bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation in cerebral palsy profile by socio‐economic status
Authors: Oskoui Maryam , Messerlian Carmen , Blair Alexandra , Gamache Philippe , Shevell Michael
Published: May 2015

Aim

Socio‐economic differences in maternal and child health are well recognized, but the role of individual‐level and area‐level determinants in cerebral palsy (CP) phenotypes is debated. We set out to examine (1) the association between area‐level and individual‐level measures of socio‐economic deprivation and CP phenotype among children, including subtype, severity, and comorbidities; and (2) the direct effect of area‐level deprivation not mediated through individual‐level deprivation.

Method

Regional data from a provincial CP register were analyzed. The outcome of interest was CP phenotype. The area‐level exposure was measured using the Pampalon Deprivation Index. Individual‐level socio‐economic status (SES) was determined using maternal education. We conducted multiple regression models, stratified by preterm birth, controlling for key covariates, and a mediation analysis of area‐level deprivation on the association between individual SES and CP phenotype.

Results

A socio‐economic gradient in mobility was seen in our cohort, above and beyond differences in maternal and perinatal factors. The added direct effect of area‐level deprivation was seen only in children whose mothers were educated to a higher level, suggesting no additional contribution of area‐level deprivation in children of mothers with a lower level of education.

Interpretation

Contextual socio‐economic factors can impact the severity of CP. These findings indicate important areas for potential community‐level or area‐level public health intervention (i.e. neighborhood reinvestment, preventive measures), and suggest that neighborhood‐level research in maternal and perinatal health should continue to be pursued.
Postprandial Hemodynamics in Hypertrophic Cardiomyopathy
Authors: Adams Jonathon C. , Bois John P. , Masaki Mitsuru , Yuasa Toshinori , Oh Jae K. , Ommen Steve R. , Nishimura Rick A. , Klarich Kyle W.
Published: May 2015

Objectives

Prior analysis at our institution found that patients with hypertrophic cardiomyopathy (HCM) who experience postprandial symptoms (PPS) are more likely to have resting left ventricular outflow tract (LVOT) obstruction and reduced quality of life. Our objective was to determine whether PPS in patients with HCM vs healthy subjects occur as a result of measurable hemodynamic alterations in the postprandial hemodynamic response.

Methods

We conducted a prospective cross‐sectional study examining 45 patients with HCM and 10 controls who underwent fasting and postprandial 2‐dimensional Doppler echocardiography. Postprandial echocardiographic measurements were obtained at symptom onset or 30 minutes after consumption of a standardized meal, whichever occurred first.

Results

The HCM population included 18 (40%) patients with PPS and 27 (60%) without PPS. Compared to controls, mean resting peak LVOT gradient was 23.4 ± 17.6 mmHg in HCM patients with PPS and 25.1 ± 33.1 mmHg in those without PPS (P = 0.10). The mean change in peak LVOT gradient after a meal was 0.7 ± 1.1 mmHg for controls, 5.0 ± 8.3 mmHg for HCM patients with PPS, and 1.5 ± 18.2 mmHg for HCM patients without PPS (P = 0.64).

Conclusion

Although the ability to provoke an increased LVOT gradient with a postprandial, upright exercise study protocol was recently reported, the current study suggests that a resting, supine, postprandial protocol does not elicit evidence of LVOT obstruction. Therefore, future investigations should consider whether simply performing an upright postprandial study in HCM patients with PPS will provide evidence of dynamic LVOT or if the addition of an exercise component is necessary.
An Unreported Congenital Anomaly: Aneurysm of the Lateral Half of the Mitral Valve
Authors: Garcon Philippe , Lavie‐Badie Yoan , Cador Romain , Bical Olivier , Abbey‐Toby Adjé
Published: May 2015

This case draws our attention to a new type of mitral valve anomaly, which seems to be congenital. A 42‐year‐old man with symptomatic primary severe mitral regurgitation was admitted to our hospital. Echocardiography revealed an aneurysm of the half of the valve, on the anterolateral commissure side, with significant excess tissue. The other half of the valve was normal. The two parts seemed to be separated by a continuous fibrous raphe. The anterolateral papillary muscle was hyperplasic and gave the main part of chordae tendinae.
Habitual physical activity is associated with circulating irisin in healthy controls but not in subjects with diabetes mellitus type 2
Authors: Al‐Daghri Nasser M. , Alokail Majed S. , Rahman Shakilur , Amer Osama E. , Al‐Attas Omar S. , Alfawaz Hanan , Tripathi Gyanendra , Sabico Shaun , Chrousos George P. , McTernan Philip G. , Piya Milan K.
Published: May 2015

Background

Irisin, a novel myokine, has been shown to increase following vigorous exercise, with studies suggesting that it mediates some of the beneficial effects of exercise. Irisin might play a role in ‘browning’ of white adipocytes, thus increasing energy expenditure. The role of irisin in exercise and energy expenditure in subjects with diabetes mellitus type 2 (DMT2) remains largely unknown. We aimed to investigate the association between circulating irisin and habitual physical activity in subjects with and without DMT2.

Material and methods

In this cross‐sectional study, 164 Saudi adults: 81 non‐DMT2 controls [age: (mean ± SD) 51·6 ± 10·9; BMI: 29·6 ± 4·3 kg/m2] and 83 DMT2 subjects [age: 54·3 ± 10·3 year; BMI: 29·4 ± 4·7 kg/m2] were studied. Anthropometric and fasting serum biochemical data were collected. Circulating irisin was measured using an enzyme‐linked immunosorbent assay (ELISA). Frequency intensity time (FIT) index was used to assess the level of habitual physical activity.

Results

We observed significantly higher levels of irisin in DMT2 subjects than in controls (P < 0·001). FIT index was positively associated (r = 0·20, P = 0·03) with circulating irisin in controls only. Additionally, irisin levels were significantly higher in tertile 3 (0·75 ± 0·07 μg/mL) than tertile 1 (0·49 ± 0·06 μg/mL) of the FIT index in healthy controls, whilst no such relation with physical activity was observed in DMT2 subjects.

Conclusion

This cross‐sectional study has shown a weak association of irisin with physical activity levels in healthy controls but not in DMT2 subjects, suggesting the possibility of discordant regulation in the condition of DMT2.
INTERMARRIAGE AND THE LABOR MARKET OUTCOMES OF ASIAN WOMEN
Authors: Basu Sukanya
Published: May 2015

The impact of intermarriage with natives, on labor market outcomes of immigrants, is not homogeneous across ethnic groups. Wages of Asian women are compared with non‐Asians. Both ordinary least squares and instrumental variables estimates of the effects of intermarriage on the wages of Asian women are negative and significant. Non‐Asian women earn a wage premium that becomes insignificant when controls for selection into marriage are introduced. One possible explanation for the intermarriage penalty for Asians is an income effect of having a high‐earning native husband. Intermarriage penalties rise with husband's education. Assimilation patterns of intermarried Asians indicate that they have lower initial wages, market hours, and employment, but exhibit faster rates of growth over their years of stay. The results are robust across Asian subgroups and husband's ethnicity. (JEL J16, J12, J31, J61)
Consequences of infanticide for a gregarious ectoparasitoid of leafroller larvae
Authors: HOPPER JULIE V. , MILLS NICHOLAS J.
Published: May 2015

1. In this laboratory study, the clutch size and handling time of Goniozus jacintae were investigated, a comparison of its life‐history performance between primary and secondary (laid after infanticide events) broods was carried out, and the lipid and protein concentrations in the haemolymph of non‐parasitised and parasitised hosts were estimated.

2. It was found that G. jacintae temporarily paralysed its host larvae for 66 min and briefly guarded its brood for 66 min. The clutch size of G. jacintae increased from two to seven with increasing larval fresh weight of its host, and both ovicide and larvicide of primary clutches occurred in 81% of encounters.

3. Secondary clutches of G. jacintae were significantly larger than primary clutches in two of three ovicide treatments for the same host individuals. Secondary clutches also experienced greater brood survivorship than primary clutches.

4. Lipid concentrations were consistently higher in the haemolymph of parasitised hosts, and protein concentrations were initially higher (until egg hatch), but increased at a lower rate in parasitised hosts than in non‐parasitised hosts.

5. This study is the first to provide evidence that improved nutritional quality could be an important benefit of infanticide for an insect parasitoid, allowing for larger clutch size and improved brood survivorship among secondary broods.
Physical and physiological costs of ectoparasitic mites on host flight endurance
Authors: LUONG LIEN T. , PENONI LUDMILA R. , HORN COLLIN J. , POLAK MICHAL
Published: May 2015

1. Dispersal is essential for locating mates, new resources, and to escape unfavourable conditions. Parasitism can impact a host's ability to perform energetically demanding activities such as long‐distance flight, with important consequences for gene flow and meta‐population dynamics.

2. Ectoparasites, in particular, can adversely affect host flight performance by diminishing flight aerodynamics and/or by inflicting physiological damage while feeding on host tissue.

3. Experimental flight assays were conducted using two fruit fly‐mite systems:Drosophila nigrospiracula(Patterson andWheeler) – Macrocheles subbadius(Berlese) andD. hydei(Sturtevan) – M. muscaedomesticae(Scopoli). Flies that are burdened by mites are expected to exhibit lower flight endurance compared to uninfected flies.

4. The results show that the presence of mites (attached) significantly decreased flight endurance by 57% and 78% compared to uninfectedD. nigrospiraculaandD. hydei, respectively. The physiological damage caused byM. subbadiuswas revealed through a 53% decline in flight time among previously infected flies (mites removed just prior to flight assay). Surprisingly, the presumably phoreticM. muscaedomesticaealso caused a 62% reduction in flight endurance among previously infectedD. hydei.

5. These results suggest a strong deleterious effect of ectoparasitic mites on host flight performance, mediated by a reduction in flight aerodynamics and damage to host physiology. Adverse effects on host flight and/or dispersal may have broad implications for gene flow, population genetic structure, and local adaptation in both host and parasite meta‐populations.
Ketogenic diet exhibits anti‐inflammatory properties
Authors: Dupuis Nina , Curatolo Niccolo , Benoist Jean‐François , Auvin Stéphane
Published: May 2015

The ketogenic diet (KD) is an established treatment for refractory epilepsy, including some inflammation‐induced epileptic encephalopathies. In a lipopolysaccharide (LPS)–induced fever model in rats, we found that animals given the KD for 14 days showed less fever and lower proinflammatory cytokine levels than control animals. However, KD rats exhibited a decrease in circulating levels of arachidonic acid and long‐chain n‐3 polyunsaturated fatty acids (PUFAs), suggesting that the anti‐inflammatory effect of KD was probably not due to an increase in anti‐inflammatory n‐3 PUFA derivatives. These properties might be of interest in some conditions such as fever‐induced refractory epileptic encephalopathy in school‐aged children.
Climate adaptation and speciation: particular focus on reproductive barriers inFicedulaflycatchers
Authors: Qvarnström Anna , Ålund Murielle , McFarlane S. Eryn , Sirkiä Päivi M.
Published: May 2015

Climate adaptation is surprisingly rarely reported as a cause for the build‐up of reproductive isolation between diverging populations. In this review, we summarize evidence for effects of climate adaptation on pre‐ and postzygotic isolation between emerging species with a particular focus on pied (Ficedula hypoleuca) and collared (Ficedula albicollis) flycatchers as a model for research on speciation. Effects of climate adaptation on prezygotic isolation or extrinsic selection against hybrids have been documented in several taxa, but the combined action of climate adaptation and sexual selection is particularly well explored inFicedulaflycatchers. There is a general lack of evidence for divergent climate adaptation causing intrinsic postzygotic isolation. However, we argue that the profound effects of divergence in climate adaptation on the whole biochemical machinery of organisms and hence many underlying genes should increase the likelihood of genetic incompatibilities arising as side effects. Fast temperature‐dependent co‐evolution between mitochondrial and nuclear genomes may be particularly likely to lead to hybrid sterility. Thus, how climate adaptation relates to reproductive isolation is best explored in relation to fast‐evolving barriers to gene flow, while more research on later stages of divergence is needed to achieve a complete understanding of climate‐driven speciation.
Mitochondrial and lipogenic effects of vitamin D on differentiating and proliferating human keratinocytes
Authors: Consiglio Marco , Viano Marta , Casarin Stefania , Castagnoli Carlotta , Pescarmona Gianpiero , Silvagno Francesca
Published: May 2015

Even in cells that are resistant to the differentiating effects of vitamin D, the activated vitamin D receptor (VDR) can downregulate the mitochondrial respiratory chain and sustain cell growth through enhancing the activity of biosynthetic pathways. The aim of this study was to investigate whether vitamin D is effective also in modulating mitochondria and biosynthetic metabolism of differentiating cells. We compared the effect of vitamin D on two cellular models: the primary human keratinocytes, differentiating and sensitive to the genomic action of VDR, and the human keratinocyte cell line HaCaT, characterized by a rapid growth and resistance to vitamin D. We analysed the nuclear translocation and features of VDR, the effects of vitamin D on mitochondrial transcription and the consequences on lipid biosynthetic fate. We found that the negative modulation of respiratory chain is a general mechanism of action of vitamin D, but at high doses, the HaCaT cells became resistant to mitochondrial effects by upregulating the catabolic enzyme CYP24 hydroxylase. In differentiating keratinocytes, vitamin D treatment promoted intracellular lipid deposition, likewise the inhibitor of respiratory chain stigmatellin, whereas in proliferating HaCaT, this biosynthetic pathway was not inducible by the hormone. By linking the results on respiratory chain and lipid accumulation, we conclude that vitamin D, by suppressing respiratory chain transcription in all keratinocytes, is able to support both the proliferation and the specialized metabolism of differentiating cells. Through mitochondrial control, vitamin D can have an essential role in all the metabolic phenotypes occurring in healthy and diseased skin.
Sirtuin‐6 deficiency exacerbates diabetes‐induced impairment of wound healing
Authors: Thandavarayan Rajarajan A. , Garikipati Venkata Naga Srikanth , Joladarashi Darukeshwara , Suresh Babu Sahana , Jeyabal Prince , Verma Suresh K. , Mackie Alexander R. , Khan Mohsin , Arumugam Somasundaram , Watanabe Kenichi , Kishore Raj , Krishnamurthy Prasanna
Published: May 2015

Delayed wound healing is one of the major complications in diabetes and is characterized by chronic proinflammatory response, and abnormalities in angiogenesis and collagen deposition. Sirtuin family proteins regulate numerous pathophysiological processes, including those involved in promotion of longevity, DNA repair, glycolysis and inflammation. However, the role of sirtuin 6 (SIRT6), a NAD+‐dependent nuclear deacetylase, in wound healing specifically under diabetic condition remains unclear. To analyse the role of SIRT6 in cutaneous wound healing, paired 6‐mm stented wound was created in diabetic db/db mice and injected siRNA against SIRT6 in the wound margins (transfection agent alone and nonsense siRNA served as controls). Wound time to closure was assessed by digital planimetry, and wounds were harvested for histology, immunohistochemistry and Western blotting. SIRT6‐siRNA‐treated diabetic wound showed impaired healing, which was associated with reduced capillary density (CD31‐staining vessels) when compared to control treatment. Interestingly, SIRT6 deficiency decreased vascular endothelial growth factor expression and proliferation markers in the wounds. Furthermore, SIRT6 ablation in diabetic wound promotes nuclear factor‐κB (NF‐κB) activation resulting in increased expression of proinflammatory markers (intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, tumor necrosis factor‐α and interleukin‐1β) and increased oxidative stress. Collectively, our findings demonstrate that loss of SIRT6 in cutaneous wound aggravates proinflammatory response by increasing NF‐κB activation, oxidative stress and decrease in angiogenesis in the diabetic mice. Based on these findings, we speculate that the activation of SIRT6 signalling might be a potential therapeutic approach for promoting wound healing in diabetics.
Sesamol decreases melanin biosynthesis in melanocyte cells and zebrafish: Possible involvement of MITF via the intracellular cAMP and p38/JNK signalling pathways
Authors: Baek Seung‐hwa , Lee Sang‐Han
Published: May 2015

The development of antimelanogenic agents is important for the prevention of serious aesthetic problems such as melasma, freckles, age spots and chloasma. The aim of this study was to investigate the antimelanogenic effect of sesamol, an active lignan isolated from Sesamum indicum, in melan‐a cells. Sesamol strongly inhibited melanin biosynthesis and the activity of intracellular tyrosinase by decreasing cyclic adenosine monophosphate (cAMP) accumulation. Sesamol significantly decreased the expression of melanogenesis‐related genes, such as tyrosinase, tyrosinase‐related protein‐1,2 (TRP‐1,2), microphthalmia‐associated transcription factor (MITF) and melanocortin 1 receptor (MC1R). In addition, sesamol also induces phosphorylation of p38 mitogen‐activated protein kinase (p38 MAPK) and c‐Jun N‐terminal kinase (JNK). Moreover, sesamol dose‐dependently decreased zebrafish pigment formation, tyrosinase activity and expression of melanogenesis‐related genes. These findings indicate that sesamol inhibited melanin biosynthesis by down‐regulating tyrosinase activity and melanin production via regulation of gene expression of melanogenesis‐related proteins through modulation of MITF activity, which promoted phosphorylation of p38 and JNK in melan‐a cells. Together, these results suggest that sesamol strongly inhibits melanin biosynthesis, and therefore, sesamol represents a new skin‐whitening agent for use in cosmetics.
Contribution to interplay between a delamination test and a sensory analysis of mid‐range lipsticks
Authors: Richard C. , Tillé‐Salmon B. , Mofid Y.
Published: May 2015

Synopsis

Background

Lipstick is currently one of the most sold products of cosmetics industry, and the competition between the various manufacturers is significant. Customers mainly seek products with high spreadability, especially long–lasting or long wear on the lips. Evaluation tests of cosmetics are usually performed by sensory analysis. This can then represent a considerable cost.

Objectives

The object of this study was to develop a fast and simple test of delamination (objective method with calibrated instruments) and to interplay the obtained results with those of a discriminative sensory analysis (subjective method) in order to show the relevance of the instrumental test.

Methods

Three mid‐range lipsticks were randomly chosen and were tested. They were made of compositions as described by the International Nomenclature of Cosmetic Ingredients (INCI). Instrumental characterization was performed by texture profile analysis and by a special delamination test. The sensory analysis was voluntarily conducted with an untrained panel as blind test to confirm or reverse the possible interplay.

Results

The two approaches or methods gave the same type of classification. The high‐fat lipstick had the worst behaviour with the delamination test and the worst notation of the intensity of descriptors with the sensory analysis.

Conclusion

There is a high correlation between the sensory analysis and the instrumental measurements in this study. The delamination test carried out should permit to quickly determine the lasting (screening test) and in consequence optimize the basic formula of lipsticks.
Enhanced Energy Storage of Dielectric Nanocomposites at Elevated Temperatures
Authors: Rajib Mohammad , Martinez Ricardo , Shuvo Mohammad , Karim Hasanul , Delfin Diego , Afrin Samia , Rodriguez Gerardo , Chintalapalle Ramana , Lin Yirong
Published: May 2015

Enhancing the performance of dielectric capacitors toward higher energy density and higher operating temperatures has been drawing increased interest. Therefore, in this investigation, research efforts were dedicated to the fabrication and characterization of nanocomposites in order to enhance the energy density at both room temperature and elevated temperature. The dielectric capacitors are fabricated using nanocomposites composed of BaTiO nanoparticles with polyimide (PI) matrix aiming at combining the high relative dielectric permittivity of the ceramic filler and the high breakdown strength of the polymeric matrix. Dielectric energy storage performance is assessed for nanocomposites with volume fractions ranging from 0 to 20% under operating frequency from 20 Hz to 1 MHz and temperatures ranging from 20 to 120C. It is observed that with the increase of temperature, the capacitance increased while the energy density slightly decreased but significantly higher than pure polymer samples. The highest energy density was found for BaTiO/PI nanocomposites with 20% volume fraction, 9.63 J/cm at 20C and 6.79 J/cm at 120C. Overall, testing results indicate that using nanocomposites of BaTiO/PI as a dielectric component shows promise for implementation to preserve high energy density values up to temperatures of 120C.
Synthesis of High‐Performance BaMgAl10O17:Eu2+ Phosphor Through a Facile Aqua‐Suspension Method
Authors: Zhu Qiang Qiang , Xu Xin , Hao Lu Yuan
Published: May 2015

High‐performance BaMgAl10O17:Eu2+ (BAM) phosphor was prepared by a facile aqua‐suspension method, based on the in situ surface charge modification of starting powders with the aid of the γ‐Al2O3 porous structure. When stirred in de‐ionized water at 80°C, the starting powders of BaCO3, MgO, and Eu2O3 were positive surface charged, and attracted by the porous and negative charged γ‐Al2O3 powders. Through the electrostatic effect, high uniformed BAM precursor was achieved after the aqua‐medium was removed. Fourier transform infrared (FTIR) spectra indicated some new chemical bonds among the reactants of the BAM precursor, which improved the powder activity and made it possible to achieve high‐performance BAM phosphor at a lower calcination temperature. The obtained BAM phosphor exhibited a narrow particle size distribution, enhanced crystallinity, and a short decay time.
The Implementation of Fluorescence‐Based Detection in LTCC (Low‐Temperature‐Co‐Fired‐Ceramics) Microfluidic Modules
Authors: Malecha Karol
Published: May 2015

The possibility of the application of fluorescence‐based detection method in a microfluidic system is discussed. It consists of a microfluidic module and complementary housing. Both parts are made from LTCC technology. Three microfluidic module designs are analysed. They vary by way of their constructions of a transparent window, which is used for the transmission of a fluorescence signal from the module to the photodetector integrated onto the housing. The influence of the type of materials used for optical windows on performance of the system is discussed. According to the performed measurements, a concentration as low as 0.03 ng/mL was detected.
Large defects in aplasia cutis congenita treated by large‐sized thin split‐thickness skin grafting: long‐term follow‐up of 18 patients
Authors: Liu Yan , Qiu Lin , Fu Yuexian , Tian Xiaofei , Yuan Xingang , Xiao Jun , Li Tianwu
Published: May 2015

Objective

To evaluate the long‐term results of using surgical large‐sized thin split‐thickness skin grafting to treat aplasia cutis congenita (ACC) in neonates.

Methods

This study included 18 ACC neonates with large skin defects who underwent large‐sized thin split‐thickness skin grafting at our hospital from March 2002 to November 2011. The size of the lesion was >10% of the total body surface area (TBSA) in 16 patients, 7% of TBSA in one patient, and 3% of TBSA in another patient. The size of the skin graft was designed to be equal to or slightly larger than the size of the lesion.

Results

Skin grafts in 16 patients who were followed for periods of 6 months–7 years after surgery showed good survival; however, two patients were lost to follow‐up. The wound healed completely without scarring in five patients. One of the five patients who healed without scarring had failed previous conservative treatment. Several mild hypertrophic scars occurred in one patient, and flat, thin, shiny, soft, parchment‐like scars were noted in five other patients. Dark red, hard, raised hypertrophic scars occurred in five patients who had partial necrosis in the skin graft after surgery.

Conclusion

A large‐sized thin split‐thickness skin graft can be used to effectively close a wound and permit healing to occur with reduced long‐term scarring. This procedure is ideal for treating skin defects in patients with ACC.
Business model development, founders' social capital and the success of early stage internet start‐ups: a mixed‐method study
Authors: Spiegel Olav , Abbassi Puja , Zylka Matthäus Paul , Schlagwein Daniel , Fischbach Kai , Schoder Detlef
Published: May 2015

Information technology (IT) and entrepreneurship are more closely related than ever. The internet, in particular, inspires the current ‘generation start‐up’. While some early stage internet start‐ups have quickly become major successes, others fail to secure required follow‐up funding and collapse. In this paper, we build on and extend the emerging business model research stream with the aim of better understanding the differences between successful and unsuccessful early stage internet start‐ups. In the qualitative first part of our mixed‐method study, 17 expert informant interviews reveal that internet start‐up business models are in permanent flux, continually changed and adapted by founders, who identify their professional social network (i.e. their social capital) as a critically important factor for developing the business model and ultimately making their start‐ups successful. In the quantitative second part of the study, we test this claim based on a social network analysis of 70 internet start‐ups and their 145 founders. We find strong support for the critical importance of the founders' social capital for early stage internet start‐up success. The findings of this study advance our understanding of the relationship between founders' social capital, the development of business models and the success of early stage internet start‐ups.
Impact of relationships between test and training animals and among training animals on reliability of genomic prediction
Authors: Wu X. , Lund M.S. , Sun D. , Zhang Q. , Su G.
Published: May 2015

One of the factors affecting the reliability of genomic prediction is the relationship among the animals of interest. This study investigated the reliability of genomic prediction in various scenarios with regard to the relationship between test and training animals, and among animals within the training data set. Different training data sets were generated from EuroGenomics data and a group of Nordic Holstein bulls (born in 2005 and afterwards) as a common test data set. Genomic breeding values were predicted using a genomic best linear unbiased prediction model and a Bayesian mixture model. The results showed that a closer relationship between test and training animals led to a higher reliability of genomic predictions for the test animals, while a closer relationship among training animals resulted in a lower reliability. In addition, the Bayesian mixture model in general led to a slightly higher reliability of genomic prediction, especially for the scenario of distant relationships between training and test animals. Therefore, to prevent a decrease in reliability, constant updates of the training population with animals from more recent generations are required. Moreover, a training population consisting of less‐related animals is favourable for reliability of genomic prediction.
Impact on Clinical Outcome of Premature Interruption of Cryoenergy Delivery Due to Phrenic Nerve Palsy During Second Generation Cryoballoon Ablation for Paroxysmal Atrial Fibrillation
Authors: CHIERCHIA GIAN‐BATTISTA , MUGNAI GIACOMO , HUNUK BURAK , STRÖKER ERWIN , VELAGIĆ VEDRAN , SAITOH YUKIO , IRFAN GHAZALA , HACIOGLU EBRU , CICONTE GIUSEPPE , BRUGADA PEDRO , DE ASMUNDIS CARLO
Published: May 2015

Cryoenergy Interruption Due to Phrenic Nerve Palsy

Introduction

Right phrenic nerve paralysis (PNP) is the most frequently observed complication occurring during cryoballoon ablation (CB). Our aim was to analyze the impact of the premature interruption (PI) of cryoenergy delivery in a large series of consecutive patients during ablation in the right‐sided veins on clinical outcome.

Methods and Results

All consecutive patients having undergone second‐generation CB ablation for paroxysmal atrial fibrillation (AF) from July 2012 to September 2014 were included in our analysis. Exclusion criteria were persistent AF, presence of an intracavitary thrombus, uncontrolled heart failure, moderate or severe valvular disease, left atrium (LA) diameter ≥55 mm, and contraindications to general anesthesia. A total 287 consecutive patients with drug‐resistant paroxysmal AF having undergone pulmonary vein isolation by means of CB technology (male 65%, age 57.6 ± 13.1 years) were included. The incidence of PNP in the study population was 8.0% (23/287). At a mean follow‐up of 11.5 ± 3.9 months, the success rate without antiarrhythmic therapy was 81.6%. Patients with PNP had similar rates of AF recurrence compared with those without PNP (17.4% vs. 17.8%; P = 0.9); the former had a mean follow‐up of 10.9 ± 3.7 months, the latter 11.8 ± 4.5 months (P = 0.3).

Conclusion

Conclusion: Our findings show that patients in whom freezing was interrupted due to PNP had a similar outcome on 1‐year follow‐up compared with those in whom freezing cycles were completed in the septal veins. No baseline clinical or procedural characteristics were found to predict AF recurrence in patients having experienced PNP.
Treatment of Hypertension in Children With Catecholamine‐Secreting Tumors: A Systematic Approach
Authors: Romero Mauricio , Kapur Gaurav , Baracco Rossana , Valentini Rudolph P. , Mattoo Tej K. , Jain Amrish
Published: May 2015

Management of blood pressure in children with pheochromocytoma and other catecholamine‐secreting tumors (CSTs) is unique and challenging. The authors report a single‐center experience using sequential α‐adrenergic blockade (phenoxybenzamine), increased fluid intake, and β‐blockade for presurgical management of 10 CSTs in children. In this retrospective review, mean duration for blood pressure control in preparation for surgery was 4.5±2.6 weeks. Intraoperative hypertension was noted transiently (<2 hours) in eight patients (80%) and was treated with continuous infusion of short‐acting antihypertensive agents. Two (20%) patients required vasopressor medication infusion to manage intraoperative hypotension. Only two (20%) patients developed postoperative hypotension and required vasopressor medication infusion for <24 hours. All antihypertensive medications were discontinued in the immediate (≤4 days) postoperative period in 80% of patients. In conclusion, a systematic and multidisciplinary approach utilizing adrenergic blockade is effective in treating children with CSTs.
Clinical Use of Pulse Wave Analysis: Proceedings From a Symposium Sponsored by North American Artery
Authors: Townsend Raymond R. , Black Henry R. , Chirinos Julio A. , Feig Peter U. , Ferdinand Keith C. , Germain Michael , Rosendorff Clive , Steigerwalt Susan P. , Stepanek Jan A.
Published: May 2015

The use of pulse wave analysis may guide the provider in making choices about blood pressure treatment in prehypertensive or hypertensive patients. However, there is little clinical guidance on how to interpret and use pulse wave analysis data in the management of these patients. A panel of clinical researchers and clinicians who study and clinically use pulse wave analysis was assembled to discuss strategies for using pulse wave analysis in the clinical encounter. This manuscript presents an approach to the clinical application of pulse waveform analysis, how to interpret central pressure waveforms, and how to use existing knowledge about the pharmacodynamic effect of antihypertensive drug classes in combination with brachial and central pressure profiles in clinical practice. The discussion was supplemented by case‐based examples provided by panel members, which the authors hope will provoke discussion on how to understand and incorporate pulse wave analysis into clinical practice.
Inadequate Blood Pressure Control in Hypertensive Patients Referred for Cardiac Stress Test
Authors: Mousa Tarek M. , Akinseye Oluwaseun A. , Kerwin Todd C.
Published: May 2015

The current study examined the degree of blood pressure (BP) control and incidence of myocardial ischemia in hypertensive patients (n=2039) referred for cardiac stress test. Patients were categorized into well‐controlled (<140/90 mm Hg), poorly controlled (140–160/90–100 mm Hg), and very poorly controlled (>160/100 mm Hg) groups according to their resting BP. The mean age[±standard error of the mean] of the patients was 68±13 years, and 885 (43.4%) were men. The prevalence of well‐controlled hypertension (HTN) was 47.2%, poorly controlled HTN was 29.5%, and very poorly controlled HTN was 23.3%. Evidence of ischemia was seen in 19.8% and 19.3% of the well‐controlled and poorly controlled groups, respectively. The very poorly controlled group had the lowest incidence of ischemia (14.3%) (P<.05) compared with the other two groups. Symptoms that mimic ischemic heart disease in hypertensive patients may be partly explained by poorly controlled BP. Quality of care might be improved by optimally controlling BP in patients with angina symptoms prior to ordering diagnostic testing associated with radiation exposure and cost.
MMPs and angiogenesis affect the metastatic potential of a human vulvar leiomyosarcoma cell line
Authors: Alias Carlotta , Rocchi Laura , Ribatti Domenico , Caraffi Stefano , D'Angelo Alessandra , Perris Roberto , Mangieri Domenica
Published: May 2015

Gynaecological leiomyosarcoma (gLMS) represent a heterogeneous group of soft tissue sarcoma, characterized by rare incidence, high aggressiveness and propensity to infiltrate secondary organs, poor prognosis and lethality, because of the lack of biological mechanisms that underlying their progression and effective pharmaceutical treatments. This study was focused on some of the aspects of progression and dissemination of a subtype of gLMS namely vulvar LMS (vLMS). We therefore used a vulvar LMS‐derived cell line namely SK‐LMS‐1, coupled with in vitro and in vivo assays. We observed that SK‐LMS‐1 cells have a strong invasive capacity in vitro, through the activity of matrix metalloproteinases 2 and 9, while in vivo these cells induce a strong angiogenic response and disseminate to the chick embryo liver. Therefore, we postulate that metalloproteinases are involved in the spreading behaviour of SK‐LMS‐1. Further investigations are necessary to better understand the molecular and cellular machinery involved in the progression of this malignancy.
Visual system evolution and the nature of the ancestral snake
Authors: Simões B. F. , Sampaio F. L. , Jared C. , Antoniazzi M. M. , Loew E. R. , Bowmaker J. K. , Rodriguez A. , Hart N. S. , Hunt D. M. , Partridge J. C. , Gower D. J.
Published: May 2015

The dominant hypothesis for the evolutionary origin of snakes from ‘lizards’ (non‐snake squamates) is that stem snakes acquired many snake features while passing through a profound burrowing (fossorial) phase. To investigate this, we examined the visual pigments and their encoding opsin genes in a range of squamate reptiles, focusing on fossorial lizards and snakes. We sequenced opsin transcripts isolated from retinal cDNAand used microspectrophotometry to measure directly the spectral absorbance of the photoreceptor visual pigments in a subset of samples. In snakes, but not lizards, dedicated fossoriality (as in Scolecophidia and the alethinophidianAnilius scytale) corresponds with loss of all visual opsins other thanRH1 (λmax490–497 nm); all other snakes (including less dedicated burrowers) also have functionalsws1andlwsopsin genes. In contrast, the retinas of all lizards sampled, even highly fossorial amphisbaenians with reduced eyes, express functionallws,sws1,sws2andrh1genes, and most also expressrh2(i.e. they express all five of the visual opsin genes present in the ancestral vertebrate). Our evidence of visual pigment complements suggests that the visual system of stem snakes was partly reduced, with two (RH2 andSWS2) of the ancestral vertebrate visual pigments being eliminated, but that this did not extend to the extreme additional loss ofSWS1 andLWSthat subsequently occurred (probably independently) in highly fossorial extant scolecophidians andA. scytale. We therefore consider it unlikely that the ancestral snake was as fossorial as extant scolecophidians, whether or not the latter are para‐ or monophyletic.
Comparative pattern of genetic structure in two Mediterranean killifishes Aphanius fasciatus and Aphanius iberus inferred from both mitochondrial and nuclear data
Authors: Pappalardo A. M. , Gonzalez E. G. , Tigano C. , Doadrio I. , Ferrito V.
Published: May 2015

In this study, genetic variation was assessed in Aphanius fasciatus and Aphanius iberus characterized by similar ecological traits but with very different distribution ranges in the Mediterranean area. Five populations of A. iberus and five of A. fasciatus were analysed using five polymorphic microsatellite loci and partial mitochondrial control region (D‐loop) sequences. Congruent results were found with both nuclear and mitochondrial molecular markers. The results showed that similar levels of genetic divergence, based on mitochondrial control region sequences, are present among populations of A. iberus and among populations of A. fasciatus despite the very different geographic distance existing among the examined populations of the two species (low geographic distance in A. iberus and high in A. fasciatus). A possible explanation could be that the populations of A. iberus were isolated for a longer time than the populations of A. fasciatus supporting the hypothesis that the split in the lineage leading to A. iberus is older than the split in the lineage leading to A. fasciatus. The possibility that the wide circum‐Mediterranean distribution of A. fasciatus ensures the high connectivity of its populations, preventing, in some cases, local differentiation, however, cannot be ruled out.
Multi‐scale modeling of Arabidopsis thaliana response to different CO2 conditions: From gene expression to metabolic flux
Authors: Liu Lin , Shen Fangzhou , Xin Changpeng , Wang Zhuo
Published: May 2015

Multi‐scale investigation from gene transcript level to metabolic activity is important to uncover plant response to environment perturbation. Here we integrated a genome‐scale constraint‐based metabolic model with transcriptome data to explore Arabidopsis thaliana response to both elevated and low CO2 conditions. The four condition‐specific models from low to high CO2 concentrations show differences in active reaction sets, enriched pathways for increased/decreased fluxes, and putative post‐transcriptional regulation, which indicates that condition‐specific models are necessary to reflect physiological metabolic states. The simulated CO2 fixation flux at different CO2 concentrations is consistent with the measured Assimilation‐CO2intercellular curve. Interestingly, we found that reactions in primary metabolism are affected most significantly by CO2 perturbation, whereas secondary metabolic reactions are not influenced a lot. The changes predicted in key pathways are consistent with existing knowledge. Another interesting point is that Arabidopsis is required to make stronger adjustment on metabolism to adapt to the more severe low CO2 stress than elevated CO2. The challenges of identifying post‐transcriptional regulation could also be addressed by the integrative model. In conclusion, this innovative application of multi‐scale modeling in plants demonstrates potential to uncover the mechanisms of metabolic response to different conditions.
The mitochondrial uncoupler DNP triggers brain cell mTOR signaling network reprogramming and CREB pathway up‐regulation
Authors: Liu Dong , Zhang Yongqing , Gharavi Robert , Park Hee Ra , Lee Jaewon , Siddiqui Sana , Telljohann Richard , Nassar Matthew R. , Cutler Roy G. , Becker Kevin G. , Mattson Mark P.
Published: May 2015

Mitochondrial metabolism is highly responsive to nutrient availability and ongoing activity in neuronal circuits. The molecular mechanisms by which brain cells respond to an increase in cellular energy expenditure are largely unknown. Mild mitochondrial uncoupling enhances cellular energy expenditure in mitochondria and can be induced with 2,4‐dinitrophenol (DNP), a proton ionophore previously used for weight loss. We found that DNP treatment reduces mitochondrial membrane potential, increases intracellular Ca2+ levels and reduces oxidative stress in cerebral cortical neurons. Gene expression profiling of the cerebral cortex of DNP‐treated mice revealed reprogramming of signaling cascades that included suppression of the mammalian target of rapamycin (mTOR) and insulin – PI3K – MAPK pathways, and up‐regulation of tuberous sclerosis complex 2, a negative regulator of mTOR. Genes encoding proteins involved in autophagy processes were up‐regulated in response to DNP. CREB (cAMP‐response element‐binding protein) signaling, Arc and brain‐derived neurotrophic factor, which play important roles in synaptic plasticity and adaptive cellular stress responses, were up‐regulated in response to DNP, and DNP‐treated mice exhibited improved performance in a test of learning and memory. Immunoblot analysis verified that key DNP‐induced changes in gene expression resulted in corresponding changes at the protein level. Our findings suggest that mild mitochondrial uncoupling triggers an integrated signaling response in brain cells characterized by reprogramming of mTOR and insulin signaling, and up‐regulation of pathways involved in adaptive stress responses, molecular waste disposal, and synaptic plasticity.

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Physiological bioenergetic challenges such as exercise and fasting can enhance neuroplasticity and protect neurons against injury and neurodegeneration. Here, we show that the mitochondrial uncoupling agent 2,4‐dinitrophenol (DNP) elicits adaptive signaling responses in the cerebral cortex involving activation of Ca2+‐CREB and autophagy pathways, and inhibition of mTOR and insulin signaling pathways. The molecular reprogramming induced by DNP, which is similar to that of exercise and fasting, is associated with improved learning and memory, suggesting potential therapeutic applications for DNP.
Deep, Sticky, Transient, and Gracious: An Expanded Buyer–Supplier Relationship Typology
Authors: Kim Yusoon , Choi Thomas Y.
Published: May 2015

The cooperative–adversarial dichotomy has served as the prevailing buyer–supplier relationship typology in the literature. Cooperative buyer–supplier relationships have been associated with closely tied relationships, while adversarial relationships have been equated to arms‐length relationships. We propose, however, that this perspective is overly simplified; a cooperative relationship is orthogonal to a closely tied relationship and an adversarial relationship to an arms‐length relationship. That is, there can be a closely tied yet adversarial relationship and an arms‐length yet cooperative relationship. We theorize the buyer–supplier relationship in two orthogonal aspects—(1) relational posture, that is, how two firms regard each other (as cooperative partners or as adversaries) and (2) relational intensity, that is, how much two firms’ operations are interlinked (closely tied or arms‐length). By considering the two aspects concurrently, this article proposes an expanded typology of buyer–supplier relationships. We label a closely tied and cooperative buyer–supplier type as “deep”; a closely tied but adversarial type as “sticky”; an arms‐length and adversarial type as “transient”; and an arms‐length but cooperative type as “gracious.” We then present an analysis that supports the orthogonality of the two relational dimensions. This analysis suggests that the expanded relationship types are associated with different relational outcome trade‐offs. The data are collected from a global, large Japanese automaker and 163 of its suppliers in North America. Overall, the results provide empirical support for the expanded buyer–supplier relationship typology.
The legal response to safeguarding local environmental quality
Authors: Jenkins Victoria
Published: May 2015

Local environmental quality is best understood as a measure of the aesthetic complexion of public space in the urban environment. Anti‐social acts causing damage to the physical environment of local communities have, traditionally, attracted little moral opprobrium; and the role of local authorities in safeguarding local environmental quality has been undervalued. However, this is an issue that has been proven to have a significant impact on the quality of life of local communities, particularly those in deprived neighbourhoods. This paper argues, therefore, that we need to develop a comprehensive legal framework to safeguard local environmental quality in the future. This problem has so far been tackled as nuisance, local environmental crime or anti‐social behaviour. The paper concludes that an approach based on measures to tackle incivility in society is to be preferred; thus, the Anti‐social Behaviour, Crime and Policing Act 2014 will be particularly significant in this regard. However, some amendments to this legislation will be required to ensure its effective application to the problems of local environmental quality. Further measures should also be taken to support citizen participation and education as part of a comprehensive legal framework for safeguarding the local environment.
The Nasty Business of Aging
Authors: Kohn Nina A.
Published: May 2015

This essay explores the contribution of Hendrik Hartog's Someday All
This Will Be Yours to an understanding of old age policy and the aging
experience more broadly. It starts by discussing how Hartog's study
contributes to a modern understanding of the legal structure surrounding old
age. It then discusses how the narrative is colored, in part, by looking at
the cases from a caregiver's perspective, and explores the implications of
this perspective. Finally, it suggests avenues for building on Hartog's work
by using modern legal cases to explore how courts today perceive the moral
and legal obligations surrounding the duty to provide care.