3,414 research outputs found

    Reproductive performance of resident and migrant males, females and pairs in a partially migratory bird

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    We thank everyone from the Centre for Ecology & Hydrology (CEH) who contributed to data collection, and Scottish Natural Heritage for access to the Isle of May National Nature Reserve. We thank the Scottish Ornithologists’ Club (SOC) for their support, and all volunteer observers, particularly Raymond Duncan, Moray Souter and Bob Swann. HG was funded by a Natural Environment Research Council (NERC) CASE studentship supported by CEH and SOC, FD, SW, MPH, MN and SB were funded by NERC and the Joint Nature Conservation Committee, and JMR was part-funded by the Royal Society. Finally, we thank the Associate Editor and two reviewers for constructive comments on the manuscript. The data are available from the Dryad Digital Repository https://doi.org/10.5061/dryad.532j0 (Grist et al., 2017)Peer reviewedPublisher PD

    Mutation of the LXCXE Binding Cleft of pRb Facilitates Transformation by ras In Vitro but Does Not Promote Tumorigenesis In Vivo

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    Background:The Retinoblastoma protein (pRB) is a key tumor suppressor that is functionally inactivated in most cancers. pRB regulates the cell division cycle and cell cycle exit through protein-protein interactions mediated by its multiple binding interfaces. The LXCXE binding cleft region of pRB mediates interactions with cellular proteins that have chromatin regulatory functions. Chromatin regulation mediated by pRB is required for a stress responsive cell cycle arrest, including oncogene induced senescence. The in vivo role of chromatin regulation by pRB during senescence, and its relevance to cancer is not clear.Methodology/Principal Findings:Using gene-targeted mice, uniquely defective for pRB mediated chromatin regulation, we investigated its role during transformation and tumor progression in response to activation of oncogenic ras. We report that the pRBΔL mutation confers susceptibility to escape from HrasV12 induced senescence and allows transformation in vitro, although these cells possess high levels of DNA damage. Intriguingly, LSL-Kras, Rb1ΔL/ΔL mice show delayed lung tumor formation compared to controls. This is likely due to the increased apoptosis seen in the early hyperplastic lesions shortly following ras activation that inhibits tumor progression. Furthermore, DMBA treatment to induce sporadic ras mutations in other tissues also failed to reveal greater susceptibility to cancer in Rb1ΔL/ΔL mice.Conclusions/Significance:Our data suggests that chromatin regulation by pRB can function to limit proliferation, but its loss fails to contribute to cancer susceptibility in ras driven tumor models because of elevated levels of DNA damage and apoptosis. © 2013 Talluri et al

    Eating occasion situational factors and sugar-sweetened beverage consumption in young adults

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    Background: Young adulthood represents an influential transitional period marked by poor dietary habits and excess weight gain. Sugar-sweetened beverages (SSB) are a major source of excess caloric intake among young adults, yet little is known about the correlates of SSB consumption. This study examines the individual and situational correlates of SSB consumption, using real-time assessment of Australian young adults&rsquo; eating occasions.&nbsp;&nbsp;Methods: Dietary, sociodemographic and health behaviour data were collected during the Measuring EAting in Everyday Life (MEALS) study (n =&thinsp;675 adults, 18&ndash;30 y). Participants reported all foods and beverages consumed over 3&ndash;4 non-consecutive days using a real-time Smartphone food diary application (&ldquo;FoodNow&rdquo;). For every eating occasion, food and beverage intake was recorded along with situational characteristics (eating location, purchase location, presence of others and activities while eating). A beverage occasion was defined as any eating occasion where a beverage was consumed and a SSB occasion was defined as any eating occasion where a SSB was consumed. Multilevel logistic regression was used to examine individual and situational characteristics with SSB intake at beverage occasions (i.e. factors associated with choosing a SSB over other non-alcoholic beverages) and to examine factors associated with consuming a SSB at any occasion where food and/or beverages were consumed. &nbsp;Results: Thirty-five percent of participants consumed SSBs during the recording period (n =&thinsp;237). Of the 2185 beverage eating occasions reported by SSB consumers, 481 (20%) contained a SSB. SSB were rarely consumed on their own (i.e. other foods were present). Having a lower than tertiary education (odds ratio [95% confidence interval]: 1.53 [1.16, 2.01]; p &lt;&thinsp;0.01); eating in a caf&eacute;/restaurant, compared to at home (3.02 [1.58, 5.78]; p &lt;&thinsp;0.001), and purchasing beverages from a convenience outlet, compared to a supermarket/grocery store (4.58 [2.85, 7.38]; p &lt;&thinsp;0.001) were associated with SSB intake at beverage eating occasions. Similar associations were also found when all food and/or beverage eating occasions were examined. &nbsp;Conclusion: In this study, SSB were often consumed with other foods and intake was associated with individual and situational factors. Further studies are needed to confirm these findings and explore how SSB are consumed in relation to their accompanying foods.</div

    Among-individual and within-individual variation in seasonal migration covaries with subsequent reproductive success in a partially migratory bird

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    Acknowledgements: We thank Raymond Duncan (Grampian Ringing Group), whose insatiable enthusiasm for ringing was inspirational. We thank everyone who contributed to fieldwork, especially Mike Harris and David Hunter; Roger Pradel for generous advice on CMR mixture models; and UK Natural Environment Research Council for funding (NE/R000859/1, NE/P009719/1). Data accessibility Data are available from the Dryad Digital Repository: https://doi.org/10.5061/dryad.pvmcvdnhv [46]. Electronic supplementary material is available online at https://doi.org/10.6084/m9.figshare.c.5054649.Peer reviewedPostprin

    An Elixir for Veteran Teachers: The Power of Social Connections in Keeping These Teachers Passionate and Enthusiastic in Their Work

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    This article is based upon the premise that there are many veteran teachers who maintain positive attitudes towards teaching throughout their careers. According to The Grant Study (Waldinger, 2015), positive attitudes towards life and work stem from close relationships and adaptive behaviours that people engage in throughout adult life. This article describes a study undertaken in Australia which revealed that, in line with Grant Study findings, positive veteran teachers (aged 40-70+ years) build and maintain supportive social connections among colleagues in their school and others outside school, plus spouse (or long-term partner) and close family, that contribute to their sense of emotional and physical wellbeing. In a highly relational career such as teaching, our article highlights the credibility positive veteran teachers ascribe to their social connections, including the derived benefits in terms of their teaching and their own wellbeing. We then discuss the implications of the findings, including the role of school leadership in acknowledging the importance of, and fostering healthy social connections within their schools, as a way of sustaining engagement for all teachers

    A cancer derived mutation in the Retinoblastoma gene with a distinct defect for LXCXE dependent interactions

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    <p>Abstract</p> <p>Background</p> <p>The interaction between viral oncoproteins such as Simian virus 40 TAg, adenovirus E1A, and human papilloma virus E7, and the retinoblastoma protein (pRB) occurs through a well characterized peptide sequence, LXCXE, on the viral protein and a well conserved groove in the pocket domain of pRB. Cellular proteins, such as histone deacetylases, also use this mechanism to interact with the retinoblastoma protein to repress transcription at cell cycle regulated genes. For these reasons this region of the pRB pocket domain is thought to play a critical role in growth suppression.</p> <p>Results</p> <p>In this study, we identify and characterize a tumor derived allele of the retinoblastoma gene (<it>RB1</it>) that possesses a discrete defect in its ability to interact with LXCXE motif containing proteins that compromises proliferative control. To assess the frequency of similar mutations in the <it>RB1 </it>gene in human cancer, we screened blood and tumor samples for similar alleles. We screened almost 700 samples and did not detect additional mutations, indicating that this class of mutation is rare.</p> <p>Conclusions</p> <p>Our work provides proof of principal that alleles encoding distinct, partial loss of function mutations in the retinoblastoma gene that specifically lose LXCXE dependent interactions, are found in human cancer.</p

    Prevalence and causes of prescribing errors: the prescribing outcomes for trainee doctors engaged in clinical training (PROTECT) study

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    Objectives Study objectives were to investigate the prevalence and causes of prescribing errors amongst foundation doctors (i.e. junior doctors in their first (F1) or second (F2) year of post-graduate training), describe their knowledge and experience of prescribing errors, and explore their self-efficacy (i.e. confidence) in prescribing. Method A three-part mixed-methods design was used, comprising: prospective observational study; semi-structured interviews and cross-sectional survey. All doctors prescribing in eight purposively selected hospitals in Scotland participated. All foundation doctors throughout Scotland participated in the survey. The number of prescribing errors per patient, doctor, ward and hospital, perceived causes of errors and a measure of doctors' self-efficacy were established. Results 4710 patient charts and 44,726 prescribed medicines were reviewed. There were 3364 errors, affecting 1700 (36.1%) charts (overall error rate: 7.5%; F1:7.4%; F2:8.6%; consultants:6.3%). Higher error rates were associated with : teaching hospitals (p&#60;0.001), surgical (p = &#60;0.001) or mixed wards (0.008) rather thanmedical ward, higher patient turnover wards (p&#60;0.001), a greater number of prescribed medicines (p&#60;0.001) and the months December and June (p&#60;0.001). One hundred errors were discussed in 40 interviews. Error causation was multi-factorial; work environment and team factors were particularly noted. Of 548 completed questionnaires (national response rate of 35.4%), 508 (92.7% of respondents) reported errors, most of which (328 (64.6%) did not reach the patient. Pressure from other staff, workload and interruptions were cited as the main causes of errors. Foundation year 2 doctors reported greater confidence than year 1 doctors in deciding the most appropriate medication regimen. Conclusions Prescribing errors are frequent and of complex causation. Foundation doctors made more errors than other doctors, but undertook the majority of prescribing, making them a key target for intervention. Contributing causes included work environment, team, task, individual and patient factors. Further work is needed to develop and assess interventions that address these.</p

    Let Them In: Family Presence During Intensive Care Unit Procedures

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    Families have for decades advocated for full access to intensive care units (ICUs) and meaningful partnership with clinicians, resulting in gradual improvements in family access and collaboration with ICU clinicians. Despite such advances, family members in adult ICUs are still commonly asked to leave the patient’s room during invasive bedside procedures, regardless of whether the patient would prefer family to be present. Physicians may be resistant to having family members at the bedside due to concerns about trainee education, medicolegal implications, possible effects on the technical quality of procedures due to distractions, and procedural sterility. Limited evidence from parallel settings does not support these concerns. Family presence during ICU procedures, when the patient and family member both desire it, fulfills the mandates of patient-centered care. We anticipate that such inclusion will increase family engagement, improve patient and family satisfaction, and may, on the basis of studies of open visitation, pediatric ICU experience, and family presence during cardiopulmonary resuscitation, decrease psychological distress in patients and family members. We believe these goals can be achieved without compromising the quality of patient care, increasing provider burden significantly, or increasing risks of litigation. In this article, we weigh current evidence, consider historical objections to family presence at ICU procedures, and report our clinical experience with the practice. An outline for implementing family procedural presence in the ICU is also presented
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