bluuebunny/crossref_metadata_2025 huggingface dataset:
Microwave-assisted preparation of paramagnetic zwitterionic amphiphilic copolymer hybrid molybdenum disulfide for T1-weighted magnetic resonance imaging-guided photothermal therapy
Authors: Yu Yiming , Chi Bin , Lin Leping , Yang Zhe , He Qianyuan , Xu Zushun , Yi Changfeng , Wang Jing
Published: September 2018

Magnetic resonance imaging (MRI)-guided photothermal therapy (PTT) has recently attracted tremendous attention.
Gated photochromism in azobenzene-appended rhodamine cassette: through-bond energy transfer – a universal strategy towards “Lock and Unlock” system
Authors: Raman Arunachalam , Augustine George , Ayyadurai Niraikulam , Easwaramoorthi Shanmugam
Published: September 2018

A dyad 1 comprising fluorescent rhodamine and photochromic azobenzene covalently linked through a phenylene bridge, which still retains their individual electronic properties, was synthesized.
Spontaneous cross-linking of proteins at aspartate and asparagine residues is mediated via a succinimide intermediate
Authors: Friedrich Michael G. , Wang Zhen , Schey Kevin L. , Truscott Roger J. W.
Published: September 2018

The breakdown of long-lived proteins (LLPs) is associated with aging, as well as disease; however, our understanding of the molecular processes involved is still limited. Of particular relevance, cross-linked proteins are often reported in aged tissues but the mechanisms for their formation are poorly understood. In the present study, sites of protein cross-linking in human ocular lenses were characterized using proteomic techniques. In long-lived lens proteins, several sites of cross-linking were found to involve the addition of Lys to Asp or Asn residues. Using model peptides containing Asp or Asn, a mechanism was elucidated that involves a succinimide intermediate. Succinimides formed readily from Asn at neutral pH, whereas a higher rate of formation from Asp peptides was observed at more acidic pHs. Succinimides were found to be relatively stable in the absence of nucleophiles. Since racemization of Asp residues, as well as deamidation of Asn, involves a succinimide intermediate, sites of d-Asp and isoAsp in LLPs should also be considered as potential sites of protein covalent cross-linking.
The XXL Survey
Authors: Ricci M. , Benoist C. , Maurogordato S. , Adami C. , Chiappetti L. , Gastaldello F. , Guglielmo V. , Poggianti B. , Sereno M. , Adam R. , Arnouts S. , Cappi A. , Koulouridis E. , Pacaud F. , Pierre M. , Ramos-Ceja M. E.
Published: September 2018

Context. The luminosity function (LF) is a powerful statistical tool used to describe galaxies and learn about their evolution. In particular, the LFs of galaxies inside clusters allow us to better understand how galaxies evolve in these dense environments. Knowledge of the LFs of galaxies in clusters is also crucial for clusters studies in the optical and near-infrared (NIR) as they encode, along with their density profiles, most of their observational properties. However, no consensus has been reached yet about the evolution of the cluster galaxy LF with halo mass and redshift.

Aims. The main goal of this study is to investigate the LF of a sample of 142 X-ray selected clusters, with spectroscopic redshift confirmation and a well defined selection function, spanning a wide redshift and mass range, and to test the LF dependence on cluster global properties, in a homogeneous and unbiased way.

Methods. Our study is based on the Canada–France–Hawaii Telescope Legacy Survey (CFHTLS) photometric galaxy catalogue, associated with photometric redshifts. We constructed LFs inside a scaled radius using a selection in photometric redshift around the cluster spectroscopic redshift in order to reduce projection effects. The width of the photometric redshift selection was carefully determined to avoid biasing the LF and depended on both the cluster redshift and the galaxy magnitudes. The purity was then enhanced by applying a precise background subtraction. We constructed composite luminosity functions (CLFs) by stacking the individual LFs and studied their evolution with redshift and richness, analysing separately the brightest cluster galaxy (BCG) and non-BCG members. We fitted the dependences of the CLFs and BCG distributions parameters with redshift and richness conjointly in order to distinguish between these two effects.

Results. We find that the usual photometric redshift selection methods can bias the LF estimate if the redshift and magnitude dependence of the photometric redshift quality is not taken into account. Our main findings concerning the evolution of the galaxy luminosity distribution with redshift and richness are that, in the inner region of clusters and in the redshift-mass range we probe (about 0 < z < 1 and 1013 M⊙ < M500 < 5 × 1014 M⊙), the bright part of the LF (BCG excluded) does not depend much on mass or redshift except for its amplitude, whereas the BCG luminosity increases both with redshift and richness.
Spectral gradient of the thermal millimetre continuum as a diagnostic for optical thickness in the solar atmosphere
Authors: Rodger A. S. , Labrosse N.
Published: September 2018

Aims. In this Letter we aim to show how the gradient of the thermal millimetre continuum spectrum, as emitted from the quiet solar atmosphere, may be used as a diagnostic for the optical thickness regime at the centre of the observing frequency band.

Methods. We show the theoretical derivation of the gradient of the millimetre continuum for both logarithmic- and linear-scale spectra. We compare this expression with the empirical relationship between the slope of the millimetre continuum spectrum and the plasma optical thickness computed from both isothermal and multi-thermal two-dimensional cylindrical radiative transfer models.

Results. It is found that the logarithmic-scale spectral gradient provides a clear diagnostic for the optical thickness regime for both isothermal and multi-thermal plasmas, provided that a suitable correction is made for a non-constant gaunt factor over the frequency band. For the use of observers we present values for this correction at all ALMA bands and at a wide range of electron temperatures.

Conclusions. We find that the spectral gradient can be used to find (a) whether the source is fully optically thin, (b) the optical thickness of the source if it lies within the transitional regime between optically thin and thick plasma (τ ≈ 10−1−101), or (c) whether the source is fully optically thick for an isothermal plasma. A multi-thermal plasma will act the same as an isothermal plasma for case (a), however, the transitional regime will only extend from τ ≈ 10−1 to τ ≈ 100. Above τ = 1 the slope of the continuum will depend increasingly on the temperature gradient, as well as the optical thickness, reducing the reliability of the diagnostic.
Occurrence and genotyping of Giardia duodenalis and Cryptosporidium in pre-weaned dairy calves in central Sichuan province, China
Authors: Zhong Zhijun , Dan Jiaming , Yan Guangwen , Tu Rui , Tian Yinan , Cao Suizhong , Shen Liuhong , Deng Junliang , Yu Shumin , Geng Yi , Gu Xiaobin , Wang Ya , Liu Haifeng , Peng Guangneng
Published: September 2018

Giardia duodenalis and Cryptosporidium spp. are common human and animal pathogens. They have increasingly been reported in dairy calves in recent years; however, multilocus genotyping information for G. duodenalis and Cryptosporidium infecting pre-weaned dairy calves in southwestern China is limited. In the present study, the prevalence of G. duodenalis and Cryptosporidium spp. in pre-weaned dairy calves in central Sichuan province was determined and the pathogens were analyzed molecularly. Of 278 fecal samples from pre-weaned dairy calves, 26 (9.4%) were positive for G. duodenalis and 40 (14.4%) were positive for Cryptosporidium spp. Cryptosporidium bovis (n = 28), Cryptosporidium ryanae (n = 5) and Cryptosporidium parvum (n = 7) were detected. All seven C. parvum isolates were successfully subtyped based on the gp60 gene sequence, and only IIdA15G1 was detected. Multilocus sequence typing of G. duodenalis based on beta-giardin (bg), triose phosphate isomerase (tpi) and glutamate dehydrogenase (gdh) genes revealed 19 different assemblage E multilocus genotypes (two known and 17 unpublished genotypes). Based on eBURST analysis, a high degree of genetic diversity within assemblage E was observed in pre-weaned dairy calves in Sichuan province. To the best of our knowledge, this is the first study using multilocus sequence typing and eBURST analysis to characterize G. duodenalis in pre-weaned dairy calves in southwestern China.
Additions of Carbohydrate-Derived Alkoxyallenes to Imines and Subsequent Reactions to Enantiopure 2,5-Dihydropyrrole Derivatives
Authors: Reissig Hans-Ulrich , Hausherr Arndt , Zimmer Reinhold
Published: September 2018

The additions of six alkoxyallenes bearing carbohydrate-derived chiral auxiliaries to imines were systematically studied. The reactions of three lithiated 1-alkoxypropa-1,2-dienes with an N-tosyl imine revealed that the diacetone fructose-derived auxiliary provided the highest diastereoselectivity of 91:9. The preferred absolute configuration of the newly formed stereogenic center was determined by subsequent ozonolysis of the allene moiety, transesterification and comparison with literature data. The analogous reactions of three axially chiral 3-nonyl-substituted 1-alkoxyallenes with these auxiliaries confirm these results and also prove that the configuration of the generated stereogenic center was only steered by the auxiliaries, whereas the chiral axis has essentially no influence. In general, four diastereomers were obtained in various portions, depending on the ratio of the two precursor allene diastereomers and on the auxiliary employed. The obtained dia­stereomeric allenyl amines were cyclized under different conditions. As expected, under basic conditions, a stereospecific cyclization occurred, whereas under silver nitrate catalysis partial isomerization at the allene stage was observed. Under both conditions the 2,5-cis-disubstituted dihydropyrroles were formed faster than the trans-isomers. Several of the 2-substituted or 2,5-disubstituted dihydropyrrole derivatives could be isolated in diastereomerically pure form and were subsequently converted into the expected pyrrolidin-3-ones by removal of the carbohydrate-derived auxiliary under acidic conditions. The desired products were obtained in good yield and with high enantiopurity. They are suitable starting materials for the synthesis of enantiopure pyrrolidine natural products.
Two Cases of Inherited Triple Deficiency in a Large Kindred with Thrombotic Diathesis and Deficiencies of Antithrombin III, Heparin Cofactor II, Protein C and Protein S
Authors: Jobin F , Vu L , Lessard M
Published: September 2018

Thirty-three subjects, belonging to a large family with functional antithrombin III (ATIII) deficiency (type IIa) and recurrent thromboembolism, were investigated for ATIII, heparin cofactor II (HCII), protein C (PC) and protein S (PS). We report the exceptional finding of two cases of triple deficiency: ATIII combined with HCII and PC in the first case aged 15 and ATIII combined with HCII and PS in the second case aged 27. Interestingly, both are asymptomatic thus far. Twenty-five other deficient members were found, among which seven are affected with a double deficiency. Totally, the results of our study show 38 deficiencies of four distinct antithrombotic protein: ATIII (n = 9), HCII (n = 9), PC (n = 7) or PS (n = 13). Two types of HCII deficiency were observed and type I PC deficiency was found. Functional PS deficiency was characterized by reduced levels of cofactor activity for activated PC. Our report demonstrates that combined deficiencies should be sought in a family already known to be deficient in one antithrombotic protein.
Prediction of Vitamin K Response Using the Echis Time and Echis-Prothrombin Time Ratio
Authors: Solano C , Cobcroft R G , Scott D C
Published: September 2018

Echis carinatus venom contains proteases capable of activating both normal and descarboxy prothrombin. We showed this venom (Sigma) principally activates prothrombin with almost no factor X activation. Echis time in combination with prothrombin time can predict vitamin K responsiveness since the Echis time is usually normal in the presence of descarboxy prothrombin associated with vitamin K deficiency.

38 patients with abnormal routine prothrombin times (PT) had both coagulant and immunogenic factor II assays along with Echis times done before and after vitamin K. Of 22 patients responding to vitamin K, based on correction of PT, 21 had normal initial Echis times and of 16 not responding, 11 had abnormal Echis times, giving a sensitivity of 95.4% and specificity of 68.8% for vitamin K responsiveness. 90% of patients with a PT/Echis time ratio <1.3 and a prolonged Echis time did not correct their PTs with vitamin K therapy.

The 5 non-responders with normal Echis times all showed normal initial coagulant and antigenic prothrombin, but 3 had low F V and/or F VII.
Increased Heparin Cofactor II Levels in Women Taking Oral Contraceptives
Authors: Toulon P , Bardin J M , Blumenfeld N M
Published: September 2018

Heparin cofactor II (HCII) is a thrombin inhibitor present in human plasma whose activity is enhanced by heparin. HCII exhibits important homologies with antithrombin III, the main heparin-enhanced thrombin inhibitor. Cases of recurrent thromboembolism have been recently reported in patients with HCII deficiency. Since the use of oral contraceptives (OC) is associated with an increased risk of thrombosis, the study of the plasma levels of HCII was undertaken in women taking contraceptive pills. Plasma HCII levels were found significantly higher in 62 women taking low-estrogen content OC (1.20 ± 0.28 U/ml) than in 62 age matched women not taking OC (0.94 ± 0.16 U/ml) or in 62 men (0.96 ± 0.19 U/ml). Significant correlations between HCII and fibrinogen levels were reported in the three groups. From the pooled data of the two control groups (men and women not taking OC), the normal range for plasma HCII levels was defined to be between 0.60 and 1.30 U/ml (mean ± 2 SD). Two cases of low HCII levels (<0.60 U/ml) were found in the control groups, but none in the group of women taking OC. It is concluded that the use of oral contraceptives is associated with a rise in HCII levels and that the screening for HCII deficiency has to be performed at distance of any OC therapy.
Fibrin Specific Thrombolysis by Two-Chain Urokinase-Type Plasminogen Activator Cleaved after Arginine 156 by Thrombin
Authors: Abercrombie David M , Buchinski Bruce , Salvato Kathleen A , Vovis Gerald F , Stump David C , Broeze Robert J
Published: September 2018

Scu-PA was cleaved by thrombin after arginine-156 to yield a two-chain molecule with low amidolytic activity and resistance to cleavage by plasmin. 125I-fibrin-labeled clots were dissolved in vitro by thrombin-cut scu-PA, but only at concentrations 10- to 50-fold greater than that needed for scu-PA. Three hours of incubation produced 100, 80, and 31% lysis with 100, 50, and 25 pg/ml thrombin-cut scu-PA. Thrombin-cut scu-PA, scu-PA, and tcu-PA yielded linear dose responses in the rabbit jugular venous thrombosis model. The dose required to reach 40% lysis was 2 mg/kg for scu-PA, 3 mg/kg for tcu-PA, and 4 mg/kg for thrombin-cut scu-PA. No significant consumption of fibrinogen or alpha2-antiplasmin levels was observed with thrombin-cut scu-PA while the level of fibrinogen and alpha2-antiplasmin decreased to about 50 and 40%, respectively, with scu-PA and to less than 10% of baseline with tcu-PA. Thus, while less potent than scu-PA, thrombin-cut scu-PA appears to be a more fibrin-specific thrombolytic agent than scu-PA.
lncrease of Tissue Plasminogen Activator in Limbs During Venous Occlusion : A Simple Haemodynamic Model
Authors: Keber D , Blinc A , Fettich J
Published: September 2018

Venous occlusion of a limb is an established procedure for increasing the venous plasma concentration of tissue plasminogen activator (t-PA). In this paper a simple haemodynamic model was developed to describe the venous plasma t-PA concentration as a function of haemodynamic parameters and the local release rate of t-PA during venous occlusion of the limb. The venous plasma pool of a limb was regarded as a single well-mixed compartment with a constant input rate of t-PA. The intravascular volume, blood flow and total limb volume of the upper extremity were also measured in three healthy subjects in order to characterise the haemodynamics during venous occlusion. Venous occlusion was shown to cause such an intense decrease of blood flow through the limb that the postocclusion increase in concentration of t-PA need not be explained by an increased release rate of t-PA but could be attributed merely to the diminished dilution of the venous compartment by inflowing arterial plasma. According to our model and haemodynamic measurements, the significant differences in the postocclusion concentration of t-PA between the arrn and leg can be explained by different local release rates of t-PA.
Psychopharmacology curriculum for psychiatric residents
Authors: Baumann P. , Möller H.-J. , Laux G.
Published: September 2018

Background: Postgraduate teaching of psychiatric residents in the important field of psychopharmacology and pharmacotherapy is insufficient regarding number of hours of theoretical teaching and practical training, content and structure and varies widely. Education based on controlled trials (evidence-based) may interfere with daily life real world experience and questions of doctors. Method: Data available from national psychiatric societies and from the literature are presented as well as a recently proposed German curriculum and learning catalogue. The latter includes general pharmacology including pharmacokinetics, neurobiological principles, clinical pharmacology of different classes of psychotropics (antidepressants, antipsychotics, mood stabilizers, anxiolytics, hypnotics, stimulants etc.), special aspects (e.g. pregnancy, geriatric patients) as well as ethical, legal and economic aspects. About 160 hours of theoretical education are proposed, clinical teaching should be interactive, with vignettes and supervision covering about 300 hours. There is a need for standardization of psychopharmacology-pharmacopsychiatry teaching at the European level.
Structure, magnetism and electrical transport in epitaxial La0.23Pr0.41Ca0.36MnO3 thin films: Consequences of film thickness
Authors: Singh Sandeep , Tyagi P. K. , Singh H. K.
Published: September 2018

A systematic study of the consequences of in-plane tensile strain on the correlation between structure/microstructure and magneto-electrical properties of La0.23Pr0.41Ca0.36MnO3/SrTiO3 (001) thin films is performed. At lower film thickness (d≤27 nm) the dominant tensile strain supports layered morphology. At d=41 nm structural/microstructural crossover takes place and at d≥41 nm relaxation induced tilt and dilations of the lattice generate defects like dislocations, which in turn transforms the layer by layer growth into disordered brick type morphology. It appears that the relaxation even at higher thickness (∼81 nm) is partial only and the strain may have a self-sustained nature. The domination of the tensile strain suppresses the ferromagnetic-metallic phase due to the possible electronic reconstruction which could give rise to a magnetically disordered insulator ‘dead’ layer and a sizeable non-magnetic insulator state at d≤27 nm. In this thickness regime the possible selective orbital stabilization could also contribute to carrier localization. At d≥41 nm the severity of the impact of the interfacial electronic reconstruction is reduced with concomitant relaxation of the tensile strain which favors carrier delocalization and yields well defined metallic-ferromagnetic phase transitions. The hysteretic nature of the phase transitions reflects the thermal cycle dependent nature of the metallic-ferromagnetic and insulating antiferromagnetic phases in this strongly phase separated material.
Fine structure of the phloem of Pisum sativum. I. The sieve element ontogeny
Authors: Wark MC , Chambers TC
Published: September 2018

An ontogenetic study of secondary phloem sieve elements of Pisum sativum L.,
fixed on the intact plant for electron microscopy, indicates that the connecting strands
across the sieve plates are continuities of the endoplasmic reticulum. Each connecting
strand is surrounded by a callose cylinder. The peripheral cytoplasm of the nucleate
"young" sieve elements contains longitudinally oriented tubules of endoplasmic
reticulum. As the sieve elements develop, nuclear material is extruded into the cytoplasm
by way of a fibrotubular body which is structurally distinct from the slime
body. When the cells are fully expanded the slime bodies disperse. This process is
followed by breakdown of a number of organelles including the nucleus and tonoplast.
This apparently leaves the endoplasmic reticulum free in the cell lumen.
Growth of Themeda australis tussock grassland at St. Albans, Victoria
Authors: Groves RH
Published: September 2018

Seasonal changes in biomass of a tussock grassland dominated by Themeda
australis (R.Br.) Stapf were followed for a 15-month period. Results for both the
shoot and root components of the grassland are presented. The period for maximum
dry matter production of the shoots is shown to occur 1-2 months after that of an
introduced pasture in a similar environment. The significance of this fact is discussed
in relation to the growth of various pastures and heath vegetation in southern Australia.
A species list for the grassland is given, together with the flowering times of the
major species.
Social learning and partisan bias in the interpretation of climate trends
Authors: Guilbeault Douglas , Becker Joshua , Centola Damon
Published: September 2018

Significance

Scientific communications about climate change are frequently misinterpreted due to motivated reasoning, which leads some people to misconstrue climate data in ways that conflict with the intended message of climate scientists. Attempts to reduce partisan bias through bipartisan communication networks have found that exposure to diverse political views can exacerbate bias. Here, we find that belief exchange in structured bipartisan networks can significantly improve the ability of both conservatives and liberals to interpret climate data, eliminating belief polarization. We also find that social learning can be reduced, and polarization maintained, when the salience of partisanship is increased, either through exposure to the logos of political parties or through exposure to political identity markers.
Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter
Authors: Burnett Richard , Chen Hong , Szyszkowicz Mieczysław , Fann Neal , Hubbell Bryan , Pope C. Arden , Apte Joshua S. , Brauer Michael , Cohen Aaron , Weichenthal Scott , Coggins Jay , Di Qian , Brunekreef Bert , Frostad Joseph , Lim Stephen S. , Kan Haidong , Walker Katherine D. , Thurston George D. , Hayes Richard B. , Lim Chris C. , Turner Michelle C. , Jerrett Michael , Krewski Daniel , Gapstur Susan M. , Diver W. Ryan , Ostro Bart , Goldberg Debbie , Crouse Daniel L. , Martin Randall V. , Peters Paul , Pinault Lauren , Tjepkema Michael , van Donkelaar Aaron , Villeneuve Paul J. , Miller Anthony B. , Yin Peng , Zhou Maigeng , Wang Lijun , Janssen Nicole A. H. , Marra Marten , Atkinson Richard W. , Tsang Hilda , Quoc Thach Thuan , Cannon John B. , Allen Ryan T. , Hart Jaime E. , Laden Francine , Cesaroni Giulia , Forastiere Francesco , Weinmayr Gudrun , Jaensch Andrea , Nagel Gabriele , Concin Hans , Spadaro Joseph V.
Published: September 2018

Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5and nonaccidental mortality using data from 41 cohorts from 16 countries—the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5–10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9–8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3–4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations.
Structural titration of receptor ion channel GLIC gating by HS-AFM
Authors: Ruan Yi , Kao Kevin , Lefebvre Solène , Marchesi Arin , Corringer Pierre-Jean , Hite Richard K. , Scheuring Simon
Published: September 2018

Significance

Gloeobacter violaceus
ligand-gated ion channel (GLIC) is a proton-gated, cation-selective channel, a Cys-loop family member of the pentameric ligand-gated ion channels (pLGICs). In a pursuit to provide evidence of function-related conformational changes of a pLGIC in membrane, at ambient temperature and pressure and of the very same unlabeled molecules, we used high-speed atomic force microscopy (HS-AFM) combined with a buffer exchange system to visualize reversible changes of the supramolecular arrangement and conformations of GLIC during pH changes: a structural titration experiment. Reference-free classification of the molecules assigns conformations to states during the pH titration. We find large conformational changes with an unexpected closed-state structure with tightened extracellular domains. Furthermore, we provide evidence for the short-term existence of asymmetric channels at early stages of activation.
Acute, local infusion of angiotensin II impairs microvascular and metabolic insulin sensitivity in skeletal muscle
Authors: Premilovac Dino , Attrill Emily , Rattigan Stephen , Richards Stephen M , Kim Jeonga , Keske Michelle A
Published: September 2018

Aims

Angiotensin II (AngII) is a potent vasoconstrictor implicated in both hypertension and insulin resistance. Insulin dilates the vasculature in skeletal muscle to increase microvascular blood flow and enhance glucose disposal. In the present study, we investigated whether acute AngII infusion interferes with insulin’s microvascular and metabolic actions in skeletal muscle.

Methods and results

Adult, male Sprague-Dawley rats received a systemic infusion of either saline, AngII, insulin (hyperinsulinaemic euglycaemic clamp), or insulin (hyperinsulinaemic euglycaemic clamp) plus AngII. A final, separate group of rats received an acute local infusion of AngII into a single hindleg during systemic insulin (hyperinsulinaemic euglycaemic clamp) infusion. In all animals’ systemic metabolic effects, central haemodynamics, femoral artery blood flow, microvascular blood flow, and skeletal muscle glucose uptake (isotopic glucose) were monitored. Systemic AngII infusion increased blood pressure, decreased heart rate, and markedly increased circulating glucose and insulin concentrations. Systemic infusion of AngII during hyperinsulinaemic euglycaemic clamp inhibited insulin-mediated suppression of hepatic glucose output and insulin-stimulated microvascular blood flow in skeletal muscle but did not alter insulin’s effects on the femoral artery or muscle glucose uptake. Local AngII infusion did not alter blood pressure, heart rate, or circulating glucose and insulin. However, local AngII inhibited insulin-stimulated microvascular blood flow, and this was accompanied by reduced skeletal muscle glucose uptake.

Conclusions

Acute infusion of AngII significantly alters basal haemodynamic and metabolic homeostasis in rats. Both local and systemic AngII infusion attenuated insulin’s microvascular actions in skeletal muscle, but only local AngII infusion led to reduced insulin-stimulated muscle glucose uptake. While increased local, tissue production of AngII may be a factor that couples microvascular insulin resistance and hypertension, additional studies are needed to determine the molecular mechanisms responsible for these vascular defects.
8. EU Enlargement and Wider Europe
Authors: Sedelmeier Ulrich , Avery Graham
Published: September 2018

The EU has expanded many times and many countries still aspire to join. It has extended the prospect of membership to countries in the Balkans and Turkey and has developed a ‘neighbourhood’ policy towards other countries, some of which may want to join in the future. Enlargement illustrates the success of the European model of integration. It has also provided the EU with a powerful tool to influence domestic politics in would-be members. But enlargement also poses fundamental challenges. It has implications both for how the EU works (its structure and institutions) and for what it does (its policies). The chapter first compares ‘widening’ and ‘deepening’ before discussing enlargement as soft power. It then explains how the EU has expanded and why countries want to join. It also looks at prospective member states: the Balkan countries, Turkey, Norway, Switzerland, and Iceland. Finally, it examines the European Neighbourhood Policy.
Impact of strategic planning, organizational culture imprint and care bundles to reduce adverse events in the ICU
Authors: Álvarez-Maldonado Pablo , Reding-Bernal Arturo , Hernández-Solís Alejandro , Cicero-Sabido Raúl
Published: September 2018

Objective

To evaluate the occurrence of adverse events during a multifaceted program implementation.

Design

Cross-sectional secondary analysis.

Setting

The respiratory-ICU of a large tertiary care center.

Participants

Retrospectively collected data of patients admitted from 1 March 2010 to 28 February 2014 (usual care period) and from 1 March 2014 to 1 March 2017 (multifaceted program period) were used.

Interventions

The program integrated three components: (1) strategic planning and organizational culture imprint; (2) training and practice and (3) implementation of care bundles. Strategic planning redefined the respiratory-ICU Mission and Vision, its SWOT matrix (strengths, weaknesses, opportunities, threats) as well as its medium to long-term aims and planned actions. A ‘Wear the Institution's T-shirt’ monthly conference was given in order to foster organizational culture in healthcare personnel. Training was conducted on hand hygiene and projects ‘Pneumonia Zero’ and ‘Bacteremia Zero’. Finally, actions of both projects were implemented.

Main outcome measures

Rates of adverse events (episodes per 1000 patient/days).

Results

Out of 1662 patients (usual care, n = 981; multifaceted program, n = 681) there was a statistically significant reduction during the multifaceted program in episodes of accidental extubation ([Rate ratio, 95% CI] 0.31, 0.17–0.55), pneumothorax (0.48, 0.26–0.87), change of endotracheal tube (0.17, 0.07–0.44), atelectasis (0.37, 0.20–0.68) and death in the ICU (0.82, 0.69–0.97).

Conclusions

A multifaceted program including strategic planning, organizational culture imprint and care protocols was associated with a significant reduction of adverse events in the respiratory-ICU.
A Quantile Regression Approach to Estimate the Variance of Financial Returns*
Authors: Baur Dirk G , Dimpfl Thomas
Published: September 2018

We propose to estimate the conditional variance of a time series of financial returns through a quantile autoregressive (AR) model and demonstrate that it contains all information commonly captured in two separate equations for the mean and variance of a generalized AR conditional heteroscedasticity-type model. We show that the inter-quantile range spanned by conditional quantile estimates identifies the asymmetric response of volatility to lagged returns, resulting in wider conditional densities for negative returns than for positive returns. Finally, we estimate the conditional variance based on the estimated conditional density and illustrate its accuracy in a forecast evaluation.
The distribution and physical properties of high-redshift [O iii] emitters in a cosmological hydrodynamics simulation
Authors: Moriwaki Kana , Yoshida Naoki , Shimizu Ikkoh , Harikane Yuichi , Matsuda Yuichi , Matsuo Hiroshi , Hashimoto Takuya , Inoue Akio K , Tamura Yoichi , Nagao Tohru
Published: September 2018

Recent observations with the Atacama Large Millimeter/submillimeter Array (ALMA) detected far-infrared emission lines such as the [O iii] $88\,\mu \mathrm{ m}$ line from galaxies at z ∼ 7−9. We use a cosmological simulation of galaxy formation to study the physical properties of [O iii] $88\,\mu \mathrm{ m}$ emitters. In a comoving volume of 50 h−1 Mpc on a side, we locate 34 galaxies with stellar masses greater than $10^8\ \rm M_{\odot }$ at z = 9, and more than 270 such galaxies at z = 7. We calculate the [O iii] $88\,\mu \mathrm{ m}$ luminosities ($L_{{\rm O\,{{\rm {\small{III}}}, 88}}}$) by combining a physical model of H ii regions with emission line calculations using the photoionization code cloudy. We show that the resulting $L_{{\rm O\,{{\rm {\small{III}}}, 88}}}$, for a given star formation rate, is slightly higher than predicted from the empirical relation for local galaxies, and is consistent with recent observations of galaxies at redshifts 7–9. Bright [O iii] emitters with $L_{{\rm O\,{{\rm {\small{III}}}, 88}}}\gt 10^8\, \rm L_{\odot }$ have star formation rates higher than $3\,\rm M_{\odot }\,{\rm yr}^{-1}$, and the typical metallicity is ${\sim } 0.1\, \rm Z_{\odot }$. The galaxies are hosted by dark matter haloes with masses greater than $10^{11}\, \rm M_{\odot }$. We propose to use the [O iii] 5007 Å line, to be detected by James Webb Space Telescope, to study the properties of galaxies whose [O iii] $88\,\mu \mathrm{ m}$ line emission has been already detected with ALMA.
Pediatric Abusive Head Trauma: Return to Hospital System in the First Year Post Injury
Authors: Fraser Brittany D , Lingo P Ryan , Khan Nickalus R , Vaughn Brandy N , Klimo Jr Paul
Published: September 2018

BACKGROUND

Abusive head trauma (AHT) may result in costly, long-term sequelae.

OBJECTIVE

To describe the burden of AHT on the hospital system within the first year of injury.

METHODS

Single institution retrospective evaluation of AHT cases from January 2009 to August 2016. Demographic, clinical (including injury severity graded I-III), and charge data associated with both initial and return hospital visits within 1 yr of injury were extracted.

RESULTS

A total of 278 cases of AHT were identified: 60% male, 76% infant, and 54% African-American. Of these 278 cases, 162 (60%) returned to the hospital within the first year, resulting in 676 total visits (an average of 4.2 returns/patient). Grade I injuries were less likely to return than more serious injuries (II and III). The majority were outpatient services (n = 430, 64%); of the inpatient readmissions, neurosurgery was the most likely service to be involved (44%). Neurosurgical procedures accounted for the majority of surgeries performed during both initial admission and readmission (85% and 68%, respectively). Increasing injury severity positively correlated with charges for both the initial admission and returns (P < .001 for both). Total calculated charges, including initial admission and returns, were over $25 million USD.

CONCLUSION

AHT has a high potential for return to the hospital system within the first year. Inpatient charges dominate and account for the vast majority of hospital returns and overall charges. A more severe initial injury correlates with increased charges on initial admission and on subsequent hospital return.
Major risk factors for sexual minority young people’s mental and physical health: findings from a county-wide school-based health needs assessment
Authors: Clarke A , Beenstock J , Lukacs J N , Turner L , Limmer M
Published: September 2018

Background

Childhood health is an important adult health predictor. Sexual orientation is increasingly recognized as influential on children and young people’s (CYP) mental and physical health.

Methods

Data came from a cross-sectional survey of year 9 children attending schools in two local authorities in the north-west of England, including mental and physical health indicators, and demographic characteristics including sexual orientation. The sample of 8058 represented 67.8% of the eligible population. Data were analysed by sexual orientation, sexual majority or sexual minority.

Results

Children reporting their sexual orientation as sexual minority reported worse mental and physical health outcomes and behaviours than sexual majority peers; had higher odds of being lonely (odds ratios (OR) = 8.24, 95% C.I.: 6.56–10.37), having self-harmed (OR = 7.28, 95% C.I.: 5.78–9.15), being bullied (OR = 4.76, 95% C.I.: 3.74–6.05) or perceiving themselves as overweight (OR = 2.40, 95% C.I.: 1.89–3.06).

Conclusions

It is important to identify and support children in a sexual minority. Research is required to understand differences between children within sexual minorities and the impact on outcomes and rights. Health and social policy and services, should respond to the vulnerabilities of sexual minority CYP.
Sedentary behaviour is associated with diabetes mellitus in adults: findings of a cross-sectional analysis from the Brazilian National Health System
Authors: Lemes Ítalo Ribeiro , Sui Xuemei , Turi-Lynch Bruna Camilo , Lee Duck-chul , Blair Steven N , Fernandes Rômulo Araújo , Codogno Jamile Sanches , Monteiro Henrique Luiz
Published: September 2018

Background

Sedentary behaviour (SB) may contribute to the development of several chronic diseases, such as hypertension, diabetes mellitus (DM) and all-cause mortality. The aim of this study is to investigate the association between different domains of SB with diabetes among adult users of the Brazilian National Health System (NHS).

Methods

Cross-sectional study from the primary care system of the Brazilian NHS in the city of Bauru, Brazil. SB, physical activity (PA), DM and other chronic diseases were assessed by face-to-face interviews and medical records. As potential confounders in the adjusted model, we used gender, age, economic status, smoking status, hypertension, hypercholesterolaemia and PA.

Results

The study was composed of 147 men and 410 women. The fully adjusted model showed that Brazilian adults spending ≥3 h per day in television viewing (OR = 1.61 [95% CI: 1.11–2.33]) and overall SB (OR = 1.60 [95% CI: 1.09–2.36]) had increased prevalence of DM compared to those spending <3 h per day.

Conclusions

TV viewing and overall SB was associated with higher prevalence of DM in Brazilian adults from the NHS, even after controlling for potential confounders including PA.
Long-Run Price Elasticities of Demand for Credit: Evidence from a Countrywide Field Experiment in Mexico
Authors: Karlan Dean , Zinman Jonathan
Published: September 2018

We use randomized interest rates, offered across eighty geographically distinct regions for twenty-nine months by Mexico’s largest microlender, to sketch the adjustment from a price change to a new equilibrium. Demand is elastic, and more so over the longer run; e.g. the dollars-borrowed elasticity increases from $-$1.1 in Year one to $-$2.9 in Year three. Credit bureau data do not show evidence of crowd-out, although this and other null results are imprecisely estimated. The lender’s profits increase, albeit noisily, starting in Year two. But competitors do not respond by reducing rates. These findings, together with other results, suggest that informational frictions are important, and that cutting rates furthered Compartamos Banco’s “double bottom line” of improving social welfare subject to a profitability constraint.
Immunological characterization of a rat model of Duchenne’s disease and demonstration of improved muscle strength after anti-CD45RC antibody treatment
Authors: Ouisse Laure-Hélène , Remy Séverine , Lafoux Aude , Larcher Thibaut , Tesson Laurent , Chenouard Vanessa , Guillonneau Carole , Brusselle Lucas , Vimond Nadège , Rouger Karl , Péréon Yann , Chenouard Alexis , Guen Christèle Gras-Le , Braudeau Cécile , Josien Régis , Huchet Corinne , Anegon Ignacio
Published: September 2018

Duchenne muscular dystrophy (DMD) has as standard pharmacological therapy with corticoisteroids (CS) that decrease inflammation and immune responses present in patients and animal models. CS have however limited efficacy and important and numerous side effects. Therefore, there is a need for new anti-inflammatory and pro-tolerogenic treatments that could replace or decrease doses of CS. We first assessed the status of immune system of dystrophin-deficient rats (Dmdmdx) that closely reproduce the phenotype of DMD patients.Dmdmdxrats showed increased leukocyte infiltration in skeletal and cardiac muscles, containing mostly macrophages but also T cells, and increased expression of several cytokines. Anti-CD45RC Monoclonal antibody (Mab) treatment induced immune tolerance in models of organ transplantation and GVHD (Graft Versus Host Disease). We observed that muscles and blood of DMD patients contained T CD4+and CD8+expressing high levels of CD45RChighcells. Treatment of youngDmdmdxrats with anti-CD45RC MAb corrected skeletal muscle strength associated to a depletion of effectors CD45RChighT cells with no obvious side-effects. Prednisolone treatment ofDmdmdxrats similarly increased skeletal muscle strength and was also associated to a depletion of effectors CD45RChighcells but resulted in severe weight loss.

Overall,Dmdmdxrats display important immune inflammatory response and thus represent a useful model to analyze new anti-inflammatory and tolerogenic treatments for DMD. As an example, a new treatment with anti-CD45RC antibodies improved muscle strength inDmdmdxrats as prednisolone did but without side effects. Anti-CD45RC therapy could complement other therapies in DMD patients.
Modeling of DNA methylation in cis reveals principles of chromatin folding in vivo in the absence of crosslinking and ligation
Authors: Redolfi Josef , Zhan Yinxiu , Valdes Christian , Kryzhanovska Mariya , Guerreiro Isabel Misteli , Iesmantavicius Vytautas , Tiana Guido , Pollex Tim , Kind Jop , Smallwood Sebastien , Laat Wouter de , Giorgetti Luca
Published: September 2018

Mammalian chromosomes are folded into an intricate hierarchy of structural domains, within which topologically associating domains (TADs) and CTCF-associated loops partition the physical interactions between regulatory sequences. Current understanding of chromosome folding largely relies on chromosome conformation capture (3C)-based experiments, where chromosomal interactions are detected as ligation products after crosslinking of chromatin. To measure chromosome structure in vivo, quantitatively and without relying on crosslinking and ligation, we have implemented a new method named damC. DamC combines DNA-methylation based detection of chromosomal interactions with next-generation sequencing and a biophysical model of methylation kinetics. DamC performed in mouse embryonic stem cells provides the first in vivo validation of the existence of TADs and CTCF loops, confirms 3C-based measurements of the scaling of contact probabilities within TADs, and provides evidence that mammalian chromatin in vivo is essentially rigid below 5 kilobases. Combining damC with transposon-mediated genomic engineering shows that new loops can be formed between ectopically introduced and endogenous CTCF sites, which alters the partitioning of physical interactions within TADs. This establishes damC as a crosslinking-and ligation-free framework to measure and modify chromosome interactions combined with a solid theoretical background for rigorous data interpretation. This orthogonal approach to 3C validates the existence of key structural features of mammalian chromosomes and provides novel insights into how chromosome structure within TADs can be manipulated.
A role for Gic1 and Gic2 in Cdc42 polarization
Authors: Daniels Christine N. , Zyla Trevin R. , Lew Daniel J.
Published: September 2018

The conserved Rho-family GTPase Cdc42 is a master regulator of polarity establishment in many cell types. Cdc42 becomes activated and concentrated in a region of the cell cortex, and recruits a variety of effector proteins to that site. In turn, many effectors participate in regulation of cytoskeletal elements in order to remodel the cytoskeleton in a polarized manner. The budding yeast Saccharomyces cerevisiae has served as a tractable model system for studies of cell polarity. In yeast cells, Cdc42 polarization involves a positive feedback loop in which effectors called p21-activated kinases (PAKs) act to recruit a Cdc42-directed guanine nucleotide exchange factor (GEF), generating more GTP-Cdc42 in areas that already have GTP-Cdc42. The GTPase-interacting components (GICs) Gic1 and Gic2 are also Cdc42 effectors, and have been implicated in regulation of the actin and septin cytoskeleton. However, we report that cells lacking GICs are primarily defective in polarizing Cdc42 itself, suggesting that they act upstream as well as downstream of Cdc42 in yeast. Our findings suggest that feedback pathways involving GTPase effectors may be more prevalent than had been appreciated.