322 research outputs found

    The antibody loci of the domestic goat (Capra hircus)

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    The domestic goat (Capra hircus) is an important ruminant species both as a source of antibody-based reagents for research and biomedical applications and as an economically important animal for agriculture, particularly for developing nations that maintain most of the global goat population. Characterization of the loci encoding the goat immune repertoire would be highly beneficial for both vaccine and immune reagent development. However, in goat and other species whose reference genomes were generated using short-read sequencing technologies, the immune loci are poorly assembled as a result of their repetitive nature. Our recent construction of a long-read goat genome assembly (ARS1) has facilitated characterization of all three antibody loci with high confidence and comparative analysis to cattle. We observed broad similarity of goat and cattle antibody-encoding loci but with notable differences that likely influence formation of the functional antibody repertoire. The goat heavy-chain locus is restricted to only four functional and nearly identical IGHV genes, in contrast to the ten observed in cattle. Repertoire analysis indicates that light-chain usage is more balanced in goats, with greater representation of kappa light chains (~ 20-30%) compared to that in cattle (~ 5%). The present study represents the first characterization of the goat antibody loci and will help inform future investigations of their antibody responses to disease and vaccination

    THE ROLE OF GPR30 IN MEDIATING ESTROGEN EFFECTS ON NEURONS AND COGNITIVE PERFORMANCE

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    Basic and clinical research suggests the loss of estradiol following menopause may contribute to accelerated brain aging and the increased risk of age-related cognitive decline and dementia. Novel estrogenic compounds may confer positive cognitive effects without the added risk of side effects associated with current agents. G-1 is a recently developed agonist for the novel transmembrane estrogen receptor (ER) GPR30. Activation of the GPR30 pathway is independent of either the classical ER ι or β pathways, raising the possibility of using G-1 as a novel estrogenic agent while avoiding the risks associated with other estrogenic compounds. Previous work in our laboratory has shown that estradiol enhances cognitive performance via effects on basal forebrain cholinergic neurons. We hypothesize the effects of estradiol on cholinergic function and cognitive performance are mediated by GPR30. If correct, then selective GPR30 agonists may provide useful alternatives to current estrogenic therapies. To test this hypothesis the first goal was to characterize GPR30 expression in the rat forebrain, focusing on co-expression by cholinergic neurons. A RT-PCR assay was developed to quantify GPR30 mRNA in specific brain regions. GPR30 protein and mRNA expression were found in regions of the brain important for spatial learning and memory. Moreover, GPR30 protein appears to be expressed by the vast majority of cholinergic neurons. The second goal was to examine the effects of GPR30 activation on cholinergic neurons. In vivo microdialysis and HPLC analysis of acetylcholine levels in dialysates were used to compare effects on acetylcholine release. Administration of a GPR30 agonist or estradiol (E2) to ovariectomized (OVX) rats produced a 3-fold increase in potassium-stimulated acetylcholine release in the hippocampus relative to vehicle-treated controls. The third goal was to test the ability of GPR30 agonists and antagonists to enhance or impair cognitive performance in rats. GPR30 agonism enhanced the rate of acquisition on a delayed matching-to-position (DMP) T-maze task in OVX rats similar to estradiol while GPR30 antagonism dose-dependently impaired performance in gonadally intact and OVX+E2 rodents. Hence, GPR30 appears to play an important role in mediating direct effects of estradiol on basal forebrain cholinergic neurons, with corresponding effects on cognitive performance

    A pilot study on the validity and reliability of portable ultrasound assessment of swallowing with dysphagic patients.

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    Introduction: Ultrasound assessment of swallowing has been documented as reliable in both healthy and dysphagic participants. In addition, there is evidence of good correlation with ‘gold standard’ videofluoroscopic swallowing study (VFSS). Despite this, ultrasound has not translated into clinical practice. This may be due to the cost and accessibility of ultrasound devices as well as the time required to analyse images offline. Recent innovations have produced inexpensive, wireless, portable ultrasound technology, which has the potential for increased access and immediate results. This project explored a number of components of inter- and intra-rater reliability using portable ultrasound. Reliability of measures, from images acquired, selected and measured online in a pressured clinical environment, was compared with reliability of measurement of pre-selected images offline. The project additionally made preliminary assessments of the validity of ultrasound against the gold standard of VFSS. Methods: Participants: Eight patients, aged 33-96 with mixed aetiologies were recruited following referral for a clinical VFSS. Instrumentation: A curvilinear Clarius™ultrasound device, wirelessly connected to an iPad, was used to acquire images during dynamic swallowing gestures - hyoid excursion and thyrohyoid approximation as well as images for measures of tongue thickness at rest. A linear Clarius™ transducer was used to collect measures of cross-sectional area of submental muscles at rest. Data acquisition and measurement: Ultrasound data were independently collected by two investigators within the same day. The primary investigator completed ultrasound concurrently with VFSS for the purposes of validity assessment. Subsequent ultrasound analysis was completed by a co-investigator immediately following. Online measurements of ultrasound images were completed during the exam, using Clarius™software on an iPad. Offline analyses of ultrasound were completed by two raters with a minimum of eleven days between measures. VFSS measures were completed offline by rater one, using ImageJ software on a large screen. Reliability assessment: Inter-rater reliability was calculated with intraclass correlation coefficient (ICC) based on linear mixed effects model analyses (in R software). Effect of data acquisition on reliability was explored by calculating online inter-rater ICC and comparing with offline inter-rater ICC. Effect of environmental, equipment and time constraints on online measurement was explored by calculating ICC of online and offline measurement of the same pre-selected acquired images. Validity assessment: Hyoid excursion and thyrohyoid approximation during liquid and puree swallowing were concurrently assessed using ultrasound and the ‘gold-standard’ instrumentation, VFSS. Pearson correlation coefficients were calculated in order to make a preliminary assessment of correlation between assessment methods. Results: Reliability: Inter-rater reliability of online acquisition and measurement ranged from poor (.90) for static measures. Inter- and intra-rater reliability for offline measures was good (>.75) to excellent (>.90) for hyoid excursion and static morphometry measures and moderate (.50 –.75) for thyrohyoid approximation. Validity: Pearson coefficient of correlation calculations for hyoid excursion were moderate (r=0.76; p=0.001) for puree bolus and excellent for liquid bolus (r=0.92; p=0.03). Thyrohyoid approximation was found to have a moderate but insignificant, relationship between modalities for both puree and liquid bolus (r=0.61; p=0.11). Conclusion: The high reliability for offline measurement of ultrasound images is comparable to previous studies using sophisticated instrumentation. Reduction in reliability is noted when measuring the images online within the context of a clinical environment compared with offline measurement. Online data analyses may be affected by the pressure and lighting of a clinical environment paired with lower resolution of the device, size of the screen and use of a touch screen for measurement. Further reduction in reliability of dynamic swallowing measures is noted when data acquisition is added, this may be due to different techniques by examiners as well as variance in patient performance. The findings suggest that it is important to further explore methods of improving reliability of data acquisition as well as immediate online analysis before clinical translation of ultrasound assessment of swallowing is achieved. Preliminary data on validity of the portable ultrasound device indicates high correlation between assessment methods (ultrasound and VFSS) for hyoid excursion only. Analysis of a larger cohort is required to provide a robust assessment of the validity of ultrasound images collected with this technology for both hyoid excursion and thyrohyoid approximation

    Field tests of a portable MEMS gravimeter

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    Gravimeters are used to measure density anomalies under the ground. They are applied in many different fields from volcanology to oil and gas exploration, but present commercial systems are costly and massive. A new type of gravity sensor has been developed that utilises the same fabrication methods as those used to make mobile phone accelerometers. In this study, we describe the first results of a field-portable microelectromechanical system (MEMS) gravimeter. The stability of the gravimeter is demonstrated through undertaking a multi-day measurement with a standard deviation of 5.58 × 10−6 ms−2 . It is then demonstrated that a change in gravitational acceleration of 4.5 × 10−5 ms−2 can be measured as the device is moved between the top and the bottom of a 20.7 m lift shaft with a signal-to-noise ratio (SNR) of 14.25. Finally, the device is demonstrated to be stable in a more harsh environment: a 4.5 × 10−4 ms−2 gravity variation is measured between the top and bottom of a 275-m hill with an SNR of 15.88. These initial field-tests are an important step towards a chip-sized gravity senso

    Perreo femme-inism: an avenue to reclaim, reject, and redefine cultural norms within Borinquen society

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    Puerto Rico is positioned at the epicenter of many of the debates involving questions of colorism, misogyny, sexual liberation, and gender expression in reggaetĂłn and perreo, due to its role in shaping these cultures. What was traditionally defined as an oppressive and misogynistic expression is now being recognized as the instrument of resistance that it was created to be. The recent application of perreo, the style of dance associated with reggaetĂłn, as a tool of resistance in Black feminists and queer movements coopts themes of reclamation, rejection, and redefinition that have embedded themselves in Puerto Rican culture. By exploring these three central themes, this research begins to build a framework for a new expression of feminism, perreo femme-inism.M.S

    Assessing Peer Leader Skill Acquisition and Group Dynamics in a First-Year Calculus Course

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    Peer-led team learning (PLTL), specifically the model known as ‘Workshops’, has been shown to contribute positively and significantly to student success in STEM courses across subjects (Gosser et al., 2001). Our research adds to the SOTL literature describing the effectiveness of Workshops by reporting on the changes in student leaders. We examine the level to which leaders acquired new skills in effective teaching and describe the pedagogical interactions in the groups they led as a result of the combination of training and experience facilitating first-year Calculus Workshop sections. This was a semester-long study on twenty-two Workshop leaders for two multi-section, introductory calculus courses at a small research university. Our method is a novel overlay of two metrics that allows, with some forethought, a robust analysis of Workshop leader outcomes that would complement any assessment of PLTL implementation faculty might choose to undertake

    An organisational study into the impact of mobile devices on clinician and patient experience in Auckland, New Zealand

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    Mobile technology has potential to improve workflow, patient safety and quality of care, and has been identified as an important enabler of community services. However, little is known about the impact of mobile device use on clinician and patient experiences. Eleven community allied health clinicians were provided with live access to electronic health records, their email and electronic calendar, peer reviewed education and therapy mobile applications via a mobile device. Three data measures were collected over 19-weeks. First, quantitative time and motion data was gathered at baseline and follow-up to enable longitudinal analysis of clinician workflow. Second, a questionnaire consisting of rateable statements, multi-choice and open questions was completed at baseline and follow-up to enable analysis of clinician experience. Third, a short questionnaire was completed with a convenience sample of 101 patients who experienced mobile device use in their home. Clinicians and patients reported positive experiences associated with access to electronic health information at the point of care and the use of pictures, diagrams and videos to support clinical interactions. There was a significant reduction in time spent on patient related administration (

    Microelectromechanical system gravimeters as a new tool for gravity imaging

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    A microelectromechanical system (MEMS) gravimeter has been manufactured with a sensitivity of 40 ppb in an integration time of 1 s. This sensor has been used to measure the Earth tides: the elastic deformation of the globe due to tidal forces. No such measurement has been demonstrated before now with a MEMS gravimeter. Since this measurement, the gravimeter has been miniaturized and tested in the field. Measurements of the free-air and Bouguer effects have been demonstrated by monitoring the change in gravitational acceleration measured while going up and down a lift shaft of 20.7 m, and up and down a local hill of 275 m. These tests demonstrate that the device has the potential to be a useful field-portable instrument. The development of an even smaller device is underway, with a total package size similar to that of a smartphone

    Factors Impacting Transgender Patients’ Discomfort with Their Family Physicians: A Respondent-Driven Sampling Survey

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    BACKGROUND: Representing approximately 0.5% of the population, transgender (trans) persons in Canada depend on family physicians for both general and transition-related care. However, physicians receive little to no training on this patient population, and trans patients are often profoundly uncomfortable and may avoid health care. This study examined factors associated with patient discomfort discussing trans health issues with a family physician in Ontario, Canada. METHODS: 433 trans people age 16 and over were surveyed using respondent-driven sampling for the Trans PULSE Project; 356 had a family physician. Weighted logistic regression models were fit to produce prevalence risk ratios (PRRs) via average marginal predictions, for transmasculine (n = 184) and transfeminine (n = 172) trans persons. RESULTS: Among the 83.1% (95% CI = 77.4, 88.9) of trans Ontarians who had a family physician, approximately half reported discomfort discussing trans health issues. 37.2% of transmasculine and 38.1% of transfeminine persons reported at least one trans-specific negative experience. In unadjusted analysis, sociodemographics did not predict discomfort, but those who planned to medically transition sex, but had not begun, were more likely to report discomfort (transmasculine: PRR = 2.62 (95% CI = 1.44, 4.77); transfeminine: PRR = 1.85 (95% CI = 1.08, 3.15)). Adjusted for other factors, greater perceived physician knowledge about trans issues was associated with reduced likelihood of discomfort, and previous trans-specific negative experiences with a family physician with increased discomfort. Transfeminine persons who reported three or more types of negative experiences were 2.26 times as likely, and transmasculine persons 1.61 times as likely, to report discomfort. In adjusted analyses, sociodemographic associations differed by gender, with being previously married or having higher education associated with increased risk of discomfort among transfeminine persons, but decreased risk among transmasculine persons. CONCLUSIONS: Within this transgender population, discomfort in discussing trans health issues with a family physician was common, presenting a barrier to accessing primary care despite having a regular family physician and “universal” health insurance
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