746 research outputs found
A narrative review of adaptive testing and its application to medical education.
Adaptive testing has a long but largely unrecognized history. The advent of computer-based testing has created new opportunities to incorporate adaptive testing into conventional programmes of study. Relatively recently software has been developed that can automate the delivery of summative assessments that adapt by difficulty or content. Both types of adaptive testing require a large item bank that has been suitably quality assured. Adaptive testing by difficulty enables more reliable evaluation of individual candidate performance, although at the expense of transparency in decision making, and requiring unidirectional navigation. Adaptive testing by content enables reduction in compensation and targeted individual support to enable assurance of performance in all the required outcomes, although at the expense of discovery learning. With both types of adaptive testing, candidates are presented a different set of items to each other, and there is the potential for that to be perceived as unfair. However, when candidates of different abilities receive the same items, they may receive too many they can answer with ease, or too many that are too difficult to answer. Both situations may be considered unfair as neither provides the opportunity to demonstrate what they know. Adapting by difficulty addresses this. Similarly, when everyone is presented with the same items, but answer different items incorrectly, not providing individualized support and opportunity to demonstrate performance in all the required outcomes by revisiting content previously answered incorrectly could also be considered unfair; a point addressed when adapting by content. We review the educational rationale behind the evolution of adaptive testing and consider its inherent strengths and limitations. We explore the continuous pursuit of improvement of examination methodology and how software can facilitate personalized assessment. We highlight how this can serve as a catalyst for learning and refinement of curricula; fostering engagement of learner and educator alike
Long-term voluntary wheel running does not alter vascular amyloid burden but reduces neuroinflammation in the Tg-SwDI mouse model of cerebral amyloid angiopathy
Background: Cardiovascular exercise (CVE) has been shown to be protective against cognitive decline in aging and the risk for dementias, including Alzheimer’s Disease (AD). CVE has also been shown to have several beneficial effects on brain pathology and behavioral impairments in mouse models of AD; however, no studies have specifically examined the effects of CVE on cerebral amyloid angiopathy (CAA), which is the accumulation of amyloid-beta (Aβ) in the cerebral vasculature. CAA may be uniquely susceptible to beneficial effects of CVE interventions due to the location and nature of the pathology. Alternatively, CVE may exacerbate CAA pathology, due to added stress on already compromised cerebral vasculature.
Methods: In the current study, we examined the effects of CVE over many months in mice, thereby modeling a lifelong commitment to CVE in humans. We assessed this voluntary CVE in Tg-SwDI mice, a transgenic mouse model of CAA that exhibits behavioral deficits, fibrillar vascular Aβ pathology, and significant perivascular neuroinflammation. Various “doses” of exercise intervention (0 h (“Sedentary”), 1 h, 3 h, 12 h access to running wheel) were assessed from ~ 4 to 12 months of age for effects on physiology, behavior/cognitive performance, and pathology.
Results: The 12 h group performed the greatest volume of exercise, whereas the 1 h and 3 h groups showed high levels of exercise intensity, as defined by more frequent and longer duration running bouts. Tg-SwDI mice exhibited significant cerebral vascular Aβ pathology and increased expression of pro-inflammatory cytokines as compared to WT controls. Tg-SwDI mice did not show motor dysfunction or altered levels of anxiety or sociability compared to WT controls, though Tg-SwDI animals did appear to exhibit a reduced tendency to explore novel environments. At all running levels, CAA pathology in Tg-SwDI mice was not significantly altered, but 12-h high-volume exercise showed increased insoluble Aβ burden. However, CVE attenuated the expression of pro-inflammatory cytokines TNF-α and IL-6 and was generally effective at enhancing motor function and reducing anxiety-like behavior in Tg-SwDI mice, though alterations in learning and memory tasks were varied.
Conclusions: Taken together, these results suggest that CAA can still develop regardless of a lifespan of substantial CVE, although downstream effects on neuroinflammation may be reduced and functional outcomes improved
Structures of CD6 and Its Ligand CD166 Give Insight into Their Interaction
SummaryCD6 is a transmembrane protein with an extracellular region containing three scavenger receptor cysteine rich (SRCR) domains. The membrane proximal domain of CD6 binds the N-terminal immunoglobulin superfamily (IgSF) domain of another cell surface receptor, CD166, which also engages in homophilic interactions. CD6 expression is mainly restricted to T cells, and the interaction between CD6 and CD166 regulates T-cell activation. We have solved the X-ray crystal structures of the three SRCR domains of CD6 and two N-terminal domains of CD166. This first structure of consecutive SRCR domains reveals a nonlinear organization. We characterized the binding sites on CD6 and CD166 and showed that a SNP in CD6 causes glycosylation that hinders the CD6/CD166 interaction. Native mass spectrometry analysis showed that there is competition between the heterophilic and homophilic interactions. These data give insight into how interactions of consecutive SRCR domains are perturbed by SNPs and potential therapeutic reagents
Statistical methodologies to pool across multiple intervention studies
Combining and analyzing data from heterogeneous randomized controlled trials of complex multiple-component intervention studies, or discussing them in a systematic review, is not straightforward. The present article describes certain issues to be considered when combining data across studies, based on discussions in an NIH-sponsored workshop on pooling issues across studies in consortia (see Belle et al. in Psychol Aging, 18(3):396-405, 2003). Several statistical methodologies are described and their advantages and limitations are explored. Whether weighting the different studies data differently, or via employing random effects, one must recognize that different pooling methodologies may yield different results. Pooling can be used for comprehensive exploratory analyses of data from RCTs and should not be viewed as replacing the standard analysis plan for each study. Pooling may help to identify intervention components that may be more effective especially for subsets of participants with certain behavioral characteristics. Pooling, when supported by statistical tests, can allow exploratory investigation of potential hypotheses and for the design of future interventions
Pregnancy outcomes related to the treatment of sarcomas with anthracyclines and/or ifosfamide during pregnancy
BACKGROUND: Sarcomas are rare diagnoses but are seen with relative frequency in adolescents and young adults and thus can present in pregnancy. We sought to study the administration of anthracyclines and/or ifosfamide in pregnancy-associated sarcomas.
PATIENTS AND METHODS: We conducted a multi-institutional retrospective study, identifying sarcoma patients who received anthracyclines and/or ifosfamide during pregnancy. Chart review identified variables related to demographics, cancer diagnosis, therapies, and outcome of the patient and fetus. Wilcoxon rank-sum test compared two independent samples.
RESULTS: We identified 13 patients at seven institutions with sarcoma who received anthracyclines and/or ifosfamide during pregnancy, including four bone sarcomas and nine soft tissue sarcomas diagnosed at a mean gestational age of 16.7 ± 5.9 weeks. Only nine patients had live births (9/13, 69.2%), with mean gestational age of 30.8 ± 3.8 weeks at delivery. The four patients with pregnancy loss all received both doxorubicin and ifosfamide, with chemotherapy initiated at 15.5 weeks as compared with 21.3 weeks for those patients with live births (p = 0.016).
CONCLUSION: In this multi-institutional study of sarcoma chemotherapy regimens administered during pregnancy, we found a high rate of fetal demise that was seen only in patients receiving both doxorubicin and ifosfamide and statistically more likely with chemotherapy initiation earlier in the second trimester. While limited by a small sample size, our study represents the largest study of sarcoma patients that received anthracyclines and/or ifosfamide in pregnancy thus far reported and supports development of an international registry to study concerns raised by our study
Asymmetrically cut crystals as optical elements for highly collimated x‐ray beams
Asymmetrically cut perfect crystals, in both the Laue and Bragg geometries, are examined as single crystal monochromators for x‐ray beams that are collimated to a small fraction of the Darwin width, as is typical in experiments with coherent x rays. Both the Laue and asymmetric Bragg geometries are plagued by an inherent chromatic aberration that increases the beam divergence much beyond that of the symmetric Bragg geometry. Measurements from a recent experiment at the ESRF are presented to compare Si(220) (symmetric Bragg), diamond(111) (asymmetric Laue), and diamond(111) (symmetric Bragg inclined) geometries. © 1995 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70952/2/RSINAK-66-2-1506-1.pd
Miniature exoplanet radial velocity array I: design, commissioning, and early photometric results
The MINiature Exoplanet Radial Velocity Array (MINERVA) is a US-based observational facility dedicated to the discovery and characterization of exoplanets around a nearby sample of bright stars. MINERVA employs a robotic array of four 0.7 m telescopes outfitted for both high-resolution spec- troscopy and photometry, and is designed for completely autonomous operation. The primary science program is a dedicated radial velocity survey and the secondary science objective is to obtain high precision transit light curves. The modular design of the facility and the flexibility of our hardware allows for both science programs to be pursued simultaneously, while the robotic control software provides a robust and efficient means to carry out nightly observations. In this article, we describe the design of MINERVA including major hardware components, software, and science goals. The telescopes and photometry cameras are characterized at our test facility on the Caltech campus in Pasadena, CA, and their on-sky performance is validated. New observations from our test facility demonstrate sub-mmag photometric precision of one of our radial velocity survey targets, and we present new transit observations and fits of WASP-52b—a known hot-Jupiter with an inflated radius and misaligned orbit. The process of relocating the MINERVA hardware to its final destination at the Fred Lawrence Whipple Observatory in southern Arizona has begun, and science operations are expected to commence within 2015
The Effects of Volume Versus Intensity of Long-Term Voluntary Exercise on Physiology and Behavior in C57/Bl6 Mice
Cardiovascular exercise (CVE) is associated with healthy aging and reduced risk of disease in humans, with similar benefits seen in animals. Most rodent studies, however, have used shorter intervention periods of a few weeks to a few months, begging questions as to the effects of longer-term, or even life-long, exercise. Additionally, most animal studies have utilized a single exercise treatment group – usually unlimited running wheel access – resulting in large volumes of exercise that are not clinically relevant. It is therefore incumbent to determine the physiological and cognitive/behavioral effects of a range of exercise intensities and volumes over a long-term period that model a lifelong commitment to CVE. In the current study, C57/Bl6 mice remained sedentary or were allowed either 1, 3, or 12 h of access to a running wheel per day, 5 days/weeks, beginning at 3.5–4 months of age. Following an eight-month intervention period, animals underwent a battery of behavioral testing, then euthanized and blood and tissue were collected. Longer access to a running wheel resulted in greater volume and higher running speed, but more breaks in running. All exercise groups showed similarly reduced body weight, increased muscle mass, improved motor function on the rotarod, and reduced anxiety in the open field. While all exercise groups showed increased food intake, this was greatest in the 12 h group but did not differ between 1 h and 3 h mice. While exercise dose-dependently increased working memory performance in the y-maze, the 1 h and 12 h groups showed the largest changes in the mass of many organs, as well as alterations in several behaviors including social interaction, novel object recognition, and Barnes maze performance. These findings suggest that long-term exercise has widespread effects on physiology, behavior, and cognition, which vary by “dose” and measure, and that even relatively small amounts of daily exercise can provide benefits
Priorities for HIV and chronic pain research results from a survey of individuals with lived experience
The Global Task Force on Chronic Pain in HIV published seven research priorities in the field of HIV-associated chronic pain in 2019: (1) causes; (2) management; (3) treatment individualization and integration with addiction treatment; (4) mental and social health factors; (5) prevalence; (6) treatment cost effectiveness; and (7) prevention. The current study used a web-based survey to determine whether the research topics were aligned with the priorities of adults with lived experiences of HIV and chronic pain. We also collected information about respondents' own pain and treatment experiences. We received 311 survey responses from mostly US-based respondents. Most respondents reported longstanding, moderate to severe, multisite pain, commonly accompanied by symptoms of anxiety and/or depression. The median number of pain treatments tried was 10 (IQR = 8, 13), with medications and exercise being the most common modalities, and opioids being viewed as the most helpful. Over 80% of respondents considered all research topics either "extremely important" or "very important". Research topic #2, which focused on optimizing management of pain in people with HIV, was accorded the greatest importance by respondents. These findings suggest good alignment between the priorities of researchers and US-based people with lived experience of HIV-associated chronic pain.</p
First radial velocity results from the MINiature Exoplanet Radial Velocity Array (MINERVA)
The MINiature Exoplanet Radial Velocity Array (MINERVA) is a dedicated
observatory of four 0.7m robotic telescopes fiber-fed to a KiwiSpec
spectrograph. The MINERVA mission is to discover super-Earths in the habitable
zones of nearby stars. This can be accomplished with MINERVA's unique
combination of high precision and high cadence over long time periods. In this
work, we detail changes to the MINERVA facility that have occurred since our
previous paper. We then describe MINERVA's robotic control software, the
process by which we perform 1D spectral extraction, and our forward modeling
Doppler pipeline. In the process of improving our forward modeling procedure,
we found that our spectrograph's intrinsic instrumental profile is stable for
at least nine months. Because of that, we characterized our instrumental
profile with a time-independent, cubic spline function based on the profile in
the cross dispersion direction, with which we achieved a radial velocity
precision similar to using a conventional "sum-of-Gaussians" instrumental
profile: 1.8 m s over 1.5 months on the RV standard star HD 122064.
Therefore, we conclude that the instrumental profile need not be perfectly
accurate as long as it is stable. In addition, we observed 51 Peg and our
results are consistent with the literature, confirming our spectrograph and
Doppler pipeline are producing accurate and precise radial velocities.Comment: 22 pages, 9 figures, submitted to PASP, Peer-Reviewed and Accepte
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