bluuebunny/crossref_metadata_2025 huggingface dataset:
Creating strategic couplings in global production networks: regional institutions and lead firm investment in the Humber region, UK
Authors: Dawley Stuart , MacKinnon Danny , Pollock Robert
Published: February 2019

This article aims to unpack and analyse the institutional and political dynamics of strategic coupling from a host region perspective, adopting an actor-centred approach that focuses on regional institutions’ efforts to attract and embed lead firm investments within global production networks. We are particularly concerned with understanding the strategic agency and shifting coalitions of actors that create couplings and shape their evolution over time. This involves opening up the institutional underpinnings of strategic couplings by focusing more specifically on the key episodes in their creation and the organisation of the temporary coalitions that do the work of creating couplings. This approach is operationalised through a case study of the Siemens offshore wind turbine plant in the Humber region of England. In conclusion, we emphasise the need for regional institutions to develop adaptive coupling creation strategies that co-evolve with the reconfiguration of production networks and the reshaping of national institutional and political environments.
Self-assembled structure of dendronized CdS nanoparticles
Authors: Nakajima Hiroshi , Matsuki Daichi , Fukunaga Yumi , Toriyama Takaaki , Shigematsu Koji , Matsubara Masaki , Kanie Kiyoshi , Muramatsu Atsushi , Murakami Yasukazu
Published: February 2019

Self-assembled dendronized CdS nanoparticles have been attracting considerable attention because of their photoluminescence properties depending on annealing treatments. In this study, their annealing-induced self-assembled structure was investigated via scanning transmission electron microscopy; thin foil specimens of self-assembled dendronized CdS nanoparticles were prepared by ultramicrotomy and the STEM images revealed their ordered structure and the effect of the annealing treatment. In addition, a structural order belonging to the P213 space group was identified via an autocorrelation analysis. The results indicated that this structural order could be achieved only over a few tens of nanometers.
Methylation-Based Biological Age and Breast Cancer Risk
Authors: Kresovich Jacob K , Xu Zongli , O’Brien Katie M , Weinberg Clarice R , Sandler Dale P , Taylor Jack A
Published: February 2019

Background

Age is one of the strongest predictors of cancer, chronic disease, and mortality, but biological responses to aging differ among people. Epigenetic DNA modifications have been used to estimate “biological age,” which may be a useful predictor of disease risk. We tested this hypothesis for breast cancer.

Methods

Using a case-cohort approach, we measured baseline blood DNA methylation of 2764 women enrolled in the Sister Study, 1566 of whom subsequently developed breast cancer after an average of 6 years. Using three previously established methylation-based “clocks” (Hannum, Horvath, and Levine), we defined biological age acceleration for each woman by comparing her estimated biological age with her chronological age. Hazard ratios and 95% confidence intervals for breast cancer risk were estimated using Cox regression models. All statistical tests were two-sided.

Results

Each of the three clocks showed that biological age acceleration was statistically significantly associated with increased risk of developing breast cancer (5-year age acceleration, Hannum’s clock: hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.00 to 1.21, P = .04; Horvath’s clock: HR = 1.08, 95% CI = 1.00 to 1.17, P = .04; Levine’s clock: HR = 1.15, 95% CI = 1.07 to 1.23, P < .001). For Levine’s clock, each 5-year acceleration in biological age corresponded with a 15% increase in breast cancer risk. Although biological age may accelerate with menopausal transition, age acceleration in premenopausal women independently predicted breast cancer. Case-only analysis suggested that, among women who develop breast cancer, increased age acceleration is associated with invasive cancer (odds ratio for invasive = 1.09, 95% CI = 0.98 to 1.22, P = .10).

Conclusions

DNA methylation-based measures of biological age may be important predictors of breast cancer risk.
Subacute Aerococcus urinae Infective Endocarditis With Mycotic Aneurysms in a Pediatric Patient: Case Report and Literature Review
Authors: Sous Natalie , Piwoz Julia A , Baer Aryeh Z , Bhavsar Sejal Makvana
Published: February 2019

Aerococcus urinae has been found to cause urinary tract infection in elderly patients and has been reported as a rare cause of infective endocarditis associated with significant morbidity and death in adults. However, information regarding its occurrence in children is lacking. We report here the case of a pediatric patient with subacute A urinae infective endocarditis with mycotic aneurysms.
‘A New and Fierce Disorder’s Raging’: Monomania in Mary Barton (1848)
Authors: Stewart Lindsey
Published: February 2019

This article examines Elizabeth Gaskell’s use of the early psychiatric idea of monomania in her novel Mary Barton (1848). Digital searches show a steep rise in the textual use of the word so that by the mid-1830s it might be described as popularly familiar, albeit still invested with the esotericism and prestige of medical vocabulary. The furore in the press circulating around monomaniacal assassins would not have escaped Gaskell’s notice as she began the novel, which was written intermittently between the years 1844 and 1847 and set in c. 1834 to 1840. John Barton, and his sister-in-law, fallen woman Esther, are gripped by obsessive, avenging missions fostered by the pathogenic environments they inhabit. Their trajectories are similar: the loss of a child, a recourse to opiates and alcohol to manage misery and hunger, and an expulsion from the normalizing world of domesticity. The narrative describes both as monomaniacs. I argue that these monomanias are equivalent to a tormenting class consciousness wherein their over-abundant imaginations refuse to accept their lot. A challenge to the notion that the working class were morally at fault, monomania is presented as a condition caused by an environment that can only foster despair. The text does not simply pathologize the characters, but presents the social structure itself as pathological. Gaskell uses a gothic formulation of the disease as ‘haunting’ and ‘incessant’. It is a novelistic version which is both proto-sensational in the projects its sufferers pursue (murder and detection) whilst also signifying a nervous collapse brought about by material deprivation. Gaskell’s monomaniacs come closest to replicating the aetiologies of their ‘real’ counterparts in County Asylums.
Considerations of the importance of redox state for reactive nitrogen species action
Authors: Hancock John T
Published: February 2019

Nitric oxide (NO) and other reactive nitrogen species (RNS) are immensely important signalling molecules in plants, being involved in a range of physiological responses. However, the exact way in which NO fits into signal transduction pathways is not always easy to understand. Here, some of the issues that should be considered are discussed. This includes how NO may interact directly with other reactive signals, such as reactive oxygen and sulfur species, how NO metabolism is almost certainly compartmentalized, that threshold levels of RNS may need to be reached to have effects, and how the intracellular redox environment may impact on NO signalling. Until better tools are available to understand how NO is generated in cells, where it accumulates, and to what levels it reaches, it will be hard to get a full understanding of NO signalling. The interaction of RNS metabolism with the intracellular redox environment needs further investigation. A changing redox poise will impact on whether RNS species can thrive in or around cells. Such mechanisms will determine whether specific RNS can indeed control the responses needed by a cell.
Adolescents and Body Modification for Gender Identity Expression
Authors: Murphy Timothy F
Published: February 2019

As a matter of ethics and law, adults enjoy wide berth in securing hormonal and surgical interventions to align their bodies with their desired gender appearance. In contrast, the exercise of choice by minors is more constrained, because they can be less well situated to grasp the nature and consequences of interventions having life-long effects. Even so, some minors hope for body modifications prior to adulthood. Starting very young, some minors may assert atypical gender identity: those with female-typical bodies assert a male identity and those with male-typical bodies assert a female identity. This assertion of identity is atypical only in a descriptive sense, because it is uncharacteristic, not because it is normatively unacceptable. Not all minors persist in their atypical gender identities, but some do. For those who do, it is desirable to minimize unwanted secondary sex characteristics and to maximize desired secondary sex characteristics. I outline here a theory of respect for decisions by minors in regard to hormonal and surgical interventions that help align their bodies with their gender identity. Of particular ethical interest here are body modifications for fertility preservation since certain interventions in the body can leave people unable to have genetically related children. In general, I will show that the degree of respect owed to minors in regard to body modifications for gender identity expression should be scaled according to their decision-making capacities, in the context of robust practices of informed consent.
‘ … nur ein Gleichnis’: Heinrich Schenker and the Path To ‘Likeness’
Authors: Marston Nicholas
Published: February 2019

This article introduces to Schenker scholarship a virtually unknown, unfinished text, ‘Der Weg zum Gleichniss’ (‘The Path to Likeness’). I date it to the decade following 1895, and more specifically to 1902–4: thus, between ‘Der Geist der musikalischen Technik’ and Harmonielehre (1906). ‘Geist’ has for more than thirty years been repeatedly re-examined for its negative account of organicism in music; I show that the ‘Gleichniss’ text both reiterates Schenker’s position and argues that, through the controlling concept of ‘likeness’, music succeeded in elevating itself to the level of ‘a distinct, second, artificial and higher nature’. In short, this text may represent the ‘missing link’ between ‘Geist’ and the more positively organicist Harmonielehre. Finally, I ponder the context of ‘Geist’ and the background to Schenker’s idiosyncratic use of the term ‘Gleichniss’: this leads both forwards to the 1933 article ‘Was wird aus der Musik?’ and backwards to the Old Testament.
Malassezia japonica is part of the cutaneous microbiome of free-ranging golden-headed lion tamarins (Leontopithecus chrysomelas – Kuhl, 1820)
Authors: Coutinho Selene Dall’ Acqua , Sacristán Carlos , Bueno Marina Galvão , Marigo Juliana , Pissinatti Alcides , Kierulff Maria Cecilia , Catão-Dias José Luiz
Published: February 2019

We investigated Malassezia spp. in external ear canal and haircoat of free-ranging golden-headed lion tamarins (Leontopithecus chrysomelas). A total of 199 animals were restrained, and 597 clinical samples were collected. After the amplification of the 26S ribosomal gene by polymerase chain reaction (PCR), the RFLP technique was performed. Two additional PCR protocols were performed in 10 randomly selected strains. Malassezia sp. was isolated in 38.2% (76/199) of the animals and 14.6% (87/597) of the samples; all strains were lipodependent. The 10 sequenced strains showed a high identity with Malassezia japonica, species described in man, but not in animals, so far.
Zoonotic sporotrichosis with greater severity in Rio de Janeiro, Brazil: 118 hospitalizations and 11 deaths in the last 2 decades in a reference institution
Authors: Falcão Eduardo Mastrangelo Marinho , Pires Mariah Castro de Souza , Andrade Hugo Boechat , Gonçalves Marcelo Luiz Carvalho , Almeida-Paes Rodrigo , do Valle Antonio Carlos Francesconi , Bastos Francisco Inacio , Gutierrez-Galhardo Maria Clara , Freitas Dayvison Francis Saraiva
Published: February 2019

Since 1998, there has been an increase in the number of cat-transmitted cases of human sporotrichosis in Rio de Janeiro state, and severe forms are observed especially when associated with human immunodeficiency virus (HIV). A retrospective search of the INI/ Fiocruz database was conducted to identify sporotrichosis cases, hospitalized and deceased patients, between 1999 and 2015. There were 3917 adult patients diagnosed, 75 of them hospitalized, and 11 died. We conclude there is still a progression toward hyperendemic levels and greater severity has been demonstrated mainly in a socially excluded population.
The power spectrum of the Lyman-α Forest at z < 0.5
Authors: Khaire Vikram , Walther Michael , Hennawi Joseph F , Oñorbe Jose , Lukić Zarija , Prochaska J Xavier , Tripp Todd M , Burchett Joseph N , Rodriguez Christian
Published: February 2019

We present new measurements of the flux power-spectrum P(k) of the z < 0.5 H  i Lyman-α Forest spanning scales $k \sim 0.001\!-\!0.1\, \mathrm{s \, km}^{-1}$. These results were derived from 65 far-ultraviolet quasar spectra (resolution $R \sim 18\, 000$) observed with the Cosmic Origin Spectrograph (COS) on board the Hubble Space Telescope. The analysis required careful masking of all contaminating, coincident absorption from H  i and metal–line transitions of the Galactic interstellar medium and intervening absorbers as well as proper treatment of the complex COS line-spread function. From the P(k) measurements, we estimate the H  i photoionization rate ($\Gamma _{\rm H\,{\small I}}$) in the z < 0.5 intergalactic medium. Our results confirm most of the previous $\Gamma _{\rm H\,{\small I}}$ estimates. We conclude that previous concerns of a photon underproduction crisis are now resolved by demonstrating that the measured $\Gamma _{\rm H\,{\small I}}$ can be accounted for by ultraviolet emission from quasars alone. In a companion paper, we will present constraints on the thermal state of the z < 0.5 intergalactic medium from the P(k) measurements presented here.
Relationship between the line width of the atomic and molecular ISM in M33
Authors: Koch Eric W , Rosolowsky Erik W , Schruba Andreas , Leroy Adam , Kepley Amanda , Braine Jonathan , Dalcanton Julianne , Johnson Megan C
Published: February 2019

We investigate how the spectral properties of atomic (H i) and molecular (H2) gas, traced by CO(2−1) , are related in M33 on 80 pc scales. We find the H i  and CO(2−1)  velocity at peak intensity to be highly correlated, consistent with previous studies. By stacking spectra aligned to the velocity of H i peak intensity, we find that the CO  line width (σHWHM = 4.6 ± 0.9 ${\rm km\, s^{-1}}$ ; σHWHM is the effective Gaussian width) is consistently smaller than the H i line width (σHWHM = 6.6 ± 0.1 ${\rm km\, s^{-1}}$), with a ratio of ∼0.7, in agreement with Druard et al. The ratio of the line widths remains less than unity when the data are smoothed to a coarser spatial resolution. In other nearby galaxies, this line width ratio is close to unity which has been used as evidence for a thick, diffuse molecular disc that is distinct from the thin molecular disc dominated by molecular clouds. The smaller line width ratio found here suggests that M33 has a marginal thick molecular disc. From modelling individual lines of sight, we recover a strong correlation between H i and CO line widths when only the H i located closest to the CO component is considered. The median line width ratio of the line-of-sight line widths is 0.56 ± 0.01. There is substantial scatter in the H i –CO(2−1) line width relation, larger than the uncertainties, that results from regional variations on <500 pc scales, and there is no significant trend in the line widths, or their ratios, with galactocentric radius. These regional line width variations may be a useful probe of changes in the local cloud environment or the evolutionary state of molecular clouds.
What determines the shape of the local (z < 0.1) infrared galaxy luminosity function?
Authors: Symeonidis M , Page M J
Published: February 2019

We investigate what shapes the infrared luminosity function of local galaxies by comparing it to the local infrared active galactic nucleus (AGN) luminosity function. The former corresponds to emission from dust heated by stars and AGN, whereas the latter includes emission from AGN-heated dust only. Our results show that infrared emission from AGN starts mixing into the galaxy luminosity function in the luminous infrared galaxy (LIRG) regime and becomes significant in the ultraluminous infrared galaxy (ULIRG) regime, with the luminosity above which local ULIRGs become AGN-dominated being in the log$L_{\rm IR}/\rm L_{\odot }\sim 12.2$–12.7 range. We propose that as a result of the AGN contribution, the infrared galaxy luminosity function has a flatter high-luminosity slope than UV/optical galaxy luminosity functions. Furthermore, we note that the increased AGN contribution as a function of LIR is reflected in the average dust temperature (Tdust) of local galaxies, and may be responsible for the local LIR–Tdust relation. However, although our results show that AGN play a central role in defining the properties of local ULIRGs, we find that the dominant power source in the local ULIRG population is star formation.
Health status, health-related quality of life, and socioeconomic outcome in childhood brain tumor survivors: a German cohort study
Authors: Scholtes Cathy , Baust Katja , Weinhold Leonie , Creutzig Ursula , Gnekow Astrid , Hinz Andreas , Kaatsch Peter , Kreitz Kiana , Langer Thorsten , Rutkowski Stefan , Singer Susanne , Spix Claudia , Teske Carmen , Schmid Matthias , Dilloo Dagmar , Calaminus Gabriele
Published: February 2019

Background

With rising numbers of childhood cancer survivors, somatic and socioeconomic outcome as well as health-related quality of life (QoL) gain increasing relevance. Based on the first nationwide German Survey on Life Situation, State of Health, and Quality of Life of Childhood Cancer Survivors, the VIVE survey, we report the outcome of survivors of childhood brain tumors localized in the posterior fossa.

Methods

Two hundred seventy participants with a median follow-up period of 21.9 years completed a questionnaire on socioeconomic and somatic late effects as well as a standardized QoL questionnaire (European Organisation for Research and Treatment of Cancer QLQ-C30). Comparisons were performed between World Health Organization (WHO) grades I–II, WHO grades III–IV brain tumor survivors (BTS), and the general population adjusting for potential confounders.

Results

The socioeconomic and QoL results of WHO grades I–II BTS were largely comparable to the general population, while grades III–IV BTS were at higher risk for significantly worse outcomes. Of WHO grades III–IV BTS, 36.8% were still living with their parents or in assisted living facilities compared with 16.1% of grades I–II BTS and 7.8% of the age-adjusted general population. Of grades III–IV BTS, 60.8% achieved at least an intermediate school degree in comparison to 80.5% of grades I–II BTS and 75.6% of the general population. Grades III–IV BTS developed up to 2 times more somatic late effects than survivors of grades I–II tumors.

Conclusion

Derived from a large and homogeneous cohort, these results stress the importance of an appropriate follow-up period focusing not only on physical aspects but encompassing the entire living situation to allow patient-tailored support.
Altered trends in carbon uptake in China's terrestrial ecosystems under the enhanced summer monsoon and warming hiatus
Authors: He Honglin , Wang Shaoqiang , Zhang Li , Wang Junbang , Ren Xiaoli , Zhou Lei , Piao Shilong , Yan Hao , Ju Weimin , Gu Fengxue , Yu Shiyong , Yang Yuanhe , Wang Miaomiao , Niu Zhongen , Ge Rong , Yan Huimin , Huang Mei , Zhou Guoyi , Bai Yongfei , Xie Zongqiang , Tang Zhiyao , Wu Bingfang , Zhang Leiming , He Nianpeng , Wang Qiufeng , Yu Guirui
Published: February 2019

The carbon budgets in terrestrial ecosystems in China are strongly coupled with climate changes. Over the past decade, China has experienced dramatic climate changes characterized by enhanced summer monsoon and decelerated warming. However, the changes in the trends of terrestrial net ecosystem production (NEP) in China under climate changes are not well documented. Here, we used three ecosystem models to simulate the spatiotemporal variations in China's NEP during 1982–2010 and quantify the contribution of the strengthened summer monsoon and warming hiatus to the NEP variations in four distinct climatic regions of the country. Our results revealed a decadal-scale shift in NEP from a downtrend of –5.95 Tg C/yr2 (reduced sink) during 1982–2000 to an uptrend of 14.22 Tg C/yr2 (enhanced sink) during 2000–10. This shift was essentially induced by the strengthened summer monsoon, which stimulated carbon uptake, and the warming hiatus, which lessened the decrease in the NEP trend. Compared to the contribution of 56.3% by the climate effect, atmospheric CO2 concentration and nitrogen deposition had relatively small contributions (8.6 and 11.3%, respectively) to the shift. In conclusion, within the context of the global-warming hiatus, the strengthening of the summer monsoon is a critical climate factor that enhances carbon uptake in China due to the asymmetric response of photosynthesis and respiration. Our study not only revealed the shift in ecosystem carbon sequestration in China in recent decades, but also provides some insight for understanding ecosystem carbon dynamics in other monsoonal areas.
Allodynography: Reliability of a New Procedure for Objective Clinical Examination of Static Mechanical Allodynia
Authors: Packham Tara L , Spicher Claude J , MacDermid Joy C , Buckley Norman D
Published: February 2019

Objective

There is a need for reliable and valid clinical assessment tools for quantifying allodynia in neuropathic pain. Allodynography has been proposed as a useful standardized procedure for clinical assessment of mechanical allodynia. This study (www.clinicaltrials.gov NCT02070367) undertook preliminary investigation of the measurement properties of allodynography, a new standardized clinical examination procedure for mapping the area of cutaneous allodynia.

Methods

Persons with pain in one upper extremity after complex regional pain syndrome, a peripheral nerve injury, or who had recently experienced a hand fracture were recruited for assessment of static mechanical allodynia (based on perception of a 15g force stimulus delivered by Semmes-Weinstein monofilament #5.18 as painful) by two raters at baseline; the assessment was repeated one week later.

Results

Single-measures estimates suggested inter-rater reliability for allodynography was excellent at an intraclass correlation coefficient (ICC) of 0.97 (N = 12); test–retest reliability was also excellent at ICC = 0.89 (N = 10) for allodynography (P < 0.001 for both). Confidence intervals’ lower bounds confirm inter-rater reliability as excellent (0.90) but were less definitive for test–retest (0.59).

Conclusions

This preliminary study supports the inter-rater and test–retest reliability of allodynography. Studies on larger samples in multiple contexts and reporting other measurement properties are warranted.
Using Gossips to Spread Information: Theory and Evidence from Two Randomized Controlled Trials
Authors: Banerjee Abhijit , Chandrasekhar Arun G , Duflo Esther , Jackson Matthew O
Published: February 2019

Can we identify highly central individuals in a network without collecting network data, simply by asking community members? Can seeding information via such nominated individuals lead to significantly wider diffusion than via randomly chosen people, or even respected ones? In two separate large field experiments in India, we answer both questions in the affirmative. In particular, in 521 villages in Haryana, we provided information on monthly immunization camps to either randomly selected individuals (in some villages) or to individuals nominated by villagers as people who would be good at transmitting information (in other villages). We find that the number of children vaccinated every month is 22% higher in villages in which nominees received the information. We show that people’s knowledge of who are highly central individuals and good seeds can be explained by a model in which community members simply track how often they hear gossip about others. Indeed, we find in a third data set that nominated seeds are central in a network sense, and are not just those with many friends or in powerful positions.
Corporate Investment and Innovation in the Presence of Competitor Constraints
Authors: Grieser William , Liu Zack
Published: February 2019

We study the relation between investment behavior and competitor financial constraints. Using interfirm patent citations and text-based product market similarities to identify intransitive competitor networks, we find that firms increase investment spending, patenting activity, and opportunistic hiring when competitor constraints become more binding. In addition, firms shift their investment composition (product market and patent portfolios) to compete more aggressively with relatively constrained competitors. To mitigate endogeneity concerns, we exploit the 2004 AJCA tax holiday and the 1989 junk bond crisis as exogenous shocks to competitor constraints, and we find similar effects.

Received August 11, 2017; editorial decision November 6, 2018 by Editor David Denis. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Dynamic Interpretation of Emerging Risks in the Financial Sector
Authors: Hanley Kathleen Weiss , Hoberg Gerard
Published: February 2019

We use computational linguistics to develop a dynamic, interpretable methodology that can detect emerging risks in the financial sector. Our model can predict heightened risk exposures as early as mid-2005, well in advance of the 2008 financial crisis. Risks related to real estate, prepayment, and commercial paper are elevated. Individual bank exposure strongly predicts returns, bank failures, and return volatility. We also document a rise in market instability since 2014 related to sources of funding and mergers and acquisitions. Overall, our model predicts the buildup of emerging risk in the financial system and bank-specific exposures in a timely fashion.

Received March 1, 2018; editorial decision November 18, 2018 by Editor Itay Goldstein.
The Fix Is In: Properly Backing out Backfill Bias
Authors: Jorion Philippe , Schwarz Christopher
Published: February 2019

Researchers have long known about backfill bias in hedge fund databases. The most common treatments include either retaining all backfilled returns or truncating a fixed number of returns from each return series. However, we show that truncation largely preserves backfilled returns and document that either of these backfill treatments can lead to biased empirical findings, including cross-sectional results. Thus, our findings show that the best practice for empirical tests is to remove returns prior to the listing date. Because most databases do not have listing dates, we propose a novel method to infer unavailable listing dates.

Received August 19, 2018; editorial decision December 4, 2018 by Editor Wei Jiang.
Markers of angiogenesis and macrophage products for predicting disease course and monitoring vascular inflammation in giant cell arteritis
Authors: van Sleen Yannick , Sandovici Maria , Abdulahad Wayel H , Bijzet Johan , van der Geest Kornelis S M , Boots Annemieke M H , Brouwer Elisabeth
Published: February 2019

Objective

GCA, a systemic vasculitis, is characterized by an IL-6-dependent acute-phase response. This response is typically suppressed by treatment rendering CRP/ESR unreliable for monitoring vascular inflammation. Also, there are no accurate biomarkers predicting a non-favourable disease course. Here we investigated macrophage products and markers of angiogenesis as biomarkers for prognosis and monitoring of vascular inflammation.

Methods

Forty-one newly diagnosed, glucocorticoid-naive GCA patients were prospectively followed for relapses and glucocorticoid requirement for a median of 30 months (range 0–71). Serum markers at baseline and during follow-up were compared with 33 age-matched healthy controls and 13 infection controls. Concentrations of IL-6, serum amyloid A, soluble CD163, calprotectin, YKL-40, VEGF, angiopoietin-1 and -2 and sTie2 were determined by ELISA/Luminex assay.

Results

Serum concentrations of all markers, but not angiopoietin-1, were elevated in GCA patients at baseline when compared with healthy controls. High VEGF (P = 0.0025) and angiopoietin-1 (P = 0.0174) and low YKL-40 (P = 0.0369) levels at baseline were predictive of a short time to glucocorticoid-free remission. Elevated angiopoietin-2 levels were associated with an imminent relapse during treatment (P < 0.05). IL-6 correlated strongly with acute-phase markers and soluble CD163 but not with markers of angiogenesis, YKL-40 or calprotectin. Glucocorticoid treatment down-modulated all markers except for calprotectin and YKL-40. Tissue expression of markers in temporal arteries was confirmed.

Conclusion

Markers of angiogenesis at baseline and during treatment predict GCA disease course, suggesting utility in patient stratification for glucocorticoid-sparing therapy. Calprotectin and YKL-40 are candidate markers for monitoring vessel wall inflammation.
Effects of spring administration of extended-release eprinomectin on fescue toxicosis, performance, and reproduction of fall-born beef heifers
Authors: Volk Mareah J , Kordas Jessica M , Stokes Rebecca S , Ireland Frank A , Shike Daniel W
Published: February 2019

The objective of this experiment was to assess the effects of eprinomectin, an extended-release injectable parasiticide, on fescue toxicosis and its impacts on beef heifer performance and reproduction. Fall-born Angus × Simmental heifers (age = 246.3 ± 22.4 d; 264.8 ± 21.1 kg body weight [BW]) were randomly assigned to one of two treatments: extended-release eprinomectin injection (ERE; n = 100) or control (CON; saline; n = 99). Treatments were administered at a rate of 1 mL/50 kg BW. Prior to experiment, heifers were dosed with oral fenbendazole to minimize parasite load. All heifers grazed endophyte-infected tall fescue as a single group and were offered a 50:50 supplement mix of corn gluten feed and soybean hulls (2.7 kg as fed per heifer per day). Body condition scores (BCS), BW, hair coat score (HCS), blood, and fecal samples were collected throughout the experiment. A subset of 40 heifers were randomly selected (20 per treatment) to assess respiration rate (RR). On d 138, heifers began a 14-d controlled internal drug release + prostaglandin synchronization protocol. Following artificial insemination (AI), heifers were exposed to five bulls for 71 d. On d 214 and 291, AI and overall pregnancy rates, respectively, were determined. There was a treatment × time interaction (P < 0.01) for BW, BCS, and average daily gain (ADG). The ERE heifers had greater (P < 0.04) BW and BCS compared to CON heifers from d 55 and 112, respectively. In addition, ERE heifers had greater (P ≤ 0.04) ADG from d 0 to 56, 56 to 112, 112 to 171, and 171 to 214; however CON heifers had greater (P < 0.01) ADG from d 214 to 291. There was no treatment × time interaction or treatment difference (P ≥ 0.27) for HCS, RR, and serum prolactin concentrations. However, serum prolactin decreased (P < 0.01) in all heifers over time. There was a treatment × time interaction (P<0.01) for fecal egg counts (FEC). The FEC did not differ (P ≥ 0.32) on d −1 or 55; however, ERE heifers had decreased (P < 0.01) FEC compared with CON heifers on d 111 (1.52 vs. 13.56 eggs per gram). The ERE heifers tended (P = 0.10) to have greater AI pregnancy rates (69% vs. 58%) and had greater (P = 0.01) overall pregnancy rates (84% vs. 68%) than CON heifers. Spring administration of extended-release eprinomectin improved BW, ADG, BCS, and AI and overall pregnancy rates in fall-born beef heifers. However, the underlying mechanism is still unclear, as there were minimal to no differences in HCS, RR, serum prolactin, and FEC.
A ‘Radical Project’: Youth Culture, Leisure, and Politics in 1980s Sheffield
Authors: Kenny Sarah
Published: February 2019

The Leadmill, a cooperative arts centre and nightclub in Sheffield, opened in 1980. The venue sought to provide an accessible leisure space for the economically and socially marginalized, and received funding for this from Sheffield City Council. Focusing on the cultural policies of the new urban left Labour Council in Sheffield during the 1980s, this article explores the relationship between Sheffield City Council and the Leadmill. It builds on recent scholarship on the 1980s that has sought to look beyond Thatcherism as an explanation for the decade, and sheds light on the everyday experiences of living through this period. This article argues for the reinvigoration of local history, and demonstrates that an exploration of a site of community leisure unveils cooperation and engagement between groups with disparate and contradicting aims. It tells a different story of the 1980s, one that recognizes how Thatcherism allowed and in some cases enabled the creation of spaces within which its critics could thrive. It shows how a range of political dialogues were present in shaping the policies of local government, and how the longer tradition of state and market interaction was shaped by the specific social, economic, and political contexts of the decade. Above all, it challenges presentations of the 1980s that favour the hegemonic power of Thatcherism and the decade as one of the triumph of individualism.
Novel contributions to the peritrich family Vaginicolidae (Protista: Ciliophora), with morphological and phylogenetic analyses of poorly known species of Pyxicola, Cothurnia and Vaginicola
Authors: Lu Borong , Li Lifang , Hu Xiaozhong , Ji Daode , Al-Rasheid Khaled A S , Song Weibo
Published: February 2019

The classification of loricate peritrich ciliates is difficult because of an accumulation of several taxonomic problems. In the present work, three poorly described vaginicolids, Pyxicola pusilla, Cothurnia ceramicola and Vaginicola tincta, were isolated from the surface of two freshwater/marine algae in China. In our study, the ciliature of Pyxicola and Vaginicola is revealed for the first time, demonstrating the taxonomic value of infundibular polykineties. The small subunit rDNA, ITS1-5.8S rDNA-ITS2 region and large subunit rDNA of the above species were sequenced for the first time. Phylogenetic analyses based on these genes indicated that Pyxicola and Cothurnia are closely related. The present study suggested that the loricate species probably represent a distinct lineage in peritrich evolution and both genera Cothurnia and Thuricola are monophyletic. Pyxicola pusilla, Cothurnia ceramicola and Vaginicola tincta are recircumscribed.
Subarachnoid Hemorrhage in the Setting of Electroconvulsive Therapy in a Patient With an Unsecured Cerebral Aneurysm
Authors: Gugger James J. , Dunn Lauren E.
Published: February 2019

Objectives

The aim of the study was to report a case of a patient who experienced a fatal aneurysmal subarachnoid hemorrhage during the course of electroconvulsive therapy (ECT).

Methods

This is a case report and review of the literature.

Results

Electroconvulsive therapy is widely viewed as a safe and effective treatment for major depressive disorder; however, there remains some uncertainty regarding the safety of ECT in patients with cerebral aneurysms. Many cases exist documenting the safety of ECT in patients with both secured and unsecured cerebral aneurysms; however, these patients had aneurysms that were associated with a low (ie, ≤2.6%) 5-year cumulative rupture rate, whereas the patient in our case had an aneurysm associated with a 14.5% five-year cumulative rupture rate.

Conclusions

We stress that ECT should not be viewed as a universally safe procedure in patients with cerebral aneurysms and the 5-year cumulative aneurysm rupture rate should be used in the discussion of the risk-benefit ratio of ECT in patients with unsecured cerebral aneurysms.
Stereotactic electroencephalography in humans reveals multisensory signal in early visual and auditory cortices
Authors: Ferraro Stefania , Van Ackeren Markus J. , Mai Roberto , Tassi Laura , Cardinale Francesco , Nigri Anna , Bruzzone Maria Grazia , D’Incerti Ludovico , Hartmann Thomas , Weisz Nathan , Collignon Olivier
Published: February 2019

Unequivocally demonstrating the presence of multisensory signals at the earliest stages of cortical processing remains challenging in humans. In our study, we relied on the unique spatio-temporal resolution provided by intracranial stereotactic electroencephalographic (SEEG) recordings in patients with drug-resistant epilepsy to characterize the signal extracted from early visual (calcarine and pericalcarine) and auditory (Heschl’s gyrus and planum temporale) regions during a simple audio-visual oddball task. We provide evidences that both cross-modal responses (visual responses in auditory cortex or the reverse) and multisensory processing (alteration of the unimodal responses during bimodal stimulation) can be observed in intracranial event-related potentials (iERPs) and in power modulations of oscillatory activity at different temporal scales within the first 150 ms after stimulus onset. The temporal profiles of the iERPs are compatible with the hypothesis that MSI occurs by means of direct pathways linking early visual and auditory regions. Our data indicate, moreover, that MSI mainly relies on modulations of the low-frequency bands (foremost the theta band in the auditory cortex and the alpha band in the visual cortex), suggesting the involvement of feedback pathways between the two sensory regions. Remarkably, we also observed high-gamma power modulations by sounds in the early visual cortex, thus suggesting the presence of neuronal populations involved in auditory processing in the calcarine and pericalcarine region in humans.
SquiggleKit: A toolkit for manipulating nanopore signal data
Authors: Ferguson James M. , Smith Martin A.
Published: February 2019

The management of raw nanopore sequencing data poses a challenge that must be overcome to accelerate the development of new bioinformatics algorithms predicated on signal analysis. SquiggleKit is a toolkit for manipulating and interrogating nanopore data that simplifies file handling, data extraction, visualisation, and signal processing. Its modular tools can be used to reduce file numbers and memory footprint, identify poly-A tails, target barcodes, adapters, and find nucleotide sequence motifs in raw nanopore signal, amongst other applications. SquiggleKit serves as a bioinformatics portal into signal space, for novice and experienced users alike. It is comprehensively documented, simple to use, cross-platform compatible and freely available from (https://github.com/Psy-Fer/SquiggleKit).
Ancestral and neo-sex chromosomes contribute to population divergence in a dioecious plant
Authors: Beaudry Felix E.G. , Barrett Spencer C.H. , Wright Stephen I.
Published: February 2019

Empirical evidence from several animal groups suggests that sex chromosomes may disproportionately contribute to reproductive isolation. This occurs particularly when sex chromosomes are associated with turnover of sex determination systems resulting from structural rearrangements to the sex chromosomes. We investigated these predictions in the dioecious plantRumex hastatulus, which is comprised of populations of two sex chromosome cytotypes. Using population genomic analyses, we investigated the demographic history ofR. hastatulusand explored the contributions of ancestral and neo-sex chromosomes to population genetic divergence. Our study revealed that the cytotypes represented genetically divergent populations with evidence for historical but not contemporary gene flow between them. In agreement with classical predictions, we found that the ancestral X chromosome was disproportionately divergent compared with the rest of the genome. Excess differentiation was also observed on the Y chromosome, even when using measures of differentiation that control for differences in effective population size. Our estimates of the timing of the origin of the neo-sex chromosomes inR. hastatulusare coincident with cessation of gene flow, suggesting that the chromosomal fusion event that gave rise to the origin of the XYY cytotype may have also been a key driver of reproductive isolation.
Phytochemical evaluation, Embryotoxicity and Teratogenic effects of Curcuma longa extract in Zebrafish (Danio rerio)
Authors: Adekoya Alafiatayo Akinola , Lai Kok-Song , Syahida Ahmad , Mahmood Maziah , Shaharuddin Noor Azmi
Published: February 2019

Curcuma longa L. is a rhizome plant often used as traditional medicinal preparations in Southeast Asia. The dried powder is commonly known as cure-all herbal medicine with a wider spectrum of pharmaceutical activities. In spite of the widely reported therapeutic applications of C. longa, research on its safety and teratogenic effects on zebrafish embryos and larvae is still limited. Hence, this research was aimed to assess the toxicity of C. longa extract on zebrafish. Using a reflux flask, methanol extract of C. longa was extracted and the identification and quantification of total flavonoids were carried out with HPLC. Twelve fertilized embryos were selected to test the embryotoxicity and teratogenicity at different concentration points. The embryos were exposed to the extract in the E3M medium while the control was only exposed to E3M and different developmental endpoints were recorded with the therapeutic index calculated using the ratio of LC50/EC50. C. longa extract was detected to be highly rich in flavonoids with catechin, epicatechin and naringenin as the 3 most abundant with concentrations of 3,531.34, 688.70 and 523.83μg/mL respectively. The toxicity effects were discovered to be dose-dependent at dosage above 62.50μg/mL, while at 125.0μg/mL, mortality of embryos was observed and physical body deformities of larvae was recorded among the hatched embryos at higher concentrations. Teratogenic effect of the extract was severe at higher concentrations producing physical body deformities such as kink tail, bend trunk, enlarged yolk sac edema. Finally, the Therapeutic Index (TI) values calculated were approximately same for different concentration points tested. Overall, the result revealed that plants having therapeutic potential could also pose threats when consumed at higher doses especially on the embryos. Therefore, detailed toxicity analysis should be carried out on medicinal plants to ascertain their safety on the embryos and its development.
BrucellaEipB is a periplasmic β-spiral protein required for envelope stress resistance and infection
Authors: Herrou Julien , Willett Jonathan W. , Fiebig Aretha , Czyż Daniel M. , Cheng Jason X. , Ultee Eveline , Briegel Ariane , Bigelow Lance , Babnigg Gyorgy , Kim Youngchang , Crosson Sean
Published: February 2019

The Gram-negative cell envelope is a remarkably diverse structure with core components that include an inner membrane, an outer membrane, and a peptidoglycan layer in the periplasmic space between. We show that a conserved DUF1849-family protein, EipB, is secreted to the periplasmic space ofBrucella, a monophyletic group of intracellular pathogens. In the periplasm, EipB folds into an unusual fourteen-stranded β-spiral structure that contains a conserved disulfide bond. EipB has structural features that resemble the LolA and LolB lipoprotein delivery system, though the overall topology and fold of EipB is distinct from LolA/LolB. Deletion ofeipBresults in defects in both cell envelope integrityin vitroand in maintenance of spleen colonization in a mouse model ofB. abortusinfection. Transposon disruption ofttpA, which encodes a periplasmic tetratricopeptide repeat (TPR) protein, is synthetically lethal witheipBdeletion inB. abortus.ttpAis a known virulence determinant inB. melitensis, and our studies ofttpAdeletion and overexpression strains provide evidence thatttpA, likeeipB, contributes to cell envelope function inBrucella. We conclude thateipBandttpAfunction in theBrucellaperiplasmic space to maintain cell envelope integrity and to facilitate survival in a mammalian host.

Importance

Brucellaspecies cause brucellosis, a global zoonosis. A gene encoding a conserved uncharacterized protein, EipB, is present in all sequencedBrucellaand several other genera in the classAlphaproteobacteria.To our knowledge, this study presents the first functional and structural characterization of a protein from the DUF1849 family, to which EipB belongs. EipB is secreted to the periplasm where it forms a spiral-like anti-parallel β structure. Deletion ofBrucella eipBresults in defects of the cell envelope and in reduced virulence in an animal model of disease.eipBgenetically interacts withttpA, which also encodes a periplasmic protein. We propose that EipB and TtpA function as part of a system required for cell envelope homeostasis in selectAlphaproteobacteria.
Neuronal L-Type Calcium Channel Signaling to the Nucleus Requires a Novel CaMKIIα-Shank3 Interaction
Authors: Perfitt Tyler L. , Wang Xiaohan , Stephenson Jason R. , Nakagawa Terunaga , Colbran Roger J.
Published: February 2019

The molecular mechanisms that couple plasma membrane receptors/channels to specific intracellular responses, such as increased gene expression, are incompletely understood. The postsynaptic scaffolding protein Shank3 associates with Ca2+ permeable receptors or ion channels that can activate many downstream signaling proteins, including calcium/calmodulin-dependent protein kinase II (CaMKII). Here, we show that Shank3/CaMKIIα complexes can be specifically co-immunoprecipitated from mouse forebrain lysates, and that purified activated (Thr286 autophosphorylated) CaMKIIα binds directly to Shank3 between residues 829-1130. Mutation of three basic residues in Shank3 (R949RK951) to alanine disrupts CaMKII binding to Shank3 fragments in vitro, as well as CaMKII association with full-length Shank3 in heterologous cells. Our shRNA/rescue studies revealed that Shank3 binding to both CaMKII and L-type calcium channels (LTCCs) is required for increased phosphorylation of the nuclear CREB transcription factor induced by depolarization of cultured hippocampal neurons. Thus, this novel Shank3-CaMKII interaction is essential for the initiation of a specific long-range signal from plasma membrane LTCCs to the nucleus that is required for activity-dependent changes in neuronal gene expression during learning and memory.