44 research outputs found

    UNC System Math Pathways’ Digital Course Enhancement Collaboration to Improve Equity, Instruction, and Access During the COVID-19 Pandemic

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    This study examines how faculty members and students evaluated, perceived, and used a digital course content collection developed to support high quality remote instruction during the Covid-19 pandemic. The collections were the result of a multi-institutional, collaborative effort within the University of North Carolina System to support its students and faculty. Using surveys from faculty and demographically identified students enrolled in their classes, the authors evaluate the perceived utility and impact of the open educational resource collections. Faculty members rated the collections highly and typically found utility in at least some of the components of the collections. They found activities, videos and assessments to be the most useful tools. Students generally responded positively to the classes using the collections. While students who identified as minority found the materials useful or beneficial, they did not do so in proportional numbers to non-minority students

    Novel Analog For Muscle Deconditioning

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    Existing models of muscle deconditioning are cumbersome and expensive (ex: bedrest). We propose a new model utilizing a weighted suit to manipulate strength, power or endurance (function) relative to body weight (BW). Methods: 20 subjects performed 7 occupational astronaut tasks while wearing a suit weighted with 0-120% of BW. Models of the full relationship between muscle function/BW and task completion time were developed using fractional polynomial regression and verified by the addition of pre- and post-flight astronaut performance data using the same tasks. Spline regression was used to identify muscle function thresholds below which task performance was impaired. Results: Thresholds of performance decline were identified for each task. Seated egress & walk (most difficult task) showed thresholds of: leg press (LP) isometric peak force/BW of 18 N/kg, LP power/BW of 18 W/kg, LP work/ BW of 79 J/kg, knee extension (KE) isokinetic/BW of 6 Nm/Kg and KE torque/BW of 1.9 Nm/kg. Conclusions: Laboratory manipulation of strength / BW has promise as an appropriate analog for spaceflight-induced loss of muscle function for predicting occupational task performance and establishing operationally relevant exercise targets

    Enacting boundaries or building bridges? Language and engagement in food-energy-water systems science

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    Scientific study of issues at the nexus of food–energy–water systems (FEWS) requires grappling with multifaceted, “wicked” problems. FEWS involve interactions occurring directly and indirectly across complex and overlapping spatial and temporal scales; they are also imbued with diverse and sometimes conflicting meanings for the human and more-than-human beings that live within them. In this paper, we consider the role of language in the dynamics of boundary work, recognizing that the language often used in stakeholder and community engagement intended to address FEWS science and decision-making constructs boundaries and limits diverse and inclusive participation. In contrast, some language systems provide opportunities to build bridges rather than boundaries in engagement. Based on our experiences with engagement in FEWS science and with Indigenous knowledges and languages, we consider examples of the role of language in reflecting worldviews, values, practices, and interactions in FEWS science and engagement. We particularly focus on Indigenous knowledges from Anishinaabe and the language of Anishinaabemowin, contrasting languages of boundaries and bridges through concrete examples. These examples are used to unpack the argument of this work, which is that scientific research aiming to engage FEWS issues in working landscapes requires grappling with embedded, practical understandings. This perspective demonstrates the importance of grappling with the role of language in creating boundaries or bridges, while recognizing that training in engagement may not critically reflect on the role of language in limiting diversity and inclusivity in engagement efforts. Leaving this reflexive consideration of language unexamined may unknowingly perpetuate boundaries rather than building bridges, thus limiting the effectiveness of engagement that is intended to address wicked problems in working landscapes

    Muscle Adaptations Following Short-Duration Bed Rest with Integrated Resistance, Interval, and Aerobic Exercise

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    Unloading of the musculoskeletal system during space flight results in deconditioning that may impair mission-related task performance in astronauts. Exercise countermeasures have been frequently tested during bed rest (BR) and limb suspension; however, high-intensity, short-duration exercise prescriptions have not been fully explored. PURPOSE: To determine if a high intensity resistance, interval, and aerobic exercise program could protect against muscle atrophy and dysfunction when performed during short duration BR. METHODS: Nine subjects (1 female, 8 male) performed a combination of supine exercises during 2 weeks of horizontal BR. Resistance exercise (3 d / wk) consisted of squat, leg press, hamstring curl, and heel raise exercises (3 sets, 12 repetitions). Aerobic (6 d / wk) sessions alternated continuous (75% VO2 peak) and interval exercise (30 s, 2 min, and 4 min) and were completed on a supine cycle ergometer and vertical treadmill, respectively. Muscle volumes of the upper leg were calculated pre, mid, and post-BR using magnetic resonance imaging. Maximal isometric force (MIF), rate of force development (RFD), and peak power of the lower body extensors were measured twice before BR (averaged to represent pre) and once post BR. ANOVA with repeated measures and a priori planned contrasts were used to test for differences. RESULTS: There were no changes to quadriceps, hamstring, and adductor muscle volumes at mid and post BR time points compared to pre BR (Table 1). Peak power increased significantly from 1614 +/- 372 W to 1739 +/- 359 W post BR (+7.7%, p = 0.035). Neither MIF (pre: 1676 +/- 320 N vs. post: 1711 +/- 250 N, +2.1%, p = 0.333) nor RFD (pre: 7534 +/- 1265 N/ms vs. post: 6951 +/- 1241 N/ms, -7.7%, p = 0.136) were significantly impaired post BR

    Personalised progression prediction in patients with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma (PANGEA): a retrospective, multicohort study

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    BACKGROUND: Patients with precursors to multiple myeloma are dichotomised as having monoclonal gammopathy of undetermined significance or smouldering multiple myeloma on the basis of monoclonal protein concentrations or bone marrow plasma cell percentage. Current risk stratifications use laboratory measurements at diagnosis and do not incorporate time-varying biomarkers. Our goal was to develop a monoclonal gammopathy of undetermined significance and smouldering multiple myeloma stratification algorithm that utilised accessible, time-varying biomarkers to model risk of progression to multiple myeloma. METHODS: In this retrospective, multicohort study, we included patients who were 18 years or older with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma. We evaluated several modelling approaches for predicting disease progression to multiple myeloma using a training cohort (with patients at Dana-Farber Cancer Institute, Boston, MA, USA; annotated from Nov, 13, 2019, to April, 13, 2022). We created the PANGEA models, which used data on biomarkers (monoclonal protein concentration, free light chain ratio, age, creatinine concentration, and bone marrow plasma cell percentage) and haemoglobin trajectories from medical records to predict progression from precursor disease to multiple myeloma. The models were validated in two independent validation cohorts from National and Kapodistrian University of Athens (Athens, Greece; from Jan 26, 2020, to Feb 7, 2022; validation cohort 1), University College London (London, UK; from June 9, 2020, to April 10, 2022; validation cohort 1), and Registry of Monoclonal Gammopathies (Czech Republic, Czech Republic; Jan 5, 2004, to March 10, 2022; validation cohort 2). We compared the PANGEA models (with bone marrow [BM] data and without bone marrow [no BM] data) to current criteria (International Myeloma Working Group [IMWG] monoclonal gammopathy of undetermined significance and 20/2/20 smouldering multiple myeloma risk criteria). FINDINGS: We included 6441 patients, 4931 (77%) with monoclonal gammopathy of undetermined significance and 1510 (23%) with smouldering multiple myeloma. 3430 (53%) of 6441 participants were female. The PANGEA model (BM) improved prediction of progression from smouldering multiple myeloma to multiple myeloma compared with the 20/2/20 model, with a C-statistic increase from 0·533 (0·480-0·709) to 0·756 (0·629-0·785) at patient visit 1 to the clinic, 0·613 (0·504-0·704) to 0·720 (0·592-0·775) at visit 2, and 0·637 (0·386-0·841) to 0·756 (0·547-0·830) at visit three in validation cohort 1. The PANGEA model (no BM) improved prediction of smouldering multiple myeloma progression to multiple myeloma compared with the 20/2/20 model with a C-statistic increase from 0·534 (0·501-0·672) to 0·692 (0·614-0·736) at visit 1, 0·573 (0·518-0·647) to 0·693 (0·605-0·734) at visit 2, and 0·560 (0·497-0·645) to 0·692 (0·570-0·708) at visit 3 in validation cohort 1. The PANGEA models improved prediction of monoclonal gammopathy of undetermined significance progression to multiple myeloma compared with the IMWG rolling model at visit 1 in validation cohort 2, with C-statistics increases from 0·640 (0·518-0·718) to 0·729 (0·643-0·941) for the PANGEA model (BM) and 0·670 (0·523-0·729) to 0·879 (0·586-0·938) for the PANGEA model (no BM). INTERPRETATION: Use of the PANGEA models in clinical practice will allow patients with precursor disease to receive more accurate measures of their risk of progression to multiple myeloma, thus prompting for more appropriate treatment strategies. FUNDING: SU2C Dream Team and Cancer Research UK

    Structure of the C-terminal domain of Tup1, a corepressor of transcription in yeast

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    The Tup1–Ssn6 corepressor complex regulates the expression of several sets of genes, including genes that specify mating type in the yeast Saccharomyces cerevisiae. Repression of mating-type genes occurs when Tup1–Ssn6 is brought to the DNA by the Matα2 DNA-binding protein and assembled upstream of a- and haploid-specific genes. We have determined the 2.3 Å X-ray crystal structure of the C-terminal domain of Tup1 (accesion No. 1ERJ), a 43 kDa fragment that contains seven copies of the WD40 sequence motif and binds to the Matα2 protein. Moreover, this portion of the protein can partially substitute for full-length Tup1 in bringing about transcriptional repression. The structure reveals a seven-bladed β propeller with an N-terminal subdomain that is anchored to the side of the propeller and extends the β sheet of one of the blades. Point mutations in Tup1 that specifically affect the Tup1–Matα2 interaction cluster on one surface of the propeller. We identified regions of Tup1 that are conserved among the fungal Tup1 homologs and may be important in protein–protein interactions with additional components of the Tup1-mediated repression pathways

    The Effects of Congenital Deafness on Auditory Nerve Synapses: Type I and Type II Multipolar Cells in the Anteroventral Cochlear Nucleus of Cats

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    Sensory deprivation has been shown to exert detrimental effects on the structure and function of central sensory systems. Congenital deafness represents an extreme form of auditory deprivation, and in the adult white cat, synapses between auditory nerve endings and resident cells of the anteroventral cochlear nucleus exhibited abnormal structure. Endbulbs of Held were reduced in branching and displayed striking hypertrophy of their postsynaptic densities. So-called modified endbulbs showed no change in branching complexity but did exhibit hypertrophy of their postsynaptic densities. These differential pre- and postsynaptic effects prompted the question of how deafness might affect other primary endings and synapses. Thus, we studied type I and type II multipolar cells that receive bouton endings from auditory nerve fibers. Type I multipolar cells project to the contralateral inferior colliculus and have relatively few axosomatic endings; type II multipolar cells project to the contralateral cochlear nucleus and have many axosomatic endings. Compared with normal-hearing cats, bouton endings of congenitally deaf cats were smaller but there was no difference in synaptic vesicle density or size of postsynaptic densities. These data reveal that different classes of primary endings and second-order neurons exhibit different degrees of synaptic anomalies to deafness
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