97 research outputs found

    How do 16-17 year old school students engage with scientific research?

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    Our article explores how 16-17 year old school students discuss contemporary scientific research and how they use their current school science knowledge in thinking through open research problems in biomedical science. Contemporary research problems (somewhat simplified) were presented to school groups of six participants who were tasked with discussing possible solutions. More specifically, they were asked to devise testable hypotheses and experiments to account for cell movements that form the embryonic spinal cord. An experienced researcher presented the problem and was available to answer student questions and to prompt them when they became stuck. Our analysis shows that fruitful discussions have the following three features: authoritative scaffolding encouraging elaboration, explanation, and use of pupil knowledge; willingness of participants to problematise and revise suggestions; and collective elaboration of ideas sufficient to stimulate new questions. Students drew on knowledge through dialogue which problematised their school knowledge and opened-up its difficulties in application to a research task. We suggest that an openness to new ways of thinking and uncertainty in learning science rather than the STEM ‘pipeline’ might attract more young people from minority groups into studying science at university and open up new pedagogic possibilities in addressing science research in schools

    Some types of carbon-based nanomaterials as contrast agents for photoacoustic tomography

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    This paper is devoted to the study of various carbon-based nanomaterials as photoacoustic contrast agents. The research work was performed on agarose-based tissue phantom containing inclusions with and without carbon-based nanomaterials. The inclusion was created with the higher density compared to phantom in order to simulate a tumor. A specially designed photoacoustic probe was introduced for measuring a level of photoacoustic signal and its enhancement caused by the nanoinclusions presence. The probe consists of a buffer for time separation of the signal coming from the excitation source, piezoelectric transducer, and amplifier. A point-by-point measurement of the signal was performed to obtain a two-dimensional map from magnitude of photoacoustic signal and phase delay of the signal registration. From phase delay the 3D photoacoustic images were reconstructed by evaluation of the depth coordinate based on the tissue sound velocity. As an excitation source the light radiation from Nd:YAG laser with a 16 ns pulse duration and a 1064 nm wavelength was used. Firstly, we considered tissue phantom with a tumor covered by graphene oxide as a reference one. It has been shown that the use of graphene oxide leads to significant improvement of the image contrast. Further, the tumors labelled with nanodiamonds (NDs) and carbon fluoroxide (CFO) nanoparticles (NPs) were studied systematically. Amplitude of the photoacoustic signals registered from such tumor phantoms are one order of magnitude lower than the signal ensured by graphene oxide. All three types of the studied carbon-based nanomaterials (GO, NDs, CFO) give stable photoacoustic signal, this allows to consider them as good candidates for further in-vitro experiments in photoacoustic imaging for biological applications. The dependences of the signal level as a function of the NPs concentration were measured for types of NPs. Considering much more efficient penetration of NDs and CFO NPs inside the cells as well as their extremely low cytotoxicity, these both types of carbon nanomaterials could be used for further in-vivo experiments

    A Src-Like Inactive Conformation in the Abl Tyrosine Kinase Domain

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    The improper activation of the Abl tyrosine kinase results in chronic myeloid leukemia (CML). The recognition of an inactive conformation of Abl, in which a catalytically important Asp-Phe-Gly (DFG) motif is flipped by approximately 180° with respect to the active conformation, underlies the specificity of the cancer drug imatinib, which is used to treat CML. The DFG motif is not flipped in crystal structures of inactive forms of the closely related Src kinases, and imatinib does not inhibit c-Src. We present a structure of the kinase domain of Abl, determined in complex with an ATP–peptide conjugate, in which the protein adopts an inactive conformation that resembles closely that of the Src kinases. An interesting aspect of the Src-like inactive structure, suggested by molecular dynamics simulations and additional crystal structures, is the presence of features that might facilitate the flip of the DFG motif by providing room for the phenylalanine to move and by coordinating the aspartate side chain as it leaves the active site. One class of mutations in BCR–Abl that confers resistance to imatinib appears more likely to destabilize the inactive Src-like conformation than the active or imatinib-bound conformations. Our results suggest that interconversion between distinctly different inactive conformations is a characteristic feature of the Abl kinase domain

    Clinical and Endoscopic Characteristics do Not Reliably Differentiate PPI-Responsive Esophageal Eosinophilia and Eosinophilic Esophagitis in Patients Undergoing Upper Endoscopy: A Prospective Cohort Study

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    Proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is a newly recognized entity that must be differentiated from eosinophilic esophagitis (EoE). Little is known about this condition. We aimed to determine the prevalence of PPI-REE and EoE in patients undergoing upper endoscopy, and determine features that distinguish the two groups

    A Clinical Prediction Tool Identifies Cases of Eosinophilic Esophagitis Without Endoscopic Biopsy: A Prospective Study

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    Eosinophilic esophagitis (EoE) is difficult to distinguish from gastroesophageal reflux (GERD) and other causes of dysphagia. We assessed the utility of a set of clinical and endoscopic features for predicting EoE without obtaining esophageal biopsies

    Conversation analysis of the two-chair self-soothing task in emotion-focused therapy

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    Despite an increasing recognition of the relevance and significance of self-compassion processes, little research has explored interventions that seek to enhance these in therapy. In this study, we used conversation analysis to examine the compassionate self-soothing task of emotion-focused therapy involving two-chair work, with seven clients. The analysis yielded a detailed description of interactional practices and processes involved in the accomplishment of self-soothing, drawing on Goffman’s concept of the participation frame. In this article we show how therapists and clients collaborate to move from the ordinary frame of therapeutic conversation to a self-soothing frame and back again. Furthermore, we show that in this movement between the frames, they make use of a number interactional practices: therapists' instructions to clients, specific ways of sequencing actions in interaction, explanations and justification of the importance of the self-soothing task, pronouns as a way to distinguish among addressees (e.g., clients versus soothing agents), corrections of clients’ talk, and response tokens (hm mm, yeah, good). These practices are used to help clients accomplish self-soothing in the form of self-praise, disclosing caring, and offering of helpful advice

    Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

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    We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

    Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

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    BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years
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