bluuebunny/crossref_metadata_2025 huggingface dataset:
Financial statement filing lags: An empirical analysis among small firms
Authors: Luypaert Mathieu , Van Caneghem Tom , Van Uytbergen Steve
Published: February 2015

This article examines financial statement filing lags among a sample of Belgian small firms. Our results indicate that around one-third of small firm financial statements are filed late (after the legal deadline), but that monetary sanctions could be an effective tool to encourage compliance with legal deadlines. Whereas the deadline and late filing sanctions are filing incentives, various factors, such as firm size and presence of an external financial statement audit, also affect financial statement filing lags. Evidence indicated that extremely late filings were associated with lower financial statement quality.
MC3T3-E1 preosteoblast cell-mediated mineralization of hydroxyapatite by poly-dopamine-functionalized graphene oxide
Authors: Cheng Ju , Liu Hongyan , Zhao Bingjiang , Shen Rong , Liu Di , Hong Jinpeng , Wei Hui , Xi Pinxian , Chen Fengjuan , Bai Decheng
Published: February 2015

We report a biomimetic mineralization of hydroxyapatite induced by poly-dopamine-functionalized reduced graphene oxide (RGO-PDA). Graphene oxide was first simultaneously reduced and surface functionalized by one-step oxidative polymerization of dopamine. The resultant RGO-PDA was further used as a bioinspired surface to mimic the mineralization of hydroxyapatite during bone formation. MC3T3-E1 cells were cultured on the RGO-PDA substrates to observe various cellular activities and hydroxyapatite mineralization. The MC3T3-E1 cells on RGO-PDA substrates show higher cellular activities such as proliferation, adhesion, and osteogenic differentiation over the bare glass and graphene oxide substrates. Those results suggest the potentials of using RGO-PDA as osteogenesis-promoting scaffolds for successful applications in bone tissue regeneration.
How Good Am I? Implicit and Explicit Self-Esteem as a Function of Perceived Parenting Styles Among Children With ADHD
Authors: Kurman Jenny , Rothschild-Yakar Lily , Angel Ruth , Katz Miri
Published: February 2015

Objective: To investigate implicit and explicit self-esteem and academic self-evaluation among children with ADHD as a function of parenting styles, namely, authoritarian, authoritative and permissive parenting. Method: Participants included 43 children with ADHD and 35 non-ADHD controls who filled out self-concept and perceived parenting style questionnaires. They also took an Implicit Association Test (IAT) that measured unacknowledged self-esteem. Results: Lower self-esteem was found among children with ADHD than among controls, with stronger effect on the implicit level. Perceived authoritarian parenting was related to lower implicit self-esteem among children with ADHD. Higher self-esteem was found in the authoritative than in the permissive parenting groups in the non-ADHD control group but not among children with ADHD. Conclusion: The role of parental support versus authoritarian parenting in terms of implicit self-esteem points to the importance of promoting responsiveness strategies among parents in the treatment of children with ADHD.
The Altham–Poisson distribution
Authors: Leask Kerry L , Haines Linda M
Published: February 2015

The multiplicative binomial model was introduced as a generalization of the binomial distribution for modelling correlated binomial data. This distribution has not been extensively explored and is revisited in the present study. Some properties of the multiplicative binomial distribution, such as, expressions for the factorial moments and the information matrix, are investigated. The distribution is also extended to accommodate data arising from a Wadley's problem setting which is frequently encountered in dose–mortality studies and is one in which the number of organisms initially treated with a drug is unobserved. The Altham–Poisson distribution is introduced by modelling the unobserved initial number of organisms, as specified by [Formula: see text] in the multiplicative binomial model, with a Poisson distribution and its suitability for overdispersed data from a Wadley's problem setting is explored.
Induction processes for job entrants in car service in France and Germany
Authors: Geiben Marthe
Published: February 2015

Induction in enterprises is a crucial phase for each employee not only to become able to fulfil all relevant tasks but also to enable professional development as well as social and value-oriented integration into the new organisation. This is even more relevant for young people coming from initial vocational education and training with intermediate-level qualifications (European Qualification Framework 3 and 4). The research question of the presented doctoral thesis is to discover how induction processes are organised for these employees in two selected countries, and to interpret possible differences. Therefore, the author presents a mixed-method approach that focuses on qualitative case studies in selected enterprises in car service in France and Germany. This approach is complemented by an in-depth literature review of pedagogical literature and from other selected disciplines, for example Human Resources Development. This paper presents the conception and first results of the case studies. The focus therefore is on the description of induction processes. The few existing differences are interpreted by two aspects: Hofstede’s cultural dimensions and organisational differences between the cases.
Importing education: Europeanisation and the Bologna Process in Europe’s backyard—The case of Kazakhstan
Authors: Tampayeva Gulnara Y.
Published: February 2015

This article studies the problem of the implementation of European educational standards in Kazakhstan higher education. This is considered in the frame of post-socialist education, when reforms in several post-Soviet states were undertaken under the Bologna Process. Kazakhstan, as this article argues, is justified for consideration in the frame of those post-Soviet countries involved in the Bologna Process (the Caucasus and the Baltic states) rather than in the context of neighboring Central Asian countries, which is the case found typically in the existing literature. The outcome derives from the nature of educational reforms in Kazakhstan undertaken at the system level similar to those of states that joined the European Higher Education Area. The theme is grounded in the theory of educational policy borrowing and focuses on how the borrowed patterns display themselves in the local Kazakhstan context and how they are “recontextualized” there. This article draws upon the analysis of interviews with teaching professionals conducted in four Kazakhstan higher education institutions. While the typical package of the standards of the Bologna Process to be implemented includes a wide range of norms, this article is limited by the analysis of the implementation of a testing system in Kazakhstan higher education.
Who Makes Voting Convenient? Explaining the Adoption of Early and No-Excuse Absentee Voting in the American States
Authors: Biggers Daniel R. , Hanmer Michael J.
Published: February 2015

Recent elections have witnessed substantial debate regarding the degree to which state governments facilitate access to the polls. Despite this newfound interest, however, many of the major reforms aimed at increasing voting convenience (i.e., early voting and no-excuse absentee voting) were implemented over the past four decades. Although numerous studies examine their consequences (on turnout, the composition of the electorate, and/or electoral outcomes), we know significantly less about the factors leading to the initial adoption of these policies. We attempt to provide insights into such motivations using event history analysis to identify the impact of political and demographic considerations, as well as diffusion mechanisms, on which states opted for easier ballot access. We find that adoption responded to some factors signaling the necessity of greater voting convenience in the state, and that partisanship influenced the enactment of early voting but not no-excuse absentee voting procedures.
Diversity and Inclusion in Social Media
Authors: Daugird Debra , Everett Marlena , Jones Mary , Lewis Lisa , White Angela
Published: February 2015

A freshman student posts on her social media account remarks that reflect intolerance and bigotry. Fellow students and faculty are upset, and disciplinary action follows. Was the student’s right to free speech ignored or were the rights of others to a welcoming and inclusive environment infringed upon? This case guides the reader through some of the issues associated with the currently confusing world of social media as it intersects with diversity issues. Discussion prompts and activities will prepare faculty and administrators to consider institutional culture, professionalism, and equity issues in an educational setting.
Florida Senate Bill 1108
Authors: Bailey Michael R. P. , Bauer-Jones Kate
Published: February 2015

In the summer of 2013, the State of Florida passed legislation that, among other things, gave parents of students with significant cognitive disabilities the right to refuse a separate curriculum and/or school for their child. This case frames the legal ramifications of Florida Senate Bill 1108 through the lens of the landmark Supreme Court case Schaffer v. Weast. In doing so, it will explore how one family’s struggle to navigate the special education system has taken on a new life in light of this legislation.
Effects of vitamin D supplementation on intestinal permeability, cathelicidin and disease markers in Crohn's disease: Results from a randomised double‐blind placebo‐controlled study
Authors: Raftery Tara , Martineau Adrian R , Greiller Claire L , Ghosh Subrata , McNamara Deirdre , Bennett Kathleen , Meddings Jon , O’Sullivan Maria
Published: February 2015

Background

Vitamin D (vitD) supplementation may prolong remission in Crohn's disease (CD); however, the clinical efficacy and mechanisms are unclear.

Aim

To determine changes in intestinal permeability (IP), antimicrobial peptide (AMP) concentrations and disease markers in CD, in response to vitD supplementation.

Methods

In a double‐blind randomised placebo‐controlled study, we assigned 27 CD patients in remission to 2000 IU/day vitD or placebo for 3 mos. We determined IP, plasma cathelicidin (LL‐37 in ng/mL), human‐beta‐defensin‐2 (hBD2 in pg/mL), disease activity (Crohn's Disease Activity Index (CDAI)), C‐reactive protein (CRP in mg/L), fecal calprotectin (µg/g), Quality of Life (QoL) and serum 25‐hydroxyvitamin D (25(OH)D in nmol/L) at 0 and 3 mos.

Results

At 3 mos., 25(OH)D concentrations were significantly higher in those whom were treated (p  < 0.001). Intra‐group analysis showed increased LL‐37 concentrations (p  = 0.050) and maintenance of IP measures in the treated group. In contrast, in the placebo group, the small bowel (p  = 0.018) and gastro‐duodenal permeability (p  = 0.030) increased from baseline. At 3 mos., patients with 25(OH)D ≥ 75 nmol/L had significantly lower CRP (p  = 0.019), higher QoL (p  = 0.037), higher LL‐37 concentrations (p  < 0.001) and non‐significantly lower CDAI scores (p  = 0.082), compared to those with levels <75 nmol/L.

Conclusion

Short‐term treatment with 2000 IU/day vitD significantly increased 25(OH)D levels in CD patients in remission and it was associated with increased LL‐37 concentrations and maintenance of IP. Achieving 25(OH)D ≥ 75 nmol/l was accompanied by higher circulating LL‐37, higher QoL scores and reduced CRP. Registered at ClinicalTrials.gov (NCT01792388).
Multi-Morbidity, Functional Limitations, and Self-Rated Health Among Older Adults in India
Authors: Arokiasamy Perianayagam , Uttamacharya  , Jain Kshipra
Published: February 2015

This article describes the prevalence of multi-morbidity and its association with self-rated and functional health using Longitudinal Aging Study in India (LASI), Pilot survey, 2010 data, on 1,683 older adults aged 45+. The prevalence of multi-morbidity is assessed as count of self-reported chronic diseases for an older adult. Limitations in activities of daily living (ADL) are used as a measure of functional health. Zero-inflated Poisson regression is estimated to examine the covariates of multi-morbidity. Moreover, logit models are used to assess the association of multi-morbidity with functional health and self-rated health. Results depict a large prevalence of multi-morbidity, limitations in ADL and poor self-rated health with pronounced state variations. Prevalence of multimorbidity was higher at higher level of education, wealth, and caste. However, educational status of older adults is seen to be negatively associated with prevalence of ADL limitations and poor self-rated health. Household wealth and caste showed no clear association with limitations in ADL and poor self-rated health. Multi-morbid older adults were found with substantially high risk of ADL limitations and poor self-rated health.
Lung parenchyma-derived IL-6 promotes IL-17A–dependent acute lung injury after allogeneic stem cell transplantation
Authors: Varelias Antiopi , Gartlan Kate H. , Kreijveld Ellen , Olver Stuart D. , Lor Mary , Kuns Rachel D. , Lineburg Katie E. , Teal Bianca E. , Raffelt Neil C. , Cheong Melody , Alexander Kylie A. , Koyama Motoko , Markey Kate A. , Sturgeon Elise , Leach Justine , Reddy Pavan , Kennedy Glen A. , Yanik Gregory A. , Blazar Bruce R. , Tey Siok-Keen , Clouston Andrew D. , MacDonald Kelli P. A. , Cooke Kenneth R. , Hill Geoffrey R.
Published: February 2015

Key Points

IL-6 is dysregulated after experimental allogeneic SCT and promotes alloantigen-dependent Th17 expansion within the lung. IL-6 is dysregulated in patients with IPS after clinical allogeneic SCT.
Acute granulomatous iridocyclitis in a child with tubulointerstitial nephritis and uveitis syndrome
Authors: Barut Kenan , Rzayev Turkay , Canpolat Nur , Ozluk Yasemin , Tugal-Tutkun Ilknur , Kasapcopur Ozgur
Published: February 2015

Background

Tubulointerstitial nephritis and uveitis [TINU] syndrome is a rare disorder that may also be underdiagnosed. Patients with TINU syndrome typically present with an acute bilateral nongranulomatous anterior uveitis following symptoms of systemic illness.

Findings

We report the case of a 15-year-old girl who presented with acute granulomatous iridocyclitis and was diagnosed with TINU syndrome based on renal biopsy findings. Both her uveitis and interstitial nephritis promptly responded to high-dose corticosteroid treatment, and there were no relapses during follow-up of 20 months.

Conclusions

TINU should be included in the differential diagnosis of patients who present with acute granulomatous uveitis.
Neurally adjusted ventilatory assist and proportional assist ventilation both improve patient-ventilator interaction
Authors: Schmidt Matthieu , Kindler Felix , Cecchini Jérôme , Poitou Tymothée , Morawiec Elise , Persichini Romain , Similowski Thomas , Demoule Alexandre
Published: February 2015

Introduction

The objective was to compare the impact of three assistance levels of different modes of mechanical ventilation; neurally adjusted ventilatory assist (NAVA), proportional assist ventilation (PAV), and pressure support ventilation (PSV) on major features of patient-ventilator interaction.

Methods

PSV, NAVA, and PAV were set to obtain a tidal volume (VT) of 6 to 8 ml/kg (PSV100, NAVA100, and PAV100) in 16 intubated patients. Assistance was further decreased by 50% (PSV50, NAVA50, and PAV50) and then increased by 50% (PSV150, NAVA150, and PAV150) with all modes. The three modes were randomly applied. Airway flow and pressure, electrical activity of the diaphragm (EAdi), and blood gases were measured. VT, peak EAdi, coefficient of variation of VT and EAdi, and the prevalence of the main patient-ventilator asynchronies were calculated.

Results

PAV and NAVA prevented the increase of VT with high levels of assistance (median 7.4 (interquartile range (IQR) 5.7 to 10.1) ml/kg and 7.4 (IQR, 5.9 to 10.5) ml/kg with PAV150 and NAVA150 versus 10.9 (IQR, 8.9 to 12.0) ml/kg with PSV150, P <0.05). EAdi was higher with PAV than with PSV at level100 and level150. The coefficient of variation of VT was higher with NAVA and PAV (19 (IQR, 14 to 31)% and 21 (IQR 16 to 29)% with NAVA100 and PAV100 versus 13 (IQR 11 to 18)% with PSV100, P <0.05). The prevalence of ineffective triggering was lower with PAV and NAVA than with PSV (P <0.05), but the prevalence of double triggering was higher with NAVA than with PAV and PSV (P <0.05).

Conclusions

PAV and NAVA both prevent overdistention, improve neuromechanical coupling, restore the variability of the breathing pattern, and decrease patient-ventilator asynchrony in fairly similar ways compared with PSV. Further studies are needed to evaluate the possible clinical benefits of NAVA and PAV on clinical outcomes.

Trial registration

Clinicaltrials.gov NCT02056093. Registered 18 December 2013.
Selenium prevents microparticle-induced endothelial inflammation in patients after cardiopulmonary resuscitation
Authors: Fink Katrin , Moebes Monica , Vetter Caroline , Bourgeois Natascha , Schmid Bonaventura , Bode Christoph , Helbing Thomas , Busch Hans-Jörg
Published: February 2015

Introduction

Microparticles are elevated in patients after successful cardiopulmonary resuscitation (CPR) and may play a role in the development of endothelial dysfunction seen in post-cardiac arrest syndrome (PCAS), a life threatening disease with high mortality. To identify mechanisms of endothelial activation and to develop novel approaches in the therapy of PCAS, the impact of selenium, a trace element with antioxidative properties, was characterized in endothelial dysfunction induced by microparticles of resuscitated patients. Additionally, course of plasma selenium levels was characterized in the first 72 hours post-CPR.

Methods

Endothelial cells were exposed to microparticles isolated of the peripheral blood of resuscitated patients, and leukocyte-endothelial interaction was measured by dynamic adhesion assay. Expression of adhesion molecules was assessed by immunoblotting and flow chamber. Blood samples were drawn 24, 48 and 72 hours after CPR for determination of plasma selenium levels in 77 resuscitated patients; these were compared to 50 healthy subjects and 50 patients with stable cardiac disease and correlated with severity of illness and outcome.

Results

Microparticles of resuscitated patients enhance monocyte-endothelial interaction by up-regulation of ICAM-1 and VCAM-1. Selenium administration diminished ICAM-1 and VCAM-1-mediated monocyte adhesion induced by microparticles of resuscitated patients, suggesting that selenium has anti-inflammatory effects after CPR. Lowered selenium plasma levels were observed in resuscitated patients compared to controls and selenium levels immediately and 24 hours after CPR, inversely correlated with clinical course and outcome after resuscitation.

Conclusions

Endothelial dysfunction is a pivotal feature of PCAS and is partly driven by microparticles of resuscitated patients. Administration of selenium exerted anti-inflammatory effects and prevented microparticle-mediated endothelial dysfunction. Decline of selenium was observed in plasma of patients after CPR and is a novel predictive marker of ICU mortality, suggesting selenium consumption promotes inflammation in PCAS.
Metoclopramide or domperidone improves post-pyloric placement of spiral nasojejunal tubes in critically ill patients: a prospective, multicenter, open-label, randomized, controlled clinical trial
Authors: Hu Bei , Ye Heng , Sun Cheng , Zhang Yichen , Lao Zhigang , Wu Fanghong , Liu Zhaohui , Huang Linxi , Qu Changchun , Xian Lewu , Wu Hao , Jiao Yingjie , Liu Junling , Cai Juyu , Chen Weiying , Nie Zhiqiang , Liu Zaiyi , Chen Chunbo
Published: February 2015

Introduction

The use of prokinetic agents on post-pyloric placement of spiral nasojejunal tubes is controversial. The aim of the present study was to examine if metoclopramide or domperidone can increase the success rate of post-pyloric placement of spiral nasojejunal tubes.

Methods

A multicenter, open-label, randomized, controlled trial was conducted in seven hospitals in China between April 2012 and February 2014. Patients admitted to the intensive care unit and requiring enteral nutrition for more than three days were randomly assigned to the metoclopramide, domperidone or control groups (1:1:1 ratio). The primary outcome was defined as the success rate of post-pyloric placement of spiral nasojejunal tubes, assessed 24 hours after initial placement. Secondary outcomes included success rate of post-D1, post-D2, post-D3 and proximal jejunum placement and tube migration distance. Safety of the study drugs and the tubes during the entire study period were recorded.

Results

In total, 307 patients were allocated to the metoclopramide (n = 103), domperidone (n = 100) or control group (n = 104). The success rate of post-pyloric placement after 24 hours in the metoclopramide, domperidone and control groups was 55.0%, 51.5% and 27.3%, respectively (P = 0.0001). Logistic regression analysis identified the use of prokinetic agents, Acute Physiology and Chronic Health Evaluation (APACHE) II score <20, Sequential Organ Failure Assessment (SOFA) score <12 and without vasopressor as independent factors influencing the success rate of post-pyloric placement. No serious drug-related adverse reaction was observed.

Conclusions

Prokinetic agents, such as metoclopramide or domperidone, are effective at improving the success rate of post-pyloric placement of spiral nasojejunal tubes in critically ill patients.

Trial registration

Chinese Clinical Trial Registry ChiCTR-TRC-12001956. Registered 21 February 2012.
Set-valued G-Prešić operators on metric spaces endowed with a graph and fixed point theorems
Authors: Shahzad Naseer , Shukla Satish
Published: February 2015

In this paper, we consider the set-valued contractions defined on product spaces when the underlying space is a complete metric space endowed with a graph. Some fixed point results for the so-called set-valued G-Prešić operators are established. Our theorems extend and generalize some known results in product spaces of the recent literature. As an application of our main result, fixed point results for various types of set-valued contractions on product spaces are derived, and a sufficient condition for the existence of a weakly asymptotically stable and global attractor equilibrium point of a kth order nonlinear difference inclusion is established.
A new iterative algorithm for the sum of two different types of finitely many accretive operators in Banach space and its connection with capillarity equation
Authors: Wei Li , Duan Liling
Published: February 2015

In this paper, we present a new iterative algorithm with errors to solve the problems of finding zeros of the sum of finitely many m-accretive operators and finitely many α-inversely strongly accretive operators in a real smooth and uniformly convex Banach space. Strong convergence theorems are established, which extend the corresponding works given by some authors. Moreover, the relationship among the zero of the sum of m-accretive operator and α-inversely strongly accretive operator, the solution of one kind variational inequality, and the solution of the capillarity equation is investigated.
High throughput molecular dynamics for drug discovery
Authors: Stanley Nathaniel , De Fabritiis Gianni
Published: February 2015

Molecular dynamics simulations hold the promise to be an important tool for biological research and drug discovery. Historically, however, there were several obstacles for it to become a practical research tool. Limitations in computer hardware had previously made it difficult to simulate for long enough to see interesting biological processes. Recent improvements in hardware and algorithms have largely removed this issue, leaving data analysis as the main obstacle. Advances in Markov state modeling appear to be on the way to remove this obstacle. We outline these advances here and discuss numerous recent studies that demonstrate that molecular dynamics simulations will start to be an important tool for pharmaceutical research.
Ectosomes from neutrophil-like cells down-regulate nickel-induced dendritic cell maturation and promote Th2 polarization
Authors: Turbica Isabelle , Gallais Yann , Gueguen Claire , Tharinger Hugo , Al Sabbagh Chantal , Gorges Roseline , Gary-Gouy He´le`ne , Kerdine-Ro¨mer Saadia , Pallardy Marc , Mascarell Laurent , Gleizes Aude , Chollet-Martin Sylvie
Published: February 2015

DCs are the first immune cells to be exposed to allergens, including chemical sensitizers, such as nickel, a human TLR4 agonist that induces DC maturation. In ACD, DCs can interact with PMNs that are recruited and activated, leading, in particular, to ectosome release. The objective of this work was to characterize the effects of PMN-Ect on DC functions in an ACD context. We first developed a standardized protocol to produce, characterize, and quantify ectosomes by use of human PLB-985 cells, differentiated into mature PMN (PLB-Ect). We then studied the in vitro effects of these purified ectosomes on human moDC functions in response to NiSO4 and to LPS, another TLR4 agonist. Confocal fluorescence microscopy showed that PLB-Ect was internalized by moDCs and localized in the lysosomal compartment. We then showed that PLB-Ect down-regulated NiSO4-induced moDC maturation, as witnessed by decreased expression of CD40, CD80, CD83, CD86, PDL-1, and HLA-DR and by decreased levels of IL-1β, IL-6, TNF-α, and IL-12p40 mRNAs. These effects were related to p38MAPK and NF-κB down-regulation. However, no increase in pan-regulatory DC marker genes (GILZ, CATC, C1QA) was observed; rather, levels of effector DC markers (Mx1, NMES1) were increased. Finally, when these PLB-Ect + NiSO4-treated moDCs were cocultured with CD4+ T cells, a Th2 cytokine profile seemed to be induced, as shown, in particular, by enhanced IL-13 production. Together, these results suggest that the PMN-Ect can modulate DC maturation in response to nickel, a common chemical sensitizer responsible for ADC.
Impaired maturation of large dense-core vesicles in muted-deficient adrenal chromaffin cells
Authors: Hao Zhenhua , Wei Lisi , Feng Yaqin , Chen Xiaowei , Du Wen , Ma Jing , Zhou Zhuan , Chen Liangyi , Li Wei
Published: February 2015

The large dense-core vesicle (LDCV), a type of lysosome-related organelle, is involved in the secretion of hormones and neuropeptides in specialized secretory cells. The granin family is a driving force in LDCV biogenesis, but the machinery for granin sorting to this biogenesis pathway is largely unknown. The mu mutant mouse, which carries a spontaneous null mutation on the Muted gene (also known as Bloc1s5), which encodes a subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), is a mouse model of Hermansky–Pudlak syndrome. Here, we found that LDCVs were enlarged in mu adrenal chromaffin cells. Chromogranin A (CgA, also known as CHGA) was increased in mu adrenals and muted-knockdown cells. The increased CgA in mu mice was likely due a failure to export this molecule out of immature LDCVs, which impairs LDCV maturation and docking. In mu chromaffin cells, the size of readily releasable pool and the vesicle release frequency were reduced. Our studies suggest that the muted protein is involved in the selective export of CgA during the biogenesis of LDCVs.
The Arf and Rab11 effector FIP3 acts synergistically with ASAP1 to direct Rabin8 in ciliary receptor targeting
Authors: Wang Jing , Deretic Dusanka
Published: February 2015

Primary cilia have gained considerable importance in biology and disease now that their involvement in a wide range of human ciliopathies has been abundantly documented. However, detailed molecular mechanisms for specific targeting of sensory receptors to primary cilia are still unknown. Here, we show that the Arf and Rab11 effector FIP3 (also known as RAB11FIP3) promotes the activity of Rab11a and the Arf GTPase-activating protein (GAP) ASAP1 in the Arf4-dependent ciliary transport of the sensory receptor rhodopsin. During its passage out of the photoreceptor Golgi and trans-Golgi network (TGN), rhodopsin indirectly interacts with FIP3 through Rab11a and ASAP1. FIP3 competes with rhodopsin for binding to ASAP1 and displaces it from the ternary complex with Arf4–GTP and ASAP1. Resembling the phenotype resulting from lack of ASAP1, ablation of FIP3 abolishes ciliary targeting and causes rhodopsin mislocalization. FIP3 coordinates the interactions of ASAP1 and Rab11a with the Rab8 guanine nucleotide exchange factor Rabin8 (also known as RAB3IP). Our study implies that FIP3 functions as a crucial targeting regulator, which impinges on rhodopsin–ASAP1 interactions and shapes the binding pocket for Rabin8 within the ASAP1–Rab11a–FIP3 targeting complex, thus facilitating the orderly assembly and activation of the Rab11–Rabin8–Rab8 cascade during ciliary receptor trafficking.
Nek2A destruction marks APC/C activation at the prophase-to-prometaphase transition by spindle-checkpoint restricted Cdc20
Authors: Boekhout Michiel , Wolthuis Rob
Published: February 2015

Nek2A is a presumed APC/CCdc20 substrate, which, like cyclin A, is degraded in mitosis while the spindle checkpoint is active. Cyclin A prevents spindle checkpoint proteins from binding to Cdc20 and is recruited to the APC/C in prometaphase. We found that Nek2A and cyclin A avoid stabilization by the spindle checkpoint in different ways. First, enhancing mitotic checkpoint complex (MCC) formation by nocodazole treatment inhibited the degradation of geminin and cyclin A while Nek2A disappeared at normal rate. Secondly, depleting Cdc20 effectively stabilized cyclin A but not Nek2A. Nevertheless, Nek2A destruction critically depended on Cdc20 binding to the APC/C. Thirdly, in contrast to cyclin A, Nek2A was recruited to the APC/C before the start of mitosis. Interestingly, the spindle checkpoint very effectively stabilized an APC/C-binding mutant of Nek2A, which required the Nek2A KEN box. Apparently, in cells, the spindle checkpoint primarily prevents Cdc20 from binding destruction motifs. Nek2A disappearance marks the prophase-to-prometaphase transition, when Cdc20, regardless of the spindle checkpoint, activates the APC/C. However, Mad2 depletion accelerated Nek2A destruction, showing that spindle checkpoint release further increases APC/CCdc20 catalytic activity.
Are our hospitals ‘well led’?
Authors: Glasper Alan
Published: February 2015

Professor Alan Glasper of the University of Southampton discusses the campaign by The King's Fund to help NHS trust boards develop a positive organisational culture through good leadership
The Role of Vitamin D in the Aging Adult
Authors: Meehan Meghan , Penckofer Sue
Published: February 2015

The number of individuals aged 65 and older is expected to more than double from 2012 to 2060. The role of vitamin D in the prevention and treatment of diseases associated with aging has not been well studied. Traditionally, the role of vitamin D focused on the maintenance of skeletal health in the older adult. With the discovery of vitamin D receptors in the nervous, cardiovascular and endocrine systems, the role of vitamin D and its impact on these systems has become an important area of research. Older adults are at risk for lower levels of vitamin D as a result of decreased cutaneous synthesis and dietary intake of vitamin D. Epidemiologic evidence indicates an association between low levels of vitamin D and diseases associated with aging such as cognitive decline, depression, osteoporosis, cardiovascular disease, hypertension, type 2 diabetes, and cancer. Clinical trials to determine the benefit of vitamin D supplementation in preventing and treating such diseases are in progress. This paper highlights current evidence regarding the role that vitamin D may play in diseases associated with aging and addresses the need for well-designed randomized trials to examine its benefit on health outcomes in the older adult.
Species Senescence and Fractal Properties of Ageing
Authors: Popov Igor
Published: February 2015

The senescence of species and species groups is a real phenomenon similar to the senescence of an individual. The most remarkable evidence of it is an extinction of numerous species groups, which cannot be explained by negative impact of environmental changes. The mechanism of species senescence can be characterized as follows: the organisms tend to produce the copies of themselves, but they cannot reproduce their exact copes for indefinitely long time, that is why the species inevitably change in process of change of generations of its representatives, even if the species is already well adapted to environment; such a continuous species transformation takes place in definite directions because of various constraints even if such directions are not rational and lead to extinction. The species senescence indicates on the fractal properties of ageing: it is scaleless, and existing at all biological objects, one of which is a part of the other.
Eating Disorder among Elderly Causing Heart Attack: A Study on Impact of Life Style Management in Post Retirement Life
Authors: Adhikari Harasankar
Published: February 2015

In the era of globalization growing elderly faces multifaceted problems regardless of social, economical, cultural as well as religion in their retired life. Among such health problem is a prime concerned. The mental crises among them are a major issue. Thus thinking about their end of life they usually try to fulfill their many desires like eating. The present study was conducted to explore the relationship of eating disorder with increasing incidents heart attack among elderly. For the purpose of this study, 100 elderly populations of 60-70 years selected regardless of their gender, socio-economy, education, family relation and so forth. They were interviewed in a reputed hospital namely Rabindranath Tagore Institute of Cardiac Sciences of Kolkata Metro City of eastern India where they took admission for their treatment after their heart attack. The data was also collected from medical practitioners and family members of elderly patients. The simple random sampling method was used with case study. From the study, it was revealed that 70% of them was suffering from heart problem after taking heavy fatty foods and of them 40% was diabetic. They used to control their eating habits with strict monitoring of their family members. But they faced heart attacked after taking food from ceremonial party or otherwise. Among them, 22% were experienced for second time. So, the control of eating habits might longer their survival and for this they need counseling and guidance with supervision of their family members or immediate caregivers.
The femoral head–neck contour varies as a function of physeal development
Authors: Vo A. , Beaule P. E. , Sampaio M. L. , Rotaru C. , Rakhra K. S.
Published: February 2015

Objectives

The purpose of this study was to investigate whether the femoral head–neck contour, characterised by the alpha angle, varies with the stage of physeal maturation using MRI evaluation of an asymptomatic paediatric population.

Methods

Paediatric volunteers with asymptomatic hips were recruited to undergo MRI of both hips. Femoral head physes were graded from 1 (completely open) to 6 (completely fused). The femoral head–neck contour was evaluated using the alpha angle, measured at the 3:00 (anterior) and 1:30 (anterosuperior) positions and correlated with physeal grade, with gender sub-analysis performed.

Results

A total of 43 asymptomatic paediatric volunteers (26 male, 17 female) with mean age 13.0 years (eight to 18) were included with review of bilateral hip MRIs. Correlation between the physeal grade and alpha angle was moderate in males at both the 3:00 (r = 0.477, p < 0.001) and 1:30 (r = 0.509, p < 0.001) positions, whereas there was no significant correlation in females. A significant difference was found between the alpha angles of all the physeal grades (3:00, p = 0.030, 1:30, p = 0.005), but only in males, with the angle increasing with higher grades. For physeal grading, the inter-reader reliability was substantial (intraclass correlation coefficient (ICC) = 0.694), and the intra-reader reliability was also substantial (ICC = 0.788).

Conclusion

The femoral head–neck contour varies and correlates with the stage of physeal development, but only in males, with the alpha angle increasing with progressive physeal maturation. This suggests that gender differences exist in the natural physiological growth, development or remodelling of femoral head–neck junction. In males, pre-physeal fusion may be a critical period of vulnerability for development of morphologic abnormalities of the femoral head–neck junction. Cite this article: Bone Joint Res 2015;4:17–22
The function of narrative in public space: Witnessing performed storytelling in Northern Ireland
Authors: Weiglhofer Magdalena
Published: February 2015

In an examination of how witnessing autobiographical stories through a performance onstage affects audiences, this article considers the function of narrative in public space. Its key focus lies on exploring the concept of witnessing through an analysis of the audience’s reception of two autobiographical storytelling performances in Northern Ireland. Drawing on the affirmative response to the portrayal of suffering, the argument is developed that, in today’s ‘therapeutic culture’, people are used to, prepared and therefore keen to hear from personal experiences and emotions but are, at the same time, yearning to return to ‘real’ emotions in an environment of emotional commodification.
Starting from scratch: Forming a community of practice in an Australian late starters’ wind
Authors: Southcott Jane
Published: February 2015

Musical participation is a powerful form of community engagement, offering agency in positive ageing. Community music endeavours usually involve active music-making and acquisition of musical skills and understandings. Participants in such programmes elect to become involved, often taking responsibility for the survival of the group. This case study explores the understandings of members of a community band, the Second Wind Ensemble, formed in 1998 in Adelaide, South Australia. Initially, the band offered late starters the opportunity to learn an instrument. The ensemble now has approximately 60 players with a regular programme of concerts, rehearsals, tutorials and social gatherings. The band conductor is a professional music educator. This study chronicles the development of a community of practice with the band members gradually assuming responsibility for their ensemble. This discussion considers only the first two years in the history of the ensemble, during which time the roles of participants evolved. In this case study, the founder, conductor, organizer and a number of participants were interviewed and data analysed using Interpretative Phenomenological Analysis (IPA). The themes identified from these multiple perspectives focus on well-being, active engagement with community, the development of musical skills and understandings, and the formation of a community of practice.
Conference Reviews
Authors: Cordileone Amy , Low Katharine E.
Published: February 2015

Forum on the Teaching Artist: Navigation, Innovation, and Sustainability, New York University, Steinhardt School of Culture, Education, and Human Development Program in Educational Theatre, 25–27 April 2014

Conference Review of the TaPRA Applied and Social Theatre Working Group’s Interim Event on Heroism and the Heroic in Applied and Social Theatre, Royal Central School of Speech and Drama, London, 22 March 2014
The study of the political economy of the media in the twenty-first century
Authors: Wasko Janet
Published: February 2015

This discussion presents a brief overview of the establishment and expansion of the study of the political economy of media and communications, followed by attention to some of current directions of this approach. Themes and concepts developed by political economists of the media are reviewed, as well as internal and external critiques of the approach. Recent developments are discussed, including the growth of integrated studies, the return to classic Marxist themes, integration of digital technologies, and attention to policy and activism.
Sigmund Freud’s Experience with the Classics
Authors: Stok Fabio
Published: February 2015

Classical culture played an important role in the work of Sigmund Freud and influenced the formation of psychoanalysis. This influence concerned several aspects of Freud’s experience: the personal one, from his adolescent identification with ancient heroes to his emotional bond with Rome and Athens; the intellectual, including his use of authors such as Aristotle and Artemidorus the elaboration of psychoanalytical theory; rhetorical and expositive in his use of classical authors such as Sophocles and Vergil, and in his strategy of identifying thinkers such as Plato and Empedocles as forerunners of his theories. The present article reconstructs the evolution of this strategy, which began in 1900, in conjunction with the definition of the basic concepts of psychoanalysis. Some specific episodes of Freud’s approach to the classics are also examined: his reception of Aristotle’s concept of catharsis, and of the interpretation of this concept given by Bernays; Freud’s interest in Vergil, highlighted by his use of verses from the Aeneid in his works; his conflictual relationship with Rome; the use of Empedocles as a predecessor of the changes that Freud made, in his last years, to the theory of pulsions.
Ética e estética na música grega: a educação e o ideal da kalo-kagathía
Authors: Cerqueira Fábio Vergara
Published: February 2015

Ética e estética são duas dimensões absolutamente imbricadas no pensamento musical grego. Os princípios morais contidos, por exemplo, na teoria do éthos musical norteiam a apreciação das formas musicais, seja no que se refere à escolha dos instrumentos, dos gêneros, ou dos modos musicais (escalas). A importância que os gregos conferiam a esta intersecção entre a estética e a ética na música assumia grande relevância política, como pode ser verificado no destaque dado à educação musical. Ao avaliar a biografia dos principais homens públicos atenienses, recorrendo-se a obras como as Vidas Paralelas de Plutarco, constata-se o quanto se valorizava a influência da formação musical sobre as qualidades políticas e morais de um cidadão. Considerava-se que a música desempenhava importante papel para a constituição da virtude da kalo-kagathía (beleza-bondade), que era considerada o bem maior para um cidadão: o reconhecimento do belo e de escolha do bom, do justo. Vê-se, assim, a existência de uma pedagogia política, calcada nas noções de ética e estética, na qual o ensino musical merecia bastante atenção, como demonstram as recomendações de Platão e Aristóteles.
Variedade de gêneros e teatralidade nos dramas de Sêneca
Authors: Lohner José Eduardo dos Santos
Published: February 2015

A poesia dramática de Sêneca, como, em geral, a literatura da época imperial, é marcada pela influência estética do período helenístico. Entre outros aspectos, a mescla de gêneros discursivos, praticada por poetas alexandrinos, é em boa medida observável nos dramas senequianos, onde, aliás, há constantes referências a modelos não dramáticos, especialmente a lírica de Horácio e a épica de Virgílio e Ovídio, além do emprego de elementos formais do discurso declamatório. Considerando a questão longamente debatida pela crítica sobre o tipo de performance que o dramaturgo latino teria concebido para seus dramas, sugere-se então que a variação de formas discursivas, bem como o uso de modelos não dramáticos, seja um fator que interfere na teatralidade dessas peças. O resultado disso é um texto em que aparecem algumas cenas com conteúdo e características adequados à encenação no palco, ao lado de outras, de pouco efeito cênico e visual, nas quais se destaca antes o efeito auditivo do ttexto recitado e sua força descritiva operando na imaginação do ouvinte.
La Lugartenencia y las Subrogaciones locales de la Gobernación General de Orihuela en la Edad Moderna
Authors: Bernabé Gil David
Published: February 2015

La estructura de la Gobernación General de la Corona de Aragón contemplaba, para el Reino de Valencia, la existencia de dos altos oficiales en un primer nivel, con título de Portantveus y sedes respectivas en la capital del reino y en la ciudad de Orihuela. Y, al admitirse la delegación, para hacer efectivas sus funciones ambos contaron con Lugartenientes y Subrogados de carácter territorial. El presente trabajo se centra en el análisis de ambas fórmulas de representación, a partir fundamentalmente de las circunstancias que rodearon el nombramiento de este tipo de delegados, en el caso concreto de la Gobernación de Orihuela, durante los siglos XVI y XVII. Aspectos tales como el carácter ordinario o extraordinario de estos oficios, la duración de sus mandatos, la identidad y el perfil social de los designados y las tensiones que a veces suscitaron los correspondientes nombramientos ponen de manifiesto la importancia de estos cargos, que siempre estuvieron reservados para unas élites nobiliarias locales que encontraron en esta modalidad de servicio a la Corona una fórmula eficaz de integración.
Nonsolvability of the asymptotic Dirichlet problem for the p-Laplacian on Cartan–Hadamard manifolds
Authors: Holopainen Ilkka
Published: February 2015

We construct, by modifying Borbély's example, a 3-dimensional Cartan–Hadamard manifold M, with
sectional curvatures at most -1, such that the asymptotic Dirichlet problem for the p-Laplacian is not
solvable for any p > 1.
Uniform Estimate for Randomly Weighted Sums of Dependent Subexponential Random Variables
Authors: Liu Yan , Zhang Qinqin
Published: February 2015

This paper obtains the uniform tail asymptotics of the maximum of randomly weighted sum

max

1
≤
k
≤
n

∑

i
=
1

k

θ
i

X
i

$$\mathop {\max}\limits_{1 \le k \le n} \sum\nolimits_{i = 1}^k {\theta _i}{X_i}$$

with respective to n, in which the primary random variables

X
1

,
.
.
.
,

X
n

$${X_1},...,{X_n}$$

are real valued, dependent, and have different subexponential distributions, while the random weights

θ
1

,
.
.
.
,

θ
n

$${\theta _1},...,{\theta _n}$$

are nonnegative and arbitrarily dependent, but independent of

X
1

,
.
.
.
,

X
n

$${X_1},...,{X_n}$$

. An application to insurance risk model with investment portfolio is proposed.
Obesity and cancer
Authors: Ungefroren Hendrik , Gieseler Frank , Fliedner Stephanie , Lehnert Hendrik
Published: February 2015

The incidence of obesity in the Western world has increased dramatically during the recent decades. Epidemiological data suggest that obesity is associated with an increased risk of several but not all types of cancers, with clear sex-specific differences. The underlying mechanisms are still a matter of debate. In this review, we discuss the potential factors linking obesity to cancer, with a focus on hormone-dependent cancer types. Current experimental evidence suggests that insulin resistance and a chronic, subclinical inflammation in the visceral fat are the major metabolic events, causing alterations in the levels of insulin, glucose, free fatty acids, insulin-like growth factor-1 and -2, adipose tissue-derived proinflammatory factors (tumor necrosis factor-α and interleukin-1, -6, -12, and -23), and other bioactive molecules such as adipokines (adiponectin and leptin), vascular endothelial growth factor, sex hormones, gut microbiota, and secondary bile acids. All these factors may act directly or indirectly on the tumor microenvironment to drive tumor progression via the stimulation of cell survival/antiapoptosis, cell proliferation, angiogenesis, and invasion/metastasis of cancer cells. Therapeutic strategies (including bariatric surgery) that target dysfunctional or inflamed fat have been shown to benefit patients, whereas other cell- or hormone-directed interventions (such as the conversion of visceral fat macrophages to an anti-inflammatory M2 phenotype or the pharmacological modulation of serum adipokine levels) are still theoretical and need to be clinically evaluated for their ability to successfully treat or prevent obesity-related cancers.