216 research outputs found

    The engaged learner

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    Akt regulates centrosome migration and spindle orientation in the early Drosophila melanogaster embryo

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    Correct positioning and morphology of the mitotic spindle is achieved through regulating the interaction between microtubules (MTs) and cortical actin. Here we find that, in the Drosophila melanogaster early embryo, reduced levels of the protein kinase Akt result in incomplete centrosome migration around cortical nuclei, bent mitotic spindles, and loss of nuclei into the interior of the embryo. We show that Akt is enriched at the embryonic cortex and is required for phosphorylation of the glycogen synthase kinase-3β homologue Zeste-white 3 kinase (Zw3) and for the cortical localizations of the adenomatosis polyposis coli (APC)–related protein APC2/E-APC and the MT + Tip protein EB1. We also show that reduced levels of Akt result in mislocalization of APC2 in postcellularized embryonic mitoses and misorientation of epithelial mitotic spindles. Together, our results suggest that Akt regulates a complex containing Zw3, Armadillo, APC2, and EB1 and that this complex has a role in stabilizing MT–cortex interactions, facilitating both centrosome separation and mitotic spindle orientation

    Early respiratory viral infections in infants with cystic fibrosis

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    This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Background Viral infections contribute to morbidity in cystic fibrosis (CF), but the impact of respiratory viruses on the development of airway disease is poorly understood. Methods Infants with CF identified by newborn screening were enrolled prior to 4 months of age to participate in a prospective observational study at 4 centers. Clinical data were collected at clinic visits and weekly phone calls. Multiplex PCR assays were performed on nasopharyngeal swabs to detect respiratory viruses during routine visits and when symptomatic. Participants underwent bronchoscopy with bronchoalveolar lavage (BAL) and a subset underwent pulmonary function testing. We present findings through 8.5 months of life. Results Seventy infants were enrolled, mean age 3.1 ± 0.8 months. Rhinovirus was the most prevalent virus (66%), followed by parainfluenza (19%), and coronavirus (16%). Participants had a median of 1.5 viral positive swabs (range 0–10). Past viral infection was associated with elevated neutrophil concentrations and bacterial isolates in BAL fluid, including recovery of classic CF bacterial pathogens. When antibiotics were prescribed for respiratory-related indications, viruses were identified in 52% of those instances. Conclusions Early viral infections were associated with greater neutrophilic inflammation and bacterial pathogens. Early viral infections appear to contribute to initiation of lower airway inflammation in infants with CF. Antibiotics were commonly prescribed in the setting of a viral infection. Future investigations examining longitudinal relationships between viral infections, airway microbiome, and antibiotic use will allow us to elucidate the interplay between these factors in young children with CF

    Analysis of lesion localisation at colonoscopy: outcomes from a multi-centre U.K. study

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    Background: Colonoscopy is currently the gold standard for detection of colorectal lesions, but may be limited in anatomically localising lesions. This audit aimed to determine the accuracy of colonoscopy lesion localisation, any subsequent changes in surgical management and any potentially influencing factors. Methods: Patients undergoing colonoscopy prior to elective curative surgery for colorectal lesion/s were included from 8 registered U.K. sites (2012–2014). Three sets of data were recorded: patient factors (age, sex, BMI, screener vs. symptomatic, previous abdominal surgery); colonoscopy factors (caecal intubation, scope guide used, colonoscopist accreditation) and imaging modality. Lesion localisation was standardised with intra-operative location taken as the gold standard. Changes to surgical management were recorded. Results: 364 cases were included; majority of lesions were colonic, solitary, malignant and in symptomatic referrals. 82% patients had their lesion/s correctly located at colonoscopy. Pre-operative CT visualised lesion/s in only 73% of cases with a reduction in screening patients (64 vs. 77%; p = 0.008). 5.2% incorrectly located cases at colonoscopy underwent altered surgical management, including conversion to open. Univariate analysis found colonoscopy accreditation, scope guide use, incomplete colonoscopy and previous abdominal surgery significantly influenced lesion localisation. On multi-variate analysis, caecal intubation and scope guide use remained significant (HR 0.35, 0.20–0.60 95% CI and 0.47; 0.25–0.88, respectively). Conclusion: Lesion localisation at colonoscopy is incorrect in 18% of cases leading to potentially significant surgical management alterations. As part of accreditation, colonoscopists need lesion localisation training and awareness of when inaccuracies can occur

    First Results from COPSS: The CO Power Spectrum Survey

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    We present constraints on the abundance of carbon monoxide in the early universe from the CO Power Spectrum Survey. We utilize a data set collected between 2005 and 2008 using the Sunyaev–Zel'dovich Array (SZA), which was previously used to measure arcminute-scale fluctuations of the cosmic microwave background. This data set features observations of 44 fields, covering an effective area of 1.7 square degrees, over a frequency range of 27–35 GHz. Using the technique of intensity mapping, we are able to probe the CO(1–0) transition, with sensitivity to spatial modes between k = 0.5–2 h Mpc^(−1) over a range in redshift of z = 2.3–3.3, spanning a comoving volume of 3.6 × 10^6 h^(−3) Mpc^3. We demonstrate our ability to mitigate foregrounds, and present estimates of the impact of continuum sources on our measurement. We constrain the CO power spectrum to P_(CO) < 2.6 × 10^4 μK^2 (h^(−1) Mpc)^3, or Δ^2_(CO)(k = 1 h Mpc^(−1)) < 1.3 × 10^3 μK^2, at 95% confidence. This limit resides near optimistic predictions for the CO power spectrum. Under the assumption that CO emission is proportional to halo mass during bursts of active star formation, this corresponds to a limit on the ratio of CO(1–0) luminosity to host halo mass of A_(CO) < 1.2 × 10^(−5) L⊙_ M_⊙^(−1). Further assuming a Milky Way-like conversion factor between CO luminosity and molecular gas mass (α_(CO) = 4.3 M_⊙ (K km s^(−1) pc^(−2))^(−1)), we constrain the global density of molecular gas to ρ_(z~3) (M_H_2) ⩽ 2.8 x 10^8 M_☉ Mpc^(-3)

    Governing the governors : a case study of college governance in English further education

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    This paper addresses the nature of governors in the governance of further education colleges in an English context (1). It explores the complex relationship between governors (people/agency), government (policy/structure) and governance (practice), in a college environment. While recent research has focused on the governance of schooling and higher education there has been little attention paid to the role of governors in the lifelong learning sector. The objective of the paper is to contribute to the debate about the purpose of college governance at a time when the Learning and Skills Council (LSC) commissioning era ends, and new government bodies responsible for further education and training, including local authorities, arrive. The paper analyses the nature of FE governance through the perspectives and experiences of governors, as colleges respond to calls from government for greater improvement and accountability in the sector (LSIS, 2009a). What constitutes creative governance is complex and controversial in the wider framework of regulation and public policy reform (Stoker, 1997; Seddon, 2008). As with other tricky concepts such as leadership, professionalism and learning, college governance is best defined in the contexts, cultures and situations in which it is located. College governance does not operate in a vacuum. It involves governors, chairs, principals, professionals, senior managers, clerks, community, business and wider agencies, including external audit and inspection regimes. Governance also acts as a prism through which national education and training reforms are mediated, at local level. While governing bodies are traditionally associated with the business of FE - steering, setting the tone and style, dealing with finance, funding, audit and procedural matters – they are increasingly being challenged to be more creative and responsive to the wider society. Drawing on a recent case study of six colleges, involving governors and key policy stakeholders, this paper explores FE governance in a fast changing policy environment
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