bluuebunny/crossref_metadata_2025 huggingface dataset:
WHAT OBJECT IS FEAR?
Authors: Pernau Margrit
Published: February 2015

This article reviews two edited volumes on fear, important contributions to the newly developing field of the history of emotions. The question at the center of Jan Plamper and Benjamin Lazier's volume is how fear is constituted as an object; this question is investigated in an interdisciplinary dialogue. Focusing on the twentieth century, the editors bring together psychologists, historians of science and of emotions, and specialists in literature studies, politics, and film. Taking the dialogue beyond the social sciences is certainly an exciting and necessary exercise, but it also raises the question whether both sides are really talking about the same object.

Michael Laffan and Max Weiss place fear in a global history perspective. They cover a wide scope, from early modernity to the present, and geographically including the Americas and Indonesia. Taken together, both volumes not only give an impressive overview of the field of fear studies, and add to it through a number of case studies, but also raise the question “what object is fear?” in a new way. If this object is as fluid as appears from the two volumes—not only with respect to the different events that trigger fear, the different uses it was put to, and the politics it allowed, but as a felt emotion—this calls for further investigation notably into the words and concepts used to make sense of the experience.
UNDERDOGS IN DIALOGUE
Authors: Osterhammel Jürgen
Published: February 2015

The study of cultural interactions between Asia and Europe in modern times has moved beyond a mere description of mutual “images” and a ritualized assertion of fundamental incompatibility in the dichotomous tradition going back to the critique of Orientalism. Using “entanglement” as his guiding concept, the author unfolds a rich panorama of Indian and Germanic (including Austrian and Swiss) intellectuals in personal contact and distant dialogue from the 1880s to 1945. Their shared framework of meaning was the resistance to “empire.” The book ambitiously advances a broader vision of global intellectual history. This raises a number of theoretical issues requiring further debate.
No evidence for sex bias in winter inter‐site movements in an Arctic‐nesting goose population
Authors: Weegman Mitch D. , Fox Anthony D. , Bearhop Stuart , Hilton Geoff M. , Walsh Alyn J. , Cleasby Ian R. , Hodgson David J.
Published: February 2015

Understanding movement of individuals between sites is necessary to quantify emigration and immigration, yet previous analyses exploring sex biases in site fidelity among birds have not evaluated remigration (the return of marked birds that moved to alternative areas from the site at which they were marked). Using novel Bayesian multistate models, we tested whether between‐winter emigration, remigration and survival rates were sex‐biased among 851 Greenland White‐fronted GeeseAnser albifrons flavirostrismarked at Wexford, Ireland. We found no evidence for sex biases in emigration, remigration or survival. Thus, sex biases in winter site fidelity do not occur in any form in this population; these techniques for modelling sex‐biased movement will be useful for a better understanding of site fidelity and connectivity in other marked animal populations.
Microwave vs. convection heating of bovine Gluteus Medius muscle: impact on selected physical properties of final product and cooking yield
Authors: Półtorak A. , Wyrwisz J. , Moczkowska M. , Marcinkowska‐Lesiak M. , Stelmasiak A. , Rafalska U. , Wierzbicka A. , Sun Da‐Wen
Published: February 2015

The aim of this study was to investigate the impact of two convection–microwave heating (M100 and M30) on texture and colour properties, cooking yield and thermal shrinkage of bovine product (gluteus medius muscle) as compared with conventional roasting at constant temperature (P180 and P80) and roasting with ΔT program (Δ80 and Δ40). The product processed by the M100 method was characterised by high shear force (WBSF) and high compression force (TPA). The reduction of microwave intensity to 30% (roasting M30) could improve the tenderness of final product. In addition, microwave heating at the intensity of 30% shortened the roasting time, and the produced sample exhibited comparable process loss and heat shrinkage extent compared to those treated by the high‐temperature conventional roasting method (P180). The study indicated that combining of convection and low‐intensity microwave heating could be successfully used in catering business for beef roasting due to the shorter cooking time, reduced cooking loss and higher tenderness of meat.
Deep brain stimulation for Parkinson disease in Australia: current scientific and clinical status
Authors: Poortvliet P. C. , Silburn P. A. , Coyne T. J. , Chenery H. J.
Published: February 2015

There is currently no cure for Parkinson disease (PD). Disease management is directed primarily at motor symptom relief, but the impact of non‐motor symptoms associated with PD should not be underestimated. Medical and surgical treatment options aim to increase functional independence and quality of life. Deep brain stimulation (DBS) has proven to be a safe, effective and cost‐efficient surgical treatment option. In 2009, the Australian referral guidelines, developed to provide a synopsis of DBS therapy for PD, were introduced, and since then novel findings have been reported regarding the timing of intervention, target selection and symptom management. Our aim is to provide an update of DBS for PD in Australia. Intervention at earlier stages of the disease can potentially improve quality of life over a longer period with greater possibilities for meaningful social and professional contributions. For less responsive motor symptoms (e.g. freezing of gait, postural instability), the pedunculopontine nucleus has emerged as a promising new surgical target. Traditional PD treatment is focused on improvement of motor symptoms, but the disorder is also characterised by non‐motor symptoms, often undiagnosed or undisclosed, that have the potential to impact quality of life to a greater extent than motor symptoms. It is essential to identify and routinely monitor for non‐motor symptoms as they can emerge at all stages of the disease or can result from treatment. Many of these current advances require long‐term monitoring of treatment outcomes to improve future clinical practice, refine patient selection and ensure best patient outcomes.
No payments, copayments and faux payments: are medical practitioners adequately equipped to manage Medicare claiming and compliance?
Authors: Faux M. A. , Wardle J. L. , Adams J.
Published: February 2015

The complexity of Medicare claiming means it is often beyond the comprehension of many, including medical practitioners who are required to interpret and apply Medicare every day. A single Medicare service can be the subject of 30 different payment rates, multiple claiming methods and a myriad of rules, with severe penalties for non‐compliance, yet the administrative infrastructure and specialised human resourcing of Medicare may have decreased over time. As a result, medical practitioners experience difficulties accessing reliable information and support concerning their claiming and compliance obligations. Some commentators overlook the complexity of Medicare and suggest that deliberate misuse of the system by medical practitioners is a significant contributor to rising healthcare costs, although there is currently no empirical evidence to support this view. Quantifying the precise amount of leakage caused by inappropriate claiming has proven an impossible task, although current estimates are $1–3 billion annually. The current government's proposed copayment plan may cause increases in non‐compliance and incorrect Medicare claiming, and a causal link has been demonstrated between medical practitioner access to Medicare education and significant costs savings. Medicare claiming is a component of almost every medical interaction in Australia, yet most education in this area currently occurs on an ad hoc basis. Research examining medical practitioner experiences and understanding regarding Medicare claiming and compliance is urgently required to adapt Medicare responsibly to our rapidly changing healthcare environment.
Tadalafil therapy and severe chronic foot wound resolution
Authors: Davenport Claire , Dubin Andrew
Published: February 2015

We report an unanticipated medication effect resulting in near‐complete wound healing in a patient after beginning tadalafil therapy of 20 mg thrice daily. This patient was treated for 50 years with state‐of‐the art acute and then chronic wound interventions after a traumatic farm machinery accident which resulted in a devascularised foot wound. This infection was both life‐ and limb‐threatening. The patient had undergone multiple vascular and plastic surgeries and antimicrobial therapies in addition to hospitalisations for sepsis. Limb amputation was being considered, when his urologist placed him on daily phosphodiesterase‐5 inhibitor therapy, prior to unrelated urologic surgery. Remarkably, his foot wound underwent near‐complete resolution and has been stable for 2 years.
Combined use of fenestrated‐type artificial dermis and topical negative pressure wound therapy for the venous leg ulcer of a rheumatoid arthritis patient
Authors: Morimoto Naoki , Kuro Atsuyuki , Yamauchi Takashi , Horiuchi Ai , Kakudo Natsuko , Sakamoto Michiharu , Suzuki Kenji , Kusumoto Kenji
Published: February 2015

We report a case of circumferential venous leg ulcer in a rheumatoid arthritis patient. Mesh skin grafting was performed in another hospital, but the graft failed and the patient was referred to our hospital. This ulcer was treated by the combination therapy of a fenestrated‐type artificial dermis with negative pressure wound therapy (NPWT) and secondary mesh grafting using our ‘grip tape technique’. NPWT was started at −100 mmHg and continued until the formation of dermis‐like tissue. A section stained using haematoxylin and eosin and an anti‐αSMA (α smooth muscle actin) immunohistological section of the biopsy from dermis‐like tissue showed an abundant infiltration of fibroblasts and capillary formation beneath the fenestration of the silicone sheet. Threefold mesh skin grafting was subsequently performed and it was taken up completely. The fenestrated‐type artificial dermis in combination with NPWT produced good results without infection in the treatment of complex wounds. In addition, our ‘grip tape technique’ was useful to apply polyurethane foam to the entire surface of the lower leg.
Evolution de la réglementation et des régimes du travail en Chine: rétrospective et enjeux
Authors: CHAN Chris King‐Chi , NADVI Khalid
Published: February 2015

La puissance économique de la Chine repose sur son industrie manufacturière, forte d'une main‐d'œuvre disciplinée et qualifiée mais peu rémunérée. Face à une agitation sociale croissante, l'Etat a pris des initiatives pour réglementer et améliorer les conditions d'emploi. Les coordinateurs de ce numéro spécial de la Revue internationale du Travail replacent ici les contributions qui le composent dans le contexte des débats sur la réglementation du travail dans la production mondiale – notamment réglementation non contraignante par opposition à réglementation contraignante – et sur l'évolution du marché du travail, des normes du travail et des relations professionnelles en Chine. Ils concluent par des suggestions de recherches à venir.
Régimes de production, relations professionnelles et différends du travail dans le secteur automobile en Chine
Authors: LÜTHJE Boy
Published: February 2015

Les grèves de 2010 dans le secteur automobile du sud de la Chine ont suscité d'importantes réformes des relations professionnelles dans la province de Guangdong. S'appuyant sur un vaste travail empirique dans les grandes usines d'assemblage automobile et leurs fournisseurs, l'auteur élabore une typologie des régimes de production qui sert de cadre pour analyser les changements des relations professionnelles, mieux comprendre la diversification des activités manufacturières en Chine, et conceptualiser la fragmentation et la segmentation des relations professionnelles entre les entreprises, la cascade des sous‐traitants et les pôles régionaux dans l'industrie automobile. L'auteur conclut par des perspectives de réformes.
Determination of Boron Concentration in Geochemical Reference Materials Extracted by Pyrohydrolysis and Measured by ICP‐MS
Authors: Michel Agnès , Noireaux Johanna , Tharaud Mickaël
Published: February 2015

This article presents new boron concentrations for nine geochemical reference materials (GS‐N, FK‐N, GL‐O, BX‐N, DT‐N, AN‐G, GH, Mica‐Fe, Mica‐Mg). After extraction by a modified pyrohydrolysis technique, boron concentrations were measured by ICP‐MS. The blank levels for the whole procedure were 0.091 ± 0.020 ng ml−1 or 14 ± 5 ng of boron in total. The method was first validated by measuring nine reference materials with known boron concentrations. The determined boron concentrations are all within the range of recommended or published values, which means that the yields were 100%, and show precisions below 10% for samples containing over 2 μg g−1 of boron.
QRS Fragmentation and QTc Duration Relate to Malignant Ventricular Tachyarrhythmias and Sudden Cardiac Death in Patients with Hypertrophic Cardiomyopathy
Authors: DEBONNAIRE PHILIPPE , KATSANOS SPYRIDON , JOYCE EMER , VAN DEN BRINK OLIVIER V.W. , ATSMA DOUWE E. , SCHALIJ MARTIN J. , BAX JEROEN J. , DELGADO VICTORIA , MARSAN NINA AJMONE
Published: February 2015

QRS Fragmentation and QTc in Hypertrophic Cardiomyopathy

Background

QRS fragmentation (fQRS) and prolonged QTc interval on surface ECG are prognostic in various cardiomyopathies other than hypertrophic cardiomyopathy (HCM). The association between fQRS and prolonged QTc duration with occurrence of ventricular tachyarrhythmias or sudden cardiac death (VTA/SCD) in patients with HCM was explored.

Methods and Results

One hundred and ninety‐five clinical HCM patients were studied. QTc duration was derived applying Bazett's formula; fQRS was defined as presence of various RSR’ patterns, R or S notching and/or >1 additional R wave in any non‐aVR lead in patients without pacing or (in)complete bundle branch block. The endpoints comprised SCD, ECG documented sustained VTA (tachycardia or fibrillation) or appropriate implantable cardioverter defibrillator (ICD) therapies (antitachycardia pacing [ATP] or shock) for VTA in ICD recipients (n = 58 [30%]). QT prolonging drugs recipients were excluded. After a median follow‐up of 5.7 years (IQR 2.7–9.1), 26 (13%) patients experienced VTA or SCD. Patients with fQRS in ≥3 territories (inferior, lateral, septal, and/or anterior) (p = 0.004) or QTc ≥460 ms (p = 0.009) had worse cumulative survival free of VTA/SCD than patients with fQRS in <3 territories or QTc <460 ms. fQRS in ≥3 territories (ß 4.5, p = 0.020, 95%CI 1.41–14.1) and QTc ≥460 ms (ß 2.7, p = 0.037, 95%CI 1.12–6.33) were independently associated with VTA/SCD. Likelihood ratio test indicated assessment of fQRS and QTc on top of conventional SCD risk factors provides incremental predictive value for VTA/SCD (p = 0.035).

Conclusions

Both fQRS in ≥3 territories and QTc duration are associated with VTA/SCD in HCM patients, independently of and incremental to conventional SCD risk factors.
Electrical and Thermal Effects of Esophageal Temperature Probes on Radiofrequency Catheter Ablation of Atrial Fibrillation: Results from a Computational Modeling Study
Authors: PÉREZ JUAN J. , D'AVILA ANDRE , ARYANA ARASH , BERJANO ENRIQUE
Published: February 2015

Electrical and Thermal Effects of Esophageal Temperature Probes

Introduction

Luminal esophageal temperature (LET) monitoring is commonly employed during catheter ablation of atrial fibrillation (AF) to detect high esophageal temperatures during radiofrequency (RF) delivery along the posterior wall of the left atrium. However, it has been recently suggested that in some cases the esophageal probe itself may serve as an RF “antenna” and promote esophageal thermal injury. The aim of this study was to assess the electrical and thermal interferences induced by different types of commercially available esophageal temperature probes (ETPs) on RF ablation.

Methods and Results

In this study, we developed a computational model to assess the electrical and thermal effects of 3 different types of ETPs: a standard single‐sensor and 2 multisensor probes (1 with and 1 without metallic surfaces). LET monitoring invariably underestimated the maximum temperature reached in the esophageal wall. RF energy cessation guided by LET monitoring using an ETP yielded lower esophageal wall temperatures. Also, the phenomenon of thermal latency was observed, particularly in the setting of LET monitoring. Most importantly, while only the ETP with a metallic surface produced minimal electrical alterations, the magnitude of this interference did not appear to be clinically significant.

Conclusion

Temperature rises in both the esophageal wall and the ETP seem to be primarily produced by thermal conduction, and not caused by electrical and/or thermal interactions between the ablation catheter and the ETP, itself. As such, the proposed notion of the “antenna effect” producing satellite esophageal lesions during AF ablation was not evident in this study.
Annual Research Review: A meta‐analysis of the worldwide prevalence of mental disorders in children and adolescents
Authors: Polanczyk Guilherme V. , Salum Giovanni A. , Sugaya Luisa S. , Caye Arthur , Rohde Luis A.
Published: February 2015

Background

The literature on the prevalence of mental disorders affecting children and adolescents has expanded significantly over the last three decades around the world. Despite the field having matured significantly, there has been no meta‐analysis to calculate a worldwide‐pooled prevalence and to empirically assess the sources of heterogeneity of estimates.

Methods

We conducted a systematic review of the literature searching in PubMed, PsycINFO, and EMBASE for prevalence studies of mental disorders investigating probabilistic community samples of children and adolescents with standardized assessments methods that derive diagnoses according to the DSM or ICD. Meta‐analytical techniques were used to estimate the prevalence rates of any mental disorder and individual diagnostic groups. A meta‐regression analysis was performed to estimate the effect of population and sample characteristics, study methods, assessment procedures, and case definition in determining the heterogeneity of estimates.

Results

We included 41 studies conducted in 27 countries from every world region. The worldwide‐pooled prevalence of mental disorders was 13.4% (CI 95% 11.3–15.9). The worldwide prevalence of any anxiety disorder was 6.5% (CI 95% 4.7–9.1), any depressive disorder was 2.6% (CI 95% 1.7–3.9), attention‐deficit hyperactivity disorder was 3.4% (CI 95% 2.6–4.5), and any disruptive disorder was 5.7% (CI 95% 4.0–8.1). Significant heterogeneity was detected for all pooled estimates. The multivariate metaregression analyses indicated that sample representativeness, sample frame, and diagnostic interview were significant moderators of prevalence estimates. Estimates did not vary as a function of geographic location of studies and year of data collection. The multivariate model explained 88.89% of prevalence heterogeneity, but residual heterogeneity was still significant. Additional meta‐analysis detected significant pooled difference in prevalence rates according to requirement of funcional impairment for the diagnosis of mental disorders.

Conclusions

Our findings suggest that mental disorders affect a significant number of children and adolescents worldwide. The pooled prevalence estimates and the identification of sources of heterogeneity have important implications to service, training, and research planning around the world.
Protein kinase A directly phosphorylates metabotropic glutamate receptor 5 to modulate its function
Authors: Uematsu Ken , Heiman Myriam , Zelenina Marina , Padovan Júlio , Chait Brian T. , Aperia Anita , Nishi Akinori , Greengard Paul
Published: February 2015

Metabotropic glutamate receptor 5 (mGluR5) regulates excitatory post‐synaptic signaling in the central nervous system (CNS) and is implicated in various CNS disorders. Protein kinase A (PKA) signaling is known to play a critical role in neuropsychiatric disorders such as Parkinson's disease, schizophrenia, and addiction. Dopamine signaling is known to modulate the properties of mGluR5 in a cAMP‐ and PKA‐dependent manner, suggesting that mGluR5 may be a direct target for PKA. Our study identifies mGluR5 at Ser870 as a direct substrate for PKA phosphorylation and demonstrates that this phosphorylation plays a critical role in the PKA‐mediated modulation of mGluR5 functions such as extracellular signal‐regulated kinase phosphorylation and intracellular Ca2+ oscillations. The identification of the molecular mechanism by which PKA signaling modulates mGluR5‐mediated cellular responses contributes to the understanding of the interaction between dopaminergic and glutamatergic neuronal signaling.

image

We identified serine residue 870 (S870) in metabotropic glutamate receptor 5 (mGluR5) as a direct substrate for protein kinase A (PKA). The phosphorylation of this site regulates the ability of mGluR5 to induce extracellular signal‐regulated kinase (ERK) phosphorylation and intracellular Ca2+ oscillations. This study provides a direct molecular mechanism by which PKA signaling interacts with glutamate neurotransmission.
Ultrastructural Changes in Lactotrophs and Folliculo‐Stellate Cells in the Ovine Pituitary during the Annual Reproductive Cycle
Authors: Christian H. C. , Imirtziadis L. , Tortonese D.
Published: February 2015

In seasonal mammals living in temperate zones, photoperiod regulates prolactin secretion, such that prolactin plasma concentrations peak during the summer months and are lowest during the winter. In sheep, a short‐day breeder, circulating prolactin has important modulatory effects on the reproductive system via inhibitory actions on pituitary gonadotrophs and hypothalamic gonadotrophin‐releasing hormone release. The exact cellular mechanisms that account for the chronic hypersecretion of prolactin during the summer is not known, although evidence supports an intrapituitary mechanism regulated by melatonin. Folliculo‐stellate (FS) cells are non‐endocrine cells that play a crucial role in paracrine communication within the pituitary and produce factors controlling prolactin and gonadotrophin release. The present study examined the morphology of theFSand lactotroph cell populations and their distribution in the sheep pituitary during the annual reproductive cycle. Ovine pituitary glands were collected in the winter (breeding season;BS) and summer (nonbreeding season;NBS) and were prepared for quantitative electron microscopy to assess the effects of season onFSand lactotroph cell density, morphology and distribution, as well as on junctional contacts between cells. It was found that lactotrophs in theNBSare larger in size and contain more numerousPRLgranules than lactotrophs in theBS.FScells were also larger in theNBScompared toBSand showed altered morphology such that, in theBS, long cell processes surrounded clusters of adjacent secretory cells. Although no significant change in the number of junctions was observed between lactotrophs andFScells, or lactotrophs and gonadotrophs, there was a significant increase in the number of adherens junctions between lactotrophs and betweenFScells. These findings demonstrate seasonal plasticity in the morphology of lactotrophs andFScells that reflect changes inPRLsecretion.
Transcriptional Regulation of Glutamic Acid Decarboxylase in the Male Mouse Amygdala by Dietary Phyto‐Oestrogens
Authors: Sandhu K. V. , Yanagawa Y. , Stork O.
Published: February 2015

Phyto‐oestrogens are biologically active components of many human and laboratory animal diets. In the present study, we investigated, in adult male mice with C57BL/6 genetic background, the effects of a reduced phyto‐oestrogens intake on anxiety‐related behaviour and associated gene expression in the amygdala. After 6 weeks on a low‐phyto‐oestrogen diet (< 20 μg/g cumulative phyto‐oestrogen content), animals showed reduced centre exploration in an open‐field task compared to their littermates on a soybean‐based standard diet (300 μg/g). Freezing behaviour in an auditory fear memory task, in contrast, was not affected. We hypothesised that this mildly increased anxiety may involve changes in the function of GABAergic local circuit neurones in the amygdala. Using GAD67+/GFP mice, we could demonstrate reduced transcription of the GAD67 gene in the lateral and basolateral amygdala under the low‐phyto‐oestrogen diet. Analysis of mRNA levels in microdissected samples confirmed this regulation and demonstrated concomitant changes in expression of the second glutamic acid decarboxylase (GAD) isoform, GAD65, as well as the anxiolytic neuropeptide Y. These molecular and behavioural alterations occurred without apparent changes in circulating oestrogens or testosterone levels. Our data suggest that expression regulation of interneurone‐specific gene products in the amygdala may provide a mechanism for the control of anxiety‐related behaviour through dietary phyto‐oestrogens.
Anchoring on Credit Spreads
Authors: DOUGAL CASEY , ENGELBERG JOSEPH , PARSONS CHRISTOPHER A. , VAN WESEP EDWARD D.
Published: February 2015

This paper documents that the path of credit spreads since a firm's last loan influences the level at which it can currently borrow. If spreads have moved in the firm's favor (i.e., declined), it is charged a higher interest rate than is justified by current fundamentals, whereas if spreads have moved to the firm's detriment, it is charged a lower rate. We evaluate several possible explanations for this finding, and conclude that anchoring to past deal terms is most plausible.
Going Off Script: How Managers Make Sense of the Ending of Their Careers
Authors: Vough Heather C. , Bataille Christine D. , Noh Sung Chul , Lee Mary Dean
Published: February 2015

The extant retirement literature primarily focuses on factors that influence the decision to retire and the generic retirement decision‐making process. While these approaches have extended our understanding of retirement decision‐making, we propose a sensemaking perspective that orients our attention towards the subjective meanings people attach to the factors that trigger the retirement decision, rather than simply the factors themselves. Accordingly, we see the retirement decision‐making process as bounded by situational constraints and rooted in identity work. Based on interviews with 48 retired Canadian executives and managers, we use thematic narrative analysis to identify six types of end‐of‐career narratives. Drawing on these narratives, we present a model of identity work that distinguishes between retirement decision‐making factors that are perceived as identity opportunities and those that are perceived as identity threats. Our findings contribute to scholarly understanding of subjective meanings and identity considerations in the process of ending one's career.
In-vitro characterisation of a novel celecoxib microbead formulation for the treatment and prevention of colorectal cancer
Authors: McDonald Bernard F , Quinn Alison M , Devers Tomas , Cullen Alan , Coulter Ivan S , Marison Ian W , Loughran Sinéad T
Published: February 2015

Objectives

Colorectal cancer (CRC) is a life-threatening disease that can develop as a consequence of a sustained chronic inflammatory pathology of the colon. Although not devoid of side effects, the anti-inflammatory drug celecoxib (CLX) has been shown to exert protective effects in CRC therapy. The purpose of this study was to develop and characterise a novel CLX microbead formulation suitable for use in the treatment and prevention of CRC, which has the potential to minimise the side effects associated with CLX.

Methods

The study involved the assessment of the effectiveness of CLX formulations in an in-vitro cell model (HT29 cells) and a comparison of these effects to that of the marketed CLX product, Celebrex. Liquid CLX formulations were developed as precursors to microbead formulations. The effect of liquid CLX formulations on HT29 cell viability (MTT and flow cytometry apoptotic assays) and motility (scratch wound assay) were assessed and compared with the effect of Celebrex. A correlation between the in-vitro dissolution performance of the formulations and the effect in the cell model was also explored. Liquid CLX formulations were translated into an optimised CLX microbead formulation, and a colonic targeted sustained release coat (Surelease) was applied to the beads with the aim of producing a formulation for a future in-vivo study to compare the effect of the coated CLX microbeads versus Celebrex in the attenuation of CRC tumours and inflammation in a CRC murine model. The production of CLX microbeads was scaled-up using vibrating-jet encapsulation technology to allow for the development of an optimised dissolution profile to enable colonic release.

Key findings

In-vitro cell viability and motility were shown to be significantly reduced after treatment with CLX liquid formulations relative to the control, whereas the results for treatment with Celebrex were comparable with the control. Dissolution experiments and correlation analysis demonstrated that the formulations that showed a greater extent of drug release had reduced cell viability and motility. The CLX liquid formulations were translated into colon-targeted CLX microbeads suitable for use in a future in-vivo mouse study.

Conclusions

These results represent a significant step forward in the chemopreventative treatment of CRC using CLX, as the microbead formulation developed suggests the possibility of presenting CLX in a format that has the potential to minimise gastrointestinal and cardiovascular side effects.
Intrafirm Knowledge Transfer and Employee Innovative Behavior: The Role of Total and Balanced Knowledge Flows
Authors: Lai John , Lui Steven S. , Tsang Eric W. K.
Published: February 2015

Research on intrafirm knowledge transfer has generally found a positive impact of knowledge inflows on the innovation of an organizational unit. However, the role of knowledge outflows during knowledge transfer is less clear. This paper argues that knowledge outflows influence innovation through a self‐learning mechanism and a fairness assessment mechanism, and play a unique and important role on team innovation. Based on this new understanding on knowledge outflows, it is necessary to examine the impacts of inflows and outflows simultaneously in innovation research. This paper expresses the sum and difference of knowledge inflows and outflows as total and balanced knowledge flows. A theoretical model is proposed to examine the distinct and synergistic effects of total and balanced knowledge flows on employees' innovative behavior of an organizational unit. The model was tested on 148 retail units of an apparel firm based on survey responses from both shop managers and staff. Results showed that total and balanced flows have independent direct effects and a synergistic effect on employee innovative behavior: employees of a unit had the highest levels of innovative behavior when knowledge flows were high and balanced at the same time. This paper contributes to the literature by taking into account both the direction and magnitude of knowledge transfer to examine team innovation.
DNA barcoding the genus Chara: molecular evidence recovers fewer taxa than the classical morphological approach
Authors: Schneider Susanne C. , Rodrigues Anuar , Moe Therese Fosholt , Ballot Andreas
Published: February 2015

Charophytes (Charales) are benthic algae with a complex morphology. They are vulnerable to ecosystem changes, such as eutrophication, and are red‐listed in many countries. Accurate identification of Chara species is critical for understanding their diversity and for documenting changes in species distribution. Species delineation is, however, complicated, because of high phenotypic plasticity. We used barcodes of the ITS2, matK and rbcL regions to test if the distribution of barcode haplotypes among individuals is consistent with species boundaries as they are currently understood. The study included freshly collected and herbarium material of 91 specimens from 10 European countries, Canada and Argentina. Results showed that herbarium specimens are useful as a source of material for genetic analyses for aquatic plants like Chara. rbcL and matK had highest sequence recoverability, but rbcL had a somewhat lower discriminatory power than ITS2 and matK. The tree resulting from the concatenated data matrix grouped the samples into six main groups contrary to a traditional morphological approach that consisted of 14 different taxa. A large unresolved group consisted of C. intermedia, C. hispida, C. horrida, C. baltica, C. polyacantha, C. rudis, C. aculeolata, and C. corfuensis. A second unresolved group consisted of C. virgata and C. strigosa. The taxa within each of the unresolved groups shared identical barcode sequences on the 977 positions of the concatenated data matrix. The morphological differences of taxa within both unresolved groups include the number and length of spine cells, stipulodes, and bract cells. We suggest that these morphological traits have less taxonomic relevance than hitherto assumed.
Transparent exopolymer particle production and aggregation by a marine planktonic diatom (Thalassiosira weissflogii) at different growth rates
Authors: Chen Jie , Thornton Daniel C.O.
Published: February 2015

Transparent exopolymer particles (TEP) play an important role in the ocean carbon cycle as they are sticky and affect particle aggregation and the biological carbon pump. We investigated the effect of growth rate on TEP production in nitrogen limited semi‐continuous cultures of the diatom Thalassiosira weissflogii (Grunow) G. Fryxell & Hasle. Steady‐state diatom concentrations and other indicators of biomass (chl a, and total carbohydrate) were inversely related to growth rate, while individual cell volume increased with growth rate. There was no change in total TEP area with growth rate; however, individual TEP were larger at high growth rates and the number of individual TEP particles was lower. TEP concentration per cell was higher at higher growth rates. SYTOX Green staining showed that <5% of the diatom population had permeable cell membranes, with the proportion increasing at low growth rates. However, TEP production rates were greater at high growth rates, refuting our hypothesis that TEP formation is dependent on dying cells with compromised cell membranes in a diatom population. Measurements of particle size distribution in the cultures using laser scattering showed that they were most aggregated at high growth rates. These results indicate a coupling between TEP production and growth rate in diatoms under N limitation, with fast growing T. weissflogii producing more TEP and aggregates.
Assessing Idaho Rural Family Physician Scope of Practice Over Time
Authors: Schmitz David , Baker Ed , MacKenzie Lisa , Kinney Logan , Epperly Ted
Published: February 2015

Context

An important consideration determining health outcomes is to have an adequate supply of physicians to address the health needs of the community.

Purpose

The purpose of this investigation was to assess scope of practice factors for Idaho rural family physicians in 2012 and to compare these results to findings from a 2007 study.

Methods

The target population in this study was rural family physicians in Idaho counties with populations of fewer than 50,000. Identical surveys and methods were utilized in both 2007 and 2012.

Results

The physician survey was mailed to 252 rural physicians and was returned by 89 for a response rate of 35.3%. Parametric and nonparametric statistical analyses were conducted to analyze the 2012 results and to assess changes in scope of practice across the time periods.

Discussion

The percentage of rural family physicians in Idaho in 2012 who provided prenatal care, vaginal deliveries, and nursing home care was significantly lower than the results from the 2007 survey. Female physicians were more likely to provide prenatal care and vaginal deliveries than males in 2012. Male physicians were more likely to provide emergency room coverage and esophagogastroduodenoscopy or colonoscopy services than females in 2012. Younger physicians were found to be more likely to provide inpatient admissions and mental health services in 2012 than older physicians. Employed physicians were more likely to provide cesarean delivery, other operating room services and emergency room coverage in 2012 than nonemployed physicians. Further research is needed to assess the root causes of these changes.
Alternative eyrie use in peregrine falcons: is it a female choice?
Authors: Zuberogoitia I. , Zabala J. , Martínez J. E. , Olsen J.
Published: February 2015

All animals face the decision of where to breed, a decision that exerts a strong impact on fitness. We examined changes in choice of nest site in peregrine falcons (Falco peregrinus) over a 17‐year period in northern Spain. Falcons had a mean of 3.1 eyries per territory, each location used for a mean of 3.0 consecutive years. Surprisingly, change in eyrie location was not predicted by breeding productivity. However, breeding success decreased with the number of consecutive years that eyries were reused. Ectoparasitic infestation was not a significant predictor in the models. The number of fledglings in the previous season was the main factor explaining the eyrie‐switching decision, with successful pairs being more prone to move. Newly established females showed a higher tendency to switch (59%) than older territorial females (38%) but males did not exhibit the same tendency. High rainfall in April had a negative effect on productivity. In the case of females, changing the eyrie from one season to the next had a positive effect on productivity. In the case of models run with males as a random factor, rainfall in April and eyrie shelter reached significance. So, contrary to the ‘win–stay, lose–switch’ rule and in direct contrast with general literature, peregrines changed eyries after successfully raising large broods and eyrie switching increased the breeding success of females but not of males.
Evidence for alternative male morphs in a Tanganyikan cichlid fish
Authors: Hellmann J. K. , O'Connor C. M. , Ligocki I. Y. , Farmer T. M. , Arnold T. J. , Reddon A. R. , Garvy K. A. , Marsh‐Rollo S. E. , Balshine S. , Hamilton I. M.
Published: February 2015

Teleost fish show tremendous variation in breeding systems. In particular, indeterminate growth and external fertilization create great disparities in reproductive success among males, which drive the evolution of male reproductive polymorphisms. Here, we present evidence for alternative male reproductive tactics in Neolamprologus modestus, a substrate‐spawning African cichlid fish. We observed two types of males in our study site: (1) males that guarded large territories comprised of smaller subterritories of several females and (2) males that did not hold territories and were vigorously attacked by the guarding males upon intrusion into the guarding male's territory. We hypothesized that these intruder males constitute an alternative male phenotype. To test this hypothesis, we collected both territorial males and these intruder males to determine if there were differences in overall body size, gonad size, age or hormone profiles between the two male phenotypes that would be consistent with alternative reproductive tactics in this species. We also collected guarded offspring from territorial male and female pairs to determine if there was any extra‐pair paternity in N. modestus that could indicate the possibility of alternative reproductive tactics. We found that intruder males were significantly smaller in body size and had significantly larger testes in absolute and relative mass compared with territorial paired males. While we assigned no paternity to any collected intruder males, we found that extra‐pair paternity occurred in eight of the 12 collected broods and accounted for c. 27% of all offspring across all broods. Finally, the two sets of males did not differ significantly in age or in circulating androgen levels, suggesting that individuals may not change morphs within their lifetime, but instead may adopt distinct life history strategies. Collectively, we provide strong evidence that intruder N. modestus males represent an alternative small‐bodied male morph that may practice alternative reproductive tactics.
Triple therapy with boceprevir or telaprevir in a European cohort of cirrhotic HIV/HCV genotype 1‐coinfected patients
Authors: Miailhes Patrick , Gilbert Camille , Lacombe Karine , Arends Joop E. , Puoti Massimo , Rockstroh Jürgen K. , Sogni Philippe , Fontaine Hélène , Rosenthal Eric , Winnock Maria , Loko Marc‐Arthur , Wittkop Linda , Dabis François , Salmon Dominique ,   the ESCMID European Study Group on Viral Hepatitis
Published: February 2015

Background & Aims

The efficacy and safety of triple therapy combining boceprevir (BOC) or telaprevir (TVR) with pegylated interferon‐alfa and ribavirin (PegIFN/RBV) has rarely been investigated in human immunodeficiency virus/hepatitis C virus (HIV/HCV) genotype 1‐coinfected patients with cirrhosis.

Methods

We conducted a European (France, Italy, Germany, Netherlands) multicentre study of triple therapy in cirrhotic HIV/HCV GT1‐coinfected patients.

Results

Fifty‐nine patients (47 TVR, 12 BOC) were studied. Median CD4 cell count was 457 (293–578)/mm3, and HIV viral load was <50 copies/ml in 93% of patients. The HCV genotype was GT1a (78%) or GT1b (13%). Previous PegIFN/RBV therapy had resulted in non‐response (73%) or relapse (12%), and 15% of patients were treatment‐naïve. The sustained virological response rate at week 12 (SVR12) was 53% overall (57% with TVR, 36% with BOC). A baseline HCV‐RNA level <800 000 IU/ml tended to be associated with SVR12 (65 vs 42%, P = 0.11). In multivariate analysis, a virological response at week 4 after BOC or TVR initiation was significantly associated with SVR12 (P = 0.040). Early discontinuation of triple therapy was frequent (n = 26, 44%), because of non‐response/breakthrough (65%) or adverse events (AEs) (35%). Three patients died. Severe anaemia (<9 g/dl) occurred in 14 patients (25%), leading to RBV dose reduction (22%), erythropoietin use (56%) or blood transfusion (14%). In multivariate analysis, lack of RBV dose reduction was significantly associated with severe AEs (P = 0.006).

Conclusions

More than half of HIV/HCV GT1‐coinfected patients with cirrhosis achieved a SVR12. To avoid unnecessary adverse effects, therapy should be discontinued if no response is obtained at week 4.
The role of climate adaptation in colonization success in Arabidopsis thaliana
Authors: Hamilton Jill A. , Okada Miki , Korves Tonia , Schmitt Johanna
Published: February 2015

Understanding the genetic mechanisms that contribute to range expansion and colonization success within novel environments is important for both invasion biology and predicting species‐level responses to changing environments. If populations are adapted to local climates across a species' native range, then climate matching may predict which genotypes will successfully establish in novel environments. We examine evidence for climate adaptation and its role in colonization of novel environments in the model species, Arabidopsis thaliana. We review phenotypic and genomic evidence for climate adaptation within the native range and describe new analyses of fitness data from European accessions introduced to Rhode Island, USA, in spring and fall plantings. Accessions from climates similar to the Rhode Island site had higher fitness indicating a potential role for climate pre‐adaptation in colonization success. A genomewide association study (GWAS), and genotypic mean correlations of fitness across plantings suggest the genetic basis of fitness in Rhode Island differs between spring and autumn cohorts, and from previous fitness measurements in European field sites. In general, these observations suggest a scenario of conditional neutrality for loci contributing to colonization success, although there was evidence of a fitness trade‐off between fall plantings in Norwich, UK, and Rhode Island. GWAS suggested that antagonistic pleiotropy at a few specific loci may contribute to this trade‐off, but this conclusion depended upon the accessions included in the analysis. Increased genomic information and phenotypic information make A. thaliana a model system to test for the genetic basis of colonization success in novel environments.
The relative power of genome scans to detect local adaptation depends on sampling design and statistical method
Authors: Lotterhos Katie E. , Whitlock Michael C.
Published: February 2015

Although genome scans have become a popular approach towards understanding the genetic basis of local adaptation, the field still does not have a firm grasp on how sampling design and demographic history affect the performance of genome scans on complex landscapes. To explore these issues, we compared 20 different sampling designs in equilibrium (i.e. island model and isolation by distance) and nonequilibrium (i.e. range expansion from one or two refugia) demographic histories in spatially heterogeneous environments. We simulated spatially complex landscapes, which allowed us to exploit local maxima and minima in the environment in ‘pair’ and ‘transect’ sampling strategies. We compared FST outlier and genetic–environment association (GEA) methods for each of two approaches that control for population structure: with a covariance matrix or with latent factors. We show that while the relative power of two methods in the same category (FST or GEA) depended largely on the number of individuals sampled, overall GEA tests had higher power in the island model and FST had higher power under isolation by distance. In the refugia models, however, these methods varied in their power to detect local adaptation at weakly selected loci. At weakly selected loci, paired sampling designs had equal or higher power than transect or random designs to detect local adaptation. Our results can inform sampling designs for studies of local adaptation and have important implications for the interpretation of genome scans based on landscape data.
Hfq binds directly to the ribosome‐binding site of IS10 transposase mRNA to inhibit translation
Authors: Ellis Michael J. , Trussler Ryan S. , Haniford David B.
Published: February 2015

Hfq is a critical component of post‐transcriptional regulatory networks in most bacteria. It usually functions as a chaperone for base‐pairing small RNAs, although non‐canonical regulatory roles are continually emerging. We have previously shown that Hfq represses IS10/Tn10 transposase expression through both antisense RNA‐dependent and independent mechanisms. In the current work, we set out to define the regulatory role of Hfq in the absence of the IS10 antisense RNA. We show here that an interaction between the distal surface of Hfq and the ribosome‐binding site of transposase mRNA (RNA‐IN) is required for repressing translation initiation. Additionally, this interaction was critical for the in vivo association of Hfq and RNA‐IN. Finally, we present evidence that the small RNA ChiX activates transposase expression by titrating Hfq away from RNA‐IN. The current results are considered in the broader context of Hfq biology and implications for Hfq titration by ChiX are discussed.