bluuebunny/crossref_metadata_2025 huggingface dataset:
“Transcriptomics”: molecular diagnosis of inborn errors of metabolism via RNA‐sequencing
Authors: Kremer Laura S. , Wortmann Saskia B. , Prokisch Holger
Published: January 2018

Exome wide sequencing techniques have revolutionized molecular diagnostics in patients with suspected inborn errors of metabolism or neuromuscular disorders. However, the diagnostic yield of 25–60% still leaves a large fraction of individuals without a diagnosis. This indicates a causative role for non‐exonic regulatory variants not covered by whole exome sequencing. Here we review how systematic RNA‐sequencing analysis (RNA‐seq, “transcriptomics”) lead to a molecular diagnosis in 10–35% of patients in whom whole exome sequencing failed to do so. Importantly, RNA‐sequencing based discoveries cannot only guide molecular diagnosis but might also unravel therapeutic intervention points such as antisense oligonucleotide treatment for splicing defects as recently reported for spinal muscular atrophy.
Association of Low Bone Mineral Density with Anti-Citrullinated Protein Antibody Positivity and Disease Activity in Established Rheumatoid Arthritis: Findings from a US Observational Cohort
Authors: Ahmad Harris A. , Alemao Evo , Guo Zhenchao , Iannaccone Christine K. , Frits Michelle L. , Weinblatt Michael , Shadick Nancy A.
Published: January 2018

Introduction

To assess the relationship between low bone mineral density (BMD), anti-cyclic citrullinated peptide-2 (anti-CCP2) antibodies, and disease activity in patients with established rheumatoid arthritis (RA).

Methods

Patients enrolled in a single-center, observational cohort registry of patients with RA. Eligible patients had known BMD, as measured by digital X-ray radiogrammetry (DXR–BMD), and anti-CCP2 antibody measurements at the same time point or within 6 months. Anti-CCP2–immunoglobulin (Ig)G-positive (+) patients (≥ 20 U/mL) were distributed into three equal groups (Gp1–3), representing increasing anti-CCP2 antibody concentrations. Associations between BMD and anti-CCP2 antibody status and titer were explored in multivariate regression analyses controlling for covariates (including age, duration of RA, use of steroids, use of osteoporosis medication). Association between disease activity (DAS28 [CRP] < 2.6) and bone loss was also explored.

Results

A total of 149 patients (all women) were included (47 anti-CCP2 antibody negative [−], 102 anti-CCP2+ [34\titer group]). Mean disease duration was greater in the three anti-CCP2+ groups vs. the anti-CCP2− group. DXR–BMD was lower in the anti-CCP2+ vs. the anti-CCP2− groups (Gp1–3 vs. anti-CCP2−: P < 0.0001 for left and right hands). DXR–BMD decreased with increasing anti-CCP2 titer (P < 0.001 for left and right hands). Patients with low DXR–BMD were less likely to have a DAS28 (CRP) < 2.6 (P = 0.0181).

Conclusion

Among patients with established RA, data suggest that anti-CCP2+ patients, particularly those with high anti-CCP2 antibody titers, have lower hand BMD, and patients with lower hand BMD are less likely to have low disease activity.

Funding

Bristol-Myers Squibb.

Trial Registration

Clinicaltrials.gov identifier, NCT01793103.
First Trimester Diagnosis of Cloacal Exstrophy: A Discordant Anomaly in Monochorionic Monoamniotic (MCMA) Twins—Case Report
Authors: Shah Nupur
Published: January 2018

Cloacal exstrophy is a rare anomaly, with a severe disruption of the urogenital tract resulting in a central mass of exstrophic bowel field flanked by two hemibladders. The reported case highlights the diagnosis of this discordant anomaly in monochorionic monoanmniotic twins as early as 12 weeks. It underscores the major ultrasound criteria like non visualisation of fetal bladder and infra-umbilical protruberant heterogenous mass which have an important role in early prenatal diagnosis of the anomaly.
The emergence of the grammatical paradigm of nominal determiners in French and in Romance: Comparative and diachronic perspectives
Authors: Carlier Anne , Lamiroy Béatrice
Published: January 2018

This article is devoted to the emergence of a new paradigm in French and Romance: that of nominal determiners. Latin had no articles, and although possessives, demonstratives and indefinites could determine the noun, they could also be used as pronouns or adjectives, so that the morpho-syntactic category of nominal determiners did not exist as such. We first examine the diachronic evolution of French, where a far-reaching grammaticalization process took place. Syntagmatically, all determiners end up in the NP-initial position as the only available syntactic slot, contributing to the highly configurational NP pattern characteristic of Modern French. From a paradigmatic viewpoint, determiners no longer correspond to a syntactic function, but to a separate morpho-syntactic category. We also evaluate to what extent this evolution took place in two other Romance languages, Italian and Spanish. Through the analysis of this particular evolution, based on parallel corpora consisting of a Latin text and its translations in Old, Middle, and Modern French on the one hand, and in Spanish and Italian on the other, our study also provides evidence for more general mechanisms, analogy in particular, at work in the creation of new paradigms.
Topic and focus in Old French V1 and V2 structures
Authors: Labelle Marie , Hirschbühler Paul
Published: January 2018

The hypothesis that Old French was not a verb-second (V2) language, but rather a Topic-initial language, is evaluated in a corpus of verb initial (V1) and V2 matrix clauses extracted from a corpus of 12th- and 13th-century texts. It is shown that the initial constituent of V2 clauses is not always a Topic; it may be part of the informational Focus, or it could be an element that is neither Topic nor Focus. In addition, in V1 and V2 sentences with subject inversion, the postverbal subject may be an informational Topic, contrary to the hypothesis that subjects must move to the preverbal position to avoid being interpreted as part of the informational Focus. Therefore, from an Information-Structure point of view, Old French is similar to a standard V2 language like German. However, certain differences between 12th- and 13th-century texts could suggest that the use of the left periphery evolved during the period considered.
Quenched stochastic stability for eventually expanding-on-average random interval map cocycles
Authors: FROYLAND GARY , GONZÁLEZ-TOKMAN CECILIA , MURRAY RUA
Published: January 2018

The paper by Froyland, González-Tokman and Quas [Stability and approximation of random invariant densities for Lasota–Yorke map cocycles.Nonlinearity27(4) (2014), 647] established fibrewise stability of random absolutely continuous invariant measures (acims) for cocycles of random Lasota–Yorke maps under a variety of perturbations, including ‘Ulam’s method’, a popular numerical method for approximating acims. The expansivity requirements of Froylandet alwere that the cocycle (or powers of the cocycle) should be ‘expanding on average’ before applying a perturbation, such as Ulam’s method. In the present work, we make a significant theoretical and computational weakening of the expansivity hypotheses of Froylandet al, requiring only that the cocycle be eventually expanding on average, and importantly,allowing the perturbation to be applied after each single step of the cocycle. The family of random maps that generate our cocycle need not be close to a fixed map and our results can handle very general driving mechanisms. We provide a detailed numerical example of a random Lasota–Yorke map cocycle with expanding and contracting behaviour and illustrate the extra information carried by our fibred random acims, when compared to annealed acims or ‘physical’ random acims.
Screening for Asymptomatic Clostridium difficile Among Bone Marrow Transplant Patients: A Mixed-Methods Study of Intervention Effectiveness and Feasibility
Authors: Barker Anna K. , Krasity Benjamin , Musuuza Jackson , Safdar Nasia
Published: January 2018

OBJECTIVE

To identify facilitators and barriers to implementation of a Clostridium difficile screening intervention among bone marrow transplant (BMT) patients and to evaluate the clinical effectiveness of the intervention on the rate of hospital-onset C. difficile infection (HO-CDI).

DESIGN

Before-and-after trial

SETTING

A 505-bed tertiary-care medical center

PARTICIPANTS

All 5,357 patients admitted to the BMT and general medicine wards from January 2014 to February 2017 were included in the study. Interview participants included 3 physicians, 4 nurses, and 4 administrators.

INTERVENTION

All BMT patients were screened within 48 hours of admission. Colonized patients, as defined by a C. difficile–positive polymerase chain reaction (PCR) stool result, were placed under contact precautions for the duration of their hospital stay.

METHODS

Interview responses were coded according to the Systems Engineering Initiative for Patient Safety conceptual framework. We compared pre- and postintervention HO-CDI rates on BMT and general internal medicine units using time-series analysis.

RESULTS

Stakeholder engagement, at both the person and organizational level, facilitates standardization and optimization of intervention protocols. While the screening intervention was generally well received, tools and technology were sources of concern. The mean incidence of HO-CDI decreased on the BMT service postintervention (P<.0001). However, the effect of the change in the trend postintervention was not significantly different on BMT compared to the control wards (P=.93).

CONCLUSIONS

We report the first mixed-methods study to evaluate a C. difficile screening intervention among the BMT population. The positive nature by which the intervention was received by front-line clinical staff, laboratory staff, and administrators is promising for future implementation studies.

Infect Control Hosp Epidemiol 2018;39:177–185
Reconfiguration of elastic blades in oscillatory flow
Authors: Leclercq Tristan , de Langre Emmanuel
Published: January 2018

When subjected to a steady cross-flow, the deformation of flexible blades is known to result in the alleviation of the internal stresses in comparison to rigid structures. In the field of biomechanics, the flow-induced deformations of flexible structures leading to stress reduction have been often referred to as ‘reconfiguration’ in order to highlight the alleged benefits of such an adaptive process. In this paper, we investigate the reconfiguration of thin elastic blades and the resulting internal stresses when the flow about the blade is oscillatory. Our approach, based on numerical simulations using reduced order fluid force models, is validated by experimental observations. Through a systematic investigation of the response of the structure, we identify four kinematic regimes depending on the excursion of the fluid particles relative to the dimensions of the blade and on the frequency of the flow oscillations relative to the characteristic frequency of the blade. When the flow amplitude is smaller than the structural width, fluid inertia dominates over drag and the fluid–structure coupling triggers resonances that may cause a magnification of the internal stresses. But the small magnitude of the fluid load in this regime is unlikely to cause any severe damage in practice. Otherwise, when drag is the dominant load, flexibility always permits a reduction of the internal stresses. As in the static case, dynamic reconfiguration results in the concentration of the stresses within a small bending length whose scaling depends on the kinematic regime. The magnitude of the stresses does not depend on the actual length of the structure anymore, which suggests the absence of mechanical limitations to the axial growth of wave-swept plants. However, the risk of resonances originating from the inertial load when the blade width compares with the flow excursion favours elongated shapes that best accommodate the oscillatory fluid loadings.
The critical point of the transition to turbulence in pipe flow
Authors: Mukund Vasudevan , Hof Björn
Published: January 2018

In pipes, turbulence sets in despite the linear stability of the laminar Hagen–Poiseuille flow. The Reynolds number ($Re$) for which turbulence first appears in a given experiment – the ‘natural transition point’ – depends on imperfections of the set-up, or, more precisely, on the magnitude of finite amplitude perturbations. At onset, turbulence typically only occupies a certain fraction of the flow, and this fraction equally is found to differ from experiment to experiment. Despite these findings, Reynolds proposed that after sufficiently long times, flows may settle to steady conditions: below a critical velocity, flows should (regardless of initial conditions) always return to laminar, while above this velocity, eddying motion should persist. As will be shown, even in pipes several thousand diameters long, the spatio-temporal intermittent flow patterns observed at the end of the pipe strongly depend on the initial conditions, and there is no indication that different flow patterns would eventually settle to a (statistical) steady state. Exploiting the fact that turbulent puffs do not age (i.e. they are memoryless), we continuously recreate the puff sequence exiting the pipe at the pipe entrance, and in doing so introduce periodic boundary conditions for the puff pattern. This procedure allows us to study the evolution of the flow patterns for arbitrary long times, and we find that after times in excess of $10^{7}$ advective time units, indeed a statistical steady state is reached. Although the resulting flows remain spatio-temporally intermittent, puff splitting and decay rates eventually reach a balance, so that the turbulent fraction fluctuates around a well-defined level which only depends on $Re$. In accordance with Reynolds’ proposition, we find that at lower $Re$ (here 2020), flows eventually always resume to laminar, while for higher $Re$ (${\geqslant}2060$), turbulence persists. The critical point for pipe flow hence falls in the interval of $2020<Re<2060$, which is in very good agreement with the recently proposed value of $Re_{c}=2040$. The latter estimate was based on single-puff statistics and entirely neglected puff interactions. Unlike in typical contact processes where such interactions strongly affect the percolation threshold, in pipe flow, the critical point is only marginally influenced. Interactions, on the other hand, are responsible for the approach to the statistical steady state. As shown, they strongly affect the resulting flow patterns, where they cause ‘puff clustering’, and these regions of large puff densities are observed to travel across the puff pattern in a wave-like fashion.
Enstrophy and circulation scaling for Navier–Stokes reconnection
Authors: Kerr Robert M.
Published: January 2018

As reconnection begins and the enstrophy$Z$grows for two configurations, helical trefoil knots and anti-parallel vortices, two regimes of self-similar collapse are observed. First, during trefoil reconnection a new$\sqrt{\unicode[STIX]{x1D708}}Z$scaling, where$\unicode[STIX]{x1D708}$is viscosity, is identified before any$\unicode[STIX]{x1D716}=\unicode[STIX]{x1D708}Z$dissipation scaling begins. Further rescaling shows linearly decreasing$B_{\unicode[STIX]{x1D708}}(t)=(\sqrt{\unicode[STIX]{x1D708}}Z)^{-1/2}$at configuration-dependent crossing times$t_{x}$. Gaps in the vortex structures identify the$t_{x}$as when reconnection ends and collapse onto$\unicode[STIX]{x1D708}$-independent curves can be obtained using$A_{\unicode[STIX]{x1D708}}(t)=(T_{c}(\unicode[STIX]{x1D708})-t_{x})(B_{\unicode[STIX]{x1D708}}(t)-B_{\unicode[STIX]{x1D708}}(t_{x}))$. The critical times$T_{c}(\unicode[STIX]{x1D708})$are identified empirically by extrapolating the linear$B_{\unicode[STIX]{x1D708}}(t)$regimes to$B_{\unicode[STIX]{x1D708}}^{{\sim}}(T_{c})=0$, yielding an$A_{\unicode[STIX]{x1D708}}(t)$collapse that forms early as$\unicode[STIX]{x1D708}$varies by 256. These solutions are regular or non-singular, as shown by decreasing cubic velocity norms$\Vert u\Vert _{L_{\ell }^{3}}^{}$. For the anti-parallel vortices, first there is an exchange of circulation, from$\unicode[STIX]{x1D6E4}_{y}(y=0)$to$\unicode[STIX]{x1D6E4}_{z}(z=0)$, mediated by the viscous circulation exchange integral$\unicode[STIX]{x1D716}_{\unicode[STIX]{x1D6E4}}(t)$, which is followed by a modified$B_{\unicode[STIX]{x1D708}}(t)$collapse until the reconnection ends at$t_{x}$. Singular Leray scaling and mathematical bounds for higher-order Sobolev norms are used to help explain the origins of the new scaling and why the domain size$\ell$has to increase to maintain the collapse of$A_{\unicode[STIX]{x1D708}}(t)$and$\unicode[STIX]{x1D716}_{\unicode[STIX]{x1D6E4}}$as$\unicode[STIX]{x1D708}$decreases.
Offer and Use of Smoking-Cessation Support by Depression/Anxiety Status: A Cross-Sectional Survey
Authors: McGowan Jennifer A. L. , Brown Jamie , West Robert , Brose Leonie S. , Shahab Lion
Published: January 2018

Introduction: Higher levels of anxiety and depression have been found to be associated with greater difficulty in stopping smoking. This raises the question as to whether mood disturbance may be associated with exposure to, and use of, quitting support.

Aims: This study examined whether General Practitioner (GP) advice and/or offer of support, or stop-smoking service use differed between smokers reporting or not reporting depression/anxiety.

Methods: Data came from the Smoking Toolkit Study. Participants were 1,162 English adults who reported currently smoking or having stopped within the past 12 months, aged 40+ years, surveyed between April and September 2012. Anxiety/depression was assessed by the mood disturbance item of the EuroQol five dimensions questionnaire (EQ-5D). This was compared to recall of GP quit advice and/or support, and stop-smoking aid use adjusting for age, gender, and social grade.

Results/Findings: Smokers reporting depression/anxiety were more likely to recall being offered advice and support to stop smoking by their GP (OR = 1.50, 95% C.I. = 1.05–2.13). However, there were no significant differences in use of stop-smoking aids during the past year.

Conclusions: Smokers reporting depression/anxiety are more likely to be offered stop-smoking support by their GPs, but this does not appear to translate into stop-smoking aid use, despite high motivation to quit. Given higher nicotine dependence in this group, mental health specific support may need to be offered, and more needs to be done to make this offer of aid attractive.
Bi-Abundance Ionisation Structure of the Wolf–Rayet Planetary Nebula PB 8
Authors: Danehkar A.
Published: January 2018

The planetary nebula PB 8 around a [WN/WC]-hybrid central star is one of planetary nebulae with moderate abundance discrepancy factors (ADFs ~ 2–3), which could be an indication of a tiny fraction of metal-rich inclusions embedded in the nebula (bi-abundance). In this work, we have constructed photoionisation models to reproduce the optical and infrared observations of the planetary nebula PB 8 using a non-LTE stellar model atmosphere ionising source. A chemically homogeneous model initially used cannot predict the optical recombination lines. However, a bi-abundance model provides a better fit to most of the observed optical recombination lines from N and O ions. The metal-rich inclusions in the bi-abundance model occupy 5.6% of the total volume of the nebula, and are roughly 1.7 times cooler and denser than the mean values of the surrounding nebula. The N/H and O/H abundance ratios in the metal-rich inclusions are ~1.0 and 1.7 dex larger than the diffuse warm nebula, respectively. To reproduce the Spitzer spectral energy distribution of PB 8, dust grains with a dust-to-gas ratio of 0.01 (by mass) were also included. It is found that the presence of metal-rich inclusions can explain the heavy element optical recombination lines, while a dual-dust chemistry with different grain species and discrete grain sizes likely produces the infrared continuum of this planetary nebula. This study demonstrates that the bi-abundance hypothesis, which was examined in a few planetary nebulae with large abundance discrepancies (ADFs > 10), could also be applied to those typical planetary nebulae with moderate abundance discrepancies.
APPRAISAL OF MAJOR DETERMINANTS OF RICE PRODUCTION AND FARMERS’ CHOICE OF RICE IDEOTYPES IN SOUTH SUDAN: IMPLICATIONS FOR BREEDING AND POLICY INTERVENTIONS
Authors: MOGGA M. , SIBIYA J. , SHIMELIS H. , LAMO J. , OCHANDA N.
Published: January 2018

Rice (Oryza sativa L.) is an important staple crop in South Sudan. Current rice consumption in the country is approximately 23,000 mg year−1 of which more than 75% is imported. We investigated farmers’ perceived rice production and productivity constraints and choice of rice ideotypes across rainfed and irrigated rice agro-ecologies in South Sudan to guide breeding and policy interventions. Data were gathered through participatory rural approaches and a formal structured survey involving 136 rice farmers from major rice growing areas of South Sudan. Farmers generally cultivated old rice varieties with low yields varying from 0.4 to 1.6 mg ha−1. Pair-wise ranking based on respondents score indicated yield, early maturity, cooking and eating quality, nutritional importance and drought tolerance as the most desirable traits of rice ideotypes. Further, imported rice varieties were best ranked for their sweet and appealing taste, rich aroma, grain shape and size, swelling capacity and non-stickiness during cooking. Major perceived constraints to rice production were unreliable rainfall, poor access to credit facilities, poor soil and water management practices, poor rice storage facilities, inadequate and poor processing machines as well as limited technical skills in rice production. The results show a need for integration of farmers’ and stakeholders’ preferences in variety development process and the desirability of releasing site-specific rice cultivars given the differences in bio-physical, socio-cultural and farmers preferences across major rice growing areas of South Sudan.
WEED SPECIES ASSOCIATION IN ARABLE FIELDS: OLD APPROACH, NEW APPLICATION
Authors: CONCENÇO G. , ANDRES A. , SCHREIBER F. , MOISINHO I. S. , CORADINI M. C. , MARTINS M. B.
Published: January 2018

We aimed to assess the potential of the characterization of association among weed species as a tool to understand weed occurrence for further supporting long-term management programs. After a sequence of summer crops, which included irrigated rice and sorghum, the experimental area was submitted to subsoiling, limestone was applied, and ryegrass was planted in the winter season. Six months later, an ACCase-inhibitor herbicide was used to select only non-grassweed species. Field survey was carried out on 100 quadrats with 0.5-m width that were randomly sampled. Plant species were organized in 2 × 2 contingency tables. The results of the calculated chi-squares were compared to the respective tables, and results were presented as a paired chi-square matrix. The species–area curve was also obtained. The relative occurrence of species was determined by its frequency and presented as a wordcloud. The network analysis was obtained by using the Fruchterman–Reingold layout. The hypothesis of plant association aiming survival in arable fields was validated. The methodology of plant association based on the chi-square test was applicable to arable fields, where weed species (usually competitor plant types) occur in clusters. From a practical point of view, preference should be given to herbicides that are efficient on most species within a given cluster.
Effective interaction of electrons in the field of two strong laser waves with phase shifts allowance
Authors: Starodub S. S. , Roshchupkin S. P. , Dubov V. V.
Published: January 2018

The phase shift's influence of two strong-pulsed laser waves on effective interaction of electrons was studied. Considerable amplification of electron repulsion in the certain range of phase shifts and wave intensities is shown. That leads to electron scatter on greater distances than without an external field. The value of the distance can be greater on 2–3 order of magnitude. Considerable influence of the phase shift of pulses of waves on the possibility of effective attraction of electrons is also shown.
A review of Solvency II: Has it met its objectives?
Authors: Rae R. A. , Barrett A. , Brooks D. , Chotai M. A. , Pelkiewicz A. J. , Wang C.
Published: January 2018

Solvency II is currently one of the most sophisticated insurance regulatory regimes in the world. It is built around the principles of market consistency and embedding strong risk management and governance within insurance companies. For business with long-term guarantees, the original basis produced outcomes that were unacceptable to the member states. The original design was amended through Omnibus II. The working party has looked back at the outcome of the final regulation and comments on how well Solvency II has fared, principally from a UK perspective, relative to its initial goals of improved consumer protection, harmonisation, effective risk management and financial stability. We review Pillar 1’s market consistent valuation (including the risk margin and transitional measures) as well as the capital requirements (including internal models). We look at the impact this has on asset and liability management, pro-cyclicality and product design. We look at Pillars 2 and 3 in respect of the Own Risk and Solvency Assessment, liquidity and disclosure. Finally, we stand back and look at harmonisation and the implications of Brexit. In summary we conclude that Solvency II represents a huge improvement over Solvency I although it has not fully achieved the goals it aspired to. There are acknowledged shortfalls and imperfections where adjustments to Solvency II are likely. There remain other concerns around pro-cyclicality, and the appropriateness of market consistency is still open to criticism. It is hoped that the paper and the discussion that goes with it provide an insight into where Solvency II has taken European Insurance regulation and the directions in which it could evolve.
CREDIT FRICTIONS AND OPTIMAL LABOR-INCOME TAXATION
Authors: Abo-Zaid Salem
Published: January 2018

This paper studies optimal labor-income taxation in a simple model with credit constraints on firms. The labor-income tax rate and the shadow value on the credit constraint induce a wedge between the marginal product of labor and the marginal rate of substitution between labor and consumption. It is found that optimal policy prescribes a volatile path for the labor-income tax rate even in the presence of state-contingent debt and capital. In this respect, credit frictions are akin to a form of market incompleteness. Credit frictions break the equivalence between tax smoothing and wedge smoothing; therefore, as the tightness of the credit constraint varies over the business cycle, tax volatility is needed in order to counter this variation and, as a result, allow for wedge smoothing.
Trade Gains from Legal Rulings in the WTO Dispute Settlement System
Authors: SHIN WONKYU , AHN DUKGEUN
Published: January 2018

Using bilateral trade data on WTO disputes from 1995 to 2010 within the framework of multilateral trade, this paper empirically investigates whether legally winning a WTO dispute leads to actual trade gains. This study helps to illuminate the efficacy of the WTO dispute settlement system and to understand the role of the system as an institutional device for promoting multilateral trade liberalization. Assessing differential effects of the WTO dispute settlement rulings and the legal status of participants, this paper examines how trade gains are created and distributed among WTO members. Our empirical findings suggest that winning a legal dispute contributes to multilateral trade liberalization, not merely by rectifying trade problems for prevailing complainants but more so by providing better market access for all WTO members. This result reaffirms that the WTO dispute settlement system fulfills its purpose as a regulatory instrument for promoting multilateralism and market competition.
Rising inequality and the implications for the future of private insurance in Canada
Authors: Stabile Mark , Isabelle Maripier
Published: January 2018

Income and wealth inequality have risen in Canada since its low point in the 1980s. Over that same period we have also seen an increase in the amount that Canadians spend on privately financed health care, both directly and through private health insurance. This paper will explore the relationship between these two trends using both comparative data across jurisdictions and household-level data within Canada. The starting hypothesis is that the greater the level of inequality the more difficult it becomes for publicly provided insurance to satisfy the median voter. Thus, we should expect increased pressure to access privately financed alternatives as inequality increases. In the light of these implications, the paper considers the implications for the future of private insurance in Canada.
Testing Genetic and Environmental Associations Between Personality Disorders and Cocaine Use: A Population-Based Twin Study
Authors: Gillespie Nathan A. , Aggen Steven H. , Gentry Amanda E. , Neale Michael C. , Knudsen Gun P. , Krueger Robert F. , South Susan C. , Czajkowski Nikolai , Nesvåg Ragnar , Ystrom Eivind , Rosenström Tom H. , Torvik Fartein A. , Reichborn-Kjennerud Ted , Kendler Kenneth S.
Published: January 2018

Until now, data have not been available to elucidate the genetic and environmental sources of comorbidity between all 10 DSM-IV personality disorders (PDs) and cocaine use. Our aim was to determine which PD traits are linked phenotypically and genetically to cocaine use. Cross-sectional data were obtained in a face-to-face interview between 1999 and 2004. Subjects were 1,419 twins (µage= 28.2 years, range = 19–36) from the Norwegian Institute of Public Health Twin Panel, with complete lifetime cocaine use and criteria for all 10 DSM-IV PDs. Stepwise multiple and Least Absolute Shrinkage and Selection Operator (LASSO) regressions were used to identify PDs related to cocaine use. Twin models were fitted to estimate genetic and environmental associations between the PD traits and cocaine use. In the multiple regression, antisocial (OR= 4.24, 95% CI [2.66, 6.86]) and borderline (OR= 2.19, 95% CI [1.35, 3.57]) PD traits were significant predictors of cocaine use. In the LASSO regression, antisocial, borderline, and histrionic were significant predictors of cocaine use. Antisocial and borderline PD traits each explained 72% and 25% of the total genetic risks in cocaine use, respectively. Genetic risks in histrionic PD were not significantly related to cocaine use. Importantly, after removing criteria referencing substance use, antisocial PD explained 65% of the total genetic variance in cocaine use, whereas borderline explained only 4%. Among PD traits, antisocial is the strongest correlate of cocaine use, for which the association is driven largely by common genetic risks.
Seed Longevity and Dormancy State Suggest Management Strategies for Garlic Mustard (Alliaria petiolata) and Japanese Stiltgrass (Microstegium vimineum) in Deciduous Forest Sites
Authors: Redwood Mame E. , Matlack Glenn R. , Huebner Cynthia D.
Published: January 2018

An effective management plan for invasive herb populations must consider the potential for regeneration from the soil seedbank. To test this potential, we examined two species, Japanese stiltgrass and garlic mustard, at deciduous forest sites in southeastern Ohio. Seeds were buried in nylon mesh bags and recovered at regular intervals over 24 mo. Recovered seeds were tested for germination and viability. Burial was replicated on north- and south-facing slopes to test for environmental control of dormancy state. Stiltgrass seeds experienced severe mortality in the soil, rarely surviving the full 24 mo. Stiltgrass showed fractional germination in the lab ranging from 86% to 89% of viable seeds in late spring (the season of natural seedling emergence) to complete nongermination in winter. Most garlic mustard seeds survived through the experimental period (82% and 88% survival across 24 mo) with consistently low mortality (0% to 13%) unrelated to season. Slope aspect had no significant effect on survival or dormancy state in either species. Extrapolation of garlic mustard mortality implies that reproduction would need to be suppressed for a substantial period (perhaps >10 yr) to ensure eradication of a population. In stiltgrass, rapid seed mortality suggests that control can be achieved in 2 to 4 yr.
Generating kidney tissue from pluripotent stem cells
Authors: Little MH
Published: January 2018

With the isolation of human pluripotent stem cells came the possibility of generating specific cell types for regenerative medicine. This has required the development of protocols for directed differentiation into many distinct cell types. One of the more complicated tissue types to recreate is the kidney. Here we review recent progress towards the recreation of not only specific kidney cell types but complex kidney organoids, models of the developing human organ, in vitro. We will also discuss potential short and long term applications of these approaches.
Mesenchymal stem cells to treat diabetic neuropathy: a long and strenuous way from bench to the clinic
Authors: Zhou J Y , Zhang Z , Qian G S
Published: January 2018

As one of the most common complications of diabetes, diabetic neuropathy often causes foot ulcers and even limb amputations. Inspite of continuous development in antidiabetic drugs, there is still no efficient therapy to cure diabetic neuropathy. Diabetic neuropathy shows declined vascularity in peripheral nerves and lack of angiogenic and neurotrophic factors. Mesenchymal stem cells (MSCs) have been indicated as a novel emerging regenerative therapy for diabetic neuropathy because of their multipotency. We will briefly review the pathogenesis of diabetic neuropathy, characteristic of MSCs, effects of MSC therapies for diabetic neuropathy and its related mechanisms. In order to treat diabetic neuropathy, neurotrophic or angiogenic factors in the form of protein or gene therapy are delivered to diabetic neuropathy, but therapeutic efficiencies are very modest if not ineffective. MSC treatment reverses manifestations of diabetic neuropathy. MSCs have an important role to repair tissue and to lower blood glucose level. MSCs even paracrinely secrete neurotrophic factors, angiogenic factors, cytokines, and immunomodulatory substances to ameliorate diabetic neuropathy. There are still several challenges in the clinical translation of MSC therapy, such as safety, optimal dose of administration, optimal mode of cell delivery, issues of MSC heterogeneity, clinically meaningful engraftment, autologous or allogeneic approach, challenges with cell manufacture, and further mechanisms.
Single-cell measurement of ammonium and bicarbonate uptake within a photosymbiotic bioeroding sponge
Authors: Achlatis Michelle , Pernice Mathieu , Green Kathryn , Guagliardo Paul , Kilburn Matthew R , Hoegh-Guldberg Ove , Dove Sophie
Published: January 2018

Some of the most aggressive coral-excavating sponges host intracellular dinoflagellates from the genus Symbiodinium, which are hypothesized to provide the sponges with autotrophic energy that powers bioerosion. Investigations of the contribution of Symbiodinium to host metabolism and particularly inorganic nutrient recycling are complicated, however, by the presence of alternative prokaryotic candidates for this role. Here, novel methods are used to study nutrient assimilation and transfer within and between the outer-layer cells of the Indopacific bioeroding sponge Cliona orientalis. Combining stable isotope labelling, transmission electron microscopy (TEM) and nanoscale secondary ion mass spectrometry (NanoSIMS), we visualize and measure metabolic activity at the individual cell level, tracking the fate of 15N-ammonium and 13C-bicarbonate within the intact holobiont. We found strong uptake of both inorganic sources (especially 13C-bicarbonate) by Symbiodinium cells. Labelled organic nutrients were translocated from Symbiodinium to the Symbiodinium-hosting sponge cells within 6 h, and occasionally to other sponge cells within 3 days. By contrast, prokaryotic symbionts were not observed to participate in inorganic nutrient assimilation in the outer layers of the sponge. Our findings strongly support the metabolic interaction between the sponge and dinoflagellates, shedding light on the ecological advantages and adaptive capacity of photosymbiotic bioeroding sponges in oligotrophic marine habitats.
Immunological consequences of kidney cell death
Authors: Sarhan Maysa , von Mässenhausen Anne , Hugo Christian , Oberbauer Rainer , Linkermann Andreas
Published: January 2018

Death of renal cells is central to the pathophysiology of acute tubular necrosis, autoimmunity, necrotizing glomerulonephritis, cystic kidney disease, urosepsis, delayed graft function and transplant rejection. By means of regulated necrosis, immunogenic damage-associated molecular patterns (DAMPs) and highly reactive organelles such as lysosomes, peroxisomes and mitochondria are released from the dying cells, thereby causing an overwhelming immunologic response. The rupture of the plasma membrane exhibits the “point of no return” for the immunogenicity of regulated cell death, explaining why apoptosis, a highly organized cell death subroutine with long-lasting plasma membrane integrity, elicits hardly any immune response. Ferroptosis, an iron-dependent necrotic type cell death, results in the release of DAMPs and large amounts of lipid peroxides. In contrast, anti-inflammatory cytokines are actively released from cells that die by necroptosis, limiting the DAMP-induced immune response to a surrounding microenvironment, whereas at the same time, inflammasome-associated caspases drive maturation of intracellularly expressed interleukin-1β (IL-1β). In a distinct setting, additionally interleukin-18 (IL-18) is expressed during pyroptosis, initiated by gasdermin-mediated plasma membrane rupture. As all of these pathways are druggable, we provide an overview of regulated necrosis in kidney diseases with a focus on immunogenicity and potential therapeutic interventions.
Cell death-based treatment of lung adenocarcinoma
Authors: Denisenko Tatiana V. , Budkevich Inna N. , Zhivotovsky Boris
Published: January 2018

The most common type of lung cancer is adenocarcinoma (ADC), comprising around 40% of all lung cancer cases. In spite of achievements in understanding the pathogenesis of this disease and the development of new approaches in its treatment, unfortunately, lung ADC is still one of the most aggressive and rapidly fatal tumor types with overall survival less than 5 years. Lung ADC is often diagnosed at advanced stages involving disseminated metastatic tumors. This is particularly important for the successful development of new approaches in cancer therapy. The high resistance of lung ADC to conventional radiotherapies and chemotherapies represents a major challenge for treatment effectiveness. Here we discuss recent advances in understanding the molecular pathways driving tumor progression and related targeted therapies in lung ADCs. In addition, the cell death mechanisms induced by different treatment strategies and their contribution to therapy resistance are analyzed. The focus is on approaches to overcoming drug resistance in order to improve future treatment decisions.
Hexokinase-2 depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin
Authors: DeWaal Dannielle , Nogueira Veronique , Terry Alexander R. , Patra Krushna C. , Jeon Sang-Min , Guzman Grace , Au Jennifer , Long Christopher P. , Antoniewicz Maciek R. , Hay Nissim
Published: January 2018

Hepatocellular carcinoma (HCC) cells are metabolically distinct from normal hepatocytes by expressing the high-affinity hexokinase (HK2) and suppressing glucokinase (GCK). This is exploited to selectively target HCC. Hepatic HK2 deletion inhibits tumor incidence in a mouse model of hepatocarcinogenesis. Silencing HK2 in human HCC cells inhibits tumorigenesis and increases cell death, which cannot be restored by GCK or mitochondrial binding deficient HK2. Upon HK2 silencing, glucose flux to pyruvate and lactate is inhibited, but TCA fluxes are maintained. Serine uptake and glycine secretion are elevated suggesting increased requirement for one-carbon contribution. Consistently, vulnerability to serine depletion increases. The decrease in glycolysis is coupled to elevated oxidative phosphorylation, which is diminished by metformin, further increasing cell death and inhibiting tumor growth. Neither HK2 silencing nor metformin alone inhibits mTORC1, but their combination inhibits mTORC1 in an AMPK-independent and REDD1-dependent mechanism. Finally, HK2 silencing synergizes with sorafenib to inhibit tumor growth.
Large magneto-thermopower in MnGe with topological spin texture
Authors: Fujishiro Y. , Kanazawa N. , Shimojima T. , Nakamura A. , Ishizaka K. , Koretsune T. , Arita R. , Miyake A. , Mitamura H. , Akiba K. , Tokunaga M. , Shiogai J. , Kimura S. , Awaji S. , Tsukazaki A. , Kikkawa A. , Taguchi Y. , Tokura Y.
Published: January 2018

Quantum states characterized by nontrivial topology produce interesting electrodynamics and versatile electronic functionalities. One source for such remarkable phenomena is emergent electromagnetic field, which is the outcome of interplay between topological spin structures with scalar spin chirality and conduction electrons. However, it has scarcely been exploited for emergent function related to heat-electricity conversion. Here we report an unusually enhanced thermopower by application of magnetic field in MnGe hosting topological spin textures. By considering all conceivable origins through quantitative investigations of electronic structures and properties, a possible origin of large magneto-thermopower is assigned to the strong energy dependence of charge-transport lifetime caused by unconventional carrier scattering via the dynamics of emergent magnetic field. Furthermore, high-magnetic-field measurements corroborate the presence of residual magnetic fluctuations even in the nominally ferromagnetic region, leading to a subsisting behavior of field-enhanced thermopower. The present finding may pave a way for thermoelectric function of topological magnets.
Nucleotide resolution mapping of influenza A virus nucleoprotein-RNA interactions reveals RNA features required for replication
Authors: Williams Graham D. , Townsend Dana , Wylie Kristine M. , Kim Preston J. , Amarasinghe Gaya K. , Kutluay Sebla B. , Boon Adrianus C. M.
Published: January 2018

Influenza A virus nucleoprotein (NP) association with viral RNA (vRNA) is essential for packaging, but the pattern of NP binding to vRNA is unclear. Here we applied photoactivatable ribonucleoside enhanced cross-linking and immunoprecipitation (PAR-CLIP) to assess the native-state of NP–vRNA interactions in infected human cells. NP binds short fragments of RNA (~12 nucleotides) non-uniformly and without apparent sequence specificity. Moreover, NP binding is reduced at specific locations within the viral genome, including regions previously identified as required for viral genome segment packaging. Synonymous mutations designed to alter the predicted RNA structures in these low-NP-binding regions impact genome packaging and result in virus attenuation, whereas control mutations or mutagenesis of NP-bound regions have no effect. Finally, we demonstrate that the sequence conservation of low-NP-binding regions is required in multiple genome segments for propagation of diverse mammalian and avian IAV in host cells.
Directing lateral growth of lithium dendrites in micro-compartmented anode arrays for safe lithium metal batteries
Authors: Zou Peichao , Wang Yang , Chiang Sum-Wai , Wang Xuanyu , Kang Feiyu , Yang Cheng
Published: January 2018

Uncontrolled growth of lithium dendrites during cycling has remained a challenging issue for lithium metal batteries. Thus far, various approaches have been proposed to delay or suppress dendrite growth, yet little attention has been paid to the solutions that can make batteries keep working when lithium dendrites are already extensively present. Here we develop an industry-adoptable technology to laterally direct the growth of lithium dendrites, where all dendrites are retained inside the compartmented copper current collector in a given limited cycling capacity. This featured electrode layout renders superior cycling stability (e.g., smoothly running for over 150 cycles at 0.5 mA cm−2). Numerical simulations indicate that reduced dendritic stress and damage to the separator are achieved when the battery is abusively running over the ceiling capacity to generate protrusions. This study may contribute to a deeper comprehension of metal dendrites and provide a significant step towards ultimate safe batteries.
Asymmetric photocurrent extraction in semitransparent laminated flexible organic solar cells
Authors: Bergqvist Jonas , Österberg Thomas , Melianas Armantas , Ever Aguirre Luis , Tang Zheng , Cai Wanzhu , Ma Zaifei , Kemerink Martijn , Gedefaw Desta , Andersson Mats R. , Inganäs Olle
Published: January 2018

Scalable production methods and low-cost materials with low embodied energy are key to success for organic solar cells. PEDOT(PSS) electrodes meet these criteria and allow for low-cost and all solution-processed solar cells. However, such devices are prone to shunting. In this work we introduce a roll-to-roll lamination method to construct semitransparent solar cells with a PEDOT(PSS) anode and an polyethyleneimine (PEI) modified PEDOT(PSS) cathode. We use the polymer:PCBM active layer coated on the electrodes as the lamination adhesive. Our lamination method efficiently eliminates any shunting. Extended exposure to ambient degrades the laminated devices, which manifests in a significantly reduced photocurrent extraction when the device is illuminated through the anode, despite the fact that the PEDOT(PSS) electrodes are optically equivalent. We show that degradation-induced electron traps lead to increased trap-assisted recombination at the anode side of the device. By limiting the exposure time to ambient during production, degradation is significantly reduced. We show that lamination using the active layer as the adhesive can result in device performance equal to that of conventional sequential coating.
Monitoring cotton root rot by synthetic Sentinel-2 NDVI time series using improved spatial and temporal data fusion
Authors: Wu Mingquan , Yang Chenghai , Song Xiaoyu , Hoffmann Wesley Clint , Huang Wenjiang , Niu Zheng , Wang Changyao , Li Wang , Yu Bo
Published: January 2018

To better understand the progression of cotton root rot within the season, time series monitoring is required. In this study, an improved spatial and temporal data fusion approach (ISTDFA) was employed to combine 250-m Moderate Resolution Imaging Spectroradiometer (MODIS) Normalized Different Vegetation Index (NDVI) and 10-m Sentinetl-2 NDVI data to generate a synthetic Sentinel-2 NDVI time series for monitoring this disease. Then, the phenology of healthy cotton and infected cotton was modeled using a logistic model. Finally, several phenology parameters, including the onset day of greenness minimum (OGM), growing season length (GLS), onset of greenness increase (OGI), max NDVI value, and integral area of the phenology curve, were calculated. The results showed that ISTDFA could be used to combine time series MODIS and Sentinel-2 NDVI data with a correlation coefficient of 0.893. The logistic model could describe the phenology curves with R-squared values from 0.791 to 0.969. Moreover, the phenology curve of infected cotton showed a significant difference from that of healthy cotton. The max NDVI value, OGM, GSL and the integral area of the phenology curve for infected cotton were reduced by 0.045, 30 days, 22 days, and 18.54%, respectively, compared with those for healthy cotton.