329 research outputs found

    A new (and better) way to measure individual financial capability

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    This study aims to validate the results of a 2012 pilot study that developed a short instrument to measure financial capability, using national survey results as reference point. More importantly, this study also develops a numerical scoring system to provide respondents with a transparent and easy to interpret method for differentiating low, moderate and high levels of personal financial literacy

    Physiological and growth responses to water deficit in the bioenergy crop Miscanthus x giganteus

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    High yielding perennial biomass crops of the species Miscanthus are widely recognized as one of the most promising lignocellulosic feedstocks for the production of bioenergy and bioproducts. Miscanthus is a C(4) grass and thus has relatively high water use efficiency. Cultivated Miscanthus comprises primarily of a single clone, Miscanthus x giganteus, a sterile hybrid between M. sacchariflorus and M. sinensis. M. x giganteus is high yielding and expresses desirable combinations of many traits present in the two parental species types; however, it responds poorly to low water availability. To identify the physiological basis of the response to water stress in M. x giganteus and to identify potential targets for breeding improvements we characterized the physiological responses to water-deficit stress in a pot experiment. The experiment has provided valuable insights into the temporal aspects of drought-induced responses of M. x giganteus. Withholding water resulted in marked changes in plant physiology with growth-associated traits among the first affected, the most rapid response being a decline in the rate of stem elongation. A reduction in photosynthetic performance was among the second set of changes observed; indicated by a decrease in stomatal conductance followed by decreases in chlorophyll fluorescence and chlorophyll content. Measures reflecting the plant water status were among the last affected by the drought treatment. Metabolite analysis indicated that proline was a drought stress marker in M. x giganteus, metabolites in the proline synthesis pathway were more abundant when stomatal conductance decreased and dry weight accumulation ceased. The outcomes of this study in terms of drought-induced physiological changes, accompanied by a proof-of-concept metabolomics investigation, provide a platform for identifying targets for improved drought-tolerance of the Miscanthus bioenergy crop

    Considerations for Dietary Assessment in the Canadian Partnership for Tomorrow Project

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    Dietary factors are leading contributors to chronic disease and mortality globally and in Canada (1–3), and have been recognized as modifiable risk factors for certain cancers (4). However, much remains to be learned about how dietary factors interact with other modifiable and nonmodifiable exposures and physiologic variables to influence disease risk in humans (5,6). Information collected from large prospective cohorts plays an important role in furthering our understanding of diet-disease relationships (7,8). To advance knowledge on how to promote health and prevent disease, it is critically important to use robust tools for collecting dietary information from participants in such cohorts (9). This guide is intended to be utilized by researchers designing nutritional epidemiological research and in particular, to guide the implementation of dietary assessment tools within the CPTP cohorts. The aim is to provide guidance on method selection, data collection, and analyses of dietary data, as well as stimulate discussions of harmonization of methods across cohorts to advance the evidence base. Because objective measures such as biomarkers of diet are currently few, burdensome, costly, and limited in the information they provide about the types of foods and beverages people consume (5,6), researchers typically rely upon self-report tools. However, it has long been recognized that self-reported dietary data are affected by error, including systematic error or bias (9,10), leading some commentators to suggest that research should no longer rely on selfreport approaches (11,12). However, much work has been conducted to better understand and address error in self-report dietary intake data (9,10). Such work has informed the development of novel technology-enabled tools to allow collection of the least-biased data possible, as well as the development of rigorous statistical approaches to mitigate the effects of error (13–16). Based on what is known about sources and types of error in data captured using different types of tools, it has been recommended that a combination of tools may be the optimal way forward for cohort studies. Specifically, multiple 24-hour recalls (24HRs), administered in combination with a food frequency questionnaire (FFQ), may allow researchers to leverage the strengths of each instrument (10,14,17). Data from 24HRs provide comprehensive detail on intake and measure consumption with less bias than FFQs. On the other hand, FFQs measure intake over a longer period (e.g. past month or year) (18–20), meaning they are better able to capture intake of foods and beverages that may be consumed more episodically (e.g., whole grains, dark-green vegetables) but that may be important to diet-disease relationships. The availability of weband mobile device-based dietary assessment tools for use in Canada and emerging statistical techniques to analyze the resulting data makes this multiple-tool scenario a realistic consideration for Alberta’s Tomorrow Project (21), other cohorts within the Canadian Partnership for Tomorrow Project (CPTP) (22), and other health-related studies. With comprehensive and standardized measurement of dietary exposures across cohorts, the identification of promising strategies to reduce diet-related disease risk among Canadians can be furthered (9)

    The Protective Effects of CD39 Overexpression in Multiple Low-Dose Streptozotocin–Induced Diabetes in Mice

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    Islet allograft survival limits the long-term success of islet transplantation as a potential curative therapy for type 1 diabetes. A number of factors compromise islet survival, including recurrent diabetes. We investigated whether CD39, an ectonucleotidase that promotes the generation of extracellular adenosine, would mitigate diabetes in the T cell–mediated multiple low-dose streptozotocin (MLDS) model. Mice null for CD39 (CD39KO), wild-type mice (WT), and mice overexpressing CD39 (CD39TG) were subjected to MLDS. Adoptive transfer experiments were performed to delineate the efficacy of tissue-restricted overexpression of CD39. The role of adenosine signaling was examined using mutant mice and pharmacological inhibition. The susceptibility to MLDS-induced diabetes was influenced by the level of expression of CD39. CD39KO mice developed diabetes more rapidly and with higher frequency than WT mice. In contrast, CD39TG mice were protected. CD39 overexpression conferred protection through the activation of adenosine 2A receptor and adenosine 2B receptor. Adoptive transfer experiments indicated that tissue-restricted overexpression of CD39 conferred robust protection, suggesting that this may be a useful strategy to protect islet grafts from T cell–mediated injury

    Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.

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    Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization by unclear mechanisms. To study this process, we engineer a human cardiomyocyte model to track replication and polyploidization using fluorescently tagged cyclin B1 and cardiac troponin T. Using time-lapse imaging, in vitro cardiomyocyte replication patterns recapitulate the progressive mononuclear polyploidization and replicative arrest observed in vivo. Single-cell transcriptomics and chromatin state analyses reveal that polyploidization is preceded by sarcomere assembly, enhanced oxidative metabolism, a DNA damage response, and p53 activation. CRISPR knockout screening reveals p53 as a driver of cell-cycle arrest and polyploidization. Inhibiting sarcomere function, or scavenging ROS, inhibits cell-cycle arrest and polyploidization. Finally, we show that cardiomyocyte engraftment in infarcted rat hearts is enhanced 4-fold by the increased proliferation of troponin-knockout cardiomyocytes. Thus, the sarcomere inhibits cell division through a DNA damage response that can be targeted to improve cardiomyocyte replacement strategies

    Evaluating the feasibility of administering a combination of online dietary assessment tools in a cohort of adults in Alberta, Canada

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    Purpose: Evidence suggests that combining tools, such as 24-hour recalls and food frequency questionnaires, may allow more accurate assessment of diet in epidemiologic studies. Webbased technology should make this approach more feasible than in the past, but it is important to explore response rates and acceptability of such an approach in real-world settings. We sought to determine the feasibility of using a combination of online tools (Automated SelfAdministered 24-hour (ASA24) Dietary Assessment Tool and Diet History Questionnaire-II (DHQ-II)) in a sub-set of participants in Alberta’s Tomorrow Project (ATP); a prospective cohort of 55,000 adults >35y in Alberta, Canada. Methods: Invitations to the feasibility study were mailed to 550 ATP participants. Those who consented (n=331) were asked to complete a health questionnaire, four ASA24 recalls (approximately three weeks apart over a four month period, with staggered start dates between June and December 2016), followed by the DHQ-II, and an evaluation survey. Results: The majority of participants [mean (SD) age =57.1 (10.1)] were women (70.7%), urban residents (84.8%) and non-smokers (95.7%). Of the 229 participants who completed at least one ASA24, roughly equal proportions completed one (24.8%), two (24.5%), three (24.5%) and four recalls (26.2%). One third (n=102) of consenting participants did not respond to any ASA24 recall requests, with “lack of time” given as the primary reason. Only 41% of consenting participants (n=136) completed the DHQ-II; of these, 40% (n=55) completed all four recalls. Median (25th-75th percentile) completion times were 46 (26-64) minutes for the first ASA24 recall and 50 (40-90) minutes for the DHQ-II. Conclusions: Over half of participants completed at least two or more ASA24 recalls, and those who completed a greater number of recalls also completed the DHQ-II, demonstrating that the approach is feasible in the ATP cohort. However, response rates may be sensitive to the timing and frequency of recall administration. Future investigations will (i) evaluate the dietary data collected from each tool; (ii) explore methods of combining the data to optimize assessment of diet in the cohort, while accounting for the fact that not all participants will complete the entire dietary assessment protocol

    Distance learning improves attainment of professional milestones in the early years of surgical training

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    OBJECTIVES: To assess the impact of a surgical sciences e-learning programme in supporting the academic development of surgical trainees during their preparation for professional examination. BACKGROUND: In 2007, a 3-year online part-time Master of Surgical Sciences (MSc) degree programme was launched, utilizing an innovative platform with virtual case scenarios based on common surgical conditions addressed by the curriculum relating to the Membership Examination of the Royal Colleges of Surgeons (MRCS). Multiple-choice questions with feedback and discussion boards facilitated by expert clinical tutors provided formative assessment. Summative assessment comprised written examination at the end of each of the first 2 years (equivalent to MRCS level), culminating in submission of a research dissertation in year 3 toward an MSc. METHODS: Students' age, gender, and level at entry to the programme were documented. Anonymized student feedback from 2008 to 2012 was examined using online questionnaires, and performance in the MSc programme was compared to MRCS examination outcomes for students who had consented to release of their results. RESULTS: A total of 517 surgical trainees from 40 countries were recruited over the 6-year period, and 116 MSc students have graduated to date. Of 368 students, 279 (76%) were foundation doctors (interns) and had not commenced formal surgical training on enrolling in the MSc programme. However, level at entry did not influence performance (P > 0.05 across all 3 years). Average pass rates since the programme launched, for those students completing all of the required assessments, were 84% ± 11% in year 1, 85% ± 10% in year 2, and 88% ± 7% in year 3 of the MSc programme. MSc students had significantly higher MRCS pass rates than nonenrolled trainees (67% vs 51%, P < 0.01, n = 352). There was a significant correlation between MRCS examination performance and overall performance in the MSc (R(2) = 58%; P < 0.01, n = 37). Of 248 respondents, 202 (81%) considered that the MSc would improve their chances of gaining a surgical training post, and 224 (90%) would recommend the programme to their peers. CONCLUSIONS: The online MSc programme supports academic development of trainees in the early years of surgical training, is well received by students, and is associated with improved success in their professional examination

    The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer

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    Patterns of glycosylation are important in cancer, but the molecular mechanisms that drive changes are often poorly understood. The androgen receptor drives prostate cancer (PCa) development and progression to lethal metastatic castration-resistant disease. Here we used RNA-Seq coupled with bioinformatic analyses of androgen-receptor (AR) binding sites and clinical PCa expression array data to identify ST6GalNAc1 as a direct and rapidly activated target gene of the AR in PCa cells. ST6GalNAc1 encodes a sialytransferase that catalyses formation of the cancer-associated sialyl-Tn antigen (sTn), which we find is also induced by androgen exposure. Androgens induce expression of a novel splice variant of the ST6GalNAc1 protein in PCa cells. This splice variant encodes a shorter protein isoform that is still fully functional as a sialyltransferase and able to induce expression of the sTn-antigen. Surprisingly, given its high expression in tumours, stable expression of ST6GalNAc1 in PCa cells reduced formation of stable tumours in mice, reduced cell adhesion and induced a switch towards a more mesenchymal-like cell phenotype in vitro. ST6GalNAc1 has a dynamic expression pattern in clinical datasets, beingsignificantly up-regulated in primary prostate carcinoma but relatively down-regulated in established metastatic tissue. ST6GalNAc1 is frequently upregulated concurrently with another important glycosylation enzyme GCNT1 previously associated with prostate cancer progression and implicated in Sialyl Lewis X antigen synthesis. Together our data establishes an androgen-dependent mechanism for sTn antigen expression in PCa, and are consistent with a general role for the androgen receptor in driving important coordinate changes to the glycoproteome during PCa progression

    Auditory training changes temporal lobe connectivity in Wernicke's aphasia: a randomised trial

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    Introduction Aphasia is one of the most disabling sequelae after stroke, occurring in 25%–40% of stroke survivors. However, there remains a lack of good evidence for the efficacy or mechanisms of speech comprehension rehabilitation. Trial Design This within-subjects trial tested two concurrent interventions in 20 patients with chronic aphasia with speech comprehension impairment following left hemisphere stroke: (1) phonological training using ‘Earobics’ software and (2) a pharmacological intervention using donepezil, an acetylcholinesterase inhibitor. Donepezil was tested in a double-blind, placebo-controlled, cross-over design using block randomisation with bias minimisation. Methods The primary outcome measure was speech comprehension score on the comprehensive aphasia test. Magnetoencephalography (MEG) with an established index of auditory perception, the mismatch negativity response, tested whether the therapies altered effective connectivity at the lower (primary) or higher (secondary) level of the auditory network. Results Phonological training improved speech comprehension abilities and was particularly effective for patients with severe deficits. No major adverse effects of donepezil were observed, but it had an unpredicted negative effect on speech comprehension. The MEG analysis demonstrated that phonological training increased synaptic gain in the left superior temporal gyrus (STG). Patients with more severe speech comprehension impairments also showed strengthening of bidirectional connections between the left and right STG. Conclusions Phonological training resulted in a small but significant improvement in speech comprehension, whereas donepezil had a negative effect. The connectivity results indicated that training reshaped higher order phonological representations in the left STG and (in more severe patients) induced stronger interhemispheric transfer of information between higher levels of auditory cortex

    Greater aortic inflammation and calcification in abdominal aortic aneurysmal disease than atherosclerosis: a prospective matched cohort study

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    Funder: British Heart Foundation; FundRef: http://dx.doi.org/10.13039/501100000274Objective: Using combined positron emission tomography and CT (PET-CT), we measured aortic inflammation and calcification in patients with abdominal aortic aneurysms (AAA), and compared them with matched controls with atherosclerosis. Methods: We prospectively recruited 63 patients (mean age 76.1±6.8 years) with asymptomatic aneurysm disease (mean size 4.33±0.73 cm) and 19 age-and-sex-matched patients with confirmed atherosclerosis but no aneurysm. Inflammation and calcification were assessed using combined 18F-FDG PET-CT and quantified using tissue-to-background ratios (TBRs) and Agatston scores. Results: In patients with AAA, 18F-FDG uptake was higher within the aneurysm than in other regions of the aorta (mean TBRmax2.23±0.46 vs 2.12±0.46, p=0.02). Compared with atherosclerotic control subjects, both aneurysmal and non-aneurysmal aortae showed higher 18F-FDG accumulation (total aorta mean TBRmax2.16±0.51 vs 1.70±0.22, p=0.001; AAA mean TBRmax2.23±0.45 vs 1.68±0.21, p<0.0001). Aneurysms containing intraluminal thrombus demonstrated lower 18F-FDG uptake within their walls than those without (mean TBRmax2.14±0.43 vs 2.43±0.45, p=0.018), with thrombus itself showing low tracer uptake (mean TBRmax thrombus 1.30±0.48 vs aneurysm wall 2.23±0.46, p<0.0001). Calcification in the aneurysmal segment was higher than both non-aneurysmal segments in patients with aneurysm (Agatston 4918 (2901–8008) vs 1017 (139–2226), p<0.0001) and equivalent regions in control patients (442 (304-920) vs 166 (80-374) Agatston units per cm, p=0.0042). Conclusions: The entire aorta is more inflamed in patients with aneurysm than in those with atherosclerosis, perhaps suggesting a generalised inflammatory aortopathy in patients with aneurysm. Calcification was prominent within the aneurysmal sac, with the remainder of the aorta being relatively spared. The presence of intraluminal thrombus, itself metabolically relatively inert, was associated with lower levels of inflammation in the adjacent aneurysmal wall
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