bluuebunny/crossref_metadata_2025 huggingface dataset:
Value Relevance of Environmental Provisions Pre‐ and Post‐IFRS
Authors: Wegener Matthew , Labelle Réal
Published: September 2017

The purpose of this paper is to compare the value relevance of environmental provisions as recorded under Canadian/U.S. GAAP and IFRS accounting frameworks with consideration of the impact of voluntarily issuing stand‐alone sustainability reports. The value relevance of environmental provisions is tested using a modified Ohlson (1995) model. We exploit IFRS reconciliations as a quasi‐experimental setting to conduct this comparison. Results indicate that environmental provisions recorded under either framework only act as liabilities for oil and gas firms that release stand‐alone sustainability reports. For other firms in the oil and gas industry, and the mining industry, the liability nature of these provisions appears to be discounted by the market. Furthermore, for firms in the oil and gas industry that do not have stand‐alone CSR reports, provisions appear to be interpreted by the market as a costly signal about future growth. Instead of downwardly affecting market values, this information is associated with higher market values. In terms of the transition to IFRS, we find that, while the IFRS provisions are significantly higher than under former GAAP, they do not improve value relevance for investors. Accounting standard setters should consider examining the changes in the current standards from the original Canadian environmental provision reporting requirements under Capital Assets section 3060.39, as it was rightfully shown to be a relevant proxy for unbooked liabilities (Li and McConomy, 1999; Bewley, 2005) rather than earnings expectancy. The study builds upon prior research to examine the value of accounting standards that have gone through significant changes.
The short‐term impact of the alcohol act on alcohol‐related deaths and hospital admissions in Scotland: a natural experiment
Authors: Robinson Mark , Bouttell Janet , Lewsey James , Mackay Daniel , McCartney Gerry , Beeston Clare
Published: September 2017

Background and aim

The introduction of the Alcohol Act in Scotland on 1 October 2011, which included a ban on multi‐buy promotions, was probably associated with a fall in off‐trade alcohol sales in the year after its implementation. The aim of this study was to test if the same legislation was associated with reduced levels of alcohol‐related deaths and hospital admissions in the 3‐year period after its introduction.

Design

A natural experiment design using time–series data to assess the impact of the Alcohol Act legislation in Scotland. Comparisons were made with unexposed populations in the rest of Great Britain.

Setting

Scotland with comparable data obtained for geographical control groups in other parts of Great Britain.

Participants

For alcohol‐related deaths, a total of 17 732 in Scotland and 88 001 in England and Wales throughout 169 4‐week periods between January 2001 and December 2013 and for alcohol‐related hospital admissions, a total of 121 314 in Scotland and 696 892 in England throughout 182 4‐week periods between January 2001 and December 2014.

Measurements

Deaths and hospital admissions in Scotland and control groups that were wholly attributable to alcohol for consecutive 4‐week periods between January 2001 and December 2014. Data were obtained by age, sex and area‐based socio‐economic position.

Findings

There was no evidence to suggest that the Alcohol Act was associated with changes in the overall rate of alcohol‐related deaths [incidence rate ratio (IRR) = 0.99, 95% confidence interval (CI) = 0.91–1.07)] or hospital admissions (IRR = 0.98, 95% CI = 0.95–1.02) in Scotland. In control group analyses, the pseudo intervention variable was not associated with a change in alcohol‐related death rates in England/Wales (IRR = 0.99, 95% CI = 0.95–1.02), but was associated with an increase in alcohol‐related hospital admission rates in England (IRR = 1.05, 95% CI = 1.03–1.07). In combined models, the interaction analysis did not provide support for a ‘net effect’ of the legislation on alcohol‐related deaths in Scotland compared with England/Wales (IRR 0.99, 95% CI = 0.95–1.04), but suggested a net reduction in hospital admissions for Scotland compared with England (IRR = 0.93, 95% CI = 0.87–0.98).

Conclusion

The implementation of the Alcohol Act in Scotland has not been associated clearly with a reduction in alcohol‐related deaths or hospital admissions in the 3‐year period after it was implemented in October 2011.
Oxidative Stress Increases Erythrocyte Sensitivity to Shear‐Mediated Damage
Authors: McNamee Antony P. , Horobin Jarod T. , Tansley Geoff D. , Simmonds Michael J.
Published: September 2017

Patients receiving mechanical circulatory support often present with heightened inflammation and free radical production associated with pre‐existing conditions in addition to that which is due to blood interactions with nonbiological surfaces. The aim of this experimental laboratory study was to assess the deformability of red blood cells (RBC) previously exposed to oxygen free radicals and determine the susceptibility of these cells to mechanical forces. In the present study, RBC from 15 healthy donors were washed and incubated for 60 min at 37°C with 50 µM phenazine methosulfate (PMS; an agent that generates superoxide within RBC). Incubated RBC and negative controls were assessed for their deformability and susceptibility to mechanical damage (using ektacytometry) prior to the application of shear stress, and also following exposure to 25 different shear conditions of varied magnitudes (shear stress 1, 4, 16, 32, 64 Pa) and durations (1, 4, 16, 32, 64 s). The salient findings demonstrate that incubation with PMS impaired important indices of RBC deformability indicating altered cell mechanics by ∼19% in all conditions (pre‐ and postexposure to shear stress). The typical trends in shear‐mediated changes in RBC susceptibility to mechanical damage, following conditioning shear stresses, were maintained for PMS incubated and control conditions. We demonstrated that free radicals hinder the ability of RBC to deform; however, RBC retained their typical mechanical response to shear stress, albeit at a decreased level compared with control following exposure to PMS. Our findings also indicate that low shear exposure may decrease cell sensitivity to mechanical damage upon subsequent shear stress exposures. As patients receiving mechanical circulatory support have elevated exposure to free radicals (which limits RBC deformability), concomitant exposure to high shear environments needs to be minimized.
Food elimination diets are effective for long‐term treatment of adults with eosinophilic oesophagitis
Authors: Reed C. C. , Fan C. , Koutlas N. T. , Shaheen N. J. , Dellon E. S.
Published: September 2017

Background

Limited data describe the long‐term efficacy of dietary elimination in eosinophilic oesophagitis (EoE).

Aim

To assess the long‐term outcomes of food elimination diets for treatment of adults with EoE.

Methods

We conducted a retrospective cohort study at our centre analysing all EoE patients receiving a food elimination diet without concomitant steroids. Baseline data were abstracted using standardised collection forms. Follow‐up data from a mean 24.9‐month period were collected for patients with a histological response to a food elimination diet during and after food reintroduction. The main outcomes were symptomatic, endoscopic and histological responses.

Results

Of 52 patients, 18 received a 6‐food food elimination diet, 32 received targeted diet, and two received a 6‐food food elimination diet with targeted elimination. There were 21 (40%) patients with an initial histological response. Responders reported less dysphagia after treatment (95% baseline vs 11%; P = .001) and at the end of follow‐up (95% baseline vs 33%; P = .008). Significant and durable endoscopic improvements were recorded at the same time points: Endoscopic reference score: 3.2 vs 0.7; P = .001; and 3.2 vs 1.7; P = .06. Histological findings improved after the most restrictive diet in responders (49.8 vs 4.1 eosinophils per high‐power field; P = .001) and remained suppressed in the 10 initial responders maintaining compliance at the end of follow‐up (5.2 eosinophils per high‐power field).

Conclusions

Among EoE patients responding to a food elimination diet and remaining adherent, maintenance dietary therapy produced durable long‐term symptomatic, endoscopic and histological disease control. These long‐term data confirm that a food elimination diet is an effective maintenance treatment option in select adults with EoE.
Glucocorticoid receptor is involved in the differential expression of hepatic 3β‐hydroxysteroid dehydrogenase between barrows and boars at finishing stage
Authors: Li Xian , Cong Rihua , Yao Wen , Jia Yimin , Li Runsheng , Sun Zhiyuan , Li Xi , Zhao Ruqian
Published: September 2017

The enzyme 3β‐hydroxysteroid dehydrogenase (3β‐HSD) plays an important role in androstenone metabolism in pig liver, and its defective expression is related to the development of boar taint. Early age castration is a common practice in many countries to avoid boar taint, yet whether and how castration affects porcine hepatic 3β‐HSD expression are still poorly understood. In this study, we aimed to compare the expression of 3β‐HSD between intact (boars) and castrated (barrows) male pigs, and to explore the potential factors regulating 3β‐HSD transcription. Compared to barrows, boars showed worse carcass quality. Boars had significantly higher levels of serum androstenone (P < 0.01), testosterone (P < 0.01) and hepatic cortisol (P < 0.05), which were contrary to significantly lower expression of 3β‐HSD messenger RNA (P < 0.01) and protein (P < 0.01) in the liver. Significant differences were detected for the hepatic expression of androgen receptor (AR) and CCAAT/enhancer binding protein β (C/EBPβ). Chromatin immunoprecipitation (ChIP) assay demonstrated reduced histone H3 acetylation (P < 0.05) but increased glucocorticoid receptor (GR) binding to 3β‐HSD gene promoter in boars (P < 0.05). These results indicate that GR binding to 3β‐HSD promoter is involved in the differential hepatic 3β‐HSD expression between boars and barrows.
Economic evaluation of dental sealants: A systematic literature review
Authors: Akinlotan Marvellous , Chen Bradley , Fontanilla Tiana M. , Chen Annie , Fan Victoria Y.
Published: September 2017

Objectives

To systematically review the literature on economic evaluations of dental sealants and examine the costs and effectiveness of caries prevention using sealants.

Methods

Of 21 full‐text articles examined, a total of 13 were included in this study. These studies are grouped by the type of intervention as follows: (i) sealants compared with no sealants; (ii) sealants compared with other forms of caries prevention; (iii) resin‐based sealants compared with glass‐ionomer sealants; (iv) different sealing strategies in primary teeth; (v) different sealing strategies in permanent teeth; and (vi) sealants based on school‐ or clinic‐based setting of delivery. All currency is reported in constant 2010 US$.

Results

Cost‐effectiveness analyses differed due to varying study designs, assumptions, sealant delivery settings, outcomes, caries risk assessment and study durations. Findings varied on the cost‐effectiveness of sealants compared with other caries‐preventive strategies. Under the assumption of equal caries risk, always sealing primary molars appeared to be the most effective strategy, whereas risk‐based sealing was the optimal strategy with differing caries risk. Studies that assessed sealing strategies in permanent teeth reported that risk‐based sealing was more cost‐effective than not sealing, but they differed on the cost‐effectiveness of risk‐based seal compared with non‐risk‐based seal. Sealants delivered in school settings had mixed results on costs but were as equally effective as sealants delivered in private practices.

Conclusions

The cost‐effectiveness of sealants is dependent on the conditions of delivery. The list of cost‐effectiveness ratios for each intervention can support policy makers to estimate expected returns on their investments in dental sealants.
Development of the quality of reaching in infants with cerebral palsy: a kinematic study
Authors: Boxum Anke G , La Bastide‐Van Gemert Sacha , Dijkstra Linze‐Jaap , Hamer Elisa G , Hielkema Tjitske , Reinders‐Messelink Heleen A , Hadders‐Algra Mijna
Published: September 2017

Aim

To assess development of reaching and head stability in infants at very high risk (VHR‐infants) of cerebral palsy (CP) who did and did not develop CP.

Method

This explorative longitudinal study assessed the kinematics of reaching and head sway in sitting in 37 VHR‐infants (18 CP) one to four times between 4.7 months and 22.6 months corrected age. Developmental trajectories were calculated using linear mixed effect models. Motor function was evaluated with the Infant Motor Profile (IMP) around 13 months corrected age.

Results

Throughout infancy, VHR‐infants with CP had a worse reaching quality than infants without CP, reflected for example by more movement units (factor 1.52, 95% CI 1.16–1.99) and smaller transport movement units (factor 1.86, 95% CI 1.20–2.90). Total head sway of infants with and without CP was similar, but infants with CP used more head movement units to achieve stability. The rate of developmental change in infants with and without CP was similar. Around 13 months, head control and reaching quality were interrelated; both were associated with IMP‐scores.

Interpretation

Infants with CP showed a worse kinematic reaching quality and head stability throughout infancy from early age onwards than VHR‐infants without CP, implying that kinematically they do not grow into a deficit, but exhibit deficits from early infancy on.

What this paper adds

Reaching quality improves throughout infancy in all infants at high risk (VHR‐infants).

Infants with cerebral palsy (CP) show a worse reaching quality than VHR‐infants without CP.

Infants with CP achieve head stability differently from infants without CP.

Infants with CP exhibit kinematic reaching problems from early age onwards.
Cherry (Prunus cerasus cv Montmorency) extract with standardised antioxidant potential as preservative for refrigerated storage of ground pork
Authors: Brodowska Marta , Guzek Dominka , Godziszewska Jolanta , Górska‐Horczyczak Elżbieta , Pogorzelska Ewelina , Sakowska Anna , Wojtasik‐Kalinowska Iwona , Gantner Magdalena , Wierzbicka Agnieszka
Published: September 2017

Antioxidants occurring naturally are much sought‐after for their safety of use for human nutrition and strong preservative properties. The study was performed to determine the antioxidant potential of sour cherry extract and its effect (equivalent of 20 mg and 40 mg GAE kg−1) on the quality of ground pork patties during 8‐day storage. The patties were analysed for antioxidant capacity, oxidation, profile of fatty acids, flavour, colour, sensory properties and aerobic bacteria count. Patties with addition of cherry extract (40 mg GAE kg−1) showed higher antioxidant capacity of 844 ± 149 μmol TE L‐1 on the last day of the storage than the control group where the result was 480 ± 81 μmol TE L‐1. The addition of extract caused lower overall increase in lipid oxidation and prevented loss of redness even on the last day of the storage. Flavour changes resulted from oxidation and decrease in the amount of desirable volatile compounds in storage. The application of the extract from Prunus cerasus combined with vacuum packaging inhibited both oxidation and quality deterioration of pork patties in cold storage.
What hasGWASdone forHLAand disease associations?
Authors: Kennedy A. E. , Ozbek U. , Dorak M. T.
Published: September 2017

The major histocompatibility complex (MHC) is located in chromosome 6p21 and contains crucial regulators of immune response, including human leucocyte antigen (HLA) genes, alongside other genes with nonimmunological roles. More recently, a repertoire of noncodingRNAgenes, including expressed pseudogenes, has also been identified. TheMHCis the most gene dense and most polymorphic part of the human genome. The region exhibits haplotype‐specific linkage disequilibrium patterns, contains the strongest cis‐ and trans‐eQTLs/meQTLs in the genome and is known as a hot spot for disease associations. Another layer of complexity is provided to the region by the extreme structural variation and copy number variations. While theHLA‐Bgene has the highest number of alleles, theHLA‐DR/DQsubregion is structurally most variable and shows the highest number of disease associations. Reliance on a single reference sequence has complicated the design, execution and analysis ofGWASfor theMHCregion and not infrequently, theMHCregion has even been excluded from the analysis ofGWASdata. Here, we contrast features of theMHCregion with the rest of the genome and highlight its complexities, including its functional polymorphisms beyond those determined by single nucleotide polymorphisms or single amino acid residues. One of the several issues with customaryGWASanalysis is that it does not address this additional layer of polymorphisms unique to theMHCregion. We highlight alternative approaches that may assist with the analysis ofGWASdata from theMHCregion and unravel associations with all functional polymorphisms beyond singleSNPs. We suggest that despite already showing the highest number of disease associations, the true extent of the involvement of theMHCregion in disease genetics may not have been uncovered.
Natural Disasters and Human Trafficking: Do Disasters Affect State Anti‐Trafficking Performance?
Authors: Bowersox Zack
Published: September 2017

Despite the oft noted negative connection between natural disasters and human trafficking, no quantitative study has been performed. Natural disasters, like conflict, can destroy homes and the economic security of individuals forcing them to migrate and making them targets for traffickers. This article tests the link between a state's ability to address trafficking and natural disasters, testing the popular prediction that a state's capabilities will be strained as increased natural disasters occur thus producing a negative effect. The findings though demonstrate that states are actually more likely to perform better in their efforts to confront trafficking. I argue that this is because natural disasters actually strengthen and enhance the state, and particularly its security institutions, in responding to these events. I place these findings in the context of other recent quantitative studies of trafficking that have also produced contradictory results when compared with the field's qualitative studies.
Liberalism, Civil Marriage, and Amorous Caregiving Dyads
Authors: Cave Eric M.
Published: September 2017

Recently, the US has joined many European jurisdictions in extending civil marriage to same sex as well as different sex dyads. Many liberals regard this as a development worth entrenching. But a prominent recent liberal challenge to civil marriage claims otherwise. According to this challenge, by defining and conferring civil marriage, the state privileges some relationships over others that serve equally well the important liberal goal of fostering effective liberal citizenship, in violation of a prominent interpretation of the doctrine of state neutrality. Theorists who press this challenge, such as Elizabeth Brake and Tamara Metz, argue that it can be met effectively only by dismantling civil marriage and replacing it with more inclusive state‐maintained arrangements. So far, prominent responses to this neutralist challenge to civil marriage have focused on the special value of either the relationships to which civil marriage currently extends, or the special value of civil marriage itself. In this article, I develop an alternative reply to this neutralist challenge to civil marriage, one focusing instead on the special vulnerabilities of some of the liberally valuable relationships to which civil marriage currently extends, amorous caregiving dyads.
Development and evaluation of a manual for extended brief intervention for alcohol misuse for adults with mild to moderate intellectual disabilities living in the community: The EBI‐LD study manual
Authors: Kouimtsidis Christos , Scior Katrina , Baio Gianluca , Hunter Rachael , Pezzoni Vittoria , Hassiotis Angela
Published: September 2017

Background

Extended brief interventions for alcohol misuse are effective in the general population. The process of manualising the first ever such intervention for people with mild to moderate intellectual disabilities in the UK is the focus of this study.

Methods

The manual was an adaptation of existing manuals based on Motivational Enhancement and Cognitive Behaviour Therapy and was used in a feasibility randomized controlled trial, the EBI‐LD study. The sessions were recorded and scored using an adapted version of the Yale Adherence and Competence Scale (YACS II). Feedback was provided by therapists. The trial is closed. Registered: isrctn.com; ISRCTN58783633.

Results

The quality of the sessions provided was rated as good. Therapists were able to cover all topics within each session. Main challenges included session duration and homework task completion.

Conclusions

We recommend the duration of the sessions to be extended to 40 min to accommodate carers in the session and to enhance their support in homework task completion.
Achieving Consensus on Principles of Good Practice for School Health in Independent Schools: A Delphi Study
Authors: Marshall Miguel G. , Allegrante John P.
Published: September 2017

BACKGROUND

Although the 8 components of the coordinated school health (CSH) framework have been implemented to various degrees in the nation's public schools, principles of good practice (PGPs) to guide health promotion efforts in independent schools do not exist. The purpose of this study was to generate PGPs and rate their feasibility of implementation.

METHODS

A modified Delphi process was used to generate PGPs for school health in independent schools and develop consensus regarding their feasibility of implementation. A working group of 6 independent school health professionals (ISHPs) was convened to propose draft PGPs based on the CSH framework. The proposed PGPs were then reviewed by a national and geographically diverse expert panel of 10 school health researchers and 23 ISHPs that completed 3 Delphi rounds to achieve consensus on the PGPs. Of 33 participants originally invited to participate, 27 completed the Delphi process.

RESULTS

A total of 27 panelists rated 67 PGPs, provided 399 comments, and achieved consensus using interquartile range on 56 (84%) of the proposed PGPs, 41 of which were rated feasible and 15 somewhat feasible.

CONCLUSION

This study has generated empirical support for the feasibility of PGPs for school health in independent schools.
Measuring the Implementation of a School Wellness Policy
Authors: Snelling Anastasia , Belson Sarah Irvine , Watts Erin , Malloy Elizabeth , Van Dyke Hugo , George Stephanie , Schlicker Sandra , Katz Nancy Brenowitz
Published: September 2017

BACKGROUND

With the rise in childhood obesity, school policies related to nutrition and physical activity have been written and implemented. In this paper, we present a model to evaluate the degree to which state legislation for school health policies are implemented at the school level.

METHODS

Using Washington, DC's Healthy Schools Act (HSA) and a self‐report measure of the implementation of the HSA, we illustrate the process of developing a composite score that can be used to measure compliance with the provisions of the law.

RESULTS

We calculated elementary and middle school composite scores based on the provisions within the HSA. Schools have been successful in implementing nutrition provisions; however, more resources are needed for schools to achieve the minutes of health and physical education. We found statistically significant differences between public charter and traditional public schools on the implementation of the provisions of the HSA.

CONCLUSIONS

Understanding how schools are complying with school wellness policies is a next step to determining where additional resources or support are needed in order to support school‐wide adoption of healthy policies.
A Strategic User Equilibrium for Independently Distributed Origin‐Destination Demands
Authors: Wen Tao , Cai Chen , Gardner Lauren , Dixit Vinayak , Waller S. Travis , Chen Fang
Published: September 2017

This article proposes an extension of the strategic user equilibrium proposed by Waller and colleagues and Dixit and colleagues. The proposed model relaxes the assumption of proportional Origin‐Destination (O‐D) demand, as it accounts for users’ strategic link choice under independently distributed O‐D demands. The convexity of the mathematical formulation is proved when each O‐D demand is assumed to follow a Poisson distribution independently; link flow distributions and users’ strategic link choice are also proved to be unique. Network performance measures are given analytically. A numerical analysis is conducted on the Sioux Falls network. A Monte Carlo method is used to simulate network performance measures, which are then compared to the results computed from the analytical expression. It is illustrated that the model is capable of accounting for demand volatility while maintaining computation efficiency.
Levels of interleukin (IL)‐6 and IL‐8 are elevated in serum and bronchoalveolar lavage fluid of haematological patients with invasive pulmonary aspergillosis
Authors: Heldt Sven , Eigl Susanne , Prattes Juergen , Flick Holger , Rabensteiner Jasmin , Prüller Florian , Niedrist Tobias , Neumeister Peter , Wölfler Albert , Strohmaier Heimo , Krause Robert , Hoenigl Martin
Published: September 2017

Aspergillus spp. have been shown to induce T‐helper cell (Th) 1 and Th17 subsets resulting in elevated levels of several cytokines. The objective of this study was to analyse a bundle of cytokines in serum and bronchoalveolar lavage fluid (BALF) in patients with and without invasive pulmonary aspergillosis (IPA). This nested case‐control analysis included 10 patients with probable/proven IPA and 20 matched controls without evidence of IPA, out of a pool of prospectively enrolled (2014‐2017) adult cases with underlying haematological malignancies and suspected pulmonary infection. Serum samples were collected within 24 hours of BALF sampling. All samples were stored at −70°C for retrospective determination of cytokines. IL‐6 and IL‐8 were significantly associated with IPA in both serum (P = .011 and P = .028) and BALF (P = .006 and P = .012, respectively), and a trend was observed for serum IL‐10 (P = .059). In multivariate conditional logistic regression analysis, IL‐10 remained a significant predictor of IPA in serum and IL‐8 among BALF cytokines. In conclusion, levels of IL‐6 and IL‐8 were significantly associated with probable/proven IPA, and a similar trend was observed for serum IL‐10. Future cohort studies should determine the diagnostic potential of these cytokines for IPA, and evaluate combinations with other IPA biomarkers/diagnostic tests.
Capital–Skill Complementarity: Does Capital Composition Matter?
Authors: Correa Juan A. , Lorca Miguel , Parro Francisco
Published: September 2017

We estimate the effect of capital composition on the size of capital–skill complementarity and the skill wage premium. Disaggregating the capital stock into different types according to technological content, we find that: capital is more of a q‐complement to skilled labor than to unskilled labor; the higher the technological component of capital, the larger the size of the relative q‐complementarity between capital and skilled labor; and replacing non‐technological with technological capital might increase the skill wage premium by about 9 percent. Our results highlight that changes in capital composition matter for understanding changes in the skill wage premium.
Pathogen reduction of whole blood: utility and feasibility
Authors: Allain J.‐P. , Goodrich R.
Published: September 2017

Objectives

To collect information on pathogen reduction applied to whole blood.

Background

Pathogen reduction (PR) of blood components has been developed over the past two decades, and pathogen‐reduced fresh‐frozen plasma and platelet concentrates are currently in clinical use. High cost and incomplete coverage of components make PR out of reach for low‐ and middle‐income countries (LMIC). However, should PR become applicable to whole blood (WB), the main product transfused in sub‐Saharan Africa, and be compatible with the preparation of clinically suitable components, cost would be minimised, and a range of safety measures in place at high cost in developed areas would become redundant.

Methods

All articles called with “pathogen reduction”, “pathogen inactivation” and “whole blood” were retrieved from Medline. References in articles were utilised.

Results

One such PR technology (PRT) applied to WB has been developed and has shown efficacious against viruses, bacteria and parasites in vitro; and has been able to inactivate nucleated blood cells whilst retaining the ability to prepare components with acceptable characteristics.

The efficacy of this WB PRT has been demonstrated in vivo using the inactivation of Plasmodium falciparum as a model and showing a high degree of correlation between in vitro and in vivo data. Obtaining further evidence of efficacy on other suitable targets is warranted. Shortening of the process, which is currently around 50 min, or increasing the number of units simultaneously processed would be necessary to make PRT WB conducive to LMIC blood services' needs.

Conclusions

Even if not 100% effective against agents that are present in high pathogen load titres, WB PRT could massively impact blood safety in LMIC by providing safer products at an affordable cost.
Cell-phone vs microphone recordings: Judging emotion in the voice
Authors: Green Joshua J. , Eigsti Inge-Marie
Published: September 2017

Emotional states can be conveyed by vocal cues such as pitch and intensity. Despite the ubiquity of cellular telephones, there is limited information on how vocal emotional states are perceived during cell-phone transmissions. Emotional utterances (neutral, happy, angry) were elicited from two female talkers and simultaneously recorded via microphone and cell-phone. Ten-step continua (neutral to happy, neutral to angry) were generated using the straight algorithm. Analyses compared reaction time (RT) and emotion judgment as a function of recording type (microphone vs cell-phone). Logistic regression revealed no judgment differences between recording types, though there were interactions with emotion type. Multi-level model analyses indicated that RT data were best fit by a quadratic model, with slower RT at the middle of each continuum, suggesting greater ambiguity, and slower RT for cell-phone stimuli across blocks. While preliminary, results suggest that critical acoustic cues to emotion are largely retained in cell-phone transmissions, though with effects of recording source on RT, and support the methodological utility of collecting speech samples by phone.
Subinhibitory Dalbavancin Attenuates Exotoxin Production from Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureusIn Vitro
Authors: Hobdey Sarah E. , Katahira Eva J. , Dockstader Pamela , Davidson Stephen M. , Bond Laura , Bolz Devin D. , Bryant Amy E. , Stevens Dennis L.
Published: September 2017

This study investigated the effects of subinhibitory doses of the lipoglycopeptide antibiotic dalbavancin onStaphylococcus aureustoxin productionin vitro.S. aureustoxin production levels were compared to those seen with the natural glycopeptide antibiotic vancomycin and with representative beta-lactam and oxazolidinone antibiotics. While neither dalbavancin nor vancomycin adversely affected toxin production, of these glycopeptide antibiotics, only dalbavancin significantly attenuated toxin production at subinhibitory concentrations. These findings support the recent success of dalbavancin for treatment of staphylococcal infections.
Transcriptional and Mutational Profiling of an Aminoglycoside-Resistant Pseudomonas aeruginosa Small-Colony Variant
Authors: Schniederjans Monika , Koska Michal , Häussler Susanne
Published: September 2017

Pseudomonas aeruginosa
is a major causative agent of both acute and chronic infections. Although aminoglycoside antibiotics are very potent drugs against such infections, antibiotic failure is steadily increasing mainly because of increasing resistance of the bacteria. Many molecular mechanisms that determine resistance, such as acquisition of genes encoding aminoglycoside-inactivating enzymes or overexpression of efflux pumps, have been elucidated. However, there are additional, less well-described mechanisms of aminoglycoside resistance. In this study, we profiled a clinical tobramycin-resistant
P. aeruginosa
strain that exhibited a small-colony variant (SCV) phenotype. Both the resistance and colony morphology phenotypes were lost upon passage of the isolate under rich medium conditions. Transcriptional and mutational profiling revealed that the SCV harbored activating mutations in the two-component systems AmgRS and PmrAB. Introduction of these mutations individually into type strain PA14 conferred tobramycin and colistin resistance, respectively. However, their combined introduction had an additive effect on the tobramycin resistance phenotype. Activation of the AmgRS system slightly reduced the colony size of wild-type PA14, whereas the simultaneous overexpression of
gacA
, the response regulator of the GacSA two-component system, further reduced colony size. In conclusion, we uncovered combinatorial influences of two-component systems on clinically relevant phenotypes such as resistance and the expression of the SCV phenotype. Our results clearly demonstrate that the combined activation of
P. aeruginosa
two-component systems has pleiotropic effects with unforeseen consequences.
Antagonism between Front-Line Antibiotics Clarithromycin and Amikacin in the Treatment of Mycobacterium abscessus Infections Is Mediated by the
whiB7
Gene
Authors: Pryjma Mark , Burian Ján , Kuchinski Kevin , Thompson Charles J.
Published: September 2017

Combinations of antibiotics, each individually effective against
Mycobacterium abscessus
, are routinely coadministered based on the concept that this minimizes the spread of antibiotic resistance. However, our
in vitro
data contradict this assumption and instead document antagonistic interactions between two antibiotics (clarithromycin and amikacin) used to treat
M. abscessus
infections. Clinically relevant concentrations of clarithromycin induced increased resistance to both amikacin and itself. The induction of resistance was dependent on
whiB7
, a transcriptional activator of intrinsic antibiotic resistance that is induced by exposure to many different antibiotics. In
M. abscessus
, the deletion of
whiB7
(MAB_3508c) resulted in increased sensitivity to a broad range of antibiotics. WhiB7 was required for transcriptional activation of genes that confer resistance to three commonly used anti-
M. abscessus
drugs: clarithromycin, amikacin, and tigecycline. The
whiB7
-dependent gene that conferred macrolide resistance was identified as
erm
(41) (MAB_2297), which encodes a ribosomal methyltransferase. The
whiB7
-dependent gene contributing to amikacin resistance was
eis2
(MAB_4532c), which encodes a Gcn5-related
N
-acetyltransferase (GNAT). Transcription of
whiB7
and the resistance genes in its regulon was inducible by subinhibitory concentrations of clarithromycin but not by amikacin. Thus, exposure to clarithromycin, or likely any
whiB7
-inducing antibiotic, may antagonize the activities of amikacin and other drugs. This has important implications for the management of
M. abscessus
infections, both in cystic fibrosis (CF) and non-CF patients.
Multiple Modes of Action of a Monoclonal Antibody against Multidrug-Resistant Escherichia coli Sequence Type 131-H30
Authors: Guachalla Luis M. , Hartl Katharina , Varga Cecília , Stulik Lukas , Mirkina Irina , Malafa Stefan , Nagy Eszter , Nagy Gábor , Szijártó Valéria
Published: September 2017

The multidrug-resistantH30 subclone of extraintestinal pathogenicEscherichia colisequence type 131 (ST131-H30) has spread worldwide. This clone expresses a conserved lipopolysaccharide (LPS) O antigen, O25b. Previously, we described monoclonal antibodies (MAbs) specific to the O25b antigen and characterized them as diagnostic and therapeutic tools. In this study, evidence is provided that besides the previously shown complement-mediated bactericidal effect, an O25b-specific humanized MAb, A1124, also enhances opsonophagocytic uptake by the murine macrophage cell line RAW 264.7. Both phagocyte-dependent killing and phagocyte-independent killing, triggered by A1124, were confirmed in human whole blood. Furthermore, A1124 was shown to neutralize endotoxin activity of purified LPS of clinical isolates. This activity was demonstratedin vitrousing both RAW 264.7 cells and a human Toll-like receptor 4 (TLR4) reporter cell line, as well as in a murine model of endotoxemia using purified LPS for challenge. Significant protective efficacy of A1124 at low doses (<1 mg/kg of body weight) was shown in murine and rat models of bacteremia. The contribution of the bactericidal and anti-inflammatory effects was dissected in the mouse bacteremia model through depletion of complement with cobra venom factor (CVF). Protective efficacy was lost in complement-depleted mice, suggesting the essential role of complement-mediated activities for protection in this model. These data suggest that A1124 exhibits different mechanisms of action, namely, direct complement-mediated and opsonophagocytic killing as well as endotoxin neutralization in various challenge models. Which of these activities are the most relevant in a clinical setting will need to be addressed by future translational studies.
Structure and Dynamics of FosA-Mediated Fosfomycin Resistance in Klebsiella pneumoniae and Escherichia coli
Authors: Klontz Erik H. , Tomich Adam D. , Günther Sebastian , Lemkul Justin A. , Deredge Daniel , Silverstein Zach , Shaw JoAnna F. , McElheny Christi , Doi Yohei , Wintrode Patrick L. , MacKerell Alexander D. , Sluis-Cremer Nicolas , Sundberg Eric J.
Published: September 2017

Fosfomycin exhibits broad-spectrum antibacterial activity and is being reevaluated for the treatment of extensively drug-resistant pathogens. Its activity in Gram-negative organisms, however, can be compromised by expression of FosA, a metal-dependent transferase that catalyzes the conjugation of glutathione to fosfomycin, rendering the antibiotic inactive. In this study, we solved the crystal structures of two of the most clinically relevant FosA enzymes: plasmid-encoded FosA3 fromEscherichia coliand chromosomally encoded FosA fromKlebsiella pneumoniae(FosAKP). The structure, molecular dynamics, catalytic activity, and fosfomycin resistance of FosA3 and FosAKPwere also compared to those of FosA fromPseudomonas aeruginosa(FosAPA), for which prior crystal structures exist.E. coliTOP10 transformants expressing FosA3 and FosAKPconferred significantly greater fosfomycin resistance (MIC, >1,024 μg/ml) than those expressing FosAPA(MIC, 16 μg/ml), which could be explained in part by the higher catalytic efficiencies of the FosA3 and FosAKPenzymes. Interestingly, these differences in enzyme activity could not be attributed to structural differences at their active sites. Instead, molecular dynamics simulations and hydrogen-deuterium exchange experiments with FosAKPrevealed dynamic interconnectivity between its active sites and a loop structure that extends from the active site of each monomer and traverses the dimer interface. This dimer interface loop is longer and more extended in FosAKPand FosA3 than in FosAPA, and kinetic analyses of FosAKPand FosAPAloop-swapped chimeric enzymes highlighted its importance in FosA activity. Collectively, these data yield novel insights into fosfomycin resistance that could be leveraged to develop new strategies to inhibit FosA and potentiate fosfomycin activity.
An Evolutionarily Conserved Pathway Essential for Orsay Virus Infection of
Caenorhabditis elegans
Authors: Jiang Hongbing , Chen Kevin , Sandoval Luis E. , Leung Christian , Wang David
Published: September 2017

Many fundamental biological discoveries have been made in
Caenorhabditis elegans
. The discovery of Orsay virus has enabled studies of host-virus interactions in this model organism. To identify host factors critical for Orsay virus infection, we designed a forward genetic screen that utilizes a virally induced green fluorescent protein (GFP) reporter. Following chemical mutagenesis, two Viro (
v
irus
i
nduced
r
eporter
o
ff) mutants that failed to express GFP were mapped to
sid-3
, a nonreceptor tyrosine kinase, and B0280.13 (renamed
viro-2
), an ortholog of human Wiskott-Aldrich syndrome protein (WASP). Both mutants yielded Orsay virus RNA levels comparable to that of the residual input virus, suggesting that they are not permissive for Orsay virus replication. In addition, we demonstrated that both genes affect an early prereplication stage of Orsay virus infection. Furthermore, it is known that the human ortholog of SID-3, activated CDC42-associated kinase (ACK1/TNK2), is capable of phosphorylating human WASP, suggesting that VIRO-2 may be a substrate for SID-3 in
C. elegans
. A targeted RNA interference (RNAi) knockdown screen further identified the
C. elegans
gene
nck-1
, which has a human ortholog that interacts with TNK2 and WASP, as required for Orsay virus infection. Thus, genetic screening in
C. elegans
identified critical roles in virus infection for evolutionarily conserved genes in a known human pathway.

IMPORTANCE
Orsay virus is the only known virus capable of naturally infecting the model organism
Caenorhabditis elegans
, which shares many evolutionarily conserved genes with humans. We exploited the robust genetic tractability of
C. elegans
to identify three host genes,
sid-3
,
viro-2
, and
nck-1
, which are essential for Orsay virus infection. Mutant animals that lack these three genes are highly defective in viral replication. Strikingly, the human orthologs of these three genes, activated CDC42-associated kinase (TNK2), Wiskott-Aldrich syndrome protein (WASP), and noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) are part of a known signaling pathway in mammals. These results suggest that TNK2, WASP, and NCK1 may play important roles in mammalian virus infection.
Parallel Evolution of Group B
Streptococcus
Hypervirulent Clonal Complex 17 Unveils New Pathoadaptive Mutations
Authors: Almeida Alexandre , Rosinski-Chupin Isabelle , Plainvert Céline , Douarre Pierre-Emmanuel , Borrego Maria J. , Poyart Claire , Glaser Philippe
Published: September 2017

The incidence of group B
Streptococcus
(GBS) neonatal disease continues to be a significant cause of concern worldwide. Strains belonging to clonal complex 17 (CC17) are the most frequently responsible for GBS infections in neonates, especially among late-onset disease cases. Therefore, we undertook the largest genomic study of GBS CC17 strains to date to decipher the genetic bases of their remarkable colonization and infection ability. We show that crucial functions involved in different steps of the colonization or infection process of GBS are distinctly mutated during the adaptation of CC17 to the human host. In particular, our results implicate the CovRS two-component regulator of virulence in the differentiation between carriage- and disease-associated isolates. Not only does this work raise important implications for the ongoing development of a vaccine against GBS but might also drive the discovery of key functions for GBS adaptation and pathogenesis that have been overlooked until now.
Therapeutic endoscopy-related GI bleeding and thromboembolic events in patients using warfarin or direct oral anticoagulants: results from a large nationwide database analysis
Authors: Nagata Naoyoshi , Yasunaga Hideo , Matsui Hiroki , Fushimi Kiyohide , Watanabe Kazuhiro , Akiyama Junichi , Uemura Naomi , Niikura Ryota
Published: September 2017

Objective

To compare the risks of postendoscopy outcomes associated with warfarin with direct oral anticoagulants (DOACs), taking into account heparin bridging and various types of endoscopic procedures.

Design

Using the Japanese Diagnosis Procedure Combination database, we identified 16 977 patients who underwent 13 types of high-risk endoscopic procedures and took preoperative warfarin or DOACs from 2014 to 2015. One-to-one propensity score matching was performed to compare postendoscopy GI bleeding and thromboembolism between the warfarin and DOAC groups.

Results

In the propensity score-matched analysis involving 5046 pairs, the warfarin group had a significantly higher proportion of GI bleeding than the DOAC group (12.0% vs 9.9%; p=0.002). No significant difference was observed in thromboembolism (5.4% vs 4.7%) or in-hospital mortality (5.4% vs 4.7%). The risks of GI bleeding and thromboembolism were greater in patients treated with warfarin plus heparin bridging or DOACs plus bridging than in patients treated with DOACs alone. Compared with percutaneous endoscopic gastrostomy, patients who underwent endoscopic submucosal dissection, endoscopic mucosal resection and haemostatic procedures including endoscopic variceal ligation or endoscopic injection sclerotherapy were at the highest risk of GI bleeding among the 13 types of endoscopic procedures, whereas those who underwent lower polypectomy endoscopic sphincterotomy or endoscopic ultrasound-guided fine needle aspiration were at moderate risk.

Conclusion

The risk of postendoscopy GI bleeding was higher in warfarin than DOAC users. Heparin bridging was associated with an increased risk of bleeding and did not prevent thromboembolism. The bleeding risk varied by the type of endoscopic procedure.
The study of the structure stability of hexagonal Bi(PO4)(H2O)0.67 under high pressure
Authors: Zhang Jun , Yuan Zhen , Zhao Jian-Fa , Li Wen-Min , Jia Ya-Ting , Liu Ying , Deng Zheng , Zhang Si-Jia , Feng Shao-Min , Liu Qing-Qing , Wang Xian-Cheng , Jin Chang-Qin
Published: September 2017

In this work, the structure stability of hexagonal Bi(PO[Formula: see text](H2O)[Formula: see text] has been investigated by high-pressure synchrotron X-ray diffraction measurements. The results show that the structure is stable within the pressure up to 18.3 GPa. The diffraction data are refined and the lattice constants [Formula: see text] and [Formula: see text] are determined, which is compressed by 6.3(7)% and 3.5(0)% within the experimental pressure, respectively. By fitting the pressure dependence of [Formula: see text] (unit cell volume divided by that at ambient pressure) with the second-order Birch equation of state, the bulk modulus [Formula: see text] is given to be about 87.1(0) GPa.
Design and modeling of an SJ infrared solar cell approaching upper limit of theoretical efficiency
Authors: Sahoo G. S. , Mishra G. P.
Published: September 2017

Recent trends of photovoltaics account for the conversion efficiency limit making them more cost effective. To achieve this we have to leave the golden era of silicon cell and make a path towards III–V compound semiconductor groups to take advantages like bandgap engineering by alloying these compounds. In this work we have used a low bandgap GaSb material and designed a single junction (SJ) cell with a conversion efficiency of 32.98%. SILVACO ATLAS TCAD simulator has been used to simulate the proposed model using both Ray Tracing and Transfer Matrix Method (under 1 sun and 1000 sun of AM1.5G spectrum). A detailed analyses of photogeneration rate, spectral response, potential developed, external quantum efficiency (EQE), internal quantum efficiency (IQE), short-circuit current density (J[Formula: see text]), open-circuit voltage (V[Formula: see text]), fill factor (FF) and conversion efficiency ([Formula: see text]) are discussed. The obtained results are compared with previously reported SJ solar cell reports.