bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomineralization‐Inspired Green Synthesis of Zinc Phosphate‐Based Nanosheets in Gelatin Hydrogel
Authors: Parvinzadeh Gashti Mazeyar , Helali Mohammad , Karimi Samin
Published: August 2016

Diffusion of inorganic salts in gels is a simple, inexpensive, and versatile technique for the synthesis of inorganic/organic hybrid nanocomposite particles with various morphologies. This paper introduces a novel method for producing zinc phosphate (ZP) nanosheets using single diffusion of zinc ions in gelatin at ambient temperature. FTIR spectra showed the entrapment of gelatin in ZP sheets due to electrostatic interactions between charged groups of gelatin and diffused ions. This study demonstrated that hydrogels can be used for crystallization of ZP. Such a nanocomposite particle may open a new window for producing antimicrobial and materials for use in tissue engineering.
Combustion and Coprecipitation Synthesis of Co–Zn Ferrite Nanoparticles: Comparison of Structure and Magnetic Properties
Authors: Fakhr Nabavi Houman , Aliofkhazraei Mahmood , Hasanpoor Meisam , Seyfoori Amir
Published: August 2016

In this study, we used urea and ammonia to synthesize zinc cobalt ferrites via microwave‐assisted hydrothermal method from metallic nitrates. It was figured that despite the common synthesis method and equal amount of nitrates, magnetic properties of nanoparticles were different. Changes in magnetic properties are discussed based on factors such as nanoparticles’ size, surface atom spins, cationic distribution, magnetocrystalline energy. Nanoparticles synthesized with ammonia showed lower magnetization while higher magnetocrystalline energy and greater coercivity was obtained due to better cationic distribution. It was also revealed that by increasing magnetization, the susceptibility of nanoparticles increases and then declines.
Burden of atrial fibrillation: a retrospective review of patients presenting to acute medical services
Authors: Jolliffe E. , Fu V. , Lanford J. , Weatherall M. , Rosemergy I.
Published: August 2016

Background

Atrial fibrillation (AF) is a major risk factor for stroke and is associated with increased stroke severity and greater morbidity and mortality. Anticoagulation is highly effective for preventing episodes of thromboembolism but remains under‐utilised.

Aims

The aim of this review was to estimate the short‐term risk of thromboembolic events in patients presenting with an acute medical illness, to assess rates of anticoagulation in eligible patients with AF and to describe physician decisions when prescribing anticoagulation in a hospital setting.

Methods

A retrospective cohort analysis of patients with AF presenting to acute medical services at Wellington Regional Hospital between 1 January 2012 and 31 December 2012 was performed.

Results

A total of 751 patient presentations with AF was identified; 613 unique patient encounters were eligible for analysis, and 38.8% of patients with a CHA2DS2‐VASc score ≥2 were discharged after anticoagulation. The mean CHA2DS2‐VASc score was 4.03 (SD = 1.94). The CHA2DS2‐VASc score was not associated with being started on anticoagulation, odds ratio 1.16 (95% confidence interval = 0.83–1.61), P = 0.38, but age by decade older was associated with a reduced likelihood of being started on anticoagulation, odds ratio 0.61 (95% confidence interval = 0.41–0.89), P = 0.01. In untreated patients with a CHA2DS2‐VASc score ≥2, the most frequently documented reasons not to initiate anticoagulation were decision deferred to the primary care physician, 15.6%; fall risk or frailty, 7.2%; and high bleeding risk, 6.6%. However, no reason was documented in 56.9%. The thromboembolic rate in patients discharged without anticoagulation within 3 months of presentation to acute medical services was 7/330 (2.1%).

Conclusion

Anticoagulation for stroke prevention in AF remains under‐utilised in eligible patients presenting to acute medical services at a tertiary‐level hospital.
Heart failure following cancer treatment: characteristics, survival and mortality of a linked health data analysis
Authors: Clark R. A. , Berry N. M. , Chowdhury M. H. , McCarthy A. L. , Ullah S. , Versace V. L. , Atherton J. J. , Koczwara B. , Roder D.
Published: August 2016

Background

Cardiotoxicity resulting in heart failure is a devastating complication of cancer therapy. A patient may survive cancer only to develop heart failure (HF), which has a higher mortality rate than some cancers.

Aim

This study aimed to describe the characteristics and outcomes of HF in patients with blood or breast cancer after chemotherapy treatment.

Methods

Queensland Cancer Registry, Death Registry and Hospital Administration records were linked (1996–2009). Patients were categorised as those with an index HF admission (that occurred after cancer diagnosis) and those without an index HF admission (non‐HF).

Results

A total of 15 987 patients was included, and 1062 (6.6%) had an index HF admission. Median age of HF patients was 67 years (interquartile range 58–75) versus 54 years (interquartile range 44–64) for non‐HF patients. More men than women developed HF (48.6% vs 29.5%), and a greater proportion in the HF group had haematological cancer (83.1%) compared with breast cancer (16.9%). After covariate adjustment, HF patients had increased mortality risk compared with non‐HF patients (hazard ratios 1.67 (95% confidence interval, 1.54–1.81)), and 47% of the index HF admission occurred within 1 year from cancer diagnosis and 70% within 3 years.

Conclusion

Cancer treatment may place patients at a greater risk of developing HF. The onset of HF occurred soon after chemotherapy, and those who developed HF had a greater mortality risk.
Effective antigen presentation to helper T cells by human eosinophils
Authors: Farhan Ruhaifah K. , Vickers Mark A. , Ghaemmaghami Amir M. , Hall Andrew M. , Barker Robert N. , Walsh Garry M.
Published: August 2016

Although eosinophils are inflammatory cells, there is increasing attention on their immunomodulatory roles. For example, murine eosinophils can present antigen to CD4+ T helper (Th) cells, but it remains unclear whether human eosinophils also have this ability. This study determined whether human eosinophils present a range of antigens, including allergens, to activate Th cells, and characterized their expression of MHC class II and co‐stimulatory molecules required for effective presentation. Human peripheral blood eosinophils purified from non‐allergic donors were pulsed with the antigens house dust mite extract (HDM), Timothy Grass extract (TG) or Mycobacterium tuberculosis purified protein derivative (PPD), before co‐culture with autologous CD4+ Th cells. Proliferative and cytokine responses were measured, with eosinophil expression of HLA‐DR/DP/DQ and the co‐stimulatory molecules CD40, CD80 and CD86 determined by flow cytometry. Eosinophils pulsed with HDM, TG or PPD drove Th cell proliferation, with the response strength dependent on antigen concentration. The cytokine responses varied with donor and antigen, and were not biased towards any particular Th subset, often including combinations of pro‐ and anti‐inflammatory cytokines. Eosinophils up‐regulated surface expression of HLA‐DR/DP/DQ, CD80, CD86 and CD40 in culture, increases that were sustained over 5 days when incubated with antigens, including HDM, or the major allergens it contains, Der p I or Der p II. Human eosinophils can, therefore, act as effective antigen‐presenting cells to stimulate varied Th cell responses against a panel of antigens including HDM, TG or PPD, an ability that may help to determine the development of allergic disease.
Decoupling Marriage and Parenting
Authors: Shrage Laurie
Published: August 2016

This article argues for separating the institutions of marriage and parenting, conceptually and legally. Marriage is neither necessary nor adequate for fostering cooperative and stable co‐parenting. Because promoting marriage fails to protect all children, the state should develop a more suitable formal mechanism whereby co‐parents can commit to cooperate in good faith in order to best serve the interests of their children. Like civil marriage, many of the terms of these contracts are aspirational and not enforceable, though they can guide arrangements for custody and financial support. Co‐parenting agreements need not be limited to two parents, nor need they be limited to legal parents, but can include de facto parents, such as stepparents, foster parents, and other support parents. One important aim of these agreements is to recognise and support the valuable work that married or unmarried co‐parents perform, and to protect the parental rights of caregivers in different kinds of situations.
The ecological niche and distribution of Neanderthals during the Last Interglacial
Authors: Benito Blas M. , Svenning Jens‐Christian , Kellberg‐Nielsen Trine , Riede Felix , Gil‐Romera Graciela , Mailund Thomas , Kjaergaard Peter C. , Sandel Brody S.
Published: August 2016

Aim

In this paper, we investigate the role of climate and topography in shaping the distribution of Neanderthals (Homo neanderthalensis) at different spatial scales. To this end, we compiled the most comprehensive data set on the distribution of this species during the Last Interglacial optimum (MIS 5e) available to date. This was used to calibrate a palaeo‐species distribution model, and analyse variable importance at continental and local scales.

Location

Europe and Irano‐Turanian region (20° N to 70° N, 10° W to 70° E).

Methods

We used archaeological records and palaeoclimatic and topographic predictors to calibrate a model based on an ensemble of generalized linear models fitted with different combinations of predictors and weighted background data. Area under the curve scores computed by leave‐one‐out were used to assess variable importance at the continental scale, while local regression combined with recursive partition trees was used to assess variable importance at the local scale.

Results

Annual rainfall and winter temperatures were the most important predictors at the continental scale, while topography and summer rainfall defined habitat suitability at the local scale. The highest habitat suitability scores were observed along the Mediterranean coastlines. Mountain ranges and continental plains showed low habitat suitability values.

Main conclusions

The model results confirmed that abiotic drivers played an important role in shaping Neanderthals distribution during the Last Interglacial. The high suitability of the Mediterranean coastlines and the low suitability values of most sites at the northern and eastern distribution limits (Germany, Hungary, Ukraine) challenge the notion of Neanderthals as a species with preference for colder environments.
Immediate implant placement and provisionalization in the aesthetic zone using a flapless or a flap‐involving approach: a randomized controlled trial
Authors: Stoupel Janet , Lee Chun‐Teh , Glick Jaclyn , Sanz‐Miralles Elena , Chiuzan Cody , Papapanou Panos N.
Published: August 2016

Aim

We conducted a randomized controlled trial to compare the effect of flapless (FLS) or flap‐involving (F) immediate placement and provisionalization of single‐tooth implants in the aesthetic zone.

Materials and Methods

Thirty‐nine patients were randomized following extraction of a non‐restorable tooth to a FLS or F group. All implants were immediately placed and provisionalized. We monitored prospectively changes in the peri‐implant mucosal margin, the interproximal bone and buccal horizontal ridge at 3, 6 and 12 months.

Results

At 3 months post‐surgery, the mean ± SD [median (interquartile range)] mesiobuccal peri‐implant gingival margin recession from the pre‐surgical soft tissue position amounted to 0.11 ± 0.32 mm [0 (0, 0.5)] in the FLS treatment arm versus 0.43 ± 37 mm [0.5 (0, 0.5)] in the F treatment arm (p = 0.02); corresponding values at the distobuccal surface were 0.11 ± 32 mm [0 (0, 0)] in the FLS arm versus 0.48 ± 0.44 mm [0.5 (0, 1)] in the F arm (p = 0.01). No other significant differences in soft or hard tissue remodelling between the treatment arms were observed at 3, 6 or 12 months.

Conclusions

Flapless and a flap‐involving immediate implant placement and provisionalization in the aesthetic zone resulted in comparable remodelling of the peri‐implant mucosa, interproximal bone and buccal ridge at 6 and 12 months.
Efficacy and safety of adalimumab in Chinese patients with moderate‐to‐severe plaque psoriasis: results from a phase 3, randomized, placebo‐controlled, double‐blind study
Authors: Cai L. , Gu J. , Zheng J. , Zheng M. , Wang G. , Xi L.‐Y. , Hao F. , Liu X.‐M. , Sun Q.‐N. , Wang Y. , Lai W. , Fang H. , Tu Y.‐T. , Sun Q. , Chen J. , Gao X.‐H. , Gu Y. , Teixeira H.D. , Zhang J.‐Z. , Okun M.M.
Published: August 2016

Background

This phase 3 trial is the first to evaluate the efficacy and safety of treatment with the systemic TNF‐α inhibitor, adalimumab, for Chinese patients with moderate‐to‐severe plaque psoriasis.

Methods

In the 12‐week, double‐blind, placebo‐controlled Period A, patients were randomized 4 : 1 to receive adalimumab 40 mg every‐other‐week (following a single 80 mg dose), or placebo every‐other‐week. In the subsequent 12‐week, open‐label, Period B, all patients received adalimumab 40 mg every‐other‐week starting at week 13, following a single, blinded dose at week 12 of adalimumab 80 mg or matching placebo (for patients receiving placebo or adalimumab in Period A respectively). In Period A, efficacy was analysed for all randomized patients and safety for all patients receiving ≥1 dose of the study drug.

Results

For the 425 patients in this study (87 placebo; 338 adalimumab), a higher percentage randomized to adalimumab achieved the primary endpoint of ≥75% improvement from baseline in PASI score (PASI 75) at week 12: placebo 11.5% (10/87); adalimumab 77.8% (263/338; P < 0.001). Physician's Global Assessment of clear to minimal was achieved at week 12 by 14.9% placebo (13/87) and 80.5% adalimumab (272/338; P < 0.001). For patients who received adalimumab at any time during the study (All‐adalimumab Population), treatment‐emergent adverse events (AEs) were reported by 63.4%; the most common was upper respiratory infection (16.1%). Serious AEs were reported by 3.5% of the All‐adalimumab Population, and serious infectious AEs by 1.2%, which include lung infection, pneumonia and tuberculosis [2 (0.5%) patients each]. There was one death (chronic heart failure).

Conclusion

In these Chinese patients with moderate‐to‐severe psoriasis, a significantly greater percentage treated with adalimumab compared with placebo achieved efficacy endpoints at week 12 and efficacy was sustained to week 24. Safety results were consistent with the known adalimumab safety profile; no new safety signals were identified in the 24 weeks of treatment.
Bibliometric analysis on global Behçet disease publications during 1980–2014: is there a Silk Road in the literature?
Authors: Şenel E. , Demir E. , Alkan R.M.
Published: August 2016

Background

Behçet disease (BD) is a chronic and multisystemic vasculitis characterized with recurrent oral and genital ulcers, uveitis, arthritis and skin manifestations. The highest prevalence of the disease has been reported in regions historically involved in the Silk Road routes.

Objective

We aimed to analyse Behçet literature and evaluate whether there is a concordance between ancient Silk Road regions and the distribution of publication productivity.

Methods

The bibliometric analysis of the publications published during 1980–2014 using Thomson Reuters Web of Science database was performed. We generated infographics of productivity and also analysed the correlations among economical productivities, technological advancement levels and humanity index and productivity performances of 78 countries in Behçet literature.

Results

Turkey ranked first in Behçet literature with 1837 articles followed by Japan and the USA. Turkey, Tunisia and Israel occupied the first three places in productivity. Significant correlations were noted between 2014 gross economic and technological indices and publication numbers of the countries. We found that European countries had high productivity, although they had low prevalence of BD. We detected no concordance between the productivity density of the countries and the ancient Silk Road routes.

Conclusion

Most publications were reported from developed countries although undeveloped or developing countries had higher prevalence of BD. Physicians in undeveloped and developing countries should be supported and encouraged to perform novel studies on BD.
He Paid, She Paid: Exploiting Israeli Courts' Rulings on Litigation Costs to Explore Gender Biases
Authors: Fisher Talia , Kricheli‐Katz Tamar , Rosen‐Zvi Issi , Eisenberg Theodore
Published: August 2016

This study documents gender disparities in litigation‐cost rulings in Israel. It expands on the existing literature on judicial bias in at least two important ways: by controlling for the merits of the cases and by focusing on civil litigation. The first improvement is methodological. The unique Israeli regime of litigation costs allows us to control for the merit of the cases, as well as for other typically unobservable variables, and thus to isolate and observe judicial bias. The second improvement on the existing literature on judicial bias involves focusing on outcome disparities in the civil (rather than criminal) justice system. Although numerous studies explore gender‐based disparities in the criminal justice sphere, only a very small number of studies explore such disparities in the civil arena. We found clear disparities in the allocation of litigation costs between men and women. Male plaintiffs who lost were ordered to pay the winners' legal fees more often than were losing women as sole plaintiffs or as part of all‐women plaintiff groups. Likewise, the fees women plaintiffs who lost a case were obliged to pay were less than those required of losing men, and women defendants who won cases received higher fee awards than similarly situated men.
Tetracycline marks visible in Baltic cod Gadus morhua otoliths stored for 40 years
Authors: Krumme U. , Bingel F.
Published: August 2016

Baltic cod Gadus morhua otoliths marked with oxytetracycline (OTC) in 1974–1975 had been sectioned and the sections stored in paper envelopes at room temperature in dry, dark conditions. After 40 years of storage, the historic OTC marks were still clearly visible showing that OTC is suitable for long‐term chemical marking of otoliths. They were, however, noticeably paler than marks in recently recaptured and archived Baltic G. morhua otoliths, chemically tagged with tetracycline at similar dosage to the historic otoliths.
The culture of pretence: a hidden barrier to recognising, disclosing and ending domestic violence
Authors: Francis Lyn , Loxton Deborah , James Colin
Published: August 2016

Aims and objectives

To explore in detail how women perceived their experience of domestic violence and leaving or ending the abuse. This research also examined how service providers identified their professional role in assisting women to end such relationships.

Background

Domestic violence against women continues to occur internationally. Reliable statistics are difficult to capture because of inconsistent definitions, contradictory methods of acquiring data and unreported incidents.

Design

A qualitative study, undertaken in two phases, was conducted in Australia.

Methods

Twelve women who had experienced domestic violence and ended those relationships participated in one semistructured interview (Phase 1). Twenty‐five professionals from health, social sciences and law, whose work included assisting women experiencing domestic violence, participated in three focus groups (Phase 2). Thematic analysis guided by a narrative inquiry approach forms the framework for information collection and interpretation of data in this project.

Findings

The barriers that impede women from disclosing abuse and taking action to end domestic violence are complex and varied between participants. Women did not always acknowledge or realise their relationship was precarious and often denied or minimised the abuse to cope with the domestic violence. Professionals identified that women did not always identify or acknowledge abuse inherent in their relationship although this delayed the provision of appropriate services.

Conclusion

Whether women disclose abuse or deny violence in their relationship, acceptance by service providers and the offer of support is crucial to assisting women in violent relationships.

Relevance to clinical practice

It is hoped that the findings may assist health practitioners, including nurses, to provide nonjudgemental support to women experiencing domestic violence whether women acknowledge the abusive relationship or not.
Religious Involvement and Health Over Time: Predictive Effects in a National Sample of African Americans
Authors: Roth David L. , Usher Therri , Clark Eddie M. , Holt Cheryl L.
Published: August 2016

In this study, two telephone interviews that assessed both religious involvement and health‐related quality of life were conducted approximately 2.5 years apart in a national sample of 290 African Americans. Religious involvement was assessed with an instrument that measured both personal religious beliefs (e.g., having a personal relationship with God) and more public religious behaviors (e.g., attending church services). Health‐related quality of life was measured with version 2 of the Medical Outcomes Study 12‐item short form (SF‐12v2). Structural equation models indicated that higher religious beliefs at baseline predicted better physical and mental health 2.5 years later. Higher religious behaviors at baseline contributed smaller, complementary suppression effects. Physical and mental health indicators from the SF‐12v2 at baseline did not predict changes in either religious beliefs or religious behaviors over time. These findings indicate that, for African Americans, personal religious beliefs lead to beneficial health effects over time, whereas individual differences in health do not appear to predict changes in religious involvement.
Signatures of selection and host‐adapted gene expression of the Phytophthora infestans RNA silencing suppressor PSR2
Authors: de Vries Sophie , von Dahlen Janina K. , Uhlmann Constanze , Schnake Anika , Kloesges Thorsten , Rose Laura E.
Published: August 2016

Phytophthora infestans is a devastating pathogen in agricultural systems. Recently, an RNA silencing suppressor (PSR2, ‘Phytophthora suppressor of RNA silencing 2’) has been described in P. infestans. PSR2 has been shown to increase the virulence of Phytophthora pathogens on their hosts. This gene is one of the few effectors present in many economically important Phytophthora species. In this study, we investigated: (i) the evolutionary history of PSR2 within and between species of Phytophthora; and (ii) the interaction between sequence variation, gene expression and virulence. In P. infestans, the highest PiPSR2 expression was correlated with decreased symptom expression. The highest gene expression was observed in the biotrophic phase of the pathogen, suggesting that PSR2 is important during early infection. Protein sequence conservation was negatively correlated with host range, suggesting host range as a driver of PSR2 evolution. Within species, we detected elevated amino acid variation, as observed for other effectors; however, the frequency spectrum of the mutations was inconsistent with strong balancing selection. This evolutionary pattern may be related to the conservation of the host target(s) of PSR2 and the absence of known corresponding R genes. In summary, our study indicates that PSR2 is a conserved effector that acts as a master switch to modify plant gene regulation early during infection for the pathogen's benefit. The conservation of PSR2 and its important role in virulence make it a promising target for pathogen management.
How open is too open? The mitigating role of appropriation mechanisms in R&D cooperation settings
Authors: Veer Theresa , Lorenz Annika , Blind Knut
Published: August 2016

In this article, we investigate the influence of firms’ R&D cooperation activities on their likelihood to experience imitation. Analyses of firm‐level survey data concerning the R&D cooperation behavior of 2,797 German firms reveal that companies engaging in R&D cooperation face significantly more imitation than their peers that do not cooperate on R&D. Further, we show that cooperation with all potential collaboration partner types except universities and research institutions and in all phases of the innovation process increases the risk of imitation. While we find evidence that intellectual property rights (IPR) generally work well as governance mechanisms moderating the relationship between R&D cooperation and imitation, contracts do not. Hence, IPR apparently provide better protection against imitation than contracts. Our findings indicate that the risks associated with firms’ increased engagement in R&D cooperation could eventually harm the production of new knowledge.
Novel approaches to characterize age‐related remodelling of the dermal‐epidermal junction in 2D, 3D and in vivo
Authors: Newton V. L. , Bradley R. S. , Seroul P. , Cherel M. , Griffiths C. E. M. , Rawlings A. V. , Voegeli R. , Watson R. E. B. , Sherratt M. J.
Published: August 2016

Background/purpose

The dermal‐epidermal junction (DEJ) forms epidermal protrusions down into the dermis (rete ridges) and dermal projections up into the epidermis (dermal papillae). Usually visualized in two‐dimensions (2D), our knowledge of how the DEJ changes with ageing is limited. We aimed to characterize how this structure exists in 3D and changes with age.

Methods

Photoprotected and photoexposed skin were imaged using reflectance confocal microscopy (RCM) in young and aged individuals. Biopsies of the imaged areas were processed for histological sectioning and for imaging using micro‐computed X‐ray tomography (microCT).

Results

Images obtained from RCM and microCT were used to 3D reconstruct the DEJ. DEJ heights obtained from microCT images showed strong correlation with histology‐measured heights. We proposed a novel definition of rete ridges (RRm) and dermal papillae (DPm), which allowed easier automated measurement of reduced DPm and RRm volumes in aged skin from microCT reconstructions. An algorithm to map DPm connectivity showed reduced lengths of DPm branches with age.

Conclusion

Three‐dimensional images illustrated the complex topography of the DEJ and highlighted the distinct morphology of dermal papillae compared with rete ridges, which is not evident when evaluating 2D sections. Ex vivo imaging was more successful in differentiating DEJ architecture with respect to age.
Paper of note in
Science Translational Medicine
Authors: Ferrarelli Leslie K.
Published: August 2016

This week’s article describes how the mechanical stress response could be exploited to maintain diaphragm muscle function in patients needing ventilation support.
Drug-Drug Interaction between the Direct-Acting Antiviral Regimen of Ombitasvir-Paritaprevir-Ritonavir plus Dasabuvir and the HIV Antiretroviral Agent Dolutegravir or Abacavir plus Lamivudine
Authors: Khatri Amit , Trinh Roger , Zhao Weihan , Podsadecki Thomas , Menon Rajeev
Published: August 2016

The direct-acting antiviral regimen of 25 mg ombitasvir–150 mg paritaprevir–100 mg ritonavir once daily (QD) plus 250 mg dasabuvir twice daily (BID) is approved for the treatment of hepatitis C virus genotype 1 infection, including patients coinfected with human immunodeficiency virus. This study was performed to evaluate the pharmacokinetic, safety, and tolerability effects of coadministering the regimen of 3 direct-acting antivirals with two antiretroviral therapies (dolutegravir or abacavir plus lamivudine). Healthy volunteers (
n
= 24) enrolled in this phase I, single-center, open-label, multiple-dose study received 50 mg dolutegravir QD for 7 days or 300 mg abacavir plus 300 mg lamivudine QD for 4 days, the 3-direct-acting-antiviral regimen for 14 days, followed by the 3-direct-acting-antiviral regimen with dolutegravir or abacavir plus lamivudine for 10 days. Pharmacokinetic parameters were calculated to compare combination therapy with 3-direct-acting-antiviral or antiretroviral therapy alone, and safety/tolerability were assessed throughout the study. Coadministration of the 3-direct-acting-antiviral regimen increased the geometric mean maximum plasma concentration (
C
max
) and the area under the curve (AUC) of dolutegravir by 22% (central value ratio [90% confidence intervals], 1.219 [1.153, 1.288]) and 38% (1.380 [1.295, 1.469]), respectively. Abacavir geometric mean
C
max
and AUC values decreased by 13% (0.873 [0.777, 0.979]) and 6% (0.943 [0.901, 0.986]), while those for lamivudine decreased by 22% (0.778 [0.719, 0.842]) and 12% (0.876 [0.821, 0.934]). For the 3-direct-acting-antiviral regimen, geometric mean
C
max
and AUC during coadministration were within 18% of measurements made during administration of the 3-direct-acting-antiviral regimen alone, although trough concentrations for paritaprevir were 34% (0.664 [0.585, 0.754]) and 27% (0.729 [0.627, 0.847]) lower with dolutegravir and abacavir-lamivudine, respectively. All study treatments were generally well tolerated, with no evidence of increased rates of adverse events during combination administration. These data indicate that the 3-direct-acting-antiviral regimen can be administered with dolutegravir or abacavir plus lamivudine without dose adjustment.
Preclinical and Clinical Resistance Profile of EDP-239, a Novel Hepatitis C Virus NS5A Inhibitor
Authors: Owens Christopher M. , Brasher Bradley B. , Polemeropoulos Alex , Rhodin Michael H. J. , McAllister Nicole , Wong Kelly A. , Jones Christopher T. , Jiang Lijuan , Lin Kai , Or Yat Sun
Published: August 2016

EDP-239, a potent and selective hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor developed for the treatment of HCV infection, has been investigated
in vitro
and
in vivo
. This study sought to characterize genotypic changes in the HCV NS5A sequence of genotype 1 (GT1) replicons and to compare those changes to GT1 viral RNA mutations isolated from clinical trial patients. Resistance selection experiments
in vitro
using a subgenomic replicon identified resistance-associated mutations (RAMs) at GT1a NS5A amino acid positions 24, 28, 30, 31, and 93 that confer various degrees of resistance to EDP-239. Key RAMs were similarly identified in GT1b NS5A at amino acid positions 31 and 93. Mutations F36L in GT1a and A92V in GT1b do not confer resistance to EDP-239 individually but were found to enhance the resistance of GT1a K24R and GT1b Y93H. RAMs were identified in GT1 patients at baseline or after dosing with EDP-239 that were similar to those detected
in vitro
. Baseline RAMs identified at NS5A position 93 in GT1, or positions 28 or 30 in GT1a only, correlated with a reduced treatment response. RAMs at additional positions were also detected and may have contributed to reduced EDP-239 efficacy. The most common GT1a and GT1b RAMs found to persist up to weeks 12, 24, or 48 were those at NS5A positions 28, 30, 31, 58 (GT1a only), and 93. Those RAMs persisting at the highest frequencies up to weeks 24 or 48 were L31M and Q30H/R for GT1a and L31M and Y93H for GT1b. (This study has been registered at ClinicalTrials.gov under identifier NCT01856426.)
Activity of Cysteamine against the Cystic Fibrosis Pathogen Burkholderia cepacia Complex
Authors: Fraser-Pitt Douglas , Mercer Derry , Lovie Emma , Robertson Jennifer , O'Neil Deborah
Published: August 2016

There are no wholly successful chemotherapeutic strategies againstBurkholderia cepaciacomplex (BCC) colonization in cystic fibrosis (CF). We assessed the impact of cysteamine (Lynovex) in combination with standard-of-care CF antibioticsin vitroagainst BCC CF isolates by the concentration at which 100% of bacteria were killed (MIC100) and checkerboard assays under CLSI standard conditions. Cysteamine facilitated the aminoglycoside-, fluoroquinolone- and folate pathway inhibitor-mediated killing of BCC organisms that were otherwise resistant or intermediately sensitive to these antibiotic classes. Slow-growing BCC strains are often recalcitrant to treatment and form biofilms. In assessing the impact of cysteamine on biofilms, we demonstrated inhibition of BCC biofilm formation at sub-MIC100s of cysteamine.
Transcriptomic and Phenotypic Analysis Reveals New Functions for the Tat Pathway in Yersinia pseudotuberculosis
Authors: Avican Ummehan , Beckstette Michael , Heroven Ann Kathrin , Lavander Moa , Dersch Petra , Forsberg Åke
Published: August 2016

The twin-arginine translocation (Tat) system mediates the secretion of folded proteins that are identified via an N-terminal signal peptide in bacteria, plants, and archaea. Tat systems are associated with virulence in many bacterial pathogens, and our previous studies revealed that Tat-deficient
Yersinia pseudotuberculosis
was severely attenuated for virulence. Aiming to identify Tat-dependent pathways and phenotypes of relevance for
in vivo
infection, we analyzed the global transcriptome of parental and Δ
tatC
mutant strains of
Y. pseudotuberculosis
during exponential and stationary growth at 26°C and 37°C. The most significant changes in the transcriptome of the Δ
tatC
mutant were seen at 26°C during stationary-phase growth, and these included the altered expression of genes related to virulence, stress responses, and metabolism. Subsequent phenotypic analysis based on these transcriptome changes revealed several novel Tat-dependent phenotypes, including decreased YadA expression, impaired growth under iron-limited and high-copper conditions, as well as acidic pH and SDS. Several functionally related Tat substrates were also verified to contribute to these phenotypes. Interestingly, the phenotypic defects observed in the Tat-deficient strain were generally more pronounced than those in mutants lacking the Tat substrate predicted to contribute to that specific function. Altogether, this provides new insight into the impact of Tat deficiency on
in vivo
fitness and survival/replication of
Y. pseudotuberculosis
during infection.

IMPORTANCE
In addition to its established role in mediating the secretion of housekeeping enzymes, the Tat system has been recognized as being involved in infection. In some clinically relevant bacteria, such as
Pseudomonas
spp., several key virulence determinants can readily be identified among the Tat substrates. In enteropathogens, such as
Yersinia
spp., there are no obvious virulence determinants among the Tat substrates. Tat mutants show no growth defect
in vitro
but are highly attenuated in
in vivo
. This makes Tat an attractive target for the development of novel antimicrobials. Therefore, it is important to establish the causes of the attenuation. Here, we show that the attenuation is likely due to synergistic effects of different Tat-dependent phenotypes that each contributes to lowered
in vivo
fitness.
Towards valid ‘serious non-fatal injury’ indicators for international comparisons based on probability of admission estimates
Authors: Cryer Colin , Miller Ted R , Lyons Ronan A , Macpherson Alison K , Pérez Katherine , Petridou Eleni Th , Dessypris Nick , Davie Gabrielle S , Gulliver Pauline J , Lauritsen Jens , Boufous Soufiane , Lawrence Bruce , de Graaf Brandon , Steiner Claudia A
Published: August 2016

Background

Governments wish to compare their performance in preventing serious injury. International comparisons based on hospital inpatient records are typically contaminated by variations in health services utilisation. To reduce these effects, a serious injury case definition has been proposed based on diagnoses with a high probability of inpatient admission (PrA). The aim of this paper was to identify diagnoses with estimated high PrA for selected developed countries.

Methods

The study population was injured persons of all ages who attended emergency department (ED) for their injury in regions of Canada, Denmark, Greece, Spain and the USA. International Classification of Diseases (ICD)-9 or ICD-10 4-digit/character injury diagnosis-specific ED attendance and inpatient admission counts were provided, based on a common protocol. Diagnosis-specific and region-specific PrAs with 95% CIs were calculated.

Results

The results confirmed that femoral fractures have high PrA across all countries studied. Strong evidence for high PrA also exists for fracture of base of skull with cerebral laceration and contusion; intracranial haemorrhage; open fracture of radius, ulna, tibia and fibula; pneumohaemothorax and injury to the liver and spleen. Slightly weaker evidence exists for cerebellar or brain stem laceration; closed fracture of the tibia and fibula; open and closed fracture of the ankle; haemothorax and injury to the heart and lung.

Conclusions

Using a large study size, we identified injury diagnoses with high estimated PrAs. These diagnoses can be used as the basis for more valid international comparisons of life-threatening injury, based on hospital discharge data, for countries with well-developed healthcare and data collection systems.
Selective pressure of fishways upon morphological and muscle enzymatic traits of migrating glass eels
Authors: Podgorniak T. , Angelini M. , De Oliveira E. , Daverat F. , Pierron F.
Published: August 2016

Fishways are built on obstacles to restore the connectivity between aquatic habitats. Our study investigated how species-specific fishways interact with interindividual trait differences among fish. We compared several groups of glass eels (Anguilla anguilla) climbing two types of fishways with those remaining below the water impoundments. We analyzed relative body condition factor, body length, mass, and in vitro activities and gene transcription levels of several enzymes involved in the energy metabolism (LDH, CS, CCO, PK). Differences among groups indicated that glass eel fish ladders can be size-specific, according to the type of substrate covering the surface of apparatus. Moreover, we found that climbing specific glass eel ladders can require higher endurance-related metabolic traits, triggering increased aerobic capacities. Increased aerobic efforts together with potential size selectivity of fishways should be taken into account when designing such devices and choosing appropriate location on eel migratory pathways.
The tectonic pattern in the Dalradian of the Craignish-Kilmelfort district, Argyllshire
Authors: Knill John Lawrence
Published: August 2016

The Dalradian rocks of the Craignish-Kilmelfort district form a part of the easterly dipping western limb of the Loch Awe syncline. The succession comprises phyllites, quartzites, limestones and grits which have been intruded by a large number of basic sills and sheets; this sequence is now in a low-grade metamorphic condition. Folding was initiated about a NNE.–SSW. axis, at first by flexure along the pre-existing bedding surfaces and later by slip along curved planes of slaty cleavage. Continuation of these movements, about the same axis, resulted in the development of a sequence of strain-slip and fracture cleavages; the final strain-slip cleavage is associated with steep E.–W. axial planes. The style and attitude of the minor structures are discussed in relation to the major structure.
Lévy-Flight Moth-Flame Algorithm for Function Optimization and Engineering Design Problems
Authors: Li Zhiming , Zhou Yongquan , Zhang Sen , Song Junmin
Published: August 2016

The moth-flame optimization (MFO) algorithm is a novel nature-inspired heuristic paradigm. The main inspiration of this algorithm is the navigation method of moths in nature called transverse orientation. Moths fly in night by maintaining a fixed angle with respect to the moon, a very effective mechanism for travelling in a straight line for long distances. However, these fancy insects are trapped in a spiral path around artificial lights. Aiming at the phenomenon that MFO algorithm has slow convergence and low precision, an improved version of MFO algorithm based on Lévy-flight strategy, which is named as LMFO, is proposed. Lévy-flight can increase the diversity of the population against premature convergence and make the algorithm jump out of local optimum more effectively. This approach is helpful to obtain a better trade-off between exploration and exploitation ability of MFO, thus, which can make LMFO faster and more robust than MFO. And a comparison with ABC, BA, GGSA, DA, PSOGSA, and MFO on 19 unconstrained benchmark functions and 2 constrained engineering design problems is tested. These results demonstrate the superior performance of LMFO.
A Randomized, Double-Blind, Placebo-Controlled Trial: The Efficacy of Multispecies Probiotic Supplementation in Alleviating Symptoms of Irritable Bowel Syndrome Associated with Constipation
Authors: Mezzasalma Valerio , Manfrini Enrico , Ferri Emanuele , Sandionigi Anna , La Ferla Barbara , Schiano Irene , Michelotti Angela , Nobile Vincenzo , Labra Massimo , Di Gennaro Patrizia
Published: August 2016

Background and Aim. The efficacy of supplementation treatment with two multispecies probiotic formulates on subjects diagnosed with IBS-C and the assessment of their gut microbiota were investigated.Methods. A randomized, double-blind, three-arm parallel group trial was carried out on 150 IBS-C subjects divided into three groups (F_1, F_2, and F_3). Each group received a daily oral administration of probiotic mixtures (for 60 days) F_1 or F_2 or placebo F_3, respectively. Fecal microbiological analyses were performed by species-specific qPCR to assess the different amount of probiotics.Results. The percentage of responders for each symptom was higher in the probiotic groups when compared to placebo group during the treatment period (t60) and was maintained quite similar during the follow-up period (t90). Fecal analysis demonstrated that probiotics of the formulations increased during the times of treatment only in fecal DNA from subjects treated with F_1 and F_2 and not with F_3, and the same level was maintained during the follow-up period.Conclusions. Multispecies probiotic supplementations are effective in IBS-C subjects and induce a different assessment in the composition of intestinal microbiota. This clinical study is registered with the clinical study registration numberISRCTN15032219.
Power Transformer Partial Discharge Fault Diagnosis Based on Multidimensional Feature Region
Authors: Jia Rong , Xie Yongtao , Wu Hua , Dang Jian , Dong Kaisong
Published: August 2016

Effectively extracting power transformer partial discharge (PD) signals feature is of great significance for monitoring power transformer insulation condition. However, there has been lack of practical and effective extraction methods. For this reason, this paper suggests a novel method for the PD signal feature extraction based on multidimensional feature region. Firstly, in order to better describe differences in each frequency band of fault signals, empirical mode decomposition (EMD) and Hilbert-Huang transform (HHT) band-pass filter wave for raw signal is carried out. And the component of raw signals on each frequency band can be obtained. Secondly, the sample entropy value and the energy value of each frequency band component are calculated. Using the difference of each frequency band energy and complexity, signals feature region is established by the multidimensional energy parameters and the multidimensional sample entropy parameters to describe PD signals multidimensional feature information. Finally, partial discharge faults are classified by sphere-structured support vector machines algorithm. The result indicates that this method is able to identify and classify different partial discharge faults.
Influence of Milling Media on the Mechanical Alloyed W-0.5 wt.% Ti Powder Alloy
Authors: Jahangiri Hadi , Sönmez Sultan , Öveçoğlu M. Lütfi
Published: August 2016

The effects of milling atmosphere and mechanical alloying (MA) duration on the effective lattice parameter, crystallite size, lattice strain, and amorphization rate of the W-0.5 wt.% Ti powders were investigated. W-0.5 wt.% Ti powders were mechanically alloyed (MA’d) for 10 h and 20 h in a high energy ball mill. Moreover, morphology of the powders for various MA was analyzed using SEM microscopy. Their powder density was also measured by helium pycnometer. The dry milled agglomerated powders have spherical particle, while wet milled powders have layered morphology. Milling media and increasing of milling time significantly reduce the crystallite size. The smallest crystallite size is 4.93 nm which belonged to the dry milled powders measured by Lorentzian method after 20 hours’ MA. However, after 20 hours, MA’d powders show the biggest crystallite size, as big as 57.07 nm, measured with the same method in ethanol.
Experimental Diabetes Mellitus in Different Animal Models
Authors: Al-awar Amin , Kupai Krisztina , Veszelka Médea , Szűcs Gergő , Attieh Zouhair , Murlasits Zsolt , Török Szilvia , Pósa Anikó , Varga Csaba
Published: August 2016

Animal models have historically played a critical role in the exploration and characterization of disease pathophysiology and target identification and in the evaluation of novel therapeutic agents and treatments in vivo. Diabetes mellitus disease, commonly known as diabetes, is a group of metabolic disorders characterized by high blood glucose levels for a prolonged time. To avoid late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic symptoms, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. We overviewed the pathophysiological features of diabetes in relation to its complications in type 1 and type 2 mice along with rat models, including Zucker Diabetic Fatty (ZDF) rats, BB rats, LEW 1AR1/-iddm rats, Goto-Kakizaki rats, chemically induced diabetic models, and Nonobese Diabetic mouse, and Akita mice model. The advantages and disadvantages that these models comprise were also addressed in this review. This paper briefly reviews the wide pathophysiological and molecular mechanisms associated with type 1 and type 2 diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans.
Interior Point Algorithm for Multi-UAVs Formation Autonomous Reconfiguration
Authors: Jian-hong Wang , Javed Masood Rana
Published: August 2016

Here the problem of designing multi-UAVs formation autonomous reconfiguration is considered. Combined with three kinds of cost functions, nonlinear dynamic equations, and four inequality constraints, one nonlinear multiobjective optimization problem is constructed. After applying weighted sum method and separating all equality or inequality constraints, the former nonlinear multiobjective optimization problem can be converted into a standard nonlinear single objective optimization problem. Then the interior point algorithm is applied to solve it. Further some improvements are proposed to avoid rank deficiency of some matrices. The equivalence property between multiobjective optimization and single objective optimization through weighted sum method is proved. Finally the efficiency of the proposed strategy can be confirmed by the simulation example results.