bluuebunny/crossref_metadata_2025 huggingface dataset:
A piecewise regression approach for determining biologically relevant hydraulic thresholds for the protection of fishes at river infrastructure
Authors: Boys C. A. , Robinson W. , Miller B. , Pflugrath B. , Baumgartner L. J. , Navarro A. , Brown R. , Deng Z.
Published: March 2016

A piecewise regression approach was used to objectively quantify barotrauma injury thresholds in two physoclistous species, Murray cod Maccullochella peelii and silver perch Bidyanus bidyanus, following simulated infrastructure passage in a barometric chamber. The probability of injuries such as swimbladder rupture, exophthalmia and haemorrhage, and emphysema in various organs increased as the ratio between the lowest exposure pressure and the acclimation pressure (ratio of pressure change, R(NE:A)) reduced. The relationship was typically non‐linear and piecewise regression was able to quantify thresholds in R(NE:A) that once exceeded resulted in a substantial increase in barotrauma injury. Thresholds differed among injury types and between species but by applying a multispecies precautionary principle, the maintenance of exposure pressures at river infrastructure above 70% of acclimation pressure (R(NE:A) of 0·7) should protect downstream migrating juveniles of these two physoclistous species sufficiently. These findings have important implications for determining the risk posed by current infrastructures and informing the design and operation of new ones.
Rheological Characterization and CFD Simulation of Soy White Flakes Based Dough in a Single Screw Extruder
Authors: Singh Sushil K. , Muthukumarappan Kasiviswanathan
Published: March 2016

Understanding the rheological properties such as shear profile, viscosity of a dough inside the extruder is very important for product development, process control, final product quality and scaling up operations. This study aims to characterize the rheological properties of high‐protein dough and perform isothermal flow simulation in a complex geometry for generalized Newtonian fluids. The flow of soy white flakes based dough in a single screw extruder was simulated by using computational fluid dynamics. Process conditions considered were screw speeds (40, 80, 120, 160 and 200 rpm), barrel temperature (100, 120 and 140C) and soy white flakes contents (30, 40 and 50% db). A mesh superposition technique was used to reduce the geometrical complexity. Simulation results were validated quantitatively by experimental data. The results showed good agreement between experimental and computational results. Moreover, the flow profile in the extruder was analyzed by using the influence of screw speed and level of soy white flakes content. Qualitative behavior of local shear rate and viscosity along the screw are analyzed and comparisons of different process conditions are presented. The results of these simulations can be used to optimize processing conditions and also to improve the product quality of extrudates.

Practical Applications

The flow of material within the extruder is complicated due to its helical screw configuration and the different zones of solids‐conveying, melting and melts conveying. Shear profile and viscosity of dough within the extruder directly influences the product quality. In the present study, rheological characterization of dough inside the extruder was done by using online capillary die rheometer. The flow of dough during extrusion processing was simulated using computational fluid dynamics. The results of the simulation can be used to optimize the extrusion process influenced by complex flows of relatively high concentration of soy white flakes based dough in an extruder and also to improve the product quality.
Treg subsets in inflammatory bowel disease and colorectal carcinoma: Characteristics, role, and therapeutic targets
Authors: van Herk Egbert H , te Velde Anje A
Published: March 2016

T regulatory cells (Tregs) play an important role in the regulation of autoimmunity, autoinflammation, allergic diseases, infection, and the tumor environment. Different subsets are characterized that use a number of regulatory mechanisms. Tregs can influence the progression of inflammatory bowel disease and the development of colorectal cancer. Knowledge of Tregs and their regulatory mechanisms can provide new targets for therapeutic intervention.
Real‐world medical costs of antiviral therapy among patients with chronic HCV infection and advanced hepatic fibrosis
Authors: Maan Raoel , Zaim Remziye , van der Meer Adriaan J , Feld Jordan J , Wedemeyer Heiner , Dufour Jean‐François , Lammert Frank , Manns Michael P , Zeuzem Stefan , Hansen Bettina E , Janssen Harry LA , Veldt Bart J , de Knegt Robert J , Uyl‐de Groot Carin A
Published: March 2016

Background and Aims

Very potent direct acting antivirals for the treatment of chronic hepatitis C virus infection were recently introduced into daily clinical practice. Currently, treatment uptake is hampered by their high costs, eliciting prioritization of treatment. We aimed to evaluate the direct medical costs during interferon (IFN)‐based antiviral treatment and the costs per sustained virological response (SVR) among patients with advanced hepatic fibrosis.

Methods

This retrospective cohort study included all consecutive patients with chronic hepatitis C virus infection and biopsy‐proven bridging fibrosis or cirrhosis (Ishak 4–6) treated with IFN‐based regimens in five hepatology units of tertiary care centers in Europe and Canada. Direct medical costs, expressed in 2013 Euros, during therapy were assessed. The components of care were quantified by three distinct categories: treatment, safety/ monitoring, and complications. Cost per SVR was calculated by dividing the mean cost by the SVR rate.

Results

In total, 672 interferon‐based treatments administered to 455 patients were included. Total medical costs per patient were averaged to €14 559 (95% confidence interval [CI], €13 323–€15 836). The mean cost per SVR was €38 514 (95% CI, €35 244–€41 892). The costs per SVR were €26 105 (95% CI, €23 068–€29 296) for patients with a normal platelet count and €50 907 (95% CI, €44 151–€59 612) for patients with thrombocytopenia, with the costs per SVR of €74 961 (95% CI, €55 463–€103 541) among those patients with a platelet count below 100 * 109/L.

Conclusions

Because of the lower SVR rates, the cost per SVR of IFN‐based treatment increased when patients with more advanced liver disease were treated. Additional costs of IFN‐free therapy could be limited among these patients.
When Comparing Alternative Fuel‐Vehicle Systems, Life Cycle Assessment Studies Should Consider Trends in Oil Production
Authors: Wallington Timothy J. , Anderson James E. , De Kleine Robert D. , Kim Hyung Chul , Maas Heiko , Brandt Adam R. , Keoleian Gregory A.
Published: March 2016

Petroleum from unconventional reserves is making an increasingly important contribution to the transportation fuel supply, but is generally more expensive and has greater environmental burdens than petroleum from conventional sources. Life cycle assessments (LCAs) of alternative fuel‐vehicle technologies typically consider conventional internal combustion engine vehicles fueled by gasoline produced from the average petroleum slate used in refineries as a baseline. Large‐scale deployment of alternative fuel‐vehicle technologies will decrease petroleum demand and lead to decreased production at the economic margin (unconventional oil), but this is not considered in most current LCAs. If marginal petroleum resources have larger impacts than average petroleum resources, the environmental benefits of petroleum demand reduction are underestimated by the current modeling approaches. Often, models include some consequential‐based impacts (such as indirect land‐use change for biofuels), but exclude others (such as avoided unconventional oil production). This approach is inconsistent and does not provide a robust basis for public policy and private investment strategy decisions. We provide an example to illustrate the potential scale of these impacts, but further research is needed to establish and quantify these marginal effects and incorporate them into LCAs of both conventional and alternative fuel‐vehicle technologies.
Protein interacting with NIMA (never in mitosis A)‐1 regulates axonal growth cone adhesion and spreading through myristoylated alanine‐rich C kinase substrate isomerization
Authors: Sosa Lucas J. , Malter James S. , Hu Jie , Bustos Plonka Florentyna , Oksdath Mariana , Nieto Guil Alvaro F. , Quiroga Santiago , Pfenninger Karl H.
Published: March 2016

Axonal growth cone motility requires precise regulation of adhesion to navigate the complex environment of the nervous system and reach its target. Myristoylated alanine‐rich C kinase substrate (MARCKS) protein is enriched in the developing brain and plays an important, phosphorylation‐dependent role in the modulation of axonal growth cone adhesion. The ratio of phospho‐MARCKS (MARCKS‐P) to total MARCKS controls adhesion modulation and spreading of the axonal growth cone. Pin1, a peptidyl‐prolyl cis/trans isomerase (PPIase) that recognizes and binds to phosphorylated serine/threonine residues preceded by a proline (pSer/Thr‐Pro) is also expressed in the developing brain. Here, we show that Pin1 is present in the growth cone, interacts with MARCKS‐P, and regulates its dephosphorylation. We also described morphological alterations in the corpus callosum and cerebral cortex fibers of the Pin1 knockout mouse brain that may be caused by the misregulation of MARCKS‐P and alterations of neuronal adhesion.

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We have shown that MARCKS, a critical protein in the movement of neuronal growth cones, is in turn regulated by both phosphorylation and cis‐trans peptidyl isomerization mediated by Pin1. In the absence of Pin1, MARCKS is hyperphosphorylated, leading to loss of adhesions, and collapse of the growth cone. The Pin1 KO mice exhibited disturbed neuronal projections from the cerebral cortex and reduced white matter tracks such as the corpus callosum. This study highlights a novel function of Pin1 in neurodevelopment.
Sevoflurane prevents stroke‐induced depressive and anxiety behaviors by promoting cannabinoid receptor subtype I‐dependent interaction between β‐arrestin 2 and extracellular signal‐regulated kinases 1/2 in the rat hippocampus
Authors: Zhang Houzhong , Li Li , Sun Yanli , Zhang Xingyi , Zhang Yifan , Xu Shuang , Zhao Peng , Liu Tiecheng
Published: March 2016

One of the most frequent psychological consequences of stroke is depression. Previous animal studies have demonstrated that post‐conditioning with sevoflurane protects against focal cerebral ischemia and reperfusion injury. Thus, we hypothesized that repeated exposure to sevoflurane after transient ischemia can prevent the development of depressive‐like behavior. To test this hypothesis, we induced transient cerebral ischemia via transient occlusion of bilateral common carotid arteries and examined the effects of subsequent repeated exposure to sevoflurane on sucrose preference, locomotor activity, and rearing activity in rats. To explore the putative neurobiological mechanisms, we further investigated the roles of hippocampal CB1 receptor in the behavioral effects of sevoflurane. We found that repeated sevoflurane exposures reversed ischemia‐induced depressive‐like behaviors. Furthermore, CB1 receptor inhibition in the dorsal hippocampus (DH) abolished the effects of sevoflurane exposures on ischemia‐induced depressive‐like behaviors. In addition, repeated sevoflurane exposures increased CB1 receptor expression and endocannabinoids levels in the DH of ischemic rats. Moreover, repeated sevoflurane exposures enhanced the expression of β‐arrestin 2, increased the activation of extracellular signal‐regulated kinases (ERK)1/2, and promoted the interaction of β‐arrestin 2 and ERK1/2 in the DH, and such effects were reversed by CB1 receptor antagonism in the DH. Finally, β‐arrestin 2 expression and ERK1/2 activation in the DH were critical for the preventative effects of sevoflurane exposures on ischemia‐induced depressive‐like behaviors. Taken together, our results suggested that sevoflurane exposure after brain ischemia may prevent the development of depression, and such preventative effects of sevoflurane are likely ascribed to the activation of CB1 receptor‐mediated β‐arrestin 2‐ERK1/2 signaling pathways.

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We propose that the following mechanisms are critical for the preventative effects of sevoflurane against post‐stroke depressive and anxiety behaviors: repeated sevoflurane exposure after transient brain ischemia enhances N‐arachidonoylethanolamine (AEA) and 2‐Arachidonoylglycerol (2‐AG) levels and normalize cannabinoid receptor type 1 (CB1) receptor expression in the dorsal hippocampus, which results in enhanced interaction of β‐arrestin 2 and extracellular signal‐regulated kinases (ERK1/2) and increased ERK1/2 activation, leading to decreased depressive and anxiety behaviors. We think these findings should provide a new strategy for treatment of post‐stroke depression.
Involvement of endogenous antioxidant systems in the protective activity of pituitary adenylate cyclase‐activating polypeptide against hydrogen peroxide‐induced oxidative damages in cultured rat astrocytes
Authors: Douiri Salma , Bahdoudi Seyma , Hamdi Yosra , Cubì Roger , Basille Magali , Fournier Alain , Vaudry Hubert , Tonon Marie‐Christine , Amri Mohamed , Vaudry David , Masmoudi‐Kouki Olfa
Published: March 2016

Astroglial cells possess an array of cellular defense mechanisms, including superoxide dismutase (SOD) and catalase antioxidant enzymes, to prevent damages caused by oxidative stress. Nevertheless, astroglial cell viability and functionality can be affected by significant oxidative stress. We have previously shown that pituitary adenylate cyclase‐activating polypeptide (PACAP) is a potent glioprotective agent that prevents hydrogen peroxide (H2O2)‐induced apoptosis in cultured astrocytes. The purpose of this study was to investigate the potential protective effect of PACAP against oxidative‐generated alteration of astrocytic antioxidant systems. Incubation of cells with subnanomolar concentrations of PACAP inhibited H2O2‐evoked reactive oxygen species accumulation, mitochondrial respiratory burst, and caspase‐3 mRNA level increase. PACAP also stimulated SOD and catalase activities in a concentration‐dependent manner, and counteracted the inhibitory effect of H2O2 on the activity of these two antioxidant enzymes. The protective action of PACAP against H2O2‐evoked inhibition of antioxidant systems in astrocytes was protein kinase A, PKC, and MAP‐kinase dependent. In the presence of H2O2, the SOD blocker NaCN and the catalase inhibitor 3‐aminotriazole, both suppressed the protective effects of PACAP on SOD and catalase activities, mitochondrial function, and cell survival. Taken together, these results indicate that the anti‐apoptotic effect of PACAP on astroglial cells can account for the activation of endogenous antioxidant enzymes and reduction in respiration rate, thus preserving mitochondrial integrity and preventing caspase‐3 expression provoked by oxidative stress. Considering its powerful anti‐apoptotic and anti‐oxidative properties, the PACAPergic signaling system should thus be considered for the development of new therapeutical approaches to cure various pathologies involving oxidative neurodegeneration.

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We propose the following cascade for the glioprotective action of Pituitary adenylate cyclase‐activating polypeptide (PACAP) against H2O2‐induced astrocyte damages and cell apoptosis in cultured rat astrocytes. PACAP, through activation of its receptor, PAC1‐R, and the protein kinase A (PKA), protein kinase C (PKC), and MAP‐kinases signaling pathways, prevents accumulation of ROS and inhibition of SOD and catalase activities. This allows the preservation of mitochondrial membrane integrity and the reduction in caspase‐3 activation induced by H2O2. These data may lead to the development of new strategies for cerebral injury treatment. Cat, catalase; Cyt. C, cytochrome C; SOD, superoxide dismutase.
Patients’ experience with intermittent catheterisation in everyday life
Authors: Cobussen‐Boekhorst Hanny , Hermeling Erna , Heesakkers John , van Gaal Betsie
Published: March 2016

Aims and objectives

This study reports about the experiences of 11 patients in the Netherlands who use intermittent self‐catheterisation to manage their symptoms. The aim of the study was to get insight in underlying barriers and facilitators for patients dealing with intermittent catheterisation in everyday life.

Background

Studies show that intermittent catheterisation has an impact on everyday life. A positive effect does not guarantee that patients maintain catheterisation over a longer period of time. After the implementation of a guideline, a quantitative study was performed to determine successful intermittent catheterisation. The patients of this study had previously taken part in this quantitative study.

Design

This is a qualitative multicentre study using semistructured in‐depth interviews with 11 patients between March–May 2013.

Methods

Inclusion criteria included patients of a quantitative study (n = 124) with a variety of diagnoses referred to the outpatient clinic. Those who received instruction from the researcher and who at start of the study performed catheterisation ≤3 months were excluded. Of the total number that met the inclusion criteria, every fourth patient was invited to participate in an interview. Patients were asked about the introducing of intermittent catheterisation, the incorporation into everyday life, the progress after the instruction and guidance perceived, the cause of the bladder problem and the motivation to start intermittent catheterisation.

Results

Eleven interviews were performed (six males/five females). All patients described the instruction and follow‐up care as positive. Barriers were the preparation before the handling, which is more difficult than the catheterisation itself, and the fact that patients felt constrained by the need to plan convenient times to catheterise themselves.

Conclusion

This study shows that patients who perform catheterisation are satisfied about the instruction and follow‐up care. Important barriers in everyday life are the preparation and the need to plan convenient times.

Relevance to clinical practice

Interviewing patients gave important additional information about dealing with intermittent catheterisation in everyday life. Prescribers and teachers of intermittent catheterisation must realise that they often have to high expectations of patients when it comes to being flexible in frequency of catheterisation. It is important to realise that patients experience barriers of which healthcare workers are not always aware of, such as the preparation before the handling and feeling constrained by the need to plan convenient times to catheterise. The outcome of this study can be used to improve the content of patient information brochures and guidelines for intermittent catheterisation.
Nursing implications: symptom presentation and quality of life in rectal cancer patients
Authors: O'Gorman Claire , Barry Amanda , Denieffe Suzanne , Sasiadek Wojciech , Gooney Martina
Published: March 2016

Aims and objectives

To determine the changes in symptoms experienced by rectal cancer patients during preoperative chemoradiotherapy, with a specific focus on fatigue and to explore how symptoms impact the quality of life.

Background

Rectal cancer continues to be a healthcare issue internationally, despite advances in management strategies, which includes the administration of preoperative chemoradiotherapy to improve locoregional control. It is known that this treatment may cause adverse effects; however, there is a paucity of literature that specifically examines fatigue, symptoms and quality of life in this patient cohort.

Design

A prospective, quantitative correlational design using purposive sampling was adopted.

Methods

Symptoms and quality of life were measured with validated questionnaires in 35 patients at four time points.

Results

Symptoms that changed significantly over time as examined usingrm‐anovainclude fatigue, bowel function issues, nutritional issues, pain, dermatological issues and urinary function issues. Findings indicate that fatigue leads to poorer quality of life, with constipation, bloating, stool frequency, appetite loss, weight worry, nausea and vomiting, dry mouth and pain also identified as influencing factors on quality of life.

Conclusion

Findings have highlighted the importance of thorough symptom assessment and management of patients receiving preoperative chemoradiotherapy, particularly midway through treatment, in order to optimise quality of life and minimise interruptions to treatment.

Relevance to Clinical Practice

Close monitoring of symptoms during preoperative chemoradiotherapy, particularly at week 4, will enable the implementation of timely interventions so that interruptions to treatment are prevented and the quality of life is optimised, which may hasten postoperative recovery times.
Current controversies in determining the main mechanisms of atrial fibrillation
Authors: Schotten U. , Dobrev D. , Platonov P. G. , Kottkamp H. , Hindricks G.
Published: March 2016

Despite considerable basic research into the mechanisms of atrial fibrillation (AF), not much progress has been made in the prognosis of patients with AF. With the exception of anticoagulant therapy, current treatments for AF still do not improve major cardiovascular outcomes. This may be due partly to the diverse aetiology of AF with increasingly more factors found to contribute to the arrhythmia. In addition, a strong increase has been seen in the technological complexity of the methods used to quantify the main pathophysiological alterations underlying the initiation and progression of AF. Because of the lack of standardization of the technological approaches currently used, the perception of basic mechanisms of AF varies widely in the scientific community. Areas of debate include the role of Ca2+‐handling alterations associated with AF, the contribution and noninvasive assessment of the degree of atrial fibrosis, and the best techniques to identify electrophysiological drivers of AF. In this review, we will summarize the state of the art of these controversial topics and describe the diverse approaches to investigating and the scientific opinions on leading AF mechanisms. Finally, we will highlight the need for transparency in scientific reporting and standardization of terminology, assumptions, algorithms and experimental conditions used for the development of better AF therapies.
The Life Satisfaction Advantage of Being Married and Gender Specialization
Authors: Mikucka Małgorzata
Published: March 2016

This investigation examined whether the life satisfaction advantage of married over unmarried people decreased over the past 3 decades and whether the changes in contextual gender specialization explained this trend. Contextual gender specialization was defined as a country‐year‐specific share of married women who fully specialize in household work. The author used representative data from the World Values Survey–European Values Study integrated data set for 87 countries (N = 292,525) covering a period of 29 years (1981–2009). The results showed that the life satisfaction advantage of being married decreased over time among men but not among women. Furthermore, the decline of contextual gender specialization correlated with this trend in developed but not in developing countries. In developed countries the life satisfaction of unmarried people increased as the contextual gender specialization declined, whereas the life satisfaction of married people was not affected.
3D Super‐Resolution Motion‐Corrected MRI: Validation of Fetal Posterior Fossa Measurements
Authors: Pier Danielle B. , Gholipour Ali , Afacan Onur , Velasco‐Annis Clemente , Clancy Sean , Kapur Kush , Estroff Judy A. , Warfield Simon K.
Published: March 2016

PURPOSE

Current diagnosis of fetal posterior fossa anomalies by sonography and conventional MRI is limited by fetal position, motion, and by two‐dimensional (2D), rather than three‐dimensional (3D), representation. In this study, we aimed to validate the use of a novel magnetic resonance imaging (MRI) technique, 3D super‐resolution motion‐corrected MRI, to image the fetal posterior fossa.

METHODS

From a database of pregnant women who received fetal MRIs at our institution, images of 49 normal fetal brains were reconstructed. Six measurements of the cerebellum, vermis, and pons were obtained for all cases on 2D conventional and 3D reconstructed MRI, and the agreement between the two methods was determined using concordance correlation coefficients. Concordance of axial and coronal measurements of the transcerebellar diameter was also assessed within each method.

RESULTS

Between the two methods, the concordance of measurements was high for all six structures (P < .001), and was highest for larger structures such as the transcerebellar diameter. Within each method, agreement of axial and coronal measurements of the transcerebellar diameter was superior in 3D reconstructed MRI compared to 2D conventional MRI (P < .001).

CONCLUSIONS

This comparison study validates the use of 3D super‐resolution motion‐corrected MRI for imaging the fetal posterior fossa, as this technique results in linear measurements that have high concordance with 2D conventional MRI measurements. Lengths of the transcerebellar diameter measured within a 3D reconstruction are more concordant between imaging planes, as they correct for fetal motion and orthogonal slice acquisition. This technique will facilitate further study of fetal abnormalities of the posterior fossa.
Use of photodynamic therapy and chitosan for inactivacion of Candida albicans in a murine model.
Authors: Fabio Camacho‐Alonso , Yolanda Martínez‐Beneyto , Carmen Gallego Mª , Francisco Cuello , Antonio Julián Buendía , Leonor Pérez‐Lajarin , Jesús Salinas
Published: March 2016

Background

The wide use of topical and systemic antifungal agents as the conventional treatment for oral candidiasis has caused Candida albicans to develop resistance to these agents. The aims of this study were to evaluate the effects of photodynamic therapy (PDT) and chitosan on buccal candidiasis and study the possible enhancive effect of chitosan on the photosensitizer methylene blue.

Methods

Thirty‐five DBA/2 immunosuppressed mice were orally inoculated with a suspension of Candida albicans. The animals were randomized into seven groups (n = 5 per group): Group 1 (control); Group 2 (nystatin); Group 3 (PDT); Group 4 (chitosan 1.5 mg/ml); Group 5 (chitosan 3 mg/ml); Group 6 (PDT + chitosan 1.5 mg/ml); and Group 7 (PDT + chitosan 3 mg/ml). The Candida albicans count was evaluated on days 3, 5, 7, and 11 after inoculation. At last, macroscopic and microscopic analyses of the tongue dorsa were performed.

Results

On day 7 after inoculation, the control group showed a greater number of Candida albicans (5.25 ± 0.41 log10 CFU/ml), with significant differences compared to all other groups (P ≤ 0.05). On day 11 after inoculation, animals treated with PDT showed lower CFU/ml count. Groups 2, 3, 4, 5, and 6 showed fewer microscopic candidiasis lesions than Groups 1 and 7.

Conclusions

PDT has an antifungal effect, even greater than nystatin. Chitosan has a powerful fungicide effect but did not possess any enhancive effect on methylene blue.
Immunoexpression of hoxb7 and hoxb9 in salivary gland tumours
Authors: Fonseca Felipe Paiva , Bingle Lynne , Santos‐Silva Alan Roger , Lopes Márcio Ajudarte , Coletta Ricardo D. , de Andrade Bruno Augusto Benevenuto , Mariano Fernanda Viviane , Kowalski Luiz Paulo , Rangel Ana Lúcia Carrinho Ayroza , Martins Manoela Domingues , Meurer Luise , Hunter Keith D. , Speight Paul M. , Vargas Pablo Agustin
Published: March 2016

Background

Salivary gland carcinomas are uncommon neoplasms and the identification of new prognostic indicators could improve their management. HOXB7 and HOXB9 are members of the class I homeobox‐containing genes important for normal embryogenesis and that are dysregulated in several human neoplasms. This study investigated HOXB7 and HOXB9 expressions in salivary gland tumourigenesis, their correlation with neoplastic proliferative and angiogenic features and their importance as prognostic markers.

Methods

A hundred and fifty salivary gland tumours were organized in tissue microarray and expressions of CD105, Ki67, HOXB7 and HOXB9 were determined through immunohistochemistry. Reactions were quantified and correlated with clinicopathological parameters.

Results

In normal glands, HOXB7 was found in basal cells, whereas HOXB9 was seen in serous acinar and scattered ductal cells. Malignancies exhibited an increased vascular density, proliferative index, HOXB7 and HOXB9 expressions when compared with pleomorphic adenoma and Warthin's tumour. Significant correlation was found between HOXB7 and CD105 (P = 0.004) in adenoid cystic carcinomas, and HOXB7 higher expression significantly correlated with the presence of paresthesia (P = 0.02). No marker exhibited a significant association with survival rates (P > 0.05).

Conclusion

HOXB7 and HOXB9 were expressed in normal salivary gland and were present in benign and malignant tumours derived from these structures, and HOXB7 significantly correlated with neoangiogenesis in AdCC. These findings suggest that both proteins might play a role in salivary gland tumourigenesis, but they were not significant prognostic determinants in this sample.
DO STATE BUSINESS CLIMATE INDICATORS EXPLAIN RELATIVE ECONOMIC GROWTH AT STATE BORDERS?
Authors: Artz Georgeanne M. , Duncan Kevin D. , Hall Arthur P. , Orazem Peter F.
Published: March 2016

This study submits 11 business climate indexes to tests of their ability to predict relative economic performance on either side of state borders. Our results show that most business climate indexes have no ability to predict relative economic growth regardless of how growth is measured. Some are negatively correlated with relative growth. Many are better at reporting past growth than at predicting the future. In the end, the most predictive business climate index is the Grant Thornton Index which was discontinued in 1989.
Ambiguity and Accident Law
Authors: CHAKRAVARTY SURAJEET , KELSEY DAVID
Published: March 2016

Environmental accidents often involve ambiguous risks, i.e., the relevant probabilities are unknown. This paper studies how liability rules are affected by ambiguity. The injurer and the victim choose a level of care, which is observable, and an unobservable action. Both actions may affect the size and/or likelihood of loss. We analyze the welfare implications of tort rules. First, we show that with ambiguity, negligence is likely to perform better than strict liability. Second, we propose a tort rule of negligence and punitive damages, which gives the efficient levels of both care and unobserved actions.
Optimal Fines under Announced and Surprise Inspections
Authors: DECHENAUX EMMANUEL , SAMUEL ANDREW
Published: March 2016

This paper examines optimal fines in a regulatory framework where the regulator can choose either surprise or announced inspections to monitor a firm for compliance. The firm can invest in detection avoidance, but it receives a fine if the regulator discovers that it is noncompliant. In the welfare maximization problem, we focus on the trade‐off between the frequency of inspections and the magnitude of the fine. We find that when inspections are unannounced, the optimal fine is maximal, but when they are announced, the optimal fine may be less than maximal.
Postcrystallization metasomatism in shergottites: Evidence from the paired meteorites LAR 06319 and LAR 12011
Authors: Howarth Geoffrey H. , Liu Yang , Chen Yang , Pernet‐Fisher John F. , Taylor Lawrence A.
Published: March 2016

Apatite is the major volatile‐bearing phase in Martian meteorites, containing structurally bound fluorine, chlorine, and hydroxyl ions. In apatite, F is more compatible than Cl, which in turn is more compatible than OH. During degassing, Cl strongly partitions into the exsolved phase, whereas F remains in the melt. For these reasons, the volatile concentrations within apatite are predictable during magmatic differentiation and degassing. Here, we present compositional data for apatite and merrillite in the paired enriched, olivine‐phyric shergottites LAR 12011 and LAR 06319. In addition, we calculate the relative volatile fugacities of the parental melts at the time of apatite formation. The apatites are dominantly OH‐rich (calculated by stoichiometry) with variable yet high Cl contents. Although several other studies have found evidence for degassing in the late‐stage mineral assemblage of LAR 06319, the apatite evolutionary trends cannot be reconciled with this interpretation. The variable Cl contents and high OH contents measured in apatites are not consistent with fractionation either. Volatile fugacity calculations indicate that water and fluorine activities remain relatively constant, whereas there is a large variation in the chlorine activity. The Martian crust is Cl‐rich indicating that changes in Cl contents in the apatites may be related to an external crustal source. We suggest that the high and variable Cl contents and high OH contents of the apatite are the results of postcrystallization interaction with Cl‐rich, and possibly water‐rich, crustal fluids circulating in the Martian crust.
Dating a small impact crater: An age of Kaali crater (Estonia) based on charcoal emplaced within proximal ejecta
Authors: Losiak A. , Wild E. M. , Geppert W. D. , Huber M. S. , Jõeleht A. , Kriiska A. , Kulkov A. , Paavel K. , Pirkovic I. , Plado J. , Steier P. , Välja R. , Wilk J. , Wisniowski T. , Zanetti M.
Published: March 2016

The estimates of the age of the Kaali impact structure (Saaremaa Island, Estonia) provided by different authors vary by as much as 6000 years, ranging from ~6400 to ~400 before current era (BCE). In this study, a new age is obtained based on 14C dating charred plant material within the proximal ejecta blanket, which makes it directly related to the impact structure, and not susceptible to potential reservoir effects. Our results show that the Kaali crater was most probably formed shortly after 1530–1450 BCE (3237 ± 10 14C yr BP). Saaremaa was already inhabited when the bolide hit the Earth, thus, the crater‐forming event was probably witnessed by humans. There is, however, no evidence that this event caused significant change in the material culture (e.g., known archeological artifacts) or patterns of human habitation on Saaremaa.
Meteorites found on Misfits Flat dry lake, Nevada
Authors: Harlan Scott , Jenniskens Peter , Zolensky Michael E. , Yin Qing‐Zhu , Verosub Kenneth L. , Rowland Douglas J. , Sanborn Matthew , Huyskens Magdalena , Creager Emily R. , Jull A. J. Timothy ,   (The Misfits Flat Meteorite Consortium)
Published: March 2016

Meteorites have been found on the small Misfits Flat dry lakebed near Stagecoach, Nevada (119.382W, +39.348N). Since the first find on Sept. 22, 2013, a total of 58 stones of weathering stage W2/3 with a combined mass of 339 g have been collected in 19 visits to the area. This small (3.3 × 3.6 km) lakebed is now a newly designated dense collection area (DCA). Most meteorites were found in a small 350 × 180 m area along the north shore and most are fragments of several broken individual stones. Three of these fragments were classified as an LL4/5 of shock stage S2, now named Misfits Flat 001, one of which (stone MF33) fell 8.1 ± 1.3 ka ago based on the 14C terrestrial age, assuming it came from a 20–80 cm diameter meteoroid. In addition, a small darkly crusted meteorite MF34, now named Misfits Flat 002, was found 820 m WSW from the main mass. This meteorite is classified as an LL5 ordinary chondrite with shock stage S4/5. The meteorite is saturated in 14C at 63 dpm kg−1, suggesting it originated from the center of a 0.5 m diameter meteoroid, or deep inside a ~1.0 m meteoroid, less than 300 yr ago. Accounts exist of a fireball seen at 13:15 UT on March 2, 1895, that are consistent with the find location of Misfits Flat 002.
Rare earth element measurements and mapping of minerals in the Allende CAI, 7R19‐1, by NanoSIMS ion microprobe
Authors: Ito Motoo , Messenger Scott
Published: March 2016

We have established analytical procedures for quantitative rare earth element (REE) measurements by NanoSIMS 50L ion microprobe with 2–10 μm spatial resolution. Measurements are performed by multidetection using energy filtering under several static magnetic field settings. Relative sensitivity factors and REE oxide/REE element secondary ion ratios that we determined for the NanoSIMS match values previously determined for other ion microprobes. REE measurements of 100 ppm REE glass standards yielded reproducibility and accuracy of 0.5–2.5% and 5–15%, respectively. REE measurements of minerals of an Allende type‐A CAI, 7R19‐1, were performed using three different methods: spot analysis, line profile, and imaging. These data are in excellent agreement with previous REE measurements of this inclusion by IMS‐3f ion microprobe. The higher spatial resolution NanoSIMS measurements provide additional insight into the formation process of this CAI and offer a promising new tool for analysis of fine‐grained and complexly zoned materials.
Breastfeeding booklet and proactive phone calls for increasing exclusive breastfeeding rates: RCT protocol
Authors: Zakarija‐Grković Irena , Puharić Drita , Malički Mario , Hoddinott Pat
Published: March 2016

Breastfeeding is associated with infant and maternal health benefits and considerable potential savings to health services. Despite this, only 37% of infants globally are exclusively breastfed for 6 months. Interventions are needed to improve breastfeeding rates. The aim of this study is to determine whether written breastfeeding information in pregnancy and proactive breastfeeding‐focused support phone calls, provided by a health professional educated in breastfeeding management, increase exclusive breastfeeding rates at 3 months compared with general birth‐related information with proactive support calls or standard care.

This is a single‐centre, randomised, controlled, three‐arm, superiority study with blind outcome assessment. Eligible participants will include primigravidae with singleton pregnancies who speak Croatian, attending six primary care obstetric practices. We estimate a total sample size of 459, with computer generated stratified randomisation of 153 women per arm. Participants in the intervention and active control groups will receive booklets in pregnancy, phone calls 2 weeks later, and 2, 6 and 10 weeks after birth. The primary outcome will be the proportion of women exclusively breastfeeding at 3 months. Secondary outcomes will compare: infant feeding practices and attitudes, social support, breastfeeding difficulties, breastfeeding self efficacy and utilisation of breastfeeding support services. Follow‐up at 6 months will compare exclusive and any breastfeeding and utilised support services. Analysis will be by intention to treat. This trial will contribute to future evidence syntheses identifying the most effective forms of breastfeeding support.
Identifying targets of selection in mosaic genomes with machine learning: applications in Anopheles gambiae for detecting sites within locally adapted chromosomal inversions
Authors: He Qixin , Knowles L. Lacey
Published: March 2016

Chromosomal inversions are important structural changes that may facilitate divergent selection when they capture co‐adaptive loci in the face of gene flow. However, identifying selection targets within inversions can be challenging. The high degrees of differentiation between heterokaryotypes, as well as the differences in demographic histories of collinear regions compared with inverted ones, reduce the power of traditional outlier analyses for detecting selected loci. Here, we develop a new approach that uses discriminant functions informed from inversion‐specific expectations to classify loci that are under selection (or drift). Analysis of RAD sequencing data we collected in a classic dipteran species with polymorphic inversion clines—Anopheles gambiae, a malaria vector species from sub‐Saharan Africa—demonstrates the benefits of the approach compared with traditional outlier analyses. We focus specifically on two polymorphic inversions, the 2La and 2Rb arrangements that predominate in dry habitats and the 2L+a and 2R+b arrangements in wet habitats, which contrast with the minimal geographic structure of SNPs from collinear regions. With our approach, we identify two strongly selected regions within 2La associated with dry habitat. Moreover, we also show that the prevalence of selection is greater in the arrangement 2L+a that is associated with wet habitat (unlike presumed importance of selective divergence associated with the shift of the mosquitoes into dry habitats). We discuss the implications of these results with respect to studies of rapid adaptation in these malaria vectors, and in particular, the insights our newly developed approach offers for identifying not only potential targets of selection, but also the population that has undergone adaptive change.
Distribution patterns of microbial communities in ultramafic landscape: a metagenetic approach highlights the strong relationships between diversity and environmental traits
Authors: Bordez L. , Jourand P. , Ducousso M. , Carriconde F. , Cavaloc Y. , Santini S. , Claverie J. M. , Wantiez L. , Leveau A. , Amir H.
Published: March 2016

Microbial species richness and assemblages across ultramafic ecosystems were investigated to assess the relationship between their distributional patterns and environmental traits. The structure of microorganism communities in the Koniambo massif, New Caledonia, was investigated using a metagenetic approach correlated with edaphic and floristic factors. Vegetation cover and soil properties significantly shaped the large phylogenetic distribution of operational taxonomic unit within microbial populations, with a mean per habitat of 3.477 (±317) for bacteria and 712 (±43) for fungi. Using variance partitioning, we showed that the effect of aboveground vegetation was the most significant descriptor for both bacterial and fungal communities. The floristic significant predictors explained 43% of the variation for both the bacterial and fungal community structures, while the edaphic significant predictors explained only 32% and 31% of these variations, respectively. These results confirm the previous hypothesis that the distribution of microorganisms was more structured by the vegetation cover rather than the edaphic characteristics and that microbial diversity is not limited in ultramafic ecosystems.
The hypoxia‐induced dehydrogenase HorA is required for coenzyme Q10 biosynthesis, azole sensitivity and virulence of Aspergillus fumigatus
Authors: Kroll Kristin , Shekhova Elena , Mattern Derek J. , Thywissen Andreas , Jacobsen Ilse D. , Strassburger Maria , Heinekamp Thorsten , Shelest Ekaterina , Brakhage Axel A. , Kniemeyer Olaf
Published: March 2016

Aspergillus fumigatus is the predominant airborne pathogenic fungus causing invasive aspergillosis in immunocompromised patients. During infection A. fumigatus has to adapt to oxygen‐limiting conditions in inflammatory or necrotic tissue. Previously, we identified a mitochondrial protein to be highly up‐regulated during hypoxic adaptation. Here, this protein was found to represent the novel oxidoreductase HorA. In Saccharomyces cerevisiae a homologue was shown to play a role in biosynthesis of coenzyme Q. Consistently, reduced coenzyme Q content in the generated ΔhorA mutant indicated a respective function in A. fumigatus. Since coenzyme Q is involved in cellular respiration and maintaining cellular redox homeostasis, the strain ΔhorA displayed an impaired response to both oxidative and reductive stress, a delay in germination and an accumulation of NADH. Moreover, an increased resistance against antifungal drugs was observed. All phenotypes were completely reversed by the addition of the synthetic electron carrier menadione. The deletion strain ΔhorA showed significantly attenuated virulence in two murine infection models of invasive pulmonary aspergillosis. Therefore, the biosynthesis of coenzyme Q and, particularly, the fungal‐specific protein HorA play a crucial role in virulence of A. fumigatus. Due to its absence in mammals, HorA might represent a novel therapeutic target against fungal infections.
Epithelial and organ‐related marker expression in pituitary adenomas
Authors: Cykowski Matthew D. , Takei Hidehiro , Baskin David S. , Rivera Andreana L. , Powell Suzanne Z.
Published: March 2016

The histologic expression of epithelial and organ‐related immunohistochemical markers in primary sellar region tumors has received little attention to date. This lack of empirical data may lead to mistaken assumptions in the evaluation of sellar region neoplasms. To address this issue, the frequency and specificity of epithelial (cytokeratin 7(CK7), CK20) and organ‐related differentiation markers (gross cystic disease fluid protein‐15 (GCDFP‐15), thyroid transcription factor‐1 (TTF‐1), Napsin A, paired box 8 (PAX‐8), hepatocyte paraffin 1 (HepPar1) and estrogen receptor (ER)) were studied in 40 patients with adenomas comprising five hormonal sub‐types. Non‐parametric statistical procedures were used to examine associations between marker expression and tumor sub‐type. CK7 and CK20 immunoreactivity were seen in 48% and 8% of tumors, respectively, although never in a diffuse pattern. CK20 expression was nearly exclusive to corticotrophs, whereas CK7 frequently highlighted cells with dendritic‐type morphology. The specificity of organ‐related differentiation markers was 100% (monoclonal Napsin A, GCDFP‐15 and TTF‐1), 97% (HepPar1 and PAX‐8), 90% (polyclonal Napsin A) and 72% (ER); no tumors demonstrated significant co‐expression of these organ‐related markers with either CK7 or CK20. The first major conclusion of this study is that CK7 staining in adenoma is more frequent than has been previously than has been previously described. CK7 immunoreactive cells often displayed a dendritic‐type morphology, including within large macroadenomas, which raises the question as to whether these represent tumor cells with folliculo‐stellate cell‐type differentiation, as these also have dendritic cell‐type morphology and express CK7 in non‐neoplastic glands. The second major conclusion, which confirms earlier findings, is that CK20 staining is a very infrequent immunohistochemical finding in adenomas that is virtually limited to corticotrophs and thus is helpful in diagnostic confirmation of that sub‐type. The final conclusion is in regard to those features that separate adenomas from sellar region metastases: adenomas do not demonstrate significant expression of TTF‐1, monoclonal Napsin A, PAX‐8, HepPar1 or GCDFP‐15, nor do they exhibit diffuse expression of CK7 and CK20.