of COVID-19:from an American Thoracic Society/European Respiratory Society coordinated International Task Force (29 July 2020)

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. METHODS: An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. RESULTS: The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. CONCLUSIONS: The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities.status: Published onlin

Comparison of amyloid burden in individuals with Down syndrome versus autosomal dominant Alzheimer's disease: a cross-sectional study

BackgroundImportant insights into the early pathogenesis of Alzheimer's disease can be provided by studies of autosomal dominant Alzheimer's disease and Down syndrome. However, it is unclear whether the timing and spatial distribution of amyloid accumulation differs between people with autosomal dominant Alzheimer's disease and those with Down syndrome. We aimed to directly compare amyloid changes between these two groups of people.MethodsIn this cross-sectional study, we included participants (aged ≥25 years) with Down syndrome and sibling controls who had MRI and amyloid PET scans in the first data release (January, 2020) of the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study. We also included carriers of autosomal dominant Alzheimer's disease genetic mutations and non-carrier familial controls who were within a similar age range to ABC-DS participants (25-73 years) and had MRI and amyloid PET scans at the time of a data freeze (December, 2020) of the Dominantly Inherited Alzheimer Network (DIAN) study. Controls from the two studies were combined into a single group. All DIAN study participants had genetic testing to determine PSEN1, PSEN2, or APP mutation status. APOE genotype was determined from blood samples. CSF samples were collected in a subset of ABC-DS and DIAN participants and the ratio of amyloid β42 (Aβ42) to Aβ40 (Aβ42/40) was measured to evaluate its Spearman's correlation with amyloid PET. Global PET amyloid burden was compared with regards to cognitive status, APOE ɛ4 status, sex, age, and estimated years to symptom onset. We further analysed amyloid PET deposition by autosomal dominant mutation type. We also assessed regional patterns of amyloid accumulation by estimated number of years to symptom onset. Within a subset of participants the relationship between amyloid PET and CSF Aβ42/40 was evaluated.Findings192 individuals with Down syndrome and 33 sibling controls from the ABC-DS study and 265 carriers of autosomal dominant Alzheimer's disease mutations and 169 non-carrier familial controls from the DIAN study were included in our analyses. PET amyloid centiloid and CSF Aβ42/40 were negatively correlated in carriers of autosomal dominant Alzheimer's disease mutations (n=216; r=-0·565; p<0·0001) and in people with Down syndrome (n=32; r=-0·801; p<0·0001). There was no difference in global PET amyloid burden between asymptomatic people with Down syndrome (mean 18·80 centiloids [SD 28·33]) versus asymptomatic mutation carriers (24·61 centiloids [30·27]; p=0·11) and between symptomatic people with Down syndrome (77·25 centiloids [41·76]) versus symptomatic mutation carriers (69·15 centiloids [51·10]; p=0·34). APOE ɛ4 status and sex had no effect on global amyloid PET deposition. Amyloid deposition was elevated significantly earlier in mutation carriers than in participants with Down syndrome (estimated years to symptom onset -23·0 vs -17·5; p=0·0002). PSEN1 mutations primarily drove this difference. Early amyloid accumulation occurred in striatal and cortical regions for both mutation carriers (n=265) and people with Down syndrome (n=128). Although mutation carriers had widespread amyloid accumulation in all cortical regions, the medial occipital regions were spared in people with Down syndrome.InterpretationDespite minor differences, amyloid PET changes were similar between people with autosomal dominant Alzheimer's disease versus Down syndrome and strongly supported early amyloid dysregulation in individuals with Down syndrome. Individuals with Down syndrome aged at least 35 years might benefit from early intervention and warrant future inclusion in clinical trials, particularly given the relatively high incidence of Down syndrome.FundingThe National Institute on Aging, Riney and Brennan Funds, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the German Center for Neurodegenerative Diseases, and the Japan Agency for Medical Research and Development

Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial

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\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu