Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less ...extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
While there is widespread agreement on the expected benefits of hands-on access to corpora for language learners, reports abound of the difficulties involved in realising those benefits in practice. ...A particular focus of discussion is the challenge of transferring the skills of the corpus linguist to learners, so that they can explore this type of monolingual and unmediated resource effectively in a 'learner-as-researcher' or 'learner-as-detective' role. In this paper, we present a positive experience of an apprenticeship in corpus use, which we attribute to a training approach that seeks to exploit the unmediated nature of corpora rather than treating it as a problem for learners. Our approach is not aimed at equipping learners with skills that will allow them to derive rules from the systematic analysis of corpus data. Instead we aim to inculcate in our students a propensity for open-ended searches, and an observe-and-borrow-chunks mentality, oriented to copying models from a corpus to enrich and render more accurate their written production in particular. We also see this training process as encouraging their curiosity about language patterns and authentication of the use they make of such patterns, and therefore beneficial to their ongoing development as independent language learners more generally.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
Urinary Soluble CD163 in Active Renal Vasculitis O'Reilly, Vincent P; Wong, Limy; Kennedy, Claire ...
Journal of the American Society of Nephrology,
09/2016, Volume:
27, Issue:
9
Journal Article
Peer reviewed
Open access
A specific biomarker that can separate active renal vasculitis from other causes of renal dysfunction is lacking, with a kidney biopsy often being required. Soluble CD163 (sCD163), shed by monocytes ...and macrophages, has been reported as a potential biomarker in diseases associated with excessive macrophage activation. Thus, we hypothesized that urinary sCD163 shed by crescent macrophages correlates with active glomerular inflammation. We detected sCD163 in rat urine early in the disease course of experimental vasculitis. Moreover, microdissected glomeruli from patients with small vessel vasculitis (SVV) had markedly higher levels of CD163 mRNA than did those from patients with lupus nephritis, diabetic nephropathy, or nephrotic syndrome. Both glomeruli and interstitium of patients with SVV strongly expressed CD163 protein. In 479 individuals, including patients with SVV, disease controls, and healthy controls, serum levels of sCD163 did not differ between the groups. However, in an inception cohort, including 177 patients with SVV, patients with active renal vasculitis had markedly higher urinary sCD163 levels than did patients in remission, disease controls, or healthy controls. Analyses in both internal and external validation cohorts confirmed these results. Setting a derived optimum cutoff for urinary sCD163 of 0.3 ng/mmol creatinine for detection of active renal vasculitis resulted in a sensitivity of 83%, specificity of 96%, and a positive likelihood ratio of 20.8. These data indicate that urinary sCD163 level associates very tightly with active renal vasculitis, and assessing this level may be a noninvasive method for diagnosing renal flare in the setting of a known diagnosis of SVV.
In much of the literature on the exploitation of corpora for language learning, the learners are viewed as researchers, who formulate and test their own hypotheses about language use. Having ...identified difficulties encountered in corpus investigations by our intermediate-level students of Italian in a previous study, we have designed a semester-long apprenticeship in corpus use which does not demand of them the high level of language proficiency, attention to detail in observation, and logical rigour that we consider necessary for rewarding work in the learner-as-researcher role. Instead, we introduce a corpus initially as an aid to the imagination in writing, and then to achieving accuracy through specific grammatical problem solving. We see this as the groundwork for subsequent development of the students' research skills with corpus data. This paper describes the approach we have adopted to the corpus apprenticeship and reports on an evaluation of its effectiveness through case studies of three students and their use of a corpus and bilingual dictionary as reference resources when writing. Drawing on insights from the case studies, we outline a working definition of corpus-consultation literacy for our learning context and identify some refinements to be made to our apprenticeship. (Contains 3 figures, 1 table and 12 notes.)
Medical schools increasingly incorporate teamwork in their curricula but medical students often have a negative perception of team projects, in particular when there is unequal participation. The ...purpose of this study is to evaluate whether a novel peer evaluation system improves teamwork contributions and reduces the risk of students "free loading".
A cluster randomised controlled trial (RCT) with qualitative follow up enrolled 37 teams (n = 223 students). Participating teams were randomised to intervention group (19 teams) or control group (18 teams). The validated Comprehensive Assessment Team Member Effectiveness (CATME) tool was used as the outcome measure, and was completed at baseline (week 2) and at the end of the project (week 10). The team contribution subscale was the primary outcome, with other subscales as secondary outcomes. Six focus group discussions were held with students to capture the team's experiences and perceptions of peer assessment and its effects on team work.
The results of the RCT showed that there was no difference in team contribution, and other forms of team effectiveness, between intervention and control teams. The focus group discussions highlighted students' negative attitudes, and lack of implementation of this transparent, points-based peer assessment system, out of fear of future consequences for relationships with peers. The need to assess peers in a transparent way to stimulate open discussion was perceived as threatening by participants. Teams suggested that other peer assessment systems could work such as rewarding additional or floating marks to high performing team members.
Other models of peer assessment need to be developed and tested that are non-threatening and that facilitate early acceptance of this mode of assessment.
The Independent and Supplementary Prescribing programme has been offered by the University of Leeds since 2002. Upon completion of the programme pharmacists, nurses, midwives, physiotherapists, and ...paramedics register as prescribers with their professional regulator. Trainees attend teaching sessions over a 3‐month period followed by a period of supervision in practice. All trainees undertook an objective structured clinical examination (OSCE) at the end of the 3‐month period. Usually, the OSCE takes place on the university campus over one day. With the onset of the COVID‐19 pandemic, the OSCE had to be restructured so that it could take place virtually, while maintaining the validity and reliability of the assessment. Microsoft Teams® was identified as the most appropriate platform for conducting the Virtual‐OSCE (V‐OSCE). Overall, the V‐OSCEs we ran were a success; trainees, assessors and simulated patients reported that the assessment was seamless. However, further improvements could be made to improve the efficiency of the process if this approach were to become commonplace within the programme.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Sox8 encodes a high-mobility group transcription factor that is widely expressed during development. Sox8, -9 and -10 form group E of the Sox gene family which has been implicated in several human ...developmental disorders. In contrast to other SoxE genes, the role of Sox8 is unclear and Sox8 mouse mutants reportedly showed only idiopathic weight loss and reduced bone density. The careful analysis of our Sox8 null mice, however, revealed a progressive male infertility phenotype. Sox8 null males only sporadically produced litters of reduced size at young ages. We have shown that SOX8 protein is a product of adult Sertoli cells and its elimination results in an age-dependent deregulation of spermatogenesis, characterized by sloughing of spermatocytes and round spermatids, spermiation failure and a progressive disorganization of the spermatogenic cycle, which resulted in the inappropriate placement and juxtaposition of germ cell types within the epithelium. Those sperm that did enter the epididymides displayed abnormal motility. These data show that SOX8 is a critical regulator of adult Sertoli cell function and is required for both its cytoarchitectural and paracrine interactions with germ cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This article concerns a special learning space populated by Italians and Italian learners: the choir formed in Brisbane as a joint initiative between a community association and the Italian teaching ...staff at Griffith University. Our aim, in involving our students in the choir, was to bring them together with L1 speakers in an environment that would be stimulating but supportive, given the collective, creative goal. We envisaged that interaction in this space would help develop the students' language proficiency, intercultural competence, and cultural knowledge, while also bringing the psychosocial benefits of choral singing identified by recent research. These benefits include positive emotions, social support and friendship, an antidote to anxiety and stress, and a shared sense of commitment. Evaluation of findings from the project suggest that the choir did foster students' learning together with wellbeing.
Peritoneal Dialysis in the Obese Patient Kennedy, Claire; Bargman, Joanne
Clinical journal of the American Society of Nephrology,
02/2020, Volume:
15, Issue:
2
Journal Article
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