bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell length growth patterns in fission yeast reveal a novel size control mechanism operating in late G2 phase
Authors: Horváth Anna , Rácz‐Mónus Anna , Buchwald Peter , Sveiczer Ákos 
Published: April 2016

Background informationBecause cylindrically shaped fission yeast cells grow exclusively at their tips, cell volume is proportional to length and can be easily monitored by time‐lapse microscopy. Here, we analysed the growth pattern of individual cells from several fission yeast strains to determine the growth function that describes them most adequately and to perform size control studies.ResultsThe growth pattern of most cells during their growth period is best described by a bilinear function (i.e., two linear segments of different growth rates separated by a rate‐change point). Linear growth patterns were also observed in several cases, but exponential ones only rarely. Since the bilinear patterns are separated into two segments by a breakpoint, we examined the existence of size control by regression analyses of the appropriate growth parameters in both segments. This confirmed the existence of known size controls in late G1, mid‐G2 and late G2 during the fission yeast cycle. The present analyses also revealed that, contrary to the commonly accepted current view, late G2 size control is a general characteristic third event in the cycle. The level of the critical late G2 size that needs to be reached in an individual fission yeast cell is influenced by the growth rate of the cell in a manner similar to budding yeast, suggesting an evolutionary conserved mechanism.ConclusionsThe present study of individual cell growth patterns in wild‐type and several cell cycle mutant fission yeast strains confirmed that, for most cells, growth is best described by a bilinear function. Three different size control mechanisms were found to operate in the different strains, and, as a novel observation, cell size was always found to be monitored before mitotic onset, irrespective of the existence of any earlier size checkpoints.SignificanceStudying the pattern of growth and the mechanism of size control helps to clarify the connections between cell growth and division, since their coordination must work properly to maintain size homeostasis. In this study, we argue that most individual fission yeast cells grow following a bilinear pattern, and we confirm the existence of three different size control mechanisms.
Self‐management support in patients with adrenal insufficiency
Authors: van der Meij Nick T.M. , van Leeuwaarde Rachel S. , Vervoort Sigrid C.J.M. , Zelissen Pierre M.J. 
Published: April 2016

SummaryObjectivePatient education is an important intervention to prevent an adrenal crisis in patients with adrenal insufficiency. The objective of this study was to assess the knowledge of adjusting the dose of glucocorticoids in special circumstances in patients with adrenal insufficiency who had previously been educated on this topic. In patients with insufficient knowledge, we tried to identify the underlying causes and care needs.DesignQuantitative and qualitative study.MethodsAdult patients with chronic primary and secondary adrenal insufficiency who received glucocorticoid stress management education were invited to participate in a telephone interview in which we tested their knowledge using hypothetical situations of physical and mental stress. In respondents with insufficient knowledge, we conducted a qualitative semistructured interview to elicit the underlying reasons from patients’ perspective for their lack of knowledge and determine their care needs.ResultsForty‐three of the 83 patients who previously received education had insufficient knowledge about how to act during stressful situations. We found a significant association between education level and level of knowledge after the educational consult. The following underlying factors were identified: unawareness of the seriousness of their condition, ineffective coping strategies, the lack of experience with self‐management skills and misconceptions. The most important care needs were repetition of education, the use of guidelines, learning from experience and optimizing social support.ConclusionOne or two educational consults are not effective to achieve adequate self‐management skills. There is a need for structural follow‐up where education is repeated and practical implementation of this knowledge is tested in order to identify the potential inadequate action.
Safety, tolerability, pharmacokinetics and pharmacodynamics of AZP‐531, a first‐in‐class analogue of unacylated ghrelin, in healthy and overweight/obese subjects and subjects with type 2 diabetes
Authors: Allas S. , Delale T. , Ngo N. , Julien M. , Sahakian P. , Ritter J. , Abribat T. , van der Lely A. J. 
Published: April 2016

AimTo explore the safety, pharmacokinetics and pharmacodynamics in humans of the unacylated ghrelin analogue AZP‐531, designed to improve glycaemic control and reduce weight.MethodsAssessments, including glucose measurements, were performed in a three‐part randomized study. In Part A, healthy subjects [n = 44, age 18–50 years, body mass index (BMI) 20–28 kg/m2] received a single subcutaneous dose of 0.3, 3, 15, 30, 60 or 120 µg/kg AZP‐531 or placebo. In Part B, overweight/obese subjects (n = 32, age 18–65 years, BMI 28–38 kg/m2) and in Part C, patients with type 2 diabetes [T2D; n = 36, age 18–65 years, BMI 20–40 kg/m2, glycated haemoglobin (HbA1c) 7–10%] received AZP‐531 or placebo for 14 days (daily doses of 3, 15, 30 or 60 µg/kg and 15, 2 × 30 or 60 µg/kg, respectively).ResultsAZP‐531 was well tolerated. Single‐ and multiple‐dose pharmokinetic variables were similar. Maximum AZP‐531 concentrations were typically reached at 1 h post‐dose. Observed maximum concentration (Cmax) and area under the curve were dose‐proportional. The mean terminal half‐life (t1/2) was 2–3 h. In Part B, AZP‐531 doses of ≥15 µg/kg significantly improved glucose concentrations, without increasing insulin levels, suggesting an insulin‐sensitizing effect. AZP‐531 decreased mean body weight by 2.6 kg (vs 0.8 kg for placebo). In Part C, glucose variables improved in all groups, including placebo, suggesting a study effect in uncontrolled patients at baseline. Notwithstanding, AZP‐531 60 µg/kg reduced HbA1c by 0.4% (vs 0.2% for placebo) and body weight by 2.1 kg (vs 1.3 kg for placebo).ConclusionsAZP‐531 was well tolerated in this first‐in‐human study. Its pharmacokinetic profile, suitable for once‐daily dosing, and metabolic effects support further clinical development for T2D.
A Comparison of Learning Outcomes in Skills‐Based Courses: Online Versus Face‐To‐Face Formats
Authors: Callister Ronda Roberts , Love Mary Sue 
Published: April 2016

ABSTRACTIn comparing the learning outcomes of online versus face‐to‐face courses, skills‐based forms of instruction have received little attention. This study asks the question “Can skills‐based courses taught online achieve the same outcomes as face‐to‐face courses in which the instructor and students interacting in real time may have higher levels of interaction, thus potentially facilitating higher levels of skill improvement?” If so, what are the critical success factors that influence these outcomes? These questions are examined by comparing four classes in negotiations (two face‐to‐face and two online) taught by the same professor. The courses were designed to be as similar as possible except for their delivery method. Results indicate that face‐to‐face learners earned higher negotiation outcomes than online learners even when using the same technology. Suggestions are offered for improving outcomes.
Brown shrimp (Farfantepenaeus aztecus) density distribution in the Northern Gulf of Mexico: an approach using boosted regression trees
Authors: Montero Jose T. , Chesney Tanya A. , Bauer Jennifer R. , Froeschke John T. , Graham Jim 
Published: April 2016

AbstractThe estuarine‐dependent brown shrimp, Farfantepenaeus aztecus, is a significant commercial fishery and important species in the Gulf of Mexico (GOM) ecosystem as well as being a key component in energy transfer between benthic and pelagic food web systems. Because of the economical and ecological importance of brown shrimp, we developed a spatial population model to identify places of high shrimp density under a set of spatial, environmental and temporal variables in the Northern Gulf of Mexico (NGOM). We used fisheries‐independent data collected by the Southeast Area Monitoring and Assessment Program (SEAMAP) from 1992 to 2007 (summer and fall seasons). The relationship between the predictor variables and shrimp density was modeled using Boosted Regression Trees (BRT). Within the environmental variables included in the model, bottom type and depth of the water column were the most important predictors of shrimp density in the NGOM. Spatial predictions performed using the trained BRT model for summer and fall seasons showed a spatial segregation of shrimp density. During the summer, higher densities were predicted near the Texas and Louisiana coast and during the fall, higher densities were predicted further offshore. The model performed well and allowed successful prediction of brown shrimp hot spots in the NGOM. Model results allow fisheries managers to evaluate the potential impact from fisheries on the resource and to develop future fisheries management strategies, understand the biology of brown shrimp as well as assess the potential impacts of oil spills or climate change.
Diagnostic accuracy of periapical radiography and cone beam computed tomography in detecting apical periodontitis using histopathological findings as a reference standard
Authors: Kanagasingam S. , Lim C. X. , Yong C. P. , Mannocci F. , Patel S. 
Published: April 2016

AbstractAimTo compare the diagnostic accuracy of periapical radiography (PR) and cone beam computed tomography (CBCT) in detecting apical periodontitis (AP) using histopathological findings as a reference standard.MethodologyJaw sections containing 67 teeth (86 roots) were collected from unclaimed bodies due for cremation. Imaging was carried out to detect AP by digital PR with a central view (DP group), digital PR combining central with 10˚ mesially and distally angled (parallax) views (DPS group) and CBCT scans. All specimens underwent histopathological examination to confirm the diagnosis of AP. Sensitivity, specificity and predictive values of PR and CBCT were analysed using rater mean (n = 5). Receiver‐operating characteristic (ROC) analysis was carried out.ResultsSensitivity was 0.27, 0.38 and 0.89 for DP, DPS and CBCT scans, respectively. CBCT had specificity and positive predictive value of 1.0 whilst DP and DPS had specificity and positive predictive value of 0.99. The negative predictive value was 0.39, 0.44 and 0.81 for DP, DPS and CBCT scans, respectively. Area under the curve (AUC) for the various imaging methods was 0.629 (DP), 0.688 (DPS), and 0.943 (CBCT).ConclusionsAll imaging techniques had similar specificity and positive predictive values. Additional parallax views increased the diagnostic accuracy of PR. CBCT had significantly higher diagnostic accuracy in detecting AP compared to PR, using human histopathological findings as a reference standard.
Accuracy of single and parallax film and digital periapical radiographs in diagnosing apical periodontitis – a cadaver study
Authors: Kanagasingam S. , Hussaini H. M. , Soo I. , Baharin S. , Ashar A. , Patel S. 
Published: April 2016

AbstractAimTo compare the accuracy of film and digital periapical radiography (PR) in detecting apical periodontitis (AP) using histopathological findings as a reference standard.MethodologyJaw sections containing 67 teeth (86 roots) were collected from nine fresh, unclaimed bodies that were due for cremation. Imaging was carried out to detect AP lesions using film and digital PR with a centred view (FP and DP groups); film and digital PR combining central with 10˚ mesially and distally angled (parallax) views (FPS and DPS groups). All specimens underwent histopathological examination to confirm the diagnosis of AP. Sensitivity, specificity and predictive values of PR were analysed using rater mean (n = 5). Receiver operating characteristics (ROC) analysis was carried out.ResultsSensitivity was 0.16, 0.37, 0.27 and 0.38 for FP, FPS, DP and DPS, respectively. Both FP and FPS had specificity and positive predictive values of 1.0, whilst DP and DPS had specificity and positive predictive values of 0.99. Negative predictive value was 0.36, 0.43, 0.39 and 0.44 for FP, FPS, DP and DPS, respectively. Area under the curve (AUC) for the various imaging methods was 0.562 (FP), 0.629 (DP), 0.685 (FPS), 0.6880 (DPS).ConclusionsThe diagnostic accuracy of single digital periapical radiography was significantly better than single film periapical radiography. The inclusion of two additional horizontal (parallax) angulated periapical radiograph images (mesial and distal horizontal angulations) significantly improved detection of apical periodontitis.
Knowledge translation studies in paediatric emergency medicine: A systematic review of the literature
Authors: Wilson Catherine L , Johnson David , Oakley Ed ,   on behalf of the Paediatric Research in Emergency Departments International Collaborative (PREDICT) network
Published: April 2016

AbstractAimSystematic review of knowledge translation studies focused on paediatric emergency care to describe and assess the interventions used in emergency department settings.MethodsElectronic databases were searched for knowledge translation studies conducted in the emergency department that included the care of children. Two researchers independently reviewed the studies.ResultsFrom 1305 publications identified, 15 studies of varied design were included. Four were cluster‐controlled trials, two patient‐level randomised controlled trials, two interrupted time series, one descriptive study and six before and after intervention studies. Knowledge translation interventions were predominantly aimed at the treating clinician, with some targeting the organisation. Studies assessed effectiveness of interventions over 6–12 months in before and after studies, and 3–28 months in cluster or patient level controlled trials. Changes in clinical practice were variable, with studies on single disease and single treatments in a single site showing greater improvement.ConclusionsEvidence for effective methods to translate knowledge into practice in paediatric emergency medicine is fairly limited. More optimal study designs with more explicit descriptions of interventions are needed to facilitate other groups to effectively apply these procedures in their own setting.
Alternatives to ward admission from the emergency department
Authors: Bryant Penelope A , Hopper Sandy M 
Published: April 2016

AbstractThere is ever‐increasing pressure on hospital resources in general and emergency departments (ED) in particular. At the same time, there is increasing recognition that traditional inpatient ward‐based care is not necessary for the majority of children presenting to the ED with acute illness, and that there are patient, family and hospital benefits to pursuing other options. Here, we describe alternative pathways for children presenting to the ED, including short stay and observational medicine, hospital‐in‐the‐home and non‐admission enhanced care, in other words, additional management practices or pathways for children who are discharged from the ED. We discuss the principles, models and practical considerations involved in each of these.
Paediatric emergency and acute care in resource poor settings
Authors: Duke Trevor , Cheema Baljit 
Published: April 2016

AbstractAcute care of seriously ill children is a global public health issue, and there is much scope for improving quality of care in hospitals at all levels in many developing countries. We describe the current state of paediatric emergency and acute care in the least developed regions of low and middle income countries and identify gaps and requirements for improving quality. Approaches are needed which span the continuum of care: from triage and emergency treatment, the diagnostic process, identification of co‐morbidities, treatment, monitoring and supportive care, discharge planning and follow‐up. Improvements require support and training for health workers and quality processes. Effective training is that which is ongoing, combining good technical training in under‐graduate courses and continuing professional development. Quality processes combine evidence‐based guidelines, essential medicines, appropriate technology, appropriate financing of services, standards and assessment tools and training resources. While initial emergency treatment is based on common clinical syndromes, early differentiation is required for specific treatment, and this can usually be carried out clinically without expensive tests. While global strategies are important, it is what happens locally that makes a difference and is too often neglected. In rural areas in the poorest countries in the world, public doctors and nurses who provide emergency and acute care for children are revered by their communities and demonstrate daily that much can be carried out with little.
Elevated serum ferritin is associated with increased mortality in non‐alcoholic fatty liver disease after 16 years of follow‐up
Authors: Hagström Hannes , Nasr Patrik , Bottai Matteo , Ekstedt Mattias , Kechagias Stergios , Hultcrantz Rolf , Stål Per 
Published: April 2016

AbstractBackground & AimsHigh levels of ferritin in patients with non‐alcoholic fatty liver disease (NAFLD) are associated with significant fibrosis and higher NAFLD activity score (NAS). It is unclear if this association has an impact on mortality. We investigated if high levels of ferritin, with or without iron overload, were associated with an increased mortality in NAFLD.MethodsWe included 222 patients between 1979 and 2009 with biopsy‐proven NAFLD and available serum ferritin concentrations. The cohort was divided into ‘high’ (n = 89) and ‘normal’ (n = 133) ferritin values, using a cut‐point of 350 μg/L in males, and 150 μg/L in females, and stratified upon iron overload status. Data on mortality were obtained from a national, population‐based register. Poisson regression was used to estimate hazard ratios for mortality. The estimates were adjusted for age at biopsy, sex, smoking, BMI, diabetes, hypertension, cardiovascular disease and fibrosis stage at the time of biopsy.ResultsThe median follow‐up time was 15.6 years (range: 0.5–34.2). Patients with high ferritin had more advanced fibrosis and higher NAS than patients with normal ferritin (P < 0.05). Fifteen years after diagnosis, and after adjusting for confounders, the high‐ferritin group showed an increasingly higher mortality that was statistically significant (Hazard ratio = 1.10 per year, 95% Confidence interval 1.01–1.21, P < 0.05). There was no difference in mortality between patients with different iron overload patterns.ConclusionsHigh levels of ferritin are associated with a long‐term increased risk of death.
Metaphysics Within Science: Against Radical Naturalism
Authors: Andersen Fredrik , Becker Arenhart Jonas R. 
Published: April 2016

AbstractIn Every Thing Must Go James Ladyman and Don Ross argue for a radical version of naturalistic metaphysics and propose that contemporary analytic metaphysics is detached from science and should be discontinued. The present article addresses the issues of whether (i) science and metaphysics are separable, (ii) intuitions and understanding should be excluded from scientific theory, and (iii) Ontic Structural Realism satisfies the criteria of the radical version of naturalism advanced by Ladyman and Ross. The point underlying those topics is that successful scientific research presupposes metaphysics, and that basic epistemic virtues common to metaphysics and science may allow us—as opposed to what Ladyman and Ross suggest—to increase our understanding of the world and to put constraints on allowable metaphysical theories.
Should One Be A Left or A Right Sellarsian? (And is There Really Such A Choice?)
Authors: Peregrin Jaroslav 
Published: April 2016

AbstractThe followers of Wilfrid Sellars are often divided into “right” and “left” Sellarsians, according to whether they believe, in Mark Lance's words, that “linguistic roles constitutive of meaning and captured by dot quoted words are ‘normative all the way down.’” The present article anatomizes this division and argues that it is not easy to give it a nontrivial sense. In particular, the article argues that it is not really possible to construe it as a controversy related to ontology, and goes on to argue that it is also not easy to construe it as one concerning the translatability of the normative idiom into the non‐normative one. The conclusion is that the only coherent interpretation of this disagreement is as a disagreement about the possibility and desirability of assuming a standpoint “inside” our linguistic practices.
EZH2 as a mediator of treatment resistance in melanoma
Authors: Tiffen Jessamy C. , Gallagher Stuart J. , Tseng Hsin‐Yi , Filipp Fabian V. , Fazekas de St Groth Barbara , Hersey Peter 
Published: April 2016

SummaryDirect treatments of cancer such as chemotherapy, radiotherapy and targeted therapy have been shown to depend on recruitment of the immune system for their effectiveness. Recent studies have shown that development of resistance to direct therapies such as BRAF inhibitors in melanoma is associated with suppression of immune responses. We point to emerging data that implicate activation of the polycomb repressive complex 2 (PRC2) and its catalytic component—enhancer of zeste homolog 2 (EZH2)—in progression of melanoma and suppression of immune responses. EZH2 appears to have an important role in differentiation of CD4 T cells and particularly in the function of T regulatory cells, which suppress immune responses to melanoma. We review mechanisms of EZH2 activation at the genomic level and from activation of the MAP kinase, E2F or NF‐kB2 pathways. These studies are consistent with activation of EZH2 as a common mechanism for induction of immune suppression in patients failing direct therapies and suggest EZH2 inhibitors may have a role in combination with immunotherapy and targeted therapies to prevent development of immunosuppression.