Neural substrates, dynamics and thresholds of galvanic vestibular stimulation in the behaving primate

Galvanic vestibular stimulation (GVS) uses the external application of electrical current to selectively target the vestibular system in humans. Despite its recent popularity for the assessment/treatment of clinical conditions, exactly how this non-invasive tool activates the vestibular system remains an open question. Here we directly investigate single vestibular afferent responses to GVS applied to the mastoid processes of awake-behaving monkeys. Transmastoid GVS produces robust and parallel activation of both canal and otolith afferents. Notably, afferent activation increases with intrinsic neuronal variability resulting in constant GVS-evoked neuronal detection thresholds across all afferents. Additionally, afferent tuning differs for GVS versus natural self-motion stimulation. Using a stochastic model of repetitive activity in afferents, we largely explain the main features of GVS-evoked vestibular afferent dynamics. Taken together, our results reveal the neural substrate underlying transmastoid GVS-evoked perceptual, ocular and postural responses—information that is essential to advance GVS applicability for biomedical uses in humans

Radiation damage effects in ferroelectric LiTaO

Z-cut lithium tantalate (LiTaO{sub 3}) ferroelectric single crystals were irradiated with 200 keV Ar{sup ++} ions. LiTaO{sub 3} possesses a structure that is a derivative of the corundum (Al{sub 2}O{sub 3}) crystal structure. A systematic study of the radiation damage accumulation rate as a function of ion dose was performed using ion-beam channeling experiments. An ion fluence of 2.5 x 10{sup 18} Ar{sup 2+} ions/m{sup 2} was sufficient to amorphize the irradiated volume of a LiTaO{sub 3} crystal at an irradiation temperature of approximately 120K. This represents a rather exceptional susceptibility to ion-induced amorphization, which may be related to a highly disparate rate of knock-on of constituent lattice ions, due to the large mass difference between the Li and Ta cations. The authors also observed that the c{sup {minus}} end of the ferroelectric polarization exhibits slightly higher ion dechanneling along with an apparent greater susceptibility to radiation damage, as compared to the c{sup +} end of the polarization

Glucose self-monitoring in non-insulin-treated patients with type 2 diabetes in primary care settings: A randomized trial

IMPORTANCE The value of self-monitoring of blood glucose (SMBG) levels in patients with non-insulin-treated type 2 diabetes has been debated. OBJECTIVE To compare 3 approaches of SMBG for effects on hemoglobin A1c levels and health-related quality of life (HRQOL) among people with non-insulin-treated type 2 diabetes in primary care practice. DESIGN, SETTING, AND PARTICIPANTS The Monitor Trial studywas a pragmatic, open-label randomized trial conducted in 15 primary care practices in central North Carolina. Participants were randomized between January 2014 and July 2015. Eligible patients with type 2 non-insulin-treated diabetes were: older than 30 years, established with a primary care physician at a participating practice, had glycemic control (hemoglobin A1c) levels higher than 6.5%but lower than 9.5%within the 6 months preceding screening, as obtained from the electronic medical record, and willing to comply with the results of random assignment into a study group. Of the 1032 assessed for eligibility, 450 were randomized. INTERVENTIONS No SMBG, once-daily SMBG, and once-daily SMBG with enhanced patient feedback including automatic tailored messages delivered via the meter. MAIN OUTCOMES AND MEASURES Coprimary outcomes included hemoglobin A1c levels and HRQOL at 52 weeks. RESULTS A total of 450 patients were randomized and 418 (92.9%) completed the final visit. There were no significant differences in hemoglobin A1c levels across all 3 groups (P = .74; estimated adjusted mean hemoglobin A1c difference, SMBG with messaging vs no SMBG, -0.09%; 95%CI, -0.31% to 0.14%; SMBG vs no SMBG, -0.05%; 95%CI, -0.27%to 0.17%). There were also no significant differences found in HRQOL. There were no notable differences in key adverse events including hypoglycemia frequency, health care utilization, or insulin initiation. CONCLUSIONS AND RELEVANCE In patients with non-insulin-treated type 2 diabetes, we observed no clinically or statistically significant differences at 1 year in glycemic control or HRQOL between patients who performed SMBG compared with those who did not perform SMBG. The addition of this type of tailored feedback provided through messaging via ameter did not provide any advantage in glycemic control

Social and scientific motivations to move beyond groups in allele frequencies: The TOPMed experience

For the genomics community, allele frequencies within defined groups (or “strata”) are useful across multiple research and clinical contexts. Benefits include allowing researchers to identify populations for replication or “look up” studies, enabling researchers to compare population-specific frequencies to validate findings, and facilitating assessment of variant pathogenicity in clinical contexts. However, there are potential concerns with stratified allele frequencies. These include potential re-identification (determining whether or not an individual participated in a given research study based on allele frequencies and individual-level genetic data), harm from associating stigmatizing variants with specific groups, potential reification of race as a biological rather than a socio-political category, and whether presenting stratified frequencies—and the downstream applications that this presentation enables—is consistent with participants’ informed consents. The NHLBI Trans-Omics for Precision Medicine (TOPMed) program considered the scientific and social implications of different approaches for adding stratified frequencies to the TOPMed BRAVO (Browse All Variants Online) variant server. We recommend a novel approach of presenting ancestry-specific allele frequencies using a statistical method based upon local genetic ancestry inference. Notably, this approach does not require grouping individuals by either predominant global ancestry or race/ethnicity and, therefore, mitigates re-identification and other concerns as the mixture distribution of ancestral allele frequencies varies across the genome. Here we describe our considerations and approach, which can assist other genomics research programs facing similar issues of how to define and present stratified frequencies in publicly available variant databases

Health literacy, glycemic control, and physician-advised glucose self-monitoring use in type 2 diabetes

Objective: To measure the association between health literacy and both patient-reported and clinical outcomes in patients with non-insulin-treated type 2 diabetes. Research Design and Methods: We surveyed patients with non-insulin-treated type 2 diabetes (n = 448) from 15 primary care practices. The association between health literacy and patient-reported and clinical outcomes, including numeracy of self-monitoring of blood glucose (SMBG) use, how often physicians advised patients to conduct SMBG testing, and glycemic control (as measured by A1C), was investigated. Results: Study participants included 448 patients with non-insulin-treated type 2 diabetes located within central North Carolina. Participants with limited health literacy had poorer glycemic control (A1C 7.7 ± 1.1% vs. 7.5 ± 1.0%, P = 0.016) despite using SMBG testing more frequently (daily SMBG testing 49.3 vs. 30.7%, P = 0.001) compared to individuals with adequate health literacy. The difference in how often physicians advised patients to conduct SMBG testing between limited and adequate health literacy groups was not significant (P = 0.68). Conclusion: Limited health literacy was associated with poorer glyce-mic control and an increased frequency of SMBG testing in patients with non-insulin-treated type 2 diabetes. There was no significant difference in how often physicians advised patients to conduct SMBG testing between patients with limited and adequate health literacy

Relative recency influences object-in-context memory

In two experiments rats received training on an object-in-context (OIC) task, in which they received preexposure to object A in context x, followed by exposure to object B in context y. In a subsequent test both A and B are presented in either context x or context y. Usually more exploration is seen of the object that has not previously been paired with the test context, an effect attributed to the ability to remember where an object was encountered. However, in the typical version of this task, object A has also been encountered less recently than object B at test. This is precisely the arrangement in tests of ‘relatively recency’ (RR), in which more remotely presented objects are explored more than objects experienced more recently. RR could contaminate performance on the OIC task, by enhancing the OIC effect when animals are tested in context y, and masking it when the test is in context x. This possibility was examined in two experiments, and evidence for superior performance in context y was obtained. The implications of this for theoretical interpretations of recognition memory and the procedures used to explore it are discussed

Ro 04-6790-induced cognitive enhancement: No effect in trace conditioning and novel object recognition procedures in adult male Wistar rats

The evidence for cognitively enhancing effects of 5-hydroxytryptamine6 (5-HT6) receptor antagonists such as Ro 04-6790 is inconsistent and seems to depend on the behavioural test variant in use. Trace conditioning holds promise as a behavioral assay for hippocampus-dependent working memory function. Accordingly, Experiment 1 assessed the effect of Ro 04-6790 (5 and 10 mg/kg i.p.) on associating a noise conditioned stimulus paired with foot shock (unconditioned stimulus) at a 3 or 30 s trace interval in adult male Wistar rats. Contextual conditioning was measured as suppression to the contextual cues provided by the experimental chambers and as suppression to a temporally extended light background stimulus which provided an experimental context. Experiment 2 assessed the effect of Ro 04-6790 (5 and 10 mg/kg i.p.) on recognition memory as tested by the exploration of novel relative to familiar objects in an open arena. In Experiment 1, Ro 04-6790 (5 and 10 mg/kg) was without effect on trace and contextual conditioning. In Experiment 2, there was no indication of the expected improvement under Ro 04-6790 at the same doses previously found to enhance recognition memory as measured in tests of novel object exploration. Thus, there was no evidence that treatment with the 5-HT6 receptor antagonist Ro 04-6790 acted as a cognitive enhancer in either trace conditioning or object recognition procedures. We cannot exclude the possibility that the experimental procedures used in the present study would have been sensitive to the cognitive enhancing effects of Ro 04-6790 in a different dose range, behavioral test variant, or in a different strain of rat. Nonetheless the drug treatment was not ineffective in that object exploration was reduced under 10 mg/kg Ro 04-6790

Simulated Optimisation of Disordered Structures with negative Poisson’s ratios

Copyright © 2009 Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Mechanics of Materials. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Mechanics of Materials, Vol. 41 Issue 8 (2009). DOI: 10.1016/j.mechmat.2009.04.008Two-dimensional regular theoretical units that give a negative Poisson’s ratio (NPR) are well documented and well understood. Predicted mechanical properties resulting from these models are reasonably accurate in two dimensions but fall down when used for heterogeneous real-world materials. Manufacturing processes are seldom perfect and some measure of heterogeneity is therefore required to account for the deviations from the regular unit cells in this real-life situation. Analysis of heterogeneous materials in three dimensions is a formidable problem; we must first understand heterogeneity in two dimensions. This paper approaches the problem of finding a link between heterogeneous networks and its material properties from a new angle. Existing optimisation tools are used to create random two-dimensional topologies that display NPR, and the disorder in the structure and its relationship with NPR is investigated

Community advisory boards guiding engaged research efforts within a clinical translational sciences award: Key contextual factors explored

Background: Engaging stakeholders in research carries the promise of enhancing the research relevance, transparency, and speed of getting findings into practice. By describing the context and functional aspects of stakeholder groups, like those working as community advisory boards (CABs), others can learn from these experiences and operationalize their own CABs. Our objective is to describe our experiences with diverse CABs affiliated with our community engagement group within our institution’s Clinical Translational Sciences Award (CTSA). We identify key contextual elements that are important to administering CABs. Methods: A group of investigators, staff, and community members engaged in a 6-month collaboration to describe their experiences of working with six research CABs. We identified the key contextual domains that illustrate how CABS are developed and sustained. Two lead authors, with experience with CABs and identifying contextual domains in other work, led a team of 13 through the process. Additionally, we devised a list of key tips to consider when devising CABs. Results: The final domains include (1) aligned missions among stakeholders (2) resources/support, (3) defined operational processes/shared power, (4) well-described member roles, and (5) understanding and mitigating challenges. The tips are a set of actions that support the domains. Conclusions: Identifying key contextual domains was relatively easy, despite differences in the respective CAB’s condition of focus, overall mission, or patient demographics represented. By contextualizing these five domains, other research and community partners can take an informed approach to move forward with CAB planning and engaged research