A Framework for Evaluating Learning Progressions on Features Related to Their Intended Uses

In recent years, learning progressions (LPs) have captured the interest of educators and policy makers. There have been numerous efforts to develop LPs aligned to college and career readiness standards, to unpack these standards, and to provide more clarity on the pathways students follow to reach them. There is great variation, however, in the structure, content, and features of LPs, and these have implications for the LP’s most appropriate use. The purpose of this research was to devise a framework to understand and evaluate key features of an LP, including its structure, content, usability, and validity evidence. We maintain that educators and other stakeholders should understand these key features so they can evaluate whether an LP is appropriate for an intended use

Prediction of trapezius muscle activity and shoulder, head, neck, and torso postures during computer use: results of a field study

Background: Due to difficulties in performing direct measurements as an exposure assessment technique, evidence supporting an association between physical exposures such as neck and shoulder muscle activities and postures and musculoskeletal disorders during computer use is limited. Alternative exposure assessment techniques are needed. Methods: We predicted the median and range of amplitude (90th-10th percentiles) of trapezius muscle activity and the median and range of motion (90th-10th percentiles) of shoulder, head, neck, and torso postures based on two sets of parameters: the distribution of keyboard/mouse/idle activities only (“task-based” predictions), and a comprehensive set of task, questionnaire, workstation, and anthropometric parameters (“expanded model” predictions). We compared the task-based and expanded model predictions based on R2 values, root mean squared (RMS) errors, and relative RMS errors calculated compared to direct measurements. Results: The expanded model predictions of the median and range of amplitude of trapezius muscle activity had consistently better R2 values (range 0.40-0.55 compared to 0.00-0.06), RMS errors (range 2-3%MVC compared to 3-4%MVC), and relative RMS errors (range 10-14%MVC compared to 16-19%MVC) than the task-based predictions. The expanded model predictions of the median and range of amplitude of postures also had consistently better R2 values (range 0.22-0.58 compared to 0.00-0.35), RMS errors (range 2–14 degrees compared to 3–22 degrees), and relative RMS errors (range 9–21 degrees compared to 13–42 degrees) than the task-based predictions. Conclusions: The variation in physical exposures across users performing the same task is large, especially in comparison to the variation across tasks. Thus, expanded model predictions of physical exposures during computer use should be used rather than task-based predictions to improve exposure assessment for future epidemiological studies. Clinically, this finding also indicates that computer users will have differences in their physical exposures even when performing the same tasks

A unifying framework for understanding ecological and evolutionary population connectivity

Although the concept of connectivity is ubiquitous in ecology and evolution, its definition is often inconsistent, particularly in interdisciplinary research. In an ecological context, population connectivity refers to the movement of individuals or species across a landscape. It is measured by locating organisms and tracking their occurrence across space and time. In an evolutionary context, connectivity is typically used to describe levels of current and past gene flow, calculated from the degree of genetic similarity between populations. Both connectivity definitions are useful in their specific contexts, but rarely are these two perspectives combined. Different definitions of connectivity could result in misunderstandings across subdisciplines. Here, we unite ecological and evolutionary perspectives into a single unifying framework by advocating for connectivity to be conceptualized as a generational continuum. Within this framework, connectivity can be subdivided into three timescales: (1) within a generation (e.g., movement), (2) across one parent-offspring generation (e.g., dispersal), and (3) across two or more generations (e.g., gene flow), with each timescale determining the relevant context and dictating whether the connectivity has ecological or evolutionary consequences. Applying our framework to real-world connectivity questions can help to identify sampling limitations associated with a particular methodology, further develop research questions and hypotheses, and investigate eco-evolutionary feedback interactions that span the connectivity continuum. We hope this framework will serve as a foundation for conducting and communicating research across subdisciplines, resulting in a more holistic understanding of connectivity in natural systems

Experimental Infection of Cynomolgus Macaques (Macaca fascicularis) with Aerosolized Monkeypox Virus

Monkeypox virus (MPXV) infection in humans results in clinical symptoms very similar to ordinary smallpox. Aerosol is a route of secondary transmission for monkeypox, and a primary route of smallpox transmission in humans. Therefore, an animal model for aerosol exposure to MPXV is needed to test medical countermeasures. To characterize the pathogenesis in cynomolgus macaques (Macaca fascicularis), groups of macaques were exposed to four different doses of aerosolized MPXV. Blood was collected the day before, and every other day after exposure and assessed for complete blood count (CBC), clinical chemistry analysis, and quantitative PCR. Macaques showed mild anorexia, depression, and fever on day 6 post-exposure. Lymphadenopathy, which differentiates monkeypox from smallpox, was observed in exposed macaques around day 6 post-exposure. CBC and clinical chemistries showed abnormalities similar to human monkeypox cases. Whole blood and throat swab viral loads peaked around day 10, and in survivors, gradually decreased until day 28 post-exposure. Survival was not dose dependent. As such, doses of 4×104 PFU, 1×105 PFU, or 1×106 PFU resulted in lethality for 70% of the animals, whereas a dose of 4×105 PFU resulted in 85% lethality. Overall, cynomolgus macaques exposed to aerosolized MPXV develop a clinical disease that resembles that of human monkeypox. These findings provide a strong foundation for the use of aerosolized MPXV exposure of cynomolgus macaques as an animal model to test medical countermeasures against orthopoxviruses

Flipped Instruction for Information Literacy: Five Instructional Cases of Academic Librarians

University of California, Berkeley librarians have incorporated the flipped instruction model into information literacy training by focusing on two primary elements: assigning pre-class assignments and increasing active learning techniques. We explore these two elements across five diverse instructional cases, which include one-shot and semester-long classes that were conducted through online or in-person delivery for both graduate and undergraduate students across a range of subject areas (sciences, social sciences, and humanities). We examine the enabling factors and the perceived outcomes of this instructional paradigm. Because students came to class with enhanced library understanding and experience from the pre-class assignment, they were better prepared to engage with the material and articulate additional learning needs. We note students' increased engagement during class and more time available for higher-order learning exercises and discussions. As a result, flipped instruction appears to enable more learning opportunities without increasing classroom time. The challenges of this model are the requisite commitment of time and effort, the need to foster class participation, and the facilitation of active communication within the class. We propose a framework of catalysts, building blocks, and instructional outcomes to help library instructors incorporate flipped instruction elements into their instructional design

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead