bluuebunny/crossref_metadata_2025 huggingface dataset:
Aeromonas salmonicida infection levels in pre‐ and post‐stocked cleaner fish assessed by culture and an amended qPCR assay
Authors: Gulla S , Duodu S , Nilsen A , Fossen I , Colquhoun D J
Published: October 2015

Due to increasing resistance to chemical therapeutants, the use of ‘cleaner fish’ (primarily wrasse, Labridae, species) has become popular in European salmon farming for biocontrol of the salmon louse, Lepeophtheirus salmonis (Krøyer). While being efficient de‐licers, cleaner fish mortality levels in salmon cages are commonly high, and systemic bacterial infections constitute a major problem. Atypical furunculosis, caused by Aeromonas salmonicida A‐layer types V and VI, is among the most common diagnoses reached in clinical investigations. A previously described real‐time PCR (qPCR), targeting the A. salmonicida A‐layer gene (vapA), was modified and validated for specific and sensitive detection of all presently recognized A‐layer types of this bacterium. Before stocking and during episodes of increased mortality in salmon cages, cleaner fish (primarily wild‐caught wrasse) were sampled and screened for A. salmonicida by qPCR and culture. Culture indicated that systemic bacterial infections are mainly contracted after salmon farm stocking, and qPCR revealed A. salmonicida prevalences of approximately 4% and 68% in pre‐ and post‐stocked cleaner fish, respectively. This underpins A. salmonicida's relevance as a contributing factor to cleaner fish mortality and emphasizes the need for implementation of preventive measures (e.g. vaccination) if current levels of cleaner fish use are to be continued or expanded.
Studying the Effects of Fish Muscle Incorporation on Storage Stability of a Novel Corn‐fish Snack
Authors: Shahmohammadi H.R. , Bakar J. , Russly A.R. , Noranizan M.A. , Mirhosseini H.
Published: October 2015

To investigate the effect of minced fish incorporation on storage stability of a puffed corn‐fish snack, treatments including 15% silver carp (Hypophthalmichthys molitrix) meat and 85% corn (seasoned and unseasoned) were produced by a twin screw extruder. The peroxide values (PVs) of treatments increased (P < 0.05) with storage time and reached a peak in the 12th week, then the values declined following a quadratic model. The fish was the least significant factor (P < 0.05), meaning that incorporation of minced fish slightly affected the PV. Conversely, the seasoning was the most significant factor (P < 0.05) followed by storage time. The total volatile base nitrogen and free fatty acid concentration of treatments increased linearly during storage. No significant difference (P > 0.05) was found for crispiness and color. Also, no microbial growth was observed during storage. The storage stability of the seasoned corn‐fish snack and the control was obtained 28 and 33 weeks, respectively.

Practical Applications

Starch‐based snacks are widely used. They are high in calories and low in protein. Our previous study has developed a novel extruded puffed corn‐fish snack by incorporation of fish muscle (silver carp) and corn grits using extrusion technology to improve the nutritional properties of the ordinary corn snacks and to add value to silver carp, an underutilized fish species in Iran. To commercialize the product, studying the effect of fish meat incorporation on storage stability of the developed puffed corn‐fish snack and determining the shelf life are required.
Influence of marital status on the survival of patients with gastric cancer
Authors: Zhou Rongping , Yan Shushan , Li Jun
Published: October 2015

Background and Aims:

The influence of marital status on gastric cancer (GC) survival is controversial. The aim of our study was to investigate the relationship between marital status and the survival of GC patients.

Methods:

The data of current study was from the Surveillance, Epidemiology, and End‐Results database. We identified 18 815 GC patients between 2004 and 2009, who were categorized into married, never married, widowed, and divorced/separated groups. Kaplan–Meier analysis was performed to compare gastric cancer specific survival (GCSS), and Cox regression analysis was used to estimate the risk factors for different survival outcomes in four groups with diverse marital status.

Results:

Married patients had better 5‐year GCSS compared with patients who were never married, separated/widowed, or divorced. In stratified analyses by histological type and pathological differentiation, unmarried patients with gastric adenocarcinoma, signet ring cell carcinoma, moderately differentiated caicinoma, and poorly differentiated/undifferentiated carcinoma had an increased risk of cancer mortality. Widowed patients had the highest percentage of women and elderly, and were more susceptible to well and moderately differentiated gastric carcinomars and gastric adenocarcinoma with earlier TNM stage and lowest rate of surgery and radiation therapy. In addition, they also had the worst 5‐year GCSS.

Conclusions:

Our study suggests that unmarried GC patients, especially widowed patients, are at a high risk of GCSS. Additionally, the survival benefit is more significant among married GC patients in higher malignancy status.
Cost‐effectiveness of treating chronic hepatitis C virus with direct‐acting antivirals in people who inject drugs in Australia
Authors: Scott Nick , Iser David M , Thompson Alexander J , Doyle Joseph S , Hellard Margaret E
Published: October 2015

Background and Aim:

Reducing the burden of hepatitis C virus (HCV) related liver disease will require treating people who inject drugs (PWID), the group at most risk of infection and transmission. We determine the cost‐effectiveness of treating PWID with interferon‐free direct‐acting antiviral therapy in Australia.

Methods:

Using a deterministic model of HCV treatment and liver disease progression, including a fixed rate of re‐infection, the expected healthcare costs and quality‐adjusted life years (QALYs) of a cohort of newly HCV‐infected PWID were calculated for: no treatment; treatment after initial infection (“early‐treatment”); and treatment prior to developing compensated cirrhosis (“late‐treatment”). Incremental cost‐effectiveness ratios (ICERs) were used to compare scenarios.

Results:

Late‐treatment was cost‐effective compared to no treatment, with a discounted average gain of 2.98 (95%confidence interval 2.88–5.22) QALYs per person for an additional cost of $15 132 ($11 246–18 922), giving an ICER of $5078 ($2847–5295) per QALY gained. Compared to late‐treatment, early‐treatment gained a further discounted average of 2.27 (0.58–4.80) QALYs per person for $38 794 ($34 789–41 367), giving an ICER of $17 090 ($2847–63 282), which was cost‐effective in approximately 90% of Monte‐Carlo uncertainty simulations. For every 100 newly HCV‐infected PWID, there were an estimated 40 (39–56) eventual liver‐related deaths without treatment, compared to 7 (6–11) and 8 (7–13) with early‐treatment and late‐treatment available respectively.

Conclusions:

Treating HCV‐infected PWID with new therapies is cost‐effective and could prevent a significant number of liver‐related deaths. Although late‐treatment was the most cost‐effective option, the cost per QALY gained for early‐treatment compared to late‐treatment is likely to be below unofficial Australian willingness to pay thresholds.
Novel retinoid ester in combination with salicylic acid for the treatment of acne
Authors: Draelos Zoe , Lewis Joseph , McHugh Laura , Pellegrino Arthur , Popescu Lavinia
Published: October 2015

Background

Retinoids (RC), alpha‐hydroxy acids (AHA), and salicylic acid (BHA) treat acne through differing mechanisms of action. It is theorized that optimal improvement can be achieved by combining the RC‐induced normalization of cellular differentiation, AHA‐induced exfoliation in hydrophilic areas, and BHA‐induced exfoliation in lipophilic areas. AHA and RC have been combined in a bioengineered molecule (AHA retinoid conjugate, or AHA‐RC) delivering both lactic acid (AHA) and RC in a manner reducing retinoid‐associated irritation.

Objectives

To evaluate efficacy and tolerability of a twice‐daily, three‐product skincare regimen using AHA‐RC in combination with BHA for patients with acne.

Methods

A total of 27 women (age range 20–58 years, mean 37.81 ± 10.04 years) with mild‐to‐moderate acne used a 3‐product regimen consisting of a twice‐daily cleanser and topical serum (0.1% AHA‐RC, 2% salicylic acid, and 10.4% l‐lactic acid), with broad‐spectrum SPF 50+ sunscreen as needed, over an 8‐week period. Counts were made at baseline, week 4, and week 8 of total inflammatory (papules, pustules) and noninflammatory (open comedones, closed comedones) lesions. Dryness, stinging, and other secondary endpoints were rated on a 0–5 scale.

Results

Statistically significant reduction in inflammatory and noninflammatory lesion counts (P = 0.006 and P = 0.015, respectively) was noted at 4 weeks. Improvement continued into week 8 with highly significant (P < 0.001) reductions in both lesion counts.

Conclusions

The topical combination of lactic acid, SA, and AHA‐RC produced acne improvement after 4 weeks with continuing cumulative improvement at 8 weeks. AHA‐RC represents a new molecule combining several mechanisms of action to achieve acne improvement.
Acute Brain Imaging in Children: Can MRI Replace CT as a Screening Tool?
Authors: Wagner Matthias W. , Kontzialis Marinos , Seeburg Daniel , Stern Steven E. , Oshmyansky Alexander , Poretti Andrea , Huisman Thierry A.G.M.
Published: October 2015

BACKGROUND AND PURPOSE

To determine if axial T2‐weighted imaging can serve as screening tool for pediatric brain imaging.

METHODS

We retrospectively evaluated consecutive brain magnetic resonance imaging (MRI) data of 161 children (74 girls) with a mean age of 7.44 ± 5.71 years. Standard of reference was the final report of neuroradiology attendings. Three readers with different levels of experience were blinded for clinical diagnoses and study indications. First, readers studied only the axial T2‐weighted screening sequence. Second, they studied all available anatomical and functional MRI sequences as performed per standard protocol for each clinical indication. The readings were classified as normal or abnormal. Sensitivity and specificity were measured.

RESULTS

Axial T2 screening yielded a sensitivity of 77‐88% and a specificity of 92%. The full studies/data sets had a sensitivity of 89‐95% and a specificity of 86‐93%. Nineteen of 167 studies were acquired for acute and 148 of 167 studies for nonacute clinical indication. Twenty‐five false‐negative diagnoses paneled in three groups were made by all readers together. Readers misread four of 19 studies with acute and 21 of 148 studies with nonacute clinical indication. Four of 21 misread studies with nonacute indications harbored unexpected findings needing management.

CONCLUSIONS

Axial T2 screening can detect pediatric brain abnormalities with high sensitivity and specificity and can possibly replace CT as screening tool if the reading physician is aware of possible limitations/pitfalls. The level of experience influences sensitivity and specificity. Adding diffusion‐weighted imaging and susceptibility‐weighted imaging to a 3‐dimensional T2‐weighted sequence would most likely further increase sensitivity and specificity.
Detection of Right‐to‐Left Cardiac Shunt in the Absence of Transcranial Acoustic Bone
Authors: Perren Fabienne , Kremer Christine , Iwanovski Patricia , Savva Elena , Landis Theodor
Published: October 2015

PURPOSE

Paradoxical thrombotic embolism via right‐to‐left cardiac shunt (RLS) is a risk factor of cryptogenic ischemic stroke. Transtemporal Doppler (TTD) is a valid method used in the detection of patent foramen ovale (PFO). Temporal acoustic bone windows are missing with increasing age and in some younger subjects. We studied prospectively whether Doppler ultrasound of the cervical arteries (submandibular internal carotid artery [ICA] and vertebral artery [VA]) is an alternative, when compared to TTD, in the detection and quantification of PFO.

MATERIAL AND METHODS

A total of 94 patients with sufficient temporal bone windows suffering from recent ischemic stroke underwent TTD and ICA (n = 51) or TTD and VA (n = 43). After injection of microbubbles, the numbers of artificial high‐intensity signals (HITS) were recorded at rest and after Valsalva maneuver.

RESULTS

For 47 patients in the ICA group, an RLS was found at rest in 23 patients and after Valsalva in 28 patients. At rest, sensitivity was 100%, specificity 96%, positive predictive value (ppv) 95.6%, and negative predictive value (npv) 100%. After Valsalva, sensitivity was 100%, specificity 95%, ppv 96.4%, npv 100%. For 43 patients in the VA group an RLS was found at rest in 14 patients and after Valsalva in 19 patients. At rest, sensitivity was 71.4%, specificity 100%, ppv 100%, and npv 87.8%. After Valsalva, 94.4%, 96%, 94.4%, and 96%, respectively. Pearson's correlations of the number of HITS between TTD and ICA and between TTD and VA were highly significant.

CONCLUSIONS

When transcranial acoustic bone windows are missing, Doppler ultrasound of the cervical submandibular ICA and VAs are valid screening methods to detect RLS due to a PFO.
Psychosocial characteristics and predictors of health‐care use in families of young children with cystic fibrosis in Western Australia
Authors: Douglas Tonia , Green Jennifer , Park Judy , Turkovic Lidija , Massie John , Shields Linda
Published: October 2015

Objective

Early childhood psychosocial experiences determine future health and health‐care use. Identifying psychosocial predictors in cystic fibrosis may inform intervention strategies that can reduce health‐care utilization.

Design

The study was designed as a prospective cohort study.

Setting

The study was set in the only cystic fibrosis clinic in Western Australia.

Patients

The patients were children up to 6 years diagnosed with cystic fibrosis in Western Australia between 2005 and 2011.

Main outcome measures

Psychosocial data collected for each year of life were compared with Australian population data and analysed as predictors of annual hospital, emergency and outpatient visits.

Results

Compared with the Australian population, cystic fibrosis families demonstrated lower socio‐economic status and labour supply (P < 0.001), increased residential mobility (P < 0.001) and trends towards increased rates of parental separation (P = 0.066). Marital discord and maternal and child psychological stress significantly predicted increased hospital admissions, emergency and outpatient visits.

Conclusions

Social gradients may exist for families of young children with cystic fibrosis in Western Australia with potential implications for child health. Family psychological and relationship stress predicted increased child cystic fibrosis‐related health‐care use.
Protein interactome mining defines melatonin MT1 receptors as integral component of presynaptic protein complexes of neurons
Authors: Benleulmi‐Chaachoua Abla , Chen Lina , Sokolina Kate , Wong Victoria , Jurisica Igor , Emerit Michel Boris , Darmon Michèle , Espin Almudena , Stagljar Igor , Tafelmeyer Petra , Zamponi Gerald W. , Delagrange Philippe , Maurice Pascal , Jockers Ralf
Published: October 2015

In mammals, the hormone melatonin is mainly produced by the pineal gland with nocturnal peak levels. Its peripheral and central actions rely either on its intrinsic antioxidant properties or on binding to melatonin MT1 and MT2 receptors, belonging to the G protein‐coupled receptor (GPCR) super‐family. Melatonin has been reported to be involved in many functions of the central nervous system such as circadian rhythm regulation, neurotransmission, synaptic plasticity, memory, sleep, and also in Alzheimer's disease and depression. However, little is known about the subcellular localization of melatonin receptors and the molecular aspects involved in neuronal functions of melatonin. Identification of protein complexes associated with GPCRs has been shown to be a valid approach to improve our understanding of their function. By combining proteomic and genomic approaches we built an interactome of MT1 and MT2 receptors, which comprises 378 individual proteins. Among the proteins interacting with MT1, but not with MT2, we identified several presynaptic proteins, suggesting a potential role of MT1 in neurotransmission. Presynaptic localization of MT1 receptors in the hypothalamus, striatum, and cortex was confirmed by subcellular fractionation experiments and immunofluorescence microscopy. MT1 physically interacts with the voltage‐gated calcium channel Cav2.2 and inhibits Cav2.2‐promoted Ca2+ entry in an agonist‐independent manner. In conclusion, we show that MT1 is part of the presynaptic protein network and negatively regulates Cav2.2 activity, providing a first hint for potential synaptic functions of MT1.
Melatonin set out to ER stress signaling thwarts epithelial mesenchymal transition and peritoneal dissemination via calpain‐mediated C/EBPβ and NFκB cleavage
Authors: Wu Sheng‐Mao , Lin Wan‐Yu , Shen Chin‐Chang , Pan Hung‐Chuan , Keh‐Bin Wang , Chen Yi‐Ching , Jan Yee‐Jee , Lai De‐Wei , Tang Shu‐Ching , Tien Hsing‐Ru , Chiu Chien‐Shan , Tsai Tsung‐Chih , Lai Yi‐Liang , Sheu Meei‐Ling
Published: October 2015

Peritoneal dissemination of tumor has high mortality and is associated with the loss of epithelial features, acquisition of motile mesenchymal morphology characteristics, and invasive properties by tumor cells. Melatonin is an endogenously produced molecule in all plant species that is known to exert antitumor activity, but to date, its underlying mechanisms and antiperitoneal metastasis efficacy is not well defined. This study determined the antiperitoneal dissemination potential of melatonin in vivo and assessed its association with the inhibition of epithelial‐to‐mesenchymal transition (EMT) signaling mechanism by endoplasmic reticulum (ER) stress, which may be a major molecular mechanism of melatonin against cancer. The results demonstrate that melatonin inhibited peritoneal metastasis in vivo and activated ER stress in Cignal ERSE Reporter Assay, organelle structure in transmission electron microscopy images, calpain activity, and protein biomarkers like p‐elf2α. Moreover, the overexpression of transcription factor C/EBPβ in gastric cancer interacted with NFκB and further regulates COX‐2 expression. These were dissociated and downregulated by melatonin, as proven by immunofluorescence imaging, immunoprecipitation, EMSA, and ChIP assay. Melatonin or gene silencing of C/EBPβ decreased the EMT protein markers (E‐cadherin, Snail, and Slug) and Wnt/beta‐catenin activity by Topflash activity, and increased ER stress markers. In an animal study, the results of melatonin therapy were consistent with those of in vitro findings and attenuated systemic proangiogenesis factor production. In conclusion, C/EBPβ and NFκB inhibition by melatonin may impede both gastric tumor growth and peritoneal dissemination by inducing ER stress and inhibiting EMT.
Do Rural Patients in Canada Underutilize Preventive Care for Myocardial Infarction?
Authors: Cohen Deborah , Manuel Douglas G. , Sanmartin Claudia
Published: October 2015

Purpose

The objective of this study was to explore Canadian rural‐urban differences in the use of primary and secondary preventive diagnostic services for acute myocardial infarction (AMI)—a condition that is amenable to primary health care prevention efforts.

Methods

We examined primary and secondary preventive care services utilized 2 years prior to a patient's first AMI in a cohort of 30,491 patients in Ontario, Canada, from 2010 to 2012. Using logistic regression, rural‐urban differences in lipid testing, glucose testing, stress testing, electrocardiograms, and echocardiograms in middle‐age and senior patients were examined.

Findings

The odds of rural patients receiving care for primary preventive screening were more than 50% lower than the odds for urban patients, with rural seniors being the most affected. Lipid testing: middle‐age OR 0.519 (95% CI, 0.469‐0.574), senior OR 0.422 (0.386‐0.460); glucose testing: middle‐age OR 0.471 (0.426‐0.521), senior OR 0.359 (0.328‐0.394). The odds of rural patients receiving secondary preventive diagnostic care were also lower than the odds for urban patients, but differences between the age groups were not as apparent. Stress testing: middle‐age OR 0.745 (95%CI, 0.642‐0.866), senior OR 0.726 (0.643‐0.820); electrocardiogram: middle‐age OR 0.815 (0.737‐0.901), senior OR 0.724 (0.659‐0.795); echocardiogram: middle‐age OR 0.755 (0.655‐0.869), senior OR 0.746 (0.681‐0.818).

Conclusions

Study results support ongoing concerns related to health care for rural Canadians by demonstrating underutilization of AMI preventive diagnostic care among rural patients. Rural seniors are most at risk. These results have implications for rural health care as well as seniors’ health policy in Canada.
The present and future disease burden of hepatitis C virus infections with today's treatment paradigm – volume 3
Authors: Sibley A. , Han K. H. , Abourached A. , Lesmana L. A. , Makara M. , Jafri W. , Salupere R. , Assiri A. M. , Goldis A. , Abaalkhail F. , Abbas Z. , Abdou A. , Al Braiki F. , Al Hosani F. , Al Jaberi K. , Al Khatry M. , Al Mulla M. A. , Al Quraishi H. , Al Rifai A. , Al Serkal Y. , Alam A. , Alavian S. M. , Alashgar H. I. , Alawadhi S. , Al‐Dabal L. , Aldins P. , Alfaleh F. Z. , Alghamdi A. S. , Al‐Hakeem R. , Aljumah A. A. , Almessabi A. , Alqutub A. N. , Alswat K. A. , Altraif I. , Alzaabi M. , Andrea N. , Babatin M. A. , Baqir A. , Barakat M. T. , Bergmann O. M. , Bizri A. R. , Blach S. , Chaudhry A. , Choi M. S. , Diab T. , Djauzi S. , El Hassan E. S. , El Khoury S. , Estes C. , Fakhry S. , Farooqi J. I. , Fridjonsdottir H. , Gani R. A. , Ghafoor Khan A. , Gheorghe L. , Gottfredsson M. , Gregorcic S. , Gunter J. , Hajarizadeh B. , Hamid S. , Hasan I. , Hashim A. , Horvath G. , Hunyady B. , Husni R. , Jeruma A. , Jonasson J. G. , Karlsdottir B. , Kim D. Y. , Kim Y. S. , Koutoubi Z. , Liakina V. , Lim Y. S. , Löve A. , Maimets M. , Malekzadeh R. , Matičič M. , Memon M. S. , Merat S. , Mokhbat J. E. , Mourad F. H. , Muljono D. H. , Nawaz A. , Nugrahini N. , Olafsson S. , Priohutomo S. , Qureshi H. , Rassam P. , Razavi H. , Razavi‐Shearer D. , Razavi‐Shearer K. , Rozentale B. , Sadik M. , Saeed K. , Salamat A. , Sanai F. M. , Sanityoso Sulaiman A. , Sayegh R. A. , Sharara A. I. , Siddiq M. , Siddiqui A. M. , Sigmundsdottir G. , Sigurdardottir B. , Speiciene D. , Sulaiman A. , Sultan M. A. , Taha M. , Tanaka J. , Tarifi H. , Tayyab G. , Tolmane I. , Ud din M. , Umar M. , Valantinas J. , Videčnik‐Zorman J. , Yaghi C. , Yunihastuti E. , Yusuf M. A. , Zuberi B. F. , Schmelzer J. D.
Published: October 2015

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV‐related mortality and morbidity. HCV‐related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV‐infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV‐related morbidity and mortality are to be achieved.
DHN melanin biosynthesis in the plant pathogenic fungus Botrytis cinerea is based on two developmentally regulated key enzyme (PKS)‐encoding genes
Authors: Schumacher Julia
Published: October 2015

Botrytis cinerea is the causal agent of gray mold disease in various plant species and produces grayish macroconidia and/or black sclerotia at the end of the infection cycle. It has been suggested that the pigmentation is due to the accumulation of 1,8‐dihydroxynaphthalene (DHN) melanin. To unravel its basis and regulation, the putative melanogenic and regulatory genes were identified and functionally characterized. Unlike other DHN melanin‐producing fungi, B. cinerea and other Leotiomycetes contain two key enzyme (PKS)‐encoding enzymes. Bcpks12 and bcpks13 are developmentally regulated and are required for melanogenesis in sclerotia and conidia respectively. BcYGH1 converts the BcPKS13 product and contributes thereby to conidial melanogenesis. In contrast, enzymes acting downstream in conversion of the PKS products (BcBRN2, BcSCD1 and BcBRN1) are required for both, sclerotial and conidial melanogenesis, suggesting that DHN melanogenesis in B. cinerea follows a non‐linear pathway that is rather unusual for secondary metabolic pathways. Regulation of the melanogenic genes involves three pathway‐specific transcription factors (TFs) that are clustered with bcpks12 or bcpks13 and other developmental regulators such as light‐responsive TFs. Melanogenic genes are dispensable in vegetative mycelia for proper growth and virulence. However, DHN melanin is considered to contribute to the longevity of the reproduction structures.
Transcriptome changes in STSV2‐infected Sulfolobus islandicus REY15A undergoing continuous CRISPR spacer acquisition
Authors: León‐Sobrino Carlos , Kot Witold P. , Garrett Roger A.
Published: October 2015

A transcriptome study was performed on Sulfolobus islandicus REY15A actively undergoing CRISPR spacer acquisition from the crenarchaeal monocaudavirus STSV2 in rich and basal media over a 6 day period. Spacer acquisition preceded strong host growth retardation, altered transcriptional activity of four different CRISPR‐Cas modules and changes in viral copy numbers, and with significant differences in the two media. Transcript levels of proteins involved in the cell cycle were reduced, whereas those of DNA replication, DNA repair, transcriptional regulation and some antitoxin–toxin pairs and transposases were unchanged or enhanced. Antisense RNAs were implicated in the transcriptional regulation of adaptation and interference modules of the type I‐A CRISPR‐Cas system, and evidence was found for the occurrence of functional co‐ordination between the single CRISPR‐Cas adaptation module and the functionally diverse interference modules.
Civil society, radicalism and the rediscovery of mythic nationalism
Authors: Molnár Virág
Published: October 2015

The article argues that contrary to the widely held view that traces the recent rise of illiberalism inHungary andEasternEurope to a weak civil society, the past decade has witnessed a surge of civil society activism. But rather than working exclusively towards strengthening and complementing liberal political institutions, civil society has also provided fertile soil to the spread of right‐wing populism, radicalism and xenophobia. The analysis suggests that civil society organisations have in fact played an important role in the right‐wing radicalisation of contemporaryHungarian politics. Conservative civic groups have been instrumental in reinvigorating the symbolic vocabulary of a mythic nationalism that was widespread at the turn of the nineteenth and twentieth century as well as in the 1930s. The resurrection of nationalist, irredentist and anti‐Semitic symbols and paraphernalia (e.g. greaterHungary car stickers) has been a major vehicle for increasing the public visibility and political impact of these groups. The article shows through case studies of specific organisations how this seemingly anachronistic symbolic repertoire has found new resonance in contemporaryHungarian public life.
Catherine of Siena and the New Evangelization
Authors: Cahall Perry J.
Published: October 2015

This article shows the relevance of past ages to the current project of the new evangelization. In particular, it presents St. Catherine of Siena as an example of the intuition that saints throughout the history of the Church have had regarding how to undertake the process of evangelization. The concept of the “new evangelization” is outlined by referring to the writings and speeches of Pope St. John Paul II, Pope Benedict XVI, and Pope Francis. While covering the basic features of the new evangelization, Saint Catherine's life and insights are presented as an example of how to accomplish the project of the new evangelization.
Osteoprotegerin and zoledronate bone effects during orthodontic tooth movement
Authors: Fernández‐González F. J. , López‐Caballo J. L. , Cañigral A. , Menéndez‐Díaz I. , Brizuela A. , de Cos F. J. , Cobo T. , Vega J. A.
Published: October 2015

Structured Abstract

Objectives

To assess the effects of local delivery of recombinant fusion protein osteoprotegerin (OPG‐Fc) and bisphosphonate zoledronate on bone and periodontal ligament in a rat tooth movement model.

Materials and methods

Maxillary first molars of 36 male Sprague–Dawley rats were displaced mesially using a calibrated spring connected to an anterior mini‐screw. Two different drugs were used: a single dose of Zoledronate (16 μg) and a twice‐weekly dose of OPG‐Fc (5.0 mg/kg) were injected. Tooth movement was measured on scanned plaster casts. Structural and immunohistochemical analysis of the orthodontic‐induced changes in bone included receptor activator of nuclear factor ĸ (RANK), Runx, type 1 collagen, matrix metalloproteinases (MMPs) 2 and 9, tissue inhibitors of metalloproteinases (TIMPs) 1 and 2, and vimentin.

Results

Both groups showed a reduction in mesial molar displacement. Animals receiving OPG‐Fc demonstrated only 52%, 31%, and 21% of the total mesial molar displacement compared to control rats at 7, 14, and 21 days, respectively (*p < 0.001). For rats receiving zoledronate tooth displacement decreased significantly with 52%, 46% and 30%, respectively (*p < 0.001). At 14 and 21 days, OPG‐Fc group showed significantly less molar displacement than the zoledronate group (*p < 0.001). RANK, Runx, vimentin, MMP‐9 and tissues‐inhibitor metalloproteinase 1 immunoreactivity were reduced in zoledronate treated animals and even more in OPG treated animals.

Conclusion

Local delivery of OPG‐Fc or zoledronate inhibits bone resorption and therefore tooth movement. OPG‐Fc was more effective than zoledronate in blocking the action of osteoclasts.
The Impact of Duration of Atrial Fibrillation Recurrences on Measures of Health‐Related Quality of Life and Symptoms
Authors: KOCHHÄUSER SIMON , JOZA JACQUELINE , ESSEBAG VIDAL , PROIETTI RICCARDO , KOEHLER JODI , TSANG BERNICE , WULFFHART ZAEV , PANTANO ALFREDO , KHAYKIN YAARIV , ZIEGLER PAUL D. , VERMA ATUL
Published: October 2015

Background

Little is known about the relationship between daily atrial fibrillation (AF) burden and quality of life (QOL). We sought to determine the influence of atrial tachycardia (AT) or AF burden on measures of QOL and symptoms.

Methods and Results

We retrospectively analyzed patients with dual‐chamber pacemakers from the Atrial Septal Pacing Efficacy Clinical Trial (ASPECT), Atrial Therapy Efficacy and Safety Trial (ATTEST), and aTRial arrhythmias dEtected by implaNted Device diagnostics Study (TRENDS) trials. All patients underwent at least one QOL evaluation. We predefined four AF burden groups: no AT/AF (group 1), ≤30 minutes (group 2), 30 minutes–2 hours (group 3), and >2 hours (group 4) per day. We compared QOL measures using the 12‐item Short‐Form Health Survey (SF‐12; standard 4 week recall) and the AF Symptom Checklist (SC) severity and frequency between groups 2–4 to those in group 1. A total of 798 patients were analyzed (age 72 ± 11 years, 447 male [56%]). SC frequency and severity and SF‐12 physical and mental scores worsened significantly when patients in group 4 were compared to patients with no AF. There were no statistically significant differences for any of the measures when comparing group 2 or 3 patients to group 1. By linear regression, only the 2‐hour‐cutoff had a significant impact on QOL as measured by SC frequency (+3.15, P < 0.001), severity (+3.23, P < 0.001), SF‐12 physical score (−2.42, P = 0.013), and SF‐12 mental score (−2.11, P = 0.021).

Conclusion

A daily AT/AF burden of more than 2 hours had significant impact on QOL. This might influence the choice of appropriate cut‐off points to determine the success of an AF treatment.
I Can't Relax! You're Driving me Quasi!
Authors: Ingram Stephen
Published: October 2015

Robust Realists think that there are irreducible, non‐natural, and mind‐independent moral properties. Quasi‐Realists and Relaxed Realists think the same, but interpret these commitments differently. Robust Realists interpret them as metaphysical commitments, to be defended by metaphysical argument. Quasi‐Realists and Relaxed Realists say that they can only be interpreted as moral commitments. These theories thus pose a serious threat to Robust Realism, for they apparently undermine the very possibility of articulating the robust metaphysical commitments of this theory. I clarify and respond to this threat, showing that there is in fact space to develop and defend a robust moral ontology.
Keeping it Real: Intentional Inexistents, Fineness‐of‐Grain, and the Dilemma for Extrinsic Higher‐Order Representational Theories
Authors: Picciuto Vincent
Published: October 2015

According to the standard argument from targetless higher‐order representations, the possibility of such representations presents a dilemma for higher‐order theorists. In this article I argue that there are two theoretically well‐motivated replies to the standard argument. Consequently, the standard argument against higher‐order theories fails. I then go on to argue that while certain versions of higher‐order theory can adequately respond to the standard argument, they both, nevertheless, fail to explain the fineness‐of‐grain that phenomenally conscious experience appears to have.
Associative Virtues and Hume's Narrow Circle
Authors: Frykholm Erin
Published: October 2015

This article offers a straightforward reading of Hume's ‘narrow circle’ – the boundary employed to define those with whom we sympathize in assessing an agent's moral character – that follows from a more careful look at his account of virtue. Hume employs a principle that can be understood as a virtue ethical equivalent of associative obligation, which thereby delimits the boundaries of this circle. This reading avoids concerns about unjustified partiality, moral blind spots, and demandingness, and shows a clear path for reaching uniform moral judgments; it also offers a new perspective on virtue of interest for contemporary virtue ethics.
Actin Polymerization: An Event Regulated by Tyrosine Phosphorylation During Buffalo Sperm Capacitation
Authors: Naresh S , Atreja SK
Published: October 2015

Contents

In the female reproductive tract, the spermatozoa undergo a series of physiological and biochemical changes, prior to gaining the ability to fertilize, that result to capacitation. However, the actin polymerization and protein tyrosine phosphorylation are the two necessary steps for capacitation. In this study, we have demonstrated the actin polymerization and established the correlation between protein tyrosine phosphorylation and actin reorganization during in vitro capacitation in buffalo (Bubalus bubalis) spermatozoa. Indirect immunofluorescence and Western blot techniques were used to detect actin polymerization and tyrosine phosphorylation. The time‐dependent fluorimetric studies revealed that the actin polymerization starts from the tail region and progressed towards the head region of spermatozoa during capacitation. The lysophosphatidyl choline (LPC)‐induced acrosome reaction (AR) stimulated quick actin depolymerization. The inhibitor cytochalasin D (CD) blocked the in vitro capacitation by inhibiting the actin polymerization. In addition, we also performed different inhibitor (Genistein, H‐89, PD9809 and GF‐109) and enhancer (dbcAMP, H2O2 and vanadate) studies on actin tyrosine phosphorylation and actin polymerization. The inhibitors of tyrosine phosphorylation inhibit actin tyrosine phosphorylation and polymerization, whereas enhancers of tyrosine phosphorylation stimulate F‐actin formation and tyrosine phosphorylation. These observations suggest that the tyrosine phosphorylation regulates the actin polymerization, and both are coupled processes during capacitation of buffalo spermatozoa.
Dependence Modelling with Regular Vine Copula Models: A Case-Study for Car Crash Simulation Data
Authors: Schepsmeier Ulf , Czado Claudia
Published: October 2015

The analysis of car crash output parameters such as firewall intrusion points assist the overall engineering process. Such data are nowadays collected from many numerical simulations and it is not possible for the engineer to analyse this growing amount of data by hand. Therefore, data mining and statistical methods are needed. Here, we propose to use the flexible class of regular vine (R-vine) copulas for modelling the dependence between such output variables. R-vine copulas are multivariate copulas constructed hierarchically from bivariate copulas as building blocks. We introduce the concept of such constructions and their graphical tree representation. Applied to simulated frontal crash data of a Ford Taurus such graphs help us to illustrate the dependence structure among different firewall intrusion locations. The big advantage of R-vines compared with standard approaches such as the multivariate normal distribution or the multivariate Gaussian copula is the ability to model asymmetries and dependence in the tails. Our application demonstrates the strong potential of R-vines in the engineering context and opens further application areas.
The New Cultural Conflict, Polarization, and Representation in the Swiss Party System, 1975–2011
Authors: Bornschier Simon
Published: October 2015

Party relationships in the Swiss party system have become substantially more antagonistic over the past decades. This article analyzes the actors and ideologies that have triggered the emergence of a polarizing cultural antagonism, and shows that this conflict is not primarily about Switzerland's relationship with Europe. The implications of the emergence of the new cultural conflict for democracy are far from clear. Using an innovative approach to measure the congruence between voter preferences and party positions, I show that the representation of citizens’ interests along the cultural dimension has improved significantly since the 1970s. The concomitant polarization of the economic dimension has not altered the quality of representation, on the other hand. I conclude by discussing the trade‐offs between the political articulation of a traditionalist‐communitarian conception of community that clearly resonates with an important part of the Swiss populace, and other components of liberal democracy.
Identification of a novel HLA‐B*15 variant, B*15:367, using sequence‐based typing in a Korean woman
Authors: Ham J. Y. , Yoon C. E. , Moon J. H. , Won D. I. , Suh J. S.
Published: October 2015

New allele, B*15:367, differs from B*15:11:01 by a single nucleotide exchange at codon 222 (GAG→AAG).
Meta‐Analyses of Factors Associated with Leptospirosis in Domestic Dogs
Authors: Azócar‐Aedo L. , Monti G.
Published: October 2015

Factors related with leptospirosis in domestic dogs have been reported worldwide. The aims of this study were to identify factors associated with this disease described in different observational studies and to combine the coinciding factors in at least four studies using meta‐analyses, to obtain a pooled odds ratio (OR) as measure of infection risk. A literature search was performed in electronic databases, electronic databases of specific journals and search engines to find studies published in English, Spanish and Portuguese available from January 1960 to January 2015. Two hundred and eighteen factors were identified in 31 publications including cross‐sectional and case–control studies. Finally, independent meta‐analyses were performed with six different variables, which included between 4 and 8 articles. The pooled OR indicated that the variables ‘mixed‐breed dogs’, ‘flooding occurrence in the habitat of the dog’ and ‘working dogs’ were risk factors for leptospirosis, while ‘being a dog less than 1 year old’ was a protective factor; however, all these associations were not statistically significant. Otherwise, the variables ‘male dog’ and ‘urban dog’ were statistically significant risk factors for infection. This study highlights the need for more formal studies on the epidemiology of canine leptospirosis. Nevertheless, the study revealed that some risk factors for infection coincided in different observational studies. These factors could be considered to raise suspicion about the disease, especially when there is a history of exposure to the bacteria.
Análisis de discursos de REDD+ como estrategia equitativa de conservación y uso de la biodiversidad
Authors: Orduz Salinas Natalia
Published: October 2015

El mecanismo de Reducción de Emisiones por Degradación y Deforestación (REDD+) en pocos años ha ganado respaldo institucional y presupuestal del gobierno colombiano y organismos multilaterales para implementarse. No obstante, este análisis revela que los actores de interés en el debate público de REDD+ como estrategia equitativa de conservación y uso de la biodiversidad están lejos de lograr un consenso sobre el tema y tienen diferentes niveles de apertura al diálogo. El reconocimiento de miradas culturales distintas, de derechos sobre el territorio y la autonomía, de los posibles trade-offs son asuntos prioritarios para lograr un debate abierto sobre la (in)viabilidad y condiciones de la estrategia.
Cambios en los ingresos económicos familiares por el uso de los servicios ecosistémicos debido a su afectación por el cambio climático en la Reserva Paisajística Nor Yauyos-Cochas, Perú
Authors: Mercado Waldemar , Gomez Harriet
Published: October 2015

El estudio determina el aporte de los servicios ecosistémicos (se) a los ingresos económicos de la población en la Reserva Paisajística Nor Yauyos Cochas y su zona de amortiguamiento (rpnyc) en Perú. El análisis de los bienes de capital y los ingresos económicos familiares muestra la preponderancia de los se, como el uso de forrajes (pastos naturales) y suelos agrícolas (cultivos andinos). La simulación de la afectación del cambio climático en un escenario específico prospectivo con horizonte al año 2030 evidencia variaciones en la provisión de se, lo que quizá impacte en los ingresos económicos locales. De esta manera, en algunos distritos se agravarían las condiciones de pobreza, en tanto que en otros los beneficios serían desaprovechados por la falta de estrategias.
Structural features of the two-component system LisR/LisK suggests multiple responses for the adaptation and survival of Listeria monocytogenes
Authors: Arenas Suarez Nelson , Gutiérrez Escobar Andrés , Sánchez-Goméz Myriam , Salazar Luz Mary , Reyes Montaño Edgar
Published: October 2015

Here, we characterized the structure of the two-component regulatory system, LisR/LisK, in Listeria monocytogenes. To predict the structure of both proteins and the relationship between them, we employed several bioinformatic tools and databases. Based on our results, LisK protein is embedded in the cell membrane and its modular composition (HAMP, histidine kinase and ATPase domains) is associated with its autophosphorylation (His-266). A stimulus-response likely determines the sequential signal propagation from the bacterial cell surface to its cytoplasmic components. According to our results, LisR is a cytoplasmic protein with a receptor domain (homologous to CheY) that comprises a phosphoacceptor residue (Asp-52) and a DNA-binding domain, which may allow the transmission of a specific transcriptional response. LisR/LisK has been experimentally characterized both biochemically and functionally in other Bacilli pathophysiology; our structure-function approach may facilitate the design of suitable inhibitors
Curling of a Heated Annulus
Authors: Seffen K. A.
Published: October 2015

We study the large-displacement behavior of a thin annulus subjected to thermal gradients. Following axisymmetrical deflections, the annulus buckles into a periodic mode shape, which eventually forms a number of a radial curls under sustained heating. We predict the number of curls using a simple plate-buckling analogy and an approximate energy method.
System Reliability Analysis With Dependent Component Failures During Early Design Stage—A Feasibility Study
Authors: Cheng Yao , Du Xiaoping
Published: October 2015

It is desirable to predict product reliability accurately in the early design stage, but the lack of information usually leads to the use of independent component failure assumption. This assumption makes the system reliability prediction much easier, but may produce large errors since component failures are usually dependent after the components are put into use within a mechanical system. The bounds of the system reliability can be estimated, but are usually wide. The wide reliability bounds make it difficult to make decisions in evaluating and selecting design concepts, during the early design stage. This work demonstrates the feasibility of considering dependent component failures during the early design stage with a new methodology that makes the system reliability bounds much narrower. The following situation is addressed: the reliability of each component and the distribution of its load are known, but the dependence between component failures is unknown. With a physics-based approach, an optimization model is established so that narrow bounds of the system reliability can be generated. Three examples demonstrate that it is possible to produce narrower system reliability bounds than the traditional reliability bounds, thereby better assisting decision making during the early design stage.