Prolonged Refractory Hypotension following Combined Amlodipine and Losartan Ingestion Responsive to Metaraminol

Introduction. Overdose with the calcium channel blocker amlodipine can cause profound hypotension that may be exacerbated by the concurrent ingestion of an angiotensin II receptor antagonist. Best management of such overdoses is uncertain although the use of hyperinsulinaemia-euglycaemia (HIE) has been recommended. Case report. We report a case of mixed amlodipine and losartan overdose in a 50-year-old lady. Severe hypotension was resistant to conventional vasopressors and high-dose insulin/euglycaemia, but did respond to a metaraminol infusion. Conclusion. A trial of metaraminol early in severe cases of calcium channel blocker and angiotensin II receptor antagonist toxicity may be of benefit, especially when conventional ionotropic treatment measures are failing

Growth Mindset: Associations with Apprehension, Self-Perceived Competence, and Beliefs about Public Speaking

The relationships among growth mindset for public speaking (i.e., the implicit theory that public speaking abilities can be developed and improved) and beliefs about the nature of public speaking, public speaking apprehension (PSA), and self-perceived public speaking competence (SPPSC) were investigated in intensive and traditional formats of a general education public speaking course. In general, growth mindset was associated with lower PSA, higher SPPSC, and more sophisticated beliefs about public speaking. Mindset remained somewhat stable, PSA significantly decreased, and SPPSC significantly increased from the beginning to the end of the course. More sophisticated beliefs about public speaking as an expressive, transformational, and audience-centric endeavor also tended to increase. However, there were several important differences between intensive and traditional formats. In particular, changes in the intensive format were more consistent across variables and had larger effect sizes

Slim Epistemology with a Thick Skin

The distinction between ‘thick’ and ‘thin’ value concepts, and its importance to ethical theory, has been an active topic in recent meta-ethics. This paper defends three claims regarding the parallel issue about thick and thin epistemic concepts. (1) Analogy with ethics offers no straightforward way to establish a good, clear distinction between thick and thin epistemic concepts. (2) Assuming there is such a distinction, there are no semantic grounds for assigning thick epistemic concepts priority over the thin. (3) Nor does the structure of substantive epistemological theory establish that thick epistemic concepts enjoy systematic theoretical priority over the thin. In sum, a good case has yet to be made for any radical theoretical turn to thicker epistemology

Bilateral Assessment of Functional Tasks for Robot-assisted Therapy Applications

This article presents a novel evaluation system along with methods to evaluate bilateral coordination of arm function on activities of daily living tasks before and after robot-assisted therapy. An affordable bilateral assessment system (BiAS) consisting of two mini-passive measuring units modeled as three degree of freedom robots is described. The process for evaluating functional tasks using the BiAS is presented and we demonstrate its ability to measure wrist kinematic trajectories. Three metrics, phase difference, movement overlap, and task completion time, are used to evaluate the BiAS system on a bilateral symmetric (bi-drink) and a bilateral asymmetric (bi-pour) functional task. Wrist position and velocity trajectories are evaluated using these metrics to provide insight into temporal and spatial bilateral deficits after stroke. The BiAS system quantified movements of the wrists during functional tasks and detected differences in impaired and unimpaired arm movements. Case studies showed that stroke patients compared to healthy subjects move slower and are less likely to use their arm simultaneously even when the functional task requires simultaneous movement. After robot-assisted therapy, interlimb coordination spatial deficits moved toward normal coordination on functional tasks

Quality of intervention delivery in a cluster randomised controlled trial : a qualitative observational study with lessons for implementation fidelity

Abstract Background Understanding intervention fidelity is an essential part of the evaluation of complex interventions because fidelity not only affects the validity of trial findings, but also because studies of fidelity can be used to identify barriers and facilitators to successful implementation, and so provide important information about factors likely to impact the uptake of the intervention into clinical practice. Participant observation methods have been identified as being particularly valuable in studies of fidelity, yet are rarely used. This study aimed to use these methods to explore the quality of implementation of a complex intervention (Safewards) on mental health wards during a cluster randomised controlled trial. Specific aims were firstly to describe the different ways in which the intervention was implemented, and secondly to explore the contextual factors moderating the quality of intervention delivery, in order to inform ‘real world’ implementation of the intervention. Methods Safewards was implemented on 16 mental health wards in England. We used Research Assistants (RAs) trained in participant observation to record qualitative observational data on the quality of intervention delivery (n = 565 observations). At the end of the trial, two focus groups were conducted with RAs, which were used to develop the coding framework. Data were analysed using thematic analysis. Results There was substantial variation in intervention delivery between wards. We observed modifications to the intervention which were both fidelity consistent and inconsistent, and could enhance or dilute the intervention effects. We used these data to develop a typology which describes the different ways in which the intervention was delivered. This typology could be used as a tool to collect qualitative observational data about fidelity during trials. Moderators of Safewards implementation included systemic, interpersonal, and individual factors and patient responses to the intervention. Conclusions Our study demonstrates how, with appropriate training in participant observation, RAs can collect high-quality observational data about the quality of intervention delivery during a trial, giving a more complete picture of ‘fidelity’ than measurements of adherence alone. Trial registration ISRCTN registry; IRSCTN38001825 . Registered 29 August 201

The PREVENT dementia programme: baseline demographic, lifestyle, imaging and cognitive data from a midlife cohort study investigating risk factors for dementia

PREVENT is a multi-centre prospective cohort study in the UK and Ireland that aims to examine midlife risk factors for dementia and identify and describe the earliest indices of disease development. The PREVENT dementia programme is one of the original epidemiological initiatives targeting midlife as a critical window for intervention in neurodegenerative conditions. This paper provides an overview of the study protocol and presents the first summary results from the initial baseline data to describe the cohort. Participants in the PREVENT cohort provide demographic data, biological samples (blood, saliva, urine and optional cerebrospinal fluid), lifestyle and psychological questionnaires, undergo a comprehensive cognitive test battery and are imaged using multi-modal 3-T MRI scanning, with both structural and functional sequences. The PREVENT cohort governance structure is described, which includes a steering committee, a scientific advisory board and core patient and public involvement groups. A number of sub-studies that supplement the main PREVENT cohort are also described. The PREVENT cohort baseline data include 700 participants recruited between 2014 and 2020 across five sites in the UK and Ireland (Cambridge, Dublin, Edinburgh, London and Oxford). At baseline, participants had a mean age of 51.2 years (range 40–59, SD ± 5.47), with the majority female (n = 433, 61.9%). There was a near equal distribution of participants with and without a parental history of dementia (51.4% versus 48.6%) and a relatively high prevalence of APOEɛ4 carriers (n = 264, 38.0%). Participants were highly educated (16.7 ± 3.44 years of education), were mainly of European Ancestry (n = 672, 95.9%) and were cognitively healthy as measured by the Addenbrookes Cognitive Examination-III (total score 95.6 ± 4.06). Mean white matter hyperintensity volume at recruitment was 2.26 ± 2.77 ml (median = 1.39 ml), with hippocampal volume being 8.15 ± 0.79 ml. There was good representation of known dementia risk factors in the cohort. The PREVENT cohort offers a novel data set to explore midlife risk factors and early signs of neurodegenerative disease. Data are available open access at no cost via the Alzheimer’s Disease Data Initiative platform and Dementia Platforms UK platform pending approval of the data access request from the PREVENT steering group committee

An Initial Exploration of Engineering Student Perceptions of COVID’s Impact on Connectedness, Learning, and STEM Identity

This paper studied the development of STEM identity for freshman students in Engineering. An Urban Research University received a 5-year S-STEM award in fall 2018. So far, two cohorts of scholars have received the scholarship as well as academic support, mentoring support, and customized advising from faculty and upper level peers. The objective of this project is to help underrepresented and talented students in engineering to pursue an undergraduate degree. A Multi-Layered Mentoring(MLM) Program was established, and several interviews were conducted with scholarship recipients. The qualitative and qualitative analysis of the student success shows an improvement in GPA of students in the program as compared to the rest of the school. The students not only received financial help through the program based on their unmet needs, they are were placed in an engineering learning community (ELC). The participants in ELC and MLM programs agreed to participate in research studies to assess their success. This NSF funded program also helped freshman students be involved in a hands-on Design Innovations class where they learned design process and human centered design. The students were surveyed on a regular basis to identify their needs and were approached by faculty advisor as well as their mentors to trouble shoot their concerns and help them with both social and academic aspects of their concerns. The first cohort joined the program in AY 2019-2020, as freshmen. This cohort had experienced a full semester of in-person engagement before the COVID-19 hit in the middle of the second semester of their freshman year. We have researched the impact of the pandemic on their academic progress, sense of belonging, and STEM identity. The second cohort joined the program in AY 2020-2021. They have not had the chance to experience the campus life and their perspective of college life is very different than the first cohort. The STEM identity was one of the success indicators for freshman students who entered the university in one of the most difficult and un-usual circumstances under the COVID-19 pandemic

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

The differential diagnosis of children with joint hypermobility: a review of the literature

<p>Abstract</p> <p>Background</p> <p>In this study we aimed to identify and review publications relating to the diagnosis of joint hypermobility and instability and develop an evidence based approach to the diagnosis of children presenting with joint hypermobility and related symptoms.</p> <p>Methods</p> <p>We searched Medline for papers with an emphasis on the diagnosis of joint hypermobility, including Heritable Disorders of Connective Tissue (HDCT).</p> <p>Results</p> <p>3330 papers were identified: 1534 pertained to instability of a particular joint; 1666 related to the diagnosis of Ehlers Danlos syndromes and 330 related to joint hypermobility.</p> <p>There are inconsistencies in the literature on joint hypermobility and how it relates to and overlaps with milder forms of HDCT. There is no reliable method of differentiating between Joint Hypermobility Syndrome, familial articular hypermobility and Ehlers-Danlos syndrome (hypermobile type), suggesting these three disorders may be different manifestations of the same spectrum of disorders. We describe our approach to children presenting with joint hypermobility and the published evidence and expert opinion on which this is based.</p> <p>Conclusion</p> <p>There is value in identifying both the underlying genetic cause of joint hypermobility in an individual child and those hypermobile children who have symptoms such as pain and fatigue and might benefit from multidisciplinary rehabilitation management.</p> <p>Every effort should be made to diagnose the underlying disorder responsible for joint hypermobility which may only become apparent over time. We recommend that the term "Joint Hypermobility Syndrome" is used for children with symptomatic joint hypermobility resulting from any underlying HDCT and that these children are best described using <b>both </b>the term Joint Hypermobility Syndrome <b>and </b>their HDCT diagnosis.</p

Metal A and Metal B Sites of Nuclear RNA Polymerases Pol IV and Pol V Are Required for siRNA-Dependent DNA Methylation and Gene Silencing

Plants are unique among eukaryotes in having five multi-subunit nuclear RNA polymerases: the ubiquitous RNA polymerases I, II and III plus two plant-specific activities, nuclear RNA polymerases IV and V (previously known as Polymerases IVa and IVb). Pol IV and Pol V are not required for viability but play non-redundant roles in small interfering RNA (siRNA)-mediated pathways, including a pathway that silences retrotransposons and endogenous repeats via siRNA-directed DNA methylation. RNA polymerase activity has not been demonstrated for Polymerases IV or V in vitro, making it unclear whether they are catalytically active enzymes. Their largest and second-largest subunit sequences have diverged considerably from Pol I, II and III in the vicinity of the catalytic center, yet retain the invariant Metal A and Metal B amino acid motifs that bind magnesium ions essential for RNA polymerization. By using site-directed mutagenesis in conjunction with in vivo functional assays, we show that the Metal A and Metal B motifs of Polymerases IV and V are essential for siRNA production, siRNA-directed DNA methylation, retrotransposon silencing, and the punctate nuclear localization patterns typical of both polymerases. Collectively, these data show that the minimal core sequences of polymerase active sites, the Metal A and B sites, are essential for Pol IV and Pol V biological functions, implying that both are catalytically active