bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Characterization of β‐Diketiminate Aluminum Compounds and Their Use in the Ring‐Opening Polymerization of ε‐Caprolactone
Authors: Ma Xiaoli , Yao Miaomiao , Zhong Mingdong , Deng Ziyan , Li Wenling , Yang Zhi , Roesky Herbert W.
Published: December 2016

Four aluminum alkyl compounds, [CH{(CH3)CN‐2,4,6‐MeC6H2}2AlMe2] (1), [CH{(CH3)CN‐2,4,6‐MeC6H2}2AlEt2] (2), [CH{(CH3)CN‐2‐iPrC6H4}2AlMe2] (3), and [CH{(CH3)CN‐2‐iPrC6H4}2AlEt2] (4), bearing β‐diketiminate ligands [CH{(Me)CN‐2,4,6‐MeC6H2}]2 (L1H) and [CH{(Me)CN‐2‐iPrC6H4}]2 (L2H) were obtained from the reactions of trimethylaluminum, triethylaluminum with the corresponding β‐diketiminate, respectively. All compounds were characterized by 1H NMR and 13C NMR spectroscopy, single‐crystal X‐ray structural analysis, and elemental analysis. Compounds 1–4 were found to catalyze the ring‐opening polymerization (ROP) of ε‐caprolactone (ε‐CL) with good activity.
Nonlinear Beltrami operators, Schauder estimates and bounds for the Jacobian
Authors: Jääskeläinen Jarmo , Koski Aleksis , Astala Kari , Clop Albert , Faraco Daniel
Published: December 2016

We provide Schauder estimates for nonlinear Beltrami equations and lower bounds of the Jacobians for homeomorphic solutions. The results were announced in [1] but here we give detailed proofs.
The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement
Authors: Weiner Michael W. , Veitch Dallas P. , Aisen Paul S. , Beckett Laurel A. , Cairns Nigel J. , Green Robert C. , Harvey Danielle , Jack Clifford R. , Jagust William , Morris John C. , Petersen Ronald C. , Salazar Jennifer , Saykin Andrew J. , Shaw Leslie M. , Toga Arthur W. , Trojanowski John Q. ,   Alzheimer's Disease Neuroimaging Initiative
Published: December 2016

Introduction

The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI‐3, which began on August 1, 2016, is a 5‐year renewal of the current ADNI‐2 study.

Methods

ADNI‐3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition.

Results

Multimodal analyses will provide insight into AD pathophysiology and disease progression.

Discussion

ADNI‐3 will aim to inform AD treatment trials and facilitate development of AD disease‐modifying treatments.
Efficacy of ranolazine in preventing atrial fibrillation following cardiac surgery: Results from a meta‐analysis
Authors: Trivedi Chintan , Upadhyay Ankit , Solanki Kinjal
Published: December 2016

Background

Atrial fibrillation (AF) is a common complication after cardiac surgery. Ranolazine is a Food and Drug Administration approved anti‐ischemic drug, which also has anti‐arrhythmic properties. Recent studies have demonstrated the benefit of ranolazine in preventing post‐operative AF (POAF) in patients undergoing cardiac surgery. Hence, we performed a meta‐analysis of published studies comparing ranolazine plus standard therapy versus standard therapy for POAF prevention in patients undergoing cardiac surgery.

Methods

We performed a comprehensive search of Medline, Google Scholar, PubMed, abstracts from annual scientific sessions, and Cochrane library database for studies that assessed the effectiveness of ranolazine plus standard therapy by comparing it with standard therapy alone in preventing POAF in patients undergoing cardiac surgery. From all the studies, data on POAF events among groups were collected, and the random‐effects (DerSimonian and Laird) method was used for meta‐analysis.

Results

Four studies with 663 patients were included in the final analysis, with 300 and 363 patients in the ranolazine plus standard therapy and standard therapy groups, respectively. The types of cardiac surgeries were coronary artery bypass grafting (CABG), valve surgery or combination of CABG, and valve surgeries. After pooled analysis, ranolazine plus standard therapy was associated with a significant reduction in POAF events compared to standard therapy alone (risk ratio=0.44 [0.25, 0.78], p‐value=0.005). There was no difference in adverse events between the two therapies. However, in one study, more patients in the ranolazine group had transient symptomatic hypotension after the surgery.

Conclusions

Ranolazine may prove beneficial in POAF prevention following cardiac surgeries. Although the pooled treatment effect is quite impressive with a reduction of more than 50% of risk of developing POAF, small number of studies and variation in ranolazine dose regimen in each study make our results inconclusive, but worthy of further investigation. That is why this result has to be interpreted as only hypothesis generating, rather than conclusion drawing.
Mechanism of Death after Decompressive Craniectomy in Non-Traumatic Brain Injury
Authors: Trickey Kimberley , Hornby Laura , Shemie Sam D. , Teitelbaum Jeanne
Published: December 2016

Decompressive craniectomy (DC) after devastating brain injury (DBI) may influence the manner in which patients die, having implications for end-of-life care and organ donation. We performed a retrospective review of deaths following a non-traumatic DBI between 2008 and 2012. 160 patients were reviewed; 26 were treated with DC and 134 received standard care. There was no relationship between DC and mechanism of death, (OR 1.18, 95% CI 0.44-3.17). Prospective studies are required to confirm these preliminary finding. DC studies should report the mechanism of death.
PARENTAL MORBIDITY, CHILD WORK, AND HEALTH INSURANCE IN RWANDA
Authors: Woode Maame Esi , Bousmah Marwân-al-Qays , Boucekkine Raouf
Published: December 2016

Measuring direct and indirect effects of extending health insurance coverage in developing countries is a key issue for health system development and for attaining universal health coverage. This paper investigates the role played by health insurance in the relationship between parental morbidity and child work decisions. We use a propensity score matching technique combined with hurdle models, using data from Rwanda. The results show that parental health shocks have a substantial influence on child work when households do not have health insurance. Depending on the gender of the sick parent, there is a substitution effect not only between the parent and the child on the labor market, but also between the time the child spends on different work activities. Altogether, results reveal that health insurance protects children against child work in the presence of parental health shocks.
Top 1% of Inpatients Administered Antimicrobial Agents Comprising 50% of Expenditures: A Descriptive Study and Opportunities for Stewardship Intervention
Authors: Dela-Pena Jennifer , Kerstenetzky Luiza , Schulz Lucas , Kendall Ron , Lepak Alexander , Fox Barry
Published: December 2016

OBJECTIVE

To characterize the top 1% of inpatients who contributed to the 6-month antimicrobial budget in a tertiary, academic medical center and identify cost-effective intervention opportunities targeting high-cost antimicrobial utilization.

DESIGN

Retrospective cohort study.

PATIENTS

Top 1% of the antimicrobial budget from July 1 through December 31, 2014.

METHODS

Patients were identified through a pharmacy billing database. Baseline characteristics were collected through a retrospective medical chart review. Patients were presented to the antimicrobial stewardship team to determine appropriate utilization of high-cost antimicrobials and potential intervention opportunities. Appropriate use was defined as antimicrobial therapy that was effective, safe, and most cost-effective compared with alternative agents.

RESULTS

A total of 10,460 patients received antimicrobials in 6 months; 106 patients accounted for $889,543 (47.2%) of the antimicrobial budget with an antimicrobial cost per day of $219±$192 and antimicrobial cost per admission of $4,733±$7,614. Most patients were immunocompromised (75%) and were followed by the infectious disease consult service (80%). The most commonly prescribed antimicrobials for treatment were daptomycin, micafungin, liposomal amphotericin B, and meropenem. Posaconazole and valganciclovir accounted for most of the prophylactic therapy. Cost-effective opportunities (n=71) were present in 57 (54%) of 106 patients, which included dose optimization, de-escalation, dosage form conversion, and improvement in transitions of care.

CONCLUSION

Antimicrobial stewardship oversight is important in implementing cost-effective strategies, especially in complex and immunocompromised patients who require the use of high-cost antimicrobials.

Infect Control Hosp Epidemiol 2017;38:259–265
Evaluation of an Ethanol-Based Spray Disinfectant for Decontamination of Cover Gowns Prior to Removal
Authors: Koganti Sreelatha , Alhmidi Heba , Tomas Myreen E. , Cadnum Jennifer L. , Sass Christopher , Jencson Annette L. , Donskey Curtis J.
Published: December 2016

An ethanol-based spray disinfectant significantly reduced bacteriophage MS2 contamination on material from gowns meeting ASTM standard 1671 for resistance to blood and viral penetration and on a cover gown worn by personnel. Effectiveness of disinfection was affected by the type of gown material and the correctness of fit.

Infect Control Hosp Epidemiol 2017;38:364–366
MODELS OF TORSORS AND THE FUNDAMENTAL GROUP SCHEME
Authors: ANTEI MARCO , EMSALEM MICHEL
Published: December 2016

Given a relative faithfully flat pointed scheme over the spectrum of a discrete valuation ring$X\rightarrow S$, this paper is motivated by the study of the natural morphism from the fundamental group scheme of the generic fiber$X_{\unicode[STIX]{x1D702}}$to the generic fiber of the fundamental group scheme of$X$. Given a torsor$T\rightarrow X_{\unicode[STIX]{x1D702}}$under an affine group scheme$G$over the generic fiber of$X$, we address the question of finding a model of this torsor over$X$, focusing in particular on the case where$G$is finite. We provide several answers to this question, showing for instance that, when$X$is integral and regular of relative dimension 1, such a model exists on some model$X^{\prime }$of$X_{\unicode[STIX]{x1D702}}$obtained by performing a finite number of Néron blowups along a closed subset of the special fiber of$X$. Furthermore, we show that when$G$is étale, then we can find a model of$T\rightarrow X_{\unicode[STIX]{x1D702}}$under the action of some smooth group scheme. In the first part of the paper, we show that the relative fundamental group scheme of$X$has an interpretation as the Tannaka Galois group of a Tannakian category constructed starting from the universal torsor.
Comparingcal3and other a posteriori time-scaling approaches in a case study with the pterocephaliid trilobites
Authors: Bapst David W. , Hopkins Melanie J.
Published: December 2016

Reconstructing the tree of life involves more than identifying relationships among lineages; it also entails accurately estimating when lineages diverged. Paleontologists typically scale cladograms to time a posteriori by direct reference to first appearances of taxa in the stratigraphic record. Some approaches use probabilistic models of branching, extinction, and sampling processes to date samples of trees, such as the recently developedcal3method, which stochastically draws divergence dates given a set of rates for those processes. However, these models require estimates of the rates of those processes, which may be hard to obtain, particularly for sampling. Here, we contrast the use ofcal3and other a posteriori time-scaling approaches by examining a previous study that documented a decelerating rate of morphological evolution in pterocephaliid trilobites. Although aspects of the data set make estimation of branching, extinction, and sampling rates difficult, we use a multifaceted approach to calculate and evaluate the rate estimates needed for applyingcal3. In agreement with previous simulation studies, we find that the choice of phylogenetic dating method impacts downstream macroevolutionary conclusions. We also find contradictory evolutionary inferences between analyses on ancestor–descendant contrasts (based on ancestor trait reconstruction methods) and maximum-likelihood parameter estimates. Ancestral taxon inference incal3corroborates previously hypothesized ancestor–descendant sequences, butcal3suggests greater support for budding cladogenesis than anagenesis. This case study demonstrates the potential and wide applicability of thecal3method and the benefits afforded by choosingcal3over simpler a posteriori time-scaling approaches.
The Language of Economic Growth:A New Measure of Linguistic Heterogeneity
Authors: Liu Amy H. , Pizzi Elise
Published: December 2016

Conventional wisdom holds that languages, as ethnic markers, build communities with shared preferences and strong social networks. Consequently, ethnolinguistic homogeneity can facilitate growth. This article challenges this conception of language as a cultural marker. It argues that language is also a practical vehicle of communication; people can be multilingual, and second languages can be learned. Hence language boundaries are neither (1) congruent with ethnic boundaries nor (2) static. If true, the purported advantages of ethnolinguistic homogeneity should also be evident in countries with large populations of non-native speakers conversant in official languages. The study tests this hypothesis using an original cross-national and time-variant measure that captures both mother-tongue speakers and second-language learners. The empirical results are consistent with the understanding of language as an efficiency-enhancing instrument: countries with exogenously high levels of heterogeneity can avoid the ‘growth tragedy’1by endogenously teaching the official language in schools.
Labor Union Strength and the Equality of Political Representation
Authors: Flavin Patrick
Published: December 2016

Amid growing evidence of ‘unequal democracy’ in the United States, labor unions can play a potentially important role by ensuring that low-income citizens’ opinions receive more equal consideration when elected officials make policy decisions. To investigate this possibility, this article evaluates the relationship between labor union strength and representational equality across states and finds evidence that states with higher levels of union membership weigh citizens’ opinions more equally in the policy-making process. In contrast, there is no relationship between the volume of labor union contributions to political campaigns in a state and the equality of its political representation. These findings suggest that labor unions promote greater political equality primarily by mobilizing their working-class members to political action and, more broadly, underscore the important role that organized labor continues to play in shaping the distribution of political power across American society.
Historical Polarization and Representation in South American Party Systems, 1900–1990
Authors: Bornschier Simon
Published: December 2016

Although ideological polarization can create problems for governability and democratic stability, this article argues that it also has beneficial effects in new democracies. By clarifying the political alternatives, polarization creates strong links between parties and voters, and thereby instills accountability mechanisms that force parties to remain responsive to evolving voter preferences. A comparative historical analysis of six South American cases demonstrates that the vast differences in the quality of representation in the 1980s, immediately after many countries in the region returned to democracy, were rooted in an early bifurcation of party systems in the first half of the twentieth century: while prolonged periods of ideological conflict occurred in some countries during this period, polarization was aborted by various means in others. By showing that ideological moderation may help formal democracies survive, but that aborting conflict in the long run severely hampers key aspects of the quality of democracy, this study suggests a revision of conventional views regarding ideological polarization.
Preference Representation and the Influence of Political Parties in Majoritarian vs. Proportional Systems: An Empirical Test
Authors: Stadelmann David , Portmann Marco , Eichenberger Reiner
Published: December 2016

Electoral systems determine the role that representatives’ party affiliations play in political representation. According to conventional expectations, party affiliation drives the behavior of representatives when they are elected under a proportional system, while majoritarian systems mute the role of party affiliation by forcing politicians to converge to the median position of their constituency. This study directly tests these predictions within a common party system by matching referenda decisions of constituents with voting behavior of their representatives who are elected either under a majoritarian or proportional system.
Workplace Health and Gender among Cotton Workers in America and Britain, c.1880s–1940s
Authors: Greenlees Janet
Published: December 2016

This article clarifies the differences between occupational health and workplace health and reveals how the two overlap. It unravels a multi-layered narrative about cotton textile workers’ understandings and experiences of ill-health at work in America and Britain, utilizing a combination of oral histories, government documents, company and union records, and the trade press. It aims to identify the multiple influences on contemporary debates about health at work. Contrary to current historiography, I argue that gender was only occasionally important to such discussions among workers, and that gender did not significantly influence their responses to unhealthy conditions. Workers’ understandings of, and responses to, workplace hazards were individual and related to knowledge about risk, ill-health and socioeconomic factors. American and British workers’ understandings of and responses to their working environment reveals more convergence than divergence, suggesting a universal human response to the health risks of work that is not significantly influenced by national or industrial constraints, or by gender.
Insertion of a tracheoesophageal speech valve: a novel approach in a difficult situation
Authors: Yiannakis C P , Townsley R B , Smillie I G , Picozzi G L
Published: December 2016

Background:

Functional voice rehabilitation is becoming increasingly important following total laryngectomy and pharyngolaryngectomy. Tracheoesophageal voice via a shunt valve is currently regarded as the ‘gold standard’ for voice rehabilitation. Traditional techniques usually allow for the replacement of valves in the out-patient setting; however, patient factors such as altered anatomy may occasionally prevent this.

Objective:

This paper describes a novel approach for speech valve insertion that is safe, quick and cost-effective, and which uses equipment commonly available in ENT wards and the operating theatre.
Rising incidence of head and neck mucosal melanoma in Australia
Authors: Youssef D , Vasani S , Marquess J , Cervin A
Published: December 2016

Objective:

To establish Australian population-based incidence trends for mucosal melanoma of the head and neck.

Methods:

Cases between 1985 and 2009 were identified in the Australian Cancer Database. Age-standardised incidence trends were established, including subgroup stratification by sex and site.

Results:

A continuously progressive increase in incidence was evident in the 353 cases identified over the 25-year study period. This was particularly evident in sinonasal mucosal melanoma in men, despite the overall incidence remaining higher in women.

Conclusion:

There is such paucity in published global incidence trends of head and neck mucosal melanoma. Comparisons of incidence patterns between countries can provide insight into aetiological factors of this rare disease.
Penetrating neck trauma and the need for surgical exploration: six-year experience within a regional trauma centre
Authors: Kasbekar A V , Combellack E J , Derbyshire S G , Swift A C
Published: December 2016

Background:

There has been a shift towards conservative management of penetrating neck trauma in selected patients.

Methods:

A retrospective case note review of the management of penetrating neck trauma (2007–2013) was undertaken at our large teaching hospital and compared against best-evidenced practice.

Results:

Sixty-three patients were admitted over six years. The incidence of penetrating neck trauma is reducing, contrary to our belief. Most cases were knife inflicted (33 out of 63), and of these most were attempted suicide. There was a high rate of negative findings for neck explorations under general anaesthesia (18 out of 22). Only nine cases had justification for general anaesthesia exploration according to best practice.

Conclusion:

The rate of neck explorations under general anaesthesia has dramatically fallen, in line with best practice. The need for operative intervention in patients with penetration of the aerodigestive tract or a major vascular injury should be based on clinical features, and these have been shown to be reliable indicators prior to open exploration.
A paired comparison analysis of third-party rater thyroidectomy scar preference
Authors: Rajakumar C , Doyle P C , Brandt M G , Moore C C , Nichols A , Franklin J H , Yoo J , Fung K
Published: December 2016

Objective:

To determine the length and position of a thyroidectomy scar that is cosmetically most appealing to naïve raters.

Methods:

Images of thyroidectomy scars were reproduced on male and female necks using digital imaging software. Surgical variables studied were scar position and length. Fifteen raters were presented with 56 scar pairings and asked to identify which was preferred cosmetically. Twenty duplicate pairings were included to assess rater reliability. Analysis of variance was used to determine preference.

Results:

Raters preferred low, short scars, followed by high, short scars, with long scars in either position being less desirable (p < 0.05). Twelve of 15 raters had acceptable intra-rater and inter-rater reliability.

Conclusion:

Naïve raters preferred low, short scars over the alternatives. High, short scars were the next most favourably rated. If other factors influencing incision choice are considered equal, surgeons should consider these preferences in scar position and length when planning their thyroidectomy approach.
Efficacy of steroidal vs non-steroidal agents in oral lichen planus: a randomised, open-label study
Authors: Singh A R , Rai A , Aftab M , Jain S , Singh M
Published: December 2016

Objective:

This study compared the therapeutic efficacy of steroidal and non-steroidal agents for treating oral lichen planus.

Methods:

Forty patients with clinical and/or histologically proven oral lichen planus were randomly placed into four groups and treated with topical triamcinolone, oral dapsone, topical tacrolimus or topical retinoid for three months. Pre- and post-treatment symptoms and signs were scored for each patient.

Results:

Patients in all treatment groups showed significant clinical improvement after three months (p < 0.05), with steroidal and non-steroidal agents having equal efficacy. Furthermore, of the non-steroidal drugs, oral dapsone had greater efficacy than topical retinoid (p < 0.05). However, no significant differences in outcome were recorded for oral dapsone vs topical tacrolimus (p > 0.05) and for topical retinoid vs topical tacrolimus (p > 0.05).

Conclusion:

Non-steroidal drugs such as dapsone, tacrolimus and retinoid are as efficacious as steroidal drugs for treating oral lichen planus, and avoid the side effects associated with steroids.
Sugars and health: a review of current evidence and future policy
Authors: Evans Charlotte Elizabeth Louise
Published: December 2016

The automation of the process of extracting sugars in the 1900s reduced cost and increased availability of sugars leading to a dramatic rise in consumption, which reached a peak in the 1970s. There are different definitions for sugars not naturally available in foods, and free sugars is the term used by WHO. The epidemiological evidence of the associations between sugars and obesity and type 2 diabetes mellitus is fairly strong and consistent, particularly for sugar sweetened drinks in adults. The Department of Health in the UK and many other countries have recently updated their recommendations for free sugars as a result of this scientific evidence. In the UK the recommended amount of free sugars is currently 5 % of energy (reduced from 10 %), which is difficult to meet and very different from current British dietary patterns. Reducing intakes of free sugars is a challenge and will necessitate a range of different actions and policies. Public Health England has put forward eight suggestions but the four most likely to improve dietary behaviour based on available evidence are social marketing, reduction of marketing of high sugar foods and drinks to children, reformulation and reductions in portion size and a sugar excise tax. Any action taken needs to be evaluated to check inequalities are not widened. The new childhood obesity strategy has incorporated some but not all of these strategies and may not go far enough. It is likely that government policies alone will not be sufficient and a change in the food culture is necessary to see real progress.
Half-Earth or Whole Earth? Radical ideas for conservation, and their implications
Authors: Büscher Bram , Fletcher Robert , Brockington Dan , Sandbrook Chris , Adams William M. , Campbell Lisa , Corson Catherine , Dressler Wolfram , Duffy Rosaleen , Gray Noella , Holmes George , Kelly Alice , Lunstrum Elizabeth , Ramutsindela Maano , Shanker Kartik
Published: December 2016

We question whether the increasingly popular, radical idea of turning half the Earth into a network of protected areas is either feasible or just. We argue that this Half-Earth plan would have widespread negative consequences for human populations and would not meet its conservation objectives. It offers no agenda for managing biodiversity within a human half of Earth. We call instead for alternative radical action that is both more effective and more equitable, focused directly on the main drivers of biodiversity loss by shifting the global economy from its current foundation in growth while simultaneously redressing inequality.
Exploding wire energy absorption dynamics at slow current rates
Authors: Rodríguez Prieto G. , Bilbao L. , Milanese M.
Published: December 2016

Absorption of electrical energy provided to a metal wire in an exploding wire system is thought to be terminated or greatly diminished when the plasma is formed, after the joule heating of the metallic wire by the electrical current. Accordingly, it is common to account for the electrical energy delivered to the wire that the integration of current and voltage signals is halted when the voltage peak changes its slope. Usually, this moment is synchronized with the plasma appearance, as detected by optical sensors. In this work, experimental evidence of a two-step electrical energy absorption in an exploding wire surrounded by atmospheric air is presented. During the first step of the energy absorption the plasma is not formed, indicating that the delivered energy is not enough for ionizing the wire, giving place to a dark pause that lasts until a second energy absorption produces a plasma. The delay between the two steps can reach ≈2.2 µs for copper wires of 50 µm diameter charged at an initial voltage of 10 kV. Experimental investigation of variation of the delay between the two steps with different metals, charging voltages, and wire diameters are presented. A relation of the current density with the initial kinetic energy of the plasma and the electrical current rate is devised as a possible explanation of the observed phenomena.
BUDGET IMPACT ANALYSIS OF BELIMUMAB IN TREATING SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Pierotti Francesca , Palla Iaria , Pippo Lara , Lorenzoni Valentina , Turchetti Giuseppe
Published: December 2016

Objectives: The study evaluates the costs of systemic lupus erythematosus (SLE) and the budget impact due to the introduction of belimumab in the Italian setting.

Methods: Adaptation to the Italian setting of a budget impact model with a time horizon of 4 years (year 0 without belimumab, years 1–3 with belimumab) to compare treatment, administration, and clinical monitoring costs of standard therapy and of the alternative scenario in which belimumab is administered in addition to the standard therapy to the subgroup of patients selected according to the label approved by the European Medicines Agency. The model takes also into account the costs of flares.

Results: Over 3 years, belimumab is able to prevent cumulatively 1,111 severe flares and 3,631 nonsevere flares with a total saving for the Italian National Health System (NHS) of approximately €6.2 million. Budget impact ranges from €4.4 million in the first year to €20.3 million in the third year.

Conclusions: The decrease in the number of flare partially counterbalances the costs of the new technology (impact attenuation of approximately 16 percent). These data elucidate the importance to control and monitor the disease progression and to prevent exacerbations, which are the major causes of the increase in costs paid by the NHS and by the society. The financial impact could be replicate on a regional basis, to inform local decision makers. Further developments are possible as the model does not consider the additional clinical and economic benefits of reduced damage accrual and slowed disease progression.
The development of categorical perception of Mandarin tones in four- to seven-year-old children
Authors: CHEN FEI , PENG GANG , YAN NAN , WANG LAN
Published: December 2016

To track the course of development in children's fine-grained perception of Mandarin tones, the present study explored how categorical perception (CP) of Mandarin tones emerges along age among 70 four- to seven-year-old children and 16 adults. Prominent discrimination peaks were found for both the child and the adult groups, and they were well aligned with the corresponding identification crossovers. Moreover, six-year-olds showed a much narrower width (i.e. a sharper slope) compared to younger children, and have already acquired adult-like identification competence of Mandarin high-level and mid-rising tones. Although the ability to discriminate within-category tone pairs did not change, the between-category discrimination accuracies were positively correlated with chronological ages among child participants. We assume that the perceptual refinement of Mandarin tones in young children may be driven by an accumulation of perceptual development from the tonal information of the ambient sound input.
HBsAg may reappear following reactivation in individuals with spontaneous HBsAg seroclearance 8 years previously
Authors: CHEN Q. Y. , WANG X. Y. , HARRISON T. J. , HE X. , HU L. P. , LI K. W. , JIA H. H. , YANG Q. L. , WANG C. , FANG Z. L.
Published: December 2016

HBsAg reappearance may constitute not only a risk for liver disease but also an infectious source. We aimed to determine whether HBsAg may reappear after spontaneous HBsAg seroclearance. A cohort of 2999 HBsAg-positive subjects aged 30–55 years was recruited in Guangxi, China in 2004. HBsAg was tested every 6 months from July 2004 to June 2007, then, one more time in December 2013. The results showed that spontaneous HBsAg seroclearance occurred in 41 subjects in the first 3 years, giving a 0·54% annual seroclearance rate. Thirteen of the 41 subjects were randomly tested for HBsAg in 2013. Four subjects became HBsAg positive. S gene sequences of HBV were analysed from serum collected before seroclearance and after reappearance, respectively, for subject QS840 (11 and 12 clones), subject TN98 (13 and 13 clones) and subject WX227 (10 and 8 clones). Serotype, subgenotype and amino-acid substitution pattern in each sample collected after reappearance was observed in the sample collected before HBsAg seroclearance. Nucleotide similarity between the two sequences from each subject was >99% and five sequences from subject TN98 were the same. In conclusion, following reactivation, HBsAg may reappear in individuals with spontaneous HBsAg seroclearance many years previously.
The Other Shoe: Fragmentation in the Post-Medieval Home
Authors: Houlbrook Ceri
Published: December 2016

Deposits are not always recovered whole; many are found broken and damaged. The obvious explanation is that such objects were accidentally broken; however, some have been interpreted as having been deliberately damaged by their depositors, a practice termed ‘fragmentation’. Objects are broken into parts and deposited incomplete, often in ways that make their missing parts starkly evident. Thus many fragmented deposits denote synecdoche. It is the position of this paper that the absent (part) is just as integral to an understanding of the whole as the present (part) is, and this notion is explored by focusing on the post-medieval concealed shoe: an item of footwear that was fragmented by being deposited within the fabric of a building without its counterpart, for reasons unbeknownst to us. Drawing on a sample of 100 examples, this paper questions why such shoes were deposited as singles (the present parts), what became of the ‘other shoe’ (the absent part), and how such consideration aids our understanding of this enigmatic custom.
INFLATION EXPECTATIONS AND MONETARY POLICY DESIGN: EVIDENCE FROM THE LABORATORY
Authors: Pfajfar Damjan , Žakelj Blaž
Published: December 2016

Using laboratory experiments within a New Keynesian framework, we explore the interaction between the formation of inflation expectations and monetary policy design. The central question in this paper is how to design monetary policy when expectations formation is not perfectly rational. Instrumental rules that use actual rather than forecasted inflation produce lower inflation variability and reduce expectational cycles. A forward-looking Taylor rule where a reaction coefficient equals 4 produces lower inflation variability than rules with reaction coefficients of 1.5 and 1.35. Inflation variability produced with the latter two rules is not significantly different. Moreover, the forecasting rules chosen by subjects appear to vary systematically with the policy regime, with destabilizing mechanisms chosen more often when inflation control is weaker.
Clover green manure productivity and weed suppression in an organic grain rotation
Authors: Koehler-Cole Katja , Brandle James R. , Francis Charles A. , Shapiro Charles A. , Blankenship Erin E. , Baenziger P. Stephen
Published: December 2016

Green manure crops must produce high biomass to supply biological N, increase organic matter and control weeds. The objectives of our study were to assess above-ground biomass productivity and weed suppression of clover (Trifoliumspp.) green manures in an organic soybean [Glycine max(L.) Merr.]-winter wheat (Triticum aestivumL.)-corn (Zea maysL.) rotation in eastern Nebraska in three cycles (2011–12, 2012–13, 2013–14). Treatments were green manure species [red clover (T. pratenseL.) and white clover (T. repensL.)] undersown into winter wheat in March and green manure mowing regime (one late summer mowing or no mowing). We measured wheat productivity and grain protein at wheat harvest, and clover and weed above-ground biomass as dry matter (DM) at wheat harvest, 35 days after wheat harvest, in October and in April before clover termination. Winter wheat grain yields and grain protein were not affected by undersown clovers. DM was higher for red than for white clover at most sampling times. Red clover produced between 0.4 and 5.5 Mg ha−1in the fall and 0.4–5.2 Mg ha−1in the spring. White clover produced between 0.1 and 2.5 Mg ha−1in the fall and 0.2–3.1 Mg ha−1in the spring. Weed DM was lower under red clover than under white clover at most sampling times. In the spring, weed DM ranged from 0.0 to 0.6 Mg ha−1under red clover and from 0.0 to 3.1 Mg ha−1under white clover. Mowing did not consistently affect clover or weed DM. For organic growers in eastern Nebraska, red clover undersown into winter wheat can be a productive green manure with good weed suppression potential.
Government Procurement with Strings Attached: The Uneven Control of Offsets by the World Trade Organization and Regional Trade Agreements
Authors: COLLINS David
Published: December 2016

This paper explores the practice of governments imposing domestic content-based requirements known as “offsets” on suppliers in order to secure public procurement contracts. Known to cause distortions in international trade, offsets are forbidden under the WTO’s Government Procurement Agreement and in the procurement chapters of several RTAs, although these restrictions have severe limitations with full offset prohibitions only accepted by a handful of developed countries. Given the sensitivity of procurement policy and the need to stimulate local economies, Asian countries in particular show an unwillingness to address offsets in their international agreements. While other WTO agreements restrain the use of local content rules, these regimes are ill-suited to control the harmful effects of offsets in a procurement context because of their focus on traditional commercial markets. The paper suggests that an enlargement of offset prohibitions would be advisable given the expected expansion of global procurement markets commensurate with economic development.
Making Brains run Faster: are they Becoming Smarter?
Authors: Pahor Anja , Jaušovec Norbert
Published: December 2016

A brief overview of structural and functional brain characteristics related to g is presented in the light of major neurobiological theories of intelligence: Neural Efficiency, P-FIT and Multiple-Demand system. These theories provide a framework to discuss the main objective of the paper: what is the relationship between individual alpha frequency (IAF) and g? Three studies were conducted in order to investigate this relationship: two correlational studies and a third study in which we experimentally induced changes in IAF by means of transcranial alternating current stimulation (tACS). (1) In a large scale study (n = 417), no significant correlations between IAF and IQ were observed. However, in males IAF positively correlated with mental rotation and shape manipulation and with an attentional focus on detail. (2) The second study showed sex-specific correlations between IAF (obtained during task performance) and scope of attention in males and between IAF and reaction time in females. (3) In the third study, individuals’ IAF was increased with tACS. The induced changes in IAF had a disrupting effect on male performance on Raven’s matrices, whereas a mild positive effect was observed for females. Neuro-electric activity after verum tACS showed increased desynchronization in the upper alpha band and dissociation between fronto-parietal and right temporal brain areas during performance on Raven’s matrices. The results are discussed in the light of gender differences in brain structure and activity.
Genetic and Environmental Factors in Invasive Cervical Cancer: Design and Methods of a Classical Twin Study
Authors: Machalek Dorothy A. , Wark John D. , Tabrizi Sepehr N. , Hopper John L. , Bui Minh , Dite Gillian S. , Cornall Alyssa M. , Pitts Marian , Gertig Dorota , Erbas Bircan , Garland Suzanne M.
Published: December 2016

Background:Persistent high-risk human papillomavirus (HPV) infection is a necessary prerequisite for development of cervical cancer and its precursor lesion, high-grade squamous intraepithelial lesion (HSIL). However, HPV infection is not sufficient to drive this process, and genetic and environmental factors may also play a role.Methods/Design:The Cervical Cancer, Genetics and Environment Twin Study was established to investigate the environmental and genetic influences on variation in susceptibility to cervical pre-cancer in 25- to 69-year-old monozygotic (MZ) and dizygotic (DZ) twins recruited through the Australian Twin Registry. Reviews of Papanicolaou (Pap) screening histories were undertaken to identify individual women with a history of an abnormal Pap test. This was followed by detection of HPV in archival Pap smears of selected twin pairs to determine HPV persistence. Selected twin pairs also completed a detailed questionnaire on socio-demographic characteristics, sexual behavior, and HPV knowledge. In future analyses, under the assumptions of the classical twin design, case-wise concordance for persistent HPV infection and HSIL will be calculated for MZ and DZ twin pairs, and twin pairs (both MZ and DZ) who are discordant for the above outcomes will be used to assess the contributions of measured environmental risk factors.Discussion:The study examines factors related to HPV persistence and development of HSIL among female MZ and DZ twins. The results will contribute to our understanding of the natural history of cervical HPV infection and the relative contributions of genetic and environmental factors in disease progression.
Spatiotemporal control of interferon-induced JAK/STAT signalling and gene transcription by the retromer complex
Authors: Chmiest Daniela , Sharma Nanaocha , Zanin Natacha , Viaris de Lesegno Christine , Shafaq-Zadah Massiullah , Sibut Vonick , Dingli Florent , Hupé Philippe , Wilmes Stephan , Piehler Jacob , Loew Damarys , Johannes Ludger , Schreiber Gideon , Lamaze Christophe
Published: December 2016

Type-I interferons (IFNs) play a key role in the immune defences against viral and bacterial infections, and in cancer immunosurveillance. We have established that clathrin-dependent endocytosis of the type-I interferon (IFN-α/β) receptor (IFNAR) is required for JAK/STAT signalling. Here we show that the internalized IFNAR1 and IFNAR2 subunits of the IFNAR complex are differentially sorted by the retromer at the early endosome. Binding of the retromer VPS35 subunit to IFNAR2 results in IFNAR2 recycling to the plasma membrane, whereas IFNAR1 is sorted to the lysosome for degradation. Depletion of VPS35 leads to abnormally prolonged residency and association of the IFNAR subunits at the early endosome, resulting in increased activation of STAT1- and IFN-dependent gene transcription. These experimental data establish the retromer complex as a key spatiotemporal regulator of IFNAR endosomal sorting and a new factor in type-I IFN-induced JAK/STAT signalling and gene transcription.
Actin activates Pseudomonas aeruginosa ExoY nucleotidyl cyclase toxin and ExoY-like effector domains from MARTX toxins
Authors: Belyy Alexander , Raoux-Barbot Dorothée , Saveanu Cosmin , Namane Abdelkader , Ogryzko Vasily , Worpenberg Lina , David Violaine , Henriot Veronique , Fellous Souad , Merrifield Christien , Assayag Elodie , Ladant Daniel , Renault Louis , Mechold Undine
Published: December 2016

The nucleotidyl cyclase toxin ExoY is one of the virulence factors injected by the Pseudomonas aeruginosa type III secretion system into host cells. Inside cells, it is activated by an unknown eukaryotic cofactor to synthesize various cyclic nucleotide monophosphates. ExoY-like adenylate cyclases are also found in Multifunctional-Autoprocessing Repeats-in-ToXin (MARTX) toxins produced by various Gram-negative pathogens. Here we demonstrate that filamentous actin (F-actin) is the hitherto unknown cofactor of ExoY. Association with F-actin stimulates ExoY activity more than 10,000 fold in vitro and results in stabilization of actin filaments. ExoY is recruited to actin filaments in transfected cells and alters F-actin turnover. Actin also activates an ExoY-like adenylate cyclase MARTX effector domain from Vibrio nigripulchritudo. Finally, using a yeast genetic screen, we identify actin mutants that no longer activate ExoY. Our results thus reveal a new sub-group within the class II adenylyl cyclase family, namely actin-activated nucleotidyl cyclase (AA-NC) toxins.
Jagged 1 is a major Notch ligand along cholangiocarcinoma development in mice and humans
Authors: Che L , Fan B , Pilo M G , Xu Z , Liu Y , Cigliano A , Cossu A , Palmieri G , Pascale R M , Porcu A , Vidili G , Serra M , Dombrowski F , Ribback S , Calvisi D F , Chen X
Published: December 2016

Intrahepatic cholangiocarcinoma (ICC) is a rare yet deadly malignancy with limited treatment options. Activation of the Notch signalling cascade has been implicated in cholangiocarcinogenesis. However, while several studies focused on the Notch receptors required for ICC development, little is known about the upstream inducers responsible for their activation. Here, we show that the Jagged 1 (Jag1) ligand is almost ubiquitously upregulated in human ICC samples when compared with corresponding non-tumorous counterparts. Furthermore, we found that while overexpression of Jag1 alone does not lead to liver tumour development, overexpression of Jag1 synergizes with activated AKT signalling to promote liver carcinogenesis in AKT/Jag1 mice. Histologically, tumours consisted exclusively of ICC, with hepatocellular tumours not occurring in AKT/Jag1 mice. Furthermore, tumours from AKT/Jag1 mice exhibited extensive desmoplastic reaction, an important feature of human ICC. At the molecular level, we found that both AKT/mTOR and Notch cascades are activated in AKT/Jag1 ICC tissues, and that the Notch signalling is necessary for ICC development in AKT/Jag1 mice. In human ICC cell lines, silencing of Jag1 via specific small interfering RNA reduces proliferation and increases apoptosis. Finally, combined inhibition of AKT and Notch pathways is highly detrimental for the in vitro growth of ICC cell lines. In summary, our study demonstrates that Jag1 is an important upstream inducer of the Notch signalling in human and mouse ICC. Targeting Jag1 might represent a novel therapeutic strategy for the treatment of this deadly disease.
Hepatocarcinogenesis in transgenic mice carrying hepatitis B virus pre-S/S gene with the sW172* mutation
Authors: Lai M-W , Liang K-H , Lin W-R , Huang Y-H , Huang S-F , Chen T-C , Yeh C-T
Published: December 2016

Hepatitis B virus (HBV) carrying the rtA181T/sW172* mutation conferred cross-resistance to adefovir and lamivudine. Cell-based and clinical studies indicated that HBV carrying this mutation had an increased oncogenic potential. Herein, we created transgenic mouse models to study the oncogenicity of the HBV pre-S/S gene containing this mutation. Transgenic mice were generated by transfer of the HBV pre-S/S gene together with its own promoter into C57B6 mice. Four lines of mice were created. Two of them carried wild-type gene and produced high and low levels of HBV surface antigen (HBsAg) (TgWT-H and L). The other two carried the sW172* mutation with high and low intrahepatic expression levels (TgSW172*-H and L). When sacrificed 18 months after birth, none of the TgWT mice developed hepatocellular carcinoma (HCC), whereas 6/26 (23.1%) TgSW172*-H and 2/24 (8.3%) TgSW172*-L mice developed HCC (TgWT vs TgSW172*; P=0.0021). Molecular analysis of liver tissues revealed significantly increased expression of glucose-regulated protein 78 and phosphorylated extracellular signal-regulated kinases 1 in TgSW172* mice, and decreased expression of B-cell lymphoma-extra large in TgSW172*-H mice. Higher proportion of apoptotic cells was found in TgSW172*-H mice, accompanied by increased cyclin E levels, suggesting increased hepatocyte turnover. Combined analysis of complimentary DNA microarray and microRNA array identified microRNA-873-mediated reduced expression of the CUB and Sushi multiple domains 3 (CSMD3) protein, a putative tumor suppressor, in TgSW172* mice. Our transgenic mice experiments confirmed that HBV pre-S/S gene carrying the sW172* mutation had an increased oncogenic potential. Increased endoplasmic reticulum stress response, more rapid hepatocyte turnover and decreased CSMD3 expression contributed to the hepatocarcinogenesis.