bluuebunny/crossref_metadata_2025 huggingface dataset:
AdS asymptotic symmetries from CFT mirrors
Authors: Mishra Rashmish K. , Mohd Arif , Sundrum Raman
Published: March 2019

Abstract

We study Kac-Moody asymptotic symmetries and memory effects in AdS
4
Poincaré
gauge theory and (when accompanied by 4D gravity) in its holographic CFT3 dual. While such infinite-dimensional symmetries are absent in standard asymptotic analyses of AdS4, we show how they arise with alternate AdS boundary conditions. In the 3D holographic description, these alternate boundary conditions correspond to a modified

$$ {\tilde{\mathrm{CFT}}}_3 $$

C
F
T

˜

3

obtained by Chern-Simons gauging of the CFT3 dual defined by standard boundary conditions, so that Kac-Moody symmetries then follow from the familiar Chern-Simons/Wess-Zumino-Witten correspondence. Apart from their own intrinsic interest, in abelian AdS4 gauge theories these alternate boundary conditions are equivalent to standard boundary conditions imposed on electric-magnetic dual variables. In the holographic description this corresponds to 3D “mirror” symmetries connecting the original and modified CFTs. Further, in both abelian and non-abelian theories we show that the alternative/

$$ {\tilde{\mathrm{CFT}}}_3 $$

C
F
T

˜

3

theory emerges at leading order in large Chern-Simons level from the correlators of the standard theory, upon incorporating large-wavelength limits in the holographically emergent dimension. We point out similarities and differences between 4D AdS and Minkowski gauge theories in their asymptotic symmetries, “soft” limits and memory effects.
The Impact of Evidence in Surgery of the Musculoskeletal System
Authors: Akhter Shakib , Mundi Raman , Bhandari Mohit
Published: March 2019

There have been a growing number of landmark randomized controlled trials published in the orthopedic literature over the past decade. These large‐scale trials have had a substantial impact on informing clinical orthopedic practice globally. This review highlights a selected sample of such pivotal trials, across the subspecialties of trauma, sports medicine, arthroplasty, spine, and the important topic of intimate partner violence.
Possible Preventable Causes of Unplanned Readmission After Elective Liver Resection, Results from a Non‐academic Referral HPB Center
Authors: de Klein G. W. , Brohet R. M. , Liem M. S. L. , Klaase J. M.
Published: March 2019

Introduction

Unplanned readmission is a common event after liver resection, and it is a burden for both patients and healthcare policy makers. This study evaluates the incidence of and reasons for unplanned readmission after liver resection, in order to identify possible preventable causes.

Methods

In this single‐center cohort study, data from patients who underwent liver resection for both malignant and benign indications from 2001 to 2016 at our institute were collected from a database with prospective data. Readmissions were analyzed for their reasons and risk factors. Patients with general complaints with no specific complications were categorized as failure to thrive.

Results

In 406 patients, the readmission rate was 11.6%. Most patients were readmitted because of failure to thrive (35%), deep and superficial surgical site infection (28%), or cardiopulmonary complications (15%). A multivariate analysis revealed that unplanned readmission was associated with the occurrence of complications during index admission—with an odds ratio of 4.69 (CI 2.41–9.12, p < 0.001).

Conclusion

Readmission occurs in more than 1 in 10 patients after liver resection, and it is associated with a complicated course during index admission. One‐third of readmissions occur because of failure to thrive and might be preventable. Future research in strategies to reduce readmission rates should focus on both the prevention of complications during index admission and programs at the interface between primary and secondary care.
Can passenger flow distribution be estimated solely based on network properties in public transport systems?
Authors: Luo Ding , Cats Oded , van Lint Hans
Published: March 2019

We present a pioneering investigation into the relation between passenger flow distribution and network properties in public transport systems. The methodology is designed in a reverse engineering fashion by utilizing passively measured passenger flow dynamics over the entire network. We quantify the properties of public transport networks using a range of centrality indicators in the topological representations of public transport networks with both infrastructure and service layers considered. All the employed indicators, which originate from complex network science, are interpreted in the context of public transport systems. Regression models are further developed to capture the correlative relation between passenger flow distribution and several centrality indicators that are selected based on the correlation analysis. The primary finding from the case study on the tram networks of The Hague and Amsterdam is that the selected network properties can indeed be used to approximate passenger flow distribution in public transport systems to a reasonable extent. Notwithstanding, no causality is implied, as the correlation may also reflect how well the supply allocation caters for the underlying demand distribution. The significance and relevance of this study stems from two aspects: (1) the unraveled relation provides a parsimonious alternative to existing passenger assignment models that require many assumptions on the basis of limited data; (2) the resulting model offers efficient quick-scan decision support capabilities that can help transport planners in tactical planning decisions.
FEA simulation aids development of seals for use in challenging oil and gas applications
Authors: Atkinson Simon
Published: March 2019

The range of benefits associated with finite element analysis (FEA) simulation makes the technique highly favourable when it comes to developing sealing technology and products for particularly demanding applications, such as those found in the oil and gas sector, as Precision Polymer Engineering Ltd briefly explains in this technology focus article.
Strong contrast in mass and energy balance between a coastal mountain glacier and the Greenland ice sheet
Authors: ABERMANN JAKOB , VAN AS DIRK , WACKER STEFAN , LANGLEY KIRSTY , MACHGUTH HORST , FAUSTO ROBERT SCHJØTT
Published: March 2019

We show a strong difference in surface mass and energy balance of a mountain glacier and two sites on the ice sheet at 64°N in West Greenland using stake and automated weather station observations. Net surface mass balance is on average 2.2 m w.e. less negative at the coast compared with the ice sheet in the same elevation. We find a larger energy turnover at the ice sheet margin on Qamanarssup Sermia than measured on the coastal mountain glacier Qassigiannguit with both energy input and output being of larger absolute value. More cloudiness and a thicker snow cover at the relatively humid coastal glacier result in smaller gains in net-shortwave radiation and smaller losses in net-longwave radiation and a less negative mass balance. Lower wind speeds at the coastal glacier result in weaker turbulent heat exchange between atmosphere and ice surface. On annual average, 17 W m−2more energy is available for melt at the ice-sheet margin compared with the coastal glacier in the same elevation.
Late Holocene paleohydrology of Walker Lake and the Carson Sink in the western Great Basin, Nevada, USA
Authors: Adams Kenneth D. , Rhodes Edward J.
Published: March 2019

The late Holocene histories of Walker Lake and the Carson Sink were reconstructed by synthesizing existing data in both basins along with new age constraints from key sites, supplemented with paleohydrologic modeling. The repeated diversions of the Walker River to the Carson Sink and then back to Walker Lake caused Walker Lake–level fluctuations spanning ± 50 m. Low lake levels at about 1000, 750, and 300 cal yr BP are time correlative to the ages of fluvial deposits along the Walker River paleochannel, when flow was directed toward the Carson Sink. The timing and duration of large lakes in the Carson Sink were further refined using moisture-sensitive tree-ring chronologies. The largest lakes required a fourfold to fivefold increase in discharge spanning decades. Addition of Walker River flow to the Carson Sink by itself is inadequate to account for the required discharge. Instead, increases in the runoff coefficient and larger areas of the drainage basin contributing surface runoff may explain the enhanced discharge required to create these large lakes.
European market developments in prebiotic- and probiotic-containing foodstuffs
Authors: Young John
Published: March 2019

A growing number of food manufacturers in western Europe are beginning to explore the commercial opportunities for foodstuffs containing health-promoting microbial food supplements (probiotics) and health-promoting non-digestible food ingredients (prebiotics). A prebiotic is considered to affect the host beneficially by selectively stimulating the growth and/or activity of one or a limited number of naturally present or introduced bacterial species in the colon, also leading to a claimed improvement in host health. Increasingly, probiotics and prebiotics are used in combination, this being termed a synbiotic (Gibson & Roberfroid, 1995). Throughout European history, fermented milk products in particular have been considered beneficial to health, but only in recent years has there been scientific support for these beliefs. Issues considered important to the continuing development of this growing market are proof of safety, proof of efficacy, consumer education, market positioning, price and appropriate health claims strategies. Until recently, much of the innovation in the use of probiotics and prebiotics has been in the dairy cabinet, with an ever-growing number and range of ‘health-promoting’ yoghurts and yoghurt-type fermented milk being made available to the European consumer, a market which is currently estimated to be worth in excess of $US2 billion per annum (Hilliam et al. 1997). However, prebiotics are beginning to find increasing application outside the dairy sector, particularly in baked goods. A key driver behind the broadening application of prebiotics has been the pro-active stance taken by key prebiotic suppliers such as Beghin-Say, Orafti and Cosucra. To date, market activity in probiotic- and prebiotic-containing foods has centred around three health propositions, namely improving general gut health, lowering blood cholesterol and improving the body's natural defences.
Porcine lactoferrin-derived peptide LFP-20 modulates immune homoeostasis to defend lipopolysaccharide-triggered intestinal inflammation in mice
Authors: Zong Xin , Cao Xiaoxuan , Wang Hong , Zhao Jing , Lu Zeqing , Wang Fengqin , Wang Yizhen
Published: March 2019

The performance of immune system is vital for defending the body from pathogens, and it plays a crucial role in health homoeostasis. In a previous study, we have shown that LFP-20, a twenty-amino acid antimicrobial peptide in the N terminus of porcine lactoferrin, modulated inflammatory response in colitis. Here, we further investigated the effects of LFP-20 on immune homoeostasis to elucidate the mechanism of its anti-inflammation action. A lipopolysaccharide (LPS)-triggered systemic inflammatory response mice model was established. On the basis of observed mucosal lesions and apoptosis in small intestine, we found increased macrophage and neutrophil infiltration in ileum after LPS stimulation. Expectedly, LFP-20 pre-treatment attenuated the LPS-mediated immune disorders in ileum. Moreover, the flow cytometry results indicated pre-treatment with LFP-20 sustained the balance of CD3+CD8+ T cells, B cells and natural killer cells in LPS-triggered immune disturbance. Simultaneously, we demonstrated LFP-20 modulated the secretion of both activated Th1-related IL-12p70, interferon-γ, TNF-α and Th2-related IL-4, IL-5 and IL-6. Furthermore, we found LFP-20 facilitated a balanced Th1 and Th2 response, which triggered cellular defence mechanisms and induced B cells to produce opsonising antibodies belonging to certain IgG subclasses to defend against LPS stimulation. Collectively, our study indicated pre-treatment with LFP-20 could defend against LPS-triggered systemic inflammatory response in mice via modulating immune homoeostasis.
Maternal betaine status, but not that of choline or methionine, is inversely associated with infant birth weight
Authors: Du Yu-Feng , Wei Yuan , Yang Jing , Cheng Zi-Yi , Zuo Xi-Fang , Wu Tian-Chen , Shi Hui-Feng , Wang Xiao-Li
Published: March 2019

Maternal one-carbon metabolism during pregnancy is crucial for fetal development and programming by DNA methylation. However, evidence on one-carbon biomarkers other than folate is lacking. We, therefore, investigated whether maternal plasma methyl donors, that is, choline, betaine and methionine, are associated with birth outcomes. Blood samples were obtained from 115 women during gestation (median 26·3 weeks, 90 % range 22·7–33·0 weeks). Plasma choline, betaine, methionine and dimethylglycine were measured using HPLC-tandem MS. Multivariate linear and logistic regression models were used to estimate the association between plasma biomarkers and birth weight, birth length, the risk of small-for-gestational-age and large-for-gestational-age (LGA). Higher level of maternal betaine was associated with lower birth weight (–130·3 (95 % CI –244·8, –15·9) per 1 sd increment for log-transformed betaine). Higher maternal methionine was associated with lower risk of LGA, and adjusted OR, with 95 % CI for 1 sd increase in methionine concentration was 0·44 (95 % CI 0·21, 0·89). Stratified analyses according to infant sex or maternal plasma homocysteine status showed that reduction in birth weight in relation to maternal betaine was only limited to male infants or to who had higher maternal homocysteine status (≥5·1 µmol/l). Higher maternal betaine status was associated with reduced birth weight. Maternal methionine was inversely associated with LGA risk. These findings are needed to be replicated in future larger studies.
Starch digestion kinetics and mechanisms of hydrolysing enzymes in growing pigs fed processed and native cereal-based diets
Authors: Martens Bianca M. J. , Flécher Thomas , de Vries Sonja , Schols Henk A. , Bruininx Erik M. A. M. , Gerrits Walter J. J.
Published: March 2019

This study aimed to examine in vivo starch digestion kinetics and to unravel the mechanisms of starch hydrolysing enzymes. Ninety pigs (23 (sd 2·1) kg body weight) were assigned to one of nine treatments in a 3×3 factorial arrangement, with starch source (barley, maize, high-amylose (HA) maize) and form (isolated, within cereal matrix, extruded) as factors. We determined starch digestion coefficients (DC), starch breakdown products and digesta retention times in four small-intestinal segments (SI1–4). Starch digestion in SI2 of pigs fed barley and maize, exceeded starch digestion of pigs fed HA maize by 0·20–0·33 DC units (P<0·01). In SI3–4, barley starch were completely digested, whereas the cereal matrix of maize hampered digestion and generated 16 % resistant starch in the small intestine (P<0·001). Extrusion increased the DC of maize and HA maize starch throughout the small intestine but not that of barley (P<0·05). Up to 25 % of starch residuals in the proximal small intestine of pigs was present as glucose and soluble α(1–4) maltodextrins. The high abundance of glucose, maltose and maltotriose in the proximal small intestine indicates activity of brush-border enzymes in the intestinal lumen, which is exceeded by α-amylase activity. Furthermore, we found that in vivo starch digestion exceeded our in vitro predictions for rapidly digested starch, which indicates that the role of the stomach on starch digestion is currently underestimated. Consequently, in vivo glucose release of slowly digestible starch is less gradual than expected, which challenges the prediction quality of the in vitro assay.
Detrital zircon U–Pb geochronology and geochemistry of late Neoproterozoic – early Cambrian sedimentary rocks in the Cathaysia Block: constraint on its palaeo-position in Gondwana supercontinent
Authors: Xiong Chen , Niu Yaoling , Chen Hongde , Chen Anqing , Zhang Chenggong , Li Feng , Yang Shuai , Xu Shenglin
Published: March 2019

We present updated U–Pb ages and Hf isotopic compositions of detrital zircons and whole-rock geochemical data to investigate the provenance and tectonic setting of late Neoproterozoic and early Cambrian sandstones from the Cathaysia Block, in order to offer new constraints on its tectonic evolution and its palaeo-position within the supercontinent. The source rocks for the studied sandstones were dominated by felsic–intermediate materials with moderate weathering history. U–Pb dating results show major populations atc. 2500 Ma, 1000–900 Ma and 870–716 Ma with subordinate peaks at 655–532 Ma, consistent with the global Neoarchean continental crust growth, assembly and break-up of Rodinia, and Pan-African Event associated with the formation of Gondwana. Zircon U–Pb ages and Hf isotopic data suggest that most derived from exotic terranes once connected to the Cathaysia Block. Using whole-rock geochemical analysis, it was determined that the studied sedimentary rocks were deposited in a passive continental margin and the Cathaysia and Yangtze blocks were part of the same continent; no Cambrian ocean existed between them. Compiling a detrital zircon dataset from Qiangtang, northern India, the Lhasa Terrane and Western Australia, the Cathaysia Block seems to be more similar to the Qiangtang and western part of the northern India margin, instead of having a direct connection with the Lhasa Terrane and Western Australia in the Gondwana reconstruction during the late Neoproterozoic and Cambrian eons.
Financial versus Strategic Buyers
Authors: Martos-Vila Marc , Rhodes-Kropf Matthew , Harford Jarrad
Published: March 2019

This article introduces the impact of debt misvaluation on merger and acquisition activity. We show the potential for debt misvaluation to help explain the shifting dominance of financial acquirers (private equity firms) relative to strategic acquirers (operating companies). Fundamental differences in governance and project coinsurance between the two types of acquirer would interact with debt misvaluation, resulting in variation in how assets are owned that depends on debt market conditions. We find support for our theory in merger data using a novel measure of debt misvaluation.
Getting to the bottom of things: The value of evolutionary approaches in discerning the origin of psychopathology
Authors: O Jiaqing , Brüne Martin
Published: March 2019

The network approach as a novel way of understanding psychopathology has helped address some of the existing issues associated with traditional biological interpretations. Nonetheless, it has similarly failed in explaining the fundamental etiology of mental conditions – a persistent conundrum that arguably could be adequately addressed only by evolutionary formulations, specifically evolutionary mismatch and life history theories.
Conceptualizing neurodevelopmental disorders as networks: Promises and challenges
Authors: Hens Kristien , Evers Kris , Wagemans Johan
Published: March 2019

The target article by Borsboom et al. proposes network models as an alternative to reductionist approaches in the analysis of mental disorders, using mood disorders such as depression and anxiety as examples. We ask how this framework can be applied to neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Specifically, we raise a number of promises and challenges when conceptualizing neurodevelopmental disorders as networks.
CAPITAL ALLOCATION WITH MULTIVARIATE RISK MEASURES: AN AXIOMATIC APPROACH
Authors: Wei Linxiao , Hu Yijun
Published: March 2019

Capital allocation is of central importance in portfolio management and risk-based performance measurement. Capital allocations for univariate risk measures have been extensively studied in the finance literature. In contrast to this situation, few papers dealt with capital allocations for multivariate risk measures. In this paper, we propose an axiom system for capital allocation with multivariate risk measures. We first recall the class of the positively homogeneous and subadditive multivariate risk measures, and provide the corresponding representation results. Then it is shown that for a given positively homogeneous and subadditive multivariate risk measure, there exists a capital allocation principle. Furthermore, the uniqueness of the capital allocation principe is characterized. Finally, examples are also given to derive the explicit capital allocation principles for the multivariate risk measures based on mean and standard deviation, including the multivariate mean-standard-deviation risk measures.
Characterisation of antibiotic resistance ofSalmonellaisolated from dog treats in Japan
Authors: Yukawa S. , Uchida I. , Tamura Y. , Ohshima S. , Hasegawa T.
Published: March 2019

Dog treats might be contaminated withSalmonella. In Canada and the USA, outbreaks of human salmonellosis related to exposure to animal-derived dog treats were reported. Consequently, surveillance data onSalmonellacontamination of dog treats have been gathered in many countries, but not in Japan. In the current study, we investigated whether dog treats in Japan were contaminated withSalmonella. Overall, 303 dog treats (of which 255 were domestically produced) were randomly collected and the presence ofSalmonellainvestigated. Seven samples were positive forSalmonella entericasubsp.enterica. Among these isolates, three were identified as serovar 4,5,12:i:–; two were serovar Rissen; and two were serovar Thompson. All serovar 4,5,12:i:– and Thompson isolates were resistant to one or more drugs. Two serovar Rissen isolates were fully susceptible to all tested antimicrobial agents. AllSalmonellaisolates were susceptible to cefotaxime, ciprofloxacin and nalidixic acid. The geneblaTEMwas detected in two serovar 4,5,12:i:– isolates. TheblaCTX−MandblaCMYgenes were not detected in any isolates. This study demonstrated that dog treats in Japan could constitute a potential source of dog and humanSalmonellainfections, including multidrug-resistantSalmonellaisolates.
Risk factors and epidemiologic predictors of blood stream infections with New Delhi Metallo-b-lactamase (NDM-1) producingEnterobacteriaceae
Authors: Snyder B. M. , Montague B. T. , Anandan S. , Madabhushi A. G. , Pragasam A. K. , Verghese V. P. , Balaji V. , Simões E. A. F.
Published: March 2019

Carbapenem-resistantEnterobacteriaceaeconferred by New Delhi metallo-b-lactamase (NDM-1) resistance mechanism are endemic in India and Southeast Asia. An understanding of risk factors for NDM-1 infections is necessary to guide prevention strategies. We performed a retrospective case-control study of patients admitted at Christian Medical College Hospital, Vellore, India between May 2010 and August 2014 withKlebsiella pneumoniaeblood stream infection (BSI). We compared patients with BSI caused by NDM-1 producing strains to two control groups: BSI with other multidrug resistant (MDR) strains and BSI with pan-susceptible strains. The study groups were assessed for risk factors for the outcomes: (1) infection with any MDR strain compared to pan-susceptible; and, (2) infection with NDM-1 strain as compared with other MDR and (3) Mortality. A total of 101 patients with BSI with NDM-1 producingKlebsiella pneumoniaewere matched to two groups of controls: 112 with non-NDM-1 MDR strains and 101 with pan-susceptible strains. Medical (OR 10.4) and neonatal (OR 0.7) ICU admission, central venous catheter placement (CVC, OR 7.4) predicted MDR BSI. Prior carbapenem use (OR 8.4) and CVC (OR 4.8) predicted acquisition of an NDM-1 strain. Significant predictors for mortality included ICU stay (OR 3.0), mechanical ventilation (OR 3.2), female gender (OR 2.2), diabetes (OR 0.4). CVC placement, prior carbapenem use and ICU admission were significantly associated with BSI with NDM-1 producing and other MDR strains.
Equi-affine differential invariants for invariant feature point detection
Authors: TUZNIK STANLEY L. , OLVER PETER J. , TANNENBAUM ALLEN
Published: March 2019

Image feature points are detected as pixels which locally maximise a detector function, two commonly used examples of which are the (Euclidean) image gradient and the Harris–Stephens corner detector. A major limitation of these feature detectors is that they are only Euclidean-invariant. In this work, we demonstrate the application of a 2D equi-affine-invariant image feature point detector based on differential invariants as derived through the equivariant method of moving frames. The fundamental equi-affine differential invariants for 3D image volumes are also computed.
Analysis of spreading speeds for monotone semiflows with an application to CNNs
Authors: YU ZHI-XIAN , ZHANG LEI
Published: March 2019

The purpose of this work is to investigate the properties of spreading speeds for the monotone semiflows. According to the fundamental work of Liang and Zhao [(2007) Comm. Pure Appl. Math.60, 1–40], the spreading speeds of the monotone semiflows can be derived via the principal eigenvalue of linear operators relating to the semiflows. In this paper, we establish a general method to analyse the sign and the continuity of the spreading speeds. Then we consider a limiting case that admits no spreading phenomenon. The results can be applied to the model of cellular neural networks (CNNs). In this model, we find the rule which determines the propagating phenomenon by parameters.
Pro-oxidant effects of a high α-tocopherol dose on kidney antioxidant biomarkers and histopathological aspects
Authors: Kanane Amel , Rouaki Fayrouz , Brahim Errahmani Mohamed , Laraba Abdenour , Mesbah Hayet , Ammouche Ali
Published: March 2019

Abstract. The aim of this study is to evaluate the effect of α-tocopherol supplementation at two doses (600 and 1200 mg × kg–1) on kidney antioxidant status and the histopathological changes in Wistar rats after 12 weeks of exposure at different diets. Forty rats has been divided into 4 groups of 10 rats each, the control group received basal diet with 5 % fresh sunflower oil (FSO), the second group: 5 % oxidized sunflower oil (OSO), the third group: 5 % OSO supplemented with 600 mg × kg–1 α-tocopherol and the fourth group: 5 % OSO supplemented with 1200 mg × kg–1 α-tocopherol. In OSO groups, the results showed highly significant increases of LPO (from 31.3 ± 0.9 to 53.8 ± 1.2 nmol of MDA formed/min/mg protein, p < 0.0001) with a significant decrease (p < = 0.001) of the antioxidant enzymatic activities (CAT, SOD, GPX, GR and G6PDH), body weight (339 ± 9 to 290 ± 3 g) and α-tocopherol levels (13.6 ± 0.6 to 6.5 ± 0.4 μg/mg protein). In OSO groups with 600 mg × kg–1 α-tocopherol, an antioxidant effect was found, reflected by a return of the parameters to values similar to those of the control group. However, higher doses of α-tocopherol (1200 mg × kg–1) induced a depletion of antioxidant status, α-tocopherol levels (6.0 ± 0.3 μg/mg protein, p < 0.001) and a very highly significant rise (p < 0.0001) of LPO content (54.86 ± 0.01 nmol of MDA formed/min/mg protein). The kidney tissues also showed changes in glomerular, severe inflammatory cells infiltration, and formation of novel vessels. So, we can conclude that the oxidative stress is attenuated by a moderate administration of 600 mg × kg–1 α-tocopherol, while a pro-oxidant effect occurs at 1200 mg × kg–1 α-tocopherol.
A near-infrared spectroscopy-assisted test discriminates patients	with peripheral arterial disease and venous insufficiency with changes of foot	oxygenation following light elastic compression therapy
Authors: Lamberti Nicola , Manfredini Fabio , Tessari Mirko , Menegatti Erica , Nardi Francesca , Basaglia Nino , Zamboni Paolo
Published: March 2019

Summary. Background: Elastic compression therapy (CT) in patients with peripheral artery disease (PAD) and chronic venous insufficiency (CVI) may compromise arterial perfusion. We evaluated the feasibility of a toe-flexion test, which quantifies dynamic foot perfusion by near-infrared spectroscopy (NIRS), for the assessment of hemodynamic sustainability of CT in PAD patients with CVI. Patients and methods: In this prospective observational study, PAD patients aged 50–85 with combined CVI at CEAP stages II–IV were studied. The ankle-brachial index (ABI) was measured, and foot perfusion was determined after 10 consecutive toe-flexion movements with NIRS sensors placed on the dorsum of each foot. Knee-high open-toe compression stockings were applied, and the degree of compression was measured. Toflex-area was determined by calculating the area under the curve of the oxygenated hemoglobin track recorded by NIRS. A toflex-area reduction > 20 % following CT was arbitrarily defined to identify limbs of patients with improved foot perfusion. These subjects received CT to be worn and a diary to report adherence and symptoms. Results: Forty-seven PAD patients (74 ± 9 years; ABI 0.67 ± 0.24) with CVI were enrolled. For all legs, superimposable toflex-areas were observed for the first two attempts (ICC 0.92). Following application of CT (17 ± 2 mmHg), the toflex-area improved (from –162 ± 110 a.u. to –112 ± 104 a.u.; p < .001). Sixty-two limbs (n = 32 patients) exhibited improved foot perfusion after CT, with a mean variation of 80 ± 47 a.u., while 32 limbs (n = 23 patients) showed stable or worsened values. In a regression model, favorable variations in toflex-area after CT were linked to a worse baseline toflex-area (R2 = 0.18; p < 0.001; rpartial = –0.42) while the percentage improvement directly correlated with CEAP class (p = 0.033). Conclusions: The NIRS-assisted test, which is feasible in a laboratory context, objectively discriminates the hemodynamic tolerability of the treatment and identifies subjects with combined PAD and CVI with improved perfusion after CT, in spite of the presence of PAD.
Bundesgerichtliche Urteile zum Arztrecht (2000–2017) – Überblick, ausgewählte Kasuistik und Würdigung
Authors: Vokinger Kerstin Noëlle , Mühlematter Urs Jakob
Published: March 2019

Zusammenfassung. Im Rahmen einer empirischen und kasuistischen Analyse arztrechtlicher Bundesgerichtsurteile zwischen 2000 und 2017 war das Ziel, Tendenzen und Muster der bundesgerichtlichen Rechtsprechung zum Arztrecht zu beschreiben. Unter anderem zeigte das Ergebnis, dass Fachärzte der Inneren Medizin, Psychiatrie, Gynäkologie und Geburtshilfe sowie Chirurgie verhältnismässig häufig involviert sind in bundesgerichtliche Verfahren. Demgegenüber sind Pathologen, Rechtsmediziner oder (diagnostische) Radiologen selten vertreten. Dies kann möglicherweise damit erklärt werden, dass der ersten Gruppe im Verhältnis zu den anderen Facharztrichtungen mehr Ärzte angehören. Des Weiteren wird in der ersten Gruppe entweder stärker gegen den Patientenwillen (z.B. im Rahmen der Zwangsmedikation in der Psychiatrie) vorgegangen oder eine eventuelle Sorgfaltspflichtverletzung ist für den Patienten bzw. seine Angehörigen offensichtlicher bzw. auch ohne medizinische Kenntnisse zumindest erkennbar.
Arbeitsteilung im Arztalltag – Grundzüge der rechtlichen Anforderungen an die interdisziplinäre und interprofessionelle ärztliche Zusammenarbeit
Authors: Olah Mirjam
Published: March 2019

Zusammenfassung. Sofern eine eigenhändige ärztliche Durchführung nicht infolge einer ausdrücklichen spezialgesetzlichen Vorbehaltsaufgabe angezeigt ist oder aufgrund der Einhaltung von Fachbereichsgrenzen eine höchstpersönliche fachärztliche Tätigkeit erforderlich ist, können Aufgaben ausserhalb des ärztlichen Kernbereichs auf entsprechend qualifizierte ärztliche oder nichtärztliche Fachpersonen übertragen werden. Ferner sind die Patienten unter Umständen über eine Aufgabenübertragung aufzuklären, und diese hat zu unterbleiben, wenn eine ausdrücklich arztbezogene Einwilligung vorliegt. Die stets erforderliche Gewährleistung einer Behandlung nach dem jeweils massgeblichen Facharztstandard setzt zudem voraus, dass die Beteiligten eine ganze Reihe unterschiedlicher Sorgfaltspflichten einhalten. In Konstellationen, in denen die beschriebenen Anforderungen nicht eingehalten werden, ist grundsätzlich von einem Delegationsverbot auszugehen. In dessen Anwendungsbereich ist eine Berufung auf den Vertrauensgrundsatz nicht möglich, und es liegt vielmehr ein Behandlungsfehler vor, wenn eine Aufgabenübertragung dennoch erfolgt.
Die Rolle der Ärzteschaft in der Sterbehilfe, insbesondere bei der Verschreibung von Natrium-Pentobarbital
Authors: Gächter Thomas , Truong Thuy Xuan
Published: March 2019

Zusammenfassung. Die Abgabe von Natrium-Pentobarbital (NaP) im Rahmen des assistierten Suizids setzt eine ärztliche Verschreibung voraus. Diese hat den gesetzlichen und standesrechtlichen Anforderungen sowie den entsprechenden ethischen Richtlinien zu genügen. Die derzeitige Rechtspraxis lässt die Suizidbeihilfe in dieser Form restriktiv zu, namentlich im Falle von sterbewilligen Patienten, deren Tod absehbar ist. Die neuen Richtlinien der SAMW (2018) erweitern die Möglichkeit auf Patienten, die aufgrund von Krankheitssymptomen und/oder Funktionseinschränkungen unerträglich leiden. Die Verschreibung von NaP in anderen Fällen oder in Verletzung der in den Richtlinien vorgesehenen Sorgfaltspflichten kann zu aufsichts-, standes- und strafrechtlichen Konsequenzen führen. Die Suizidbeihilfe selbst ist eine Gewissensentscheidung, keine ärztliche Aufgabe, weshalb auch kein Anspruch darauf besteht.
Changes in Intermediate Circulation in the Bay of Bengal Since the Last Glacial Maximum as Inferred From Benthic Foraminifera Assemblages and Geochemical Proxies
Authors: Ma Ruifang , Sépulcre Sophie , Licari Laetitia , Bassinot Franck , Liu Zhifei , Tisnérat‐Laborde Nadine , Kallel Nejib , Yu Zhaojie , Colin Christophe
Published: March 2019

Benthic foraminiferal assemblages and geochemical tracers (δ18O, δ13C and 14C) have been analyzed on benthic and planktonic foraminifera from core MD77‐176, located in the northern Bay of Bengal, in order to reconstruct the evolution of intermediate circulation in the northern Indian Ocean since the last glaciation. Results indicate that during the Last Glacial Maximum (LGM), Southern Sourced Water masses were dominant at the core site. A high relative abundance of intermediate and deep infaunal species during the LGM reflects low oxygen concentration and/or mesotropic to eutrophic deep water conditions, associated with depleted benthic δ13C values. During the Holocene, benthic foraminiferal assemblages indicate an oligotropic to mesotrophic environment with well‐ventilated bottom water conditions compared with LGM. Higher values for benthic foraminifera δ13C and B‐P 14C age offsets suggest an increased contribution of North Atlantic Deep Water to the northern Bay of Bengal during the Late Holocene compared to the LGM. Millennial‐scale events punctuated the last deglaciation, with a shift in the δ13C and the ɛNd values coincident with low B‐P 14C age offsets, providing strong evidence for an increased contribution of Antarctic Intermediate Water at the studied site. This was associated with enhanced upwelling in the Southern Ocean, reflecting a strong sea‐atmospheric CO2 exchange through Southern Ocean ventilation during the last deglaciation.
Postfire Soil Carbon Accumulation Does Not Recover Boreal Peatland Combustion Loss in Some Hydrogeological Settings
Authors: Ingram R. C. , Moore P. A. , Wilkinson S. , Petrone R. M. , Waddington J. M.
Published: March 2019

Deep peat burning at the interface between subhumid Boreal Plains (BP) peatlands and forestlands (margin ecotones) in some hydrogeological settings has brought into question the long‐term stability of these peatlands under current and future predicted climate. Small peatlands located at midtopographic positions on coarse sediments have been identified as hot spots for severe burning, as these peatland margins are not regularly connected to regional groundwater flow. The ability of these peatland systems to recover carbon lost from both the interior and margin within the fire return interval, however, has not yet been investigated. Here we examine peatland soil carbon accumulation along a chronosequence of time since fire for 26 BP ombrotrophic bogs located across a range of hydrogeological settings. Soil organic carbon accumulation following wildfire does not appear to be influenced by hydrogeological setting; however, the ability of a peatland to recover the quantity of carbon lost within the fire return interval is dependent on the amount of carbon that was released through smoldering, which is influenced by hydrogeological setting for peatland margins. Based on published measurements of organic soil carbon loss during wildfire and our soil carbon accumulation rates, we suggest that peatlands located at topographic lows on coarse‐grained glaciofluvial outwash sediments or on low‐relief, fine‐grained sediment deposits from glaciolacustrine or subglacial paleoenvironments are currently resilient to wildfire on the BP landscape. Peatlands that experience severe smoldering at the margins, such as ephemerally perched systems on glaciofluvial outwash sediments, will likely undergo permanent loss of legacy carbon stores.
Improving Estimates of Long-Term Climate Sensitivity
Authors: Cook Terri
Published: March 2019

New modeling casts doubt on the suitability of running experiments with fixed sea surface temperatures to understand the effects of cloud aggregation on Earth’s climate.
Net-FLICS: fast quantitative wide-field fluorescence lifetime imaging with compressed sensing – a deep learning approach
Authors: Yao Ruoyang , Ochoa Marien , Yan Pingkun , Intes Xavier
Published: March 2019

Macroscopic fluorescence lifetime imaging (MFLI) via compressed sensed (CS) measurements enables efficient and accurate quantification of molecular interactions in vivo over a large field of view (FOV). However, the current data-processing workflow is slow, complex and performs poorly under photon-starved conditions. In this paper, we propose Net-FLICS, a novel image reconstruction method based on a convolutional neural network (CNN), to directly reconstruct the intensity and lifetime images from raw time-resolved CS data. By carefully designing a large simulated dataset, Net-FLICS is successfully trained and achieves outstanding reconstruction performance on both in vitro and in vivo experimental data and even superior results at low photon count levels for lifetime quantification.
Optical orbital-angular-momentum-multiplexed data transmission under high scattering
Authors: Gong Lei , Zhao Qian , Zhang Hao , Hu Xin-Yao , Huang Kun , Yang Jia-Miao , Li Yin-Mei
Published: March 2019

Multiplexing multiple orbital angular momentum (OAM) channels enables high-capacity optical communication. However, optical scattering from ambient microparticles in the atmosphere or mode coupling in optical fibers significantly decreases the orthogonality between OAM channels for demultiplexing and eventually increases crosstalk in communication. Here, we propose a novel scattering-matrix-assisted retrieval technique (SMART) to demultiplex OAM channels from highly scattered optical fields and achieve an experimental crosstalk of –13.8 dB in the parallel sorting of 24 OAM channels after passing through a scattering medium. The SMART is implemented in a self-built data transmission system that employs a digital micromirror device to encode OAM channels and realize reference-free calibration simultaneously, thereby enabling a high tolerance to misalignment. We successfully demonstrate high-fidelity transmission of both gray and color images under scattering conditions at an error rate of <0.08%. This technique might open the door to high-performance optical communication in turbulent environments.
Fluid geochemistry, local hydrology, and metabolic activity define methanogen community size and composition in deep-sea hydrothermal vents
Authors: Stewart Lucy C , Algar Christopher K , Fortunato Caroline S , Larson Benjamin I , Vallino Joseph J , Huber Julie A , Butterfield David A , Holden James F
Published: March 2019

The size and biogeochemical impact of the subseafloor biosphere in oceanic crust remain largely unknown due to sampling limitations. We used reactive transport modeling to estimate the size of the subseafloor methanogen population, volume of crust occupied, fluid residence time, and nature of the subsurface mixing zone for two low-temperature hydrothermal vents at Axial Seamount. Monod CH4 production kinetics based on chemostat H2 availability and batch-culture Arrhenius growth kinetics for the hyperthermophile Methanocaldococcus jannaschii and thermophile Methanothermococcus thermolithotrophicus were used to develop and parameterize a reactive transport model, which was constrained by field measurements of H2, CH4, and metagenome methanogen concentration estimates in 20–40 °C hydrothermal fluids. Model results showed that hyperthermophilic methanogens dominate in systems where a narrow flow path geometry is maintained, while thermophilic methanogens dominate in systems where the flow geometry expands. At Axial Seamount, the residence time of fluid below the surface was 29–33 h. Only 1011 methanogenic cells occupying 1.8–18 m3 of ocean crust per m2 of vent seafloor area were needed to produce the observed CH4 anomalies. We show that variations in local geology at diffuse vents can create fluid flow paths that are stable over space and time, harboring persistent and distinct microbial communities.
Graft-versus-MDS effect after unrelated cord blood transplantation: a retrospective analysis of 752 patients registered at the Japanese Data Center for Hematopoietic Cell Transplantation
Authors: Ishiyama Ken , Aoki Jun , Itonaga Hidehiro , Uchida Naoyuki , Takahashi Satoshi , Ohno Yuju , Matsuhashi Yoshiko , Sakura Toru , Onizuka Makoto , Miyakoshi Shigesaburo , Takanashi Minoko , Fukuda Takahiro , Atsuta Yoshiko , Nakao Shinji , Miyazaki Yasushi
Published: March 2019

Allogeneic hematopoietic stem cell transplantation is the sole curative therapy for myelodysplastic syndrome (MDS). However, there is concern regarding graft failure and relapse in patients who undergo cord blood transplantation (CBT). We conducted a retrospective study of the CBT outcomes in MDS patients using the Japanese Data Center for Hematopoietic Cell Transplantation database. Seven hundred fifty-two de novo MDS patients of ≥18 years of age (median, 58 years) undergoing their first CBT between 2001 and 2015 were examined. Two-thirds of the patients were male, and were RAEB. The cumulative incidences of neutrophil and platelet engraftment at day 100 were 77 and 59%, respectively. The 3-year overall survival (OS) was 41% and the median survival of the patients was 1.25 years. A multivariate analysis of pre-transplant variables showed that the age, gender, cytogenetic subgroups, number of RBC transfusions, HCT-CI and year of CBT significantly influenced the outcome. The cumulative incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) was 32 and 21%, respectively. A survival benefit was observed in patients who developed cGVHD, but not aGVHD. Our results suggest that CBT is an acceptable alternative graft and that a graft-versus-MDS effect can be expected, especially in patients who develop cGVHD.
Collagen type II suppresses articular chondrocyte hypertrophy and osteoarthritis progression by promoting integrin β1−SMAD1 interaction
Authors: Lian Chengjie , Wang Xudong , Qiu Xianjian , Wu Zizhao , Gao Bo , Liu Lei , Liang Guoyan , Zhou Hang , Yang Xiaoming , Peng Yan , Liang Anjing , Xu Caixia , Huang Dongsheng , Su Peiqiang
Published: March 2019

Hypertrophic differentiation is not only the terminal process of endochondral ossification in the growth plate but is also an important pathological change in osteoarthritic cartilage. Collagen type II (COL2A1) was previously considered to be only a structural component of the cartilage matrix, but recently, it has been revealed to be an extracellular signaling molecule that can significantly suppress chondrocyte hypertrophy. However, the mechanisms by which COL2A1 regulates hypertrophic differentiation remain unclear. In our study, a Col2a1 p.Gly1170Ser mutant mouse model was constructed, and Col2a1 loss was demonstrated in homozygotes. Loss of Col2a1 was found to accelerate chondrocyte hypertrophy through the bone morphogenetic protein (BMP)-SMAD1 pathway. Upon interacting with COL2A1, integrin β1 (ITGB1), the major receptor for COL2A1, competed with BMP receptors for binding to SMAD1 and then inhibited SMAD1 activation and nuclear import. COL2A1 could also activate ITGB1-induced ERK1/2 phosphorylation and, through ERK1/2-SMAD1 interaction, it further repressed SMAD1 activation, thus inhibiting BMP-SMAD1-mediated chondrocyte hypertrophy. Moreover, COL2A1 expression was downregulated, while chondrocyte hypertrophic markers and BMP-SMAD1 signaling activity were upregulated in degenerative human articular cartilage. Our study reveals novel mechanisms for the inhibition of chondrocyte hypertrophy by COL2A1 and suggests that the degradation and decrease in COL2A1 might initiate and promote osteoarthritis progression.
Correction: Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease
Authors: Mijuskovic Martina , Saunders Edward J. , Leongamornlert Daniel A. , Wakerell Sarah , Whitmore Ian , Dadaev Tokhir , Cieza-Borrella Clara , Govindasami Koveela , Brook Mark N. , Haiman Christopher A. , Conti David V. , Eeles Rosalind A. , Kote-Jarai Zsofia
Published: March 2019

This article was originally published under the standard License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the paper have been modified accordingly.
Identification of a novel class of RIP1/RIP3 dual inhibitors that impede cell death and inflammation in mouse abdominal aortic aneurysm models
Authors: Zhou Ting , Wang Qiwei , Phan Noel , Ren Jun , Yang Huan , Feldman Conner C. , Feltenberger John B. , Ye Zhengqing , Wildman Scott A. , Tang Weiping , Liu Bo
Published: March 2019

Receptor interacting protein kinase-1 and -3 (RIP1 and RIP3) are essential mediators of cell death processes and participate in inflammatory responses. Our group recently demonstrated that gene deletion of Rip3 or pharmacological inhibition of RIP1 attenuated pathogenesis of abdominal aortic aneurysm (AAA), a life-threatening degenerative vascular disease characterized by depletion of smooth muscle cells (SMCs), inflammation, negative extracellular matrix remodeling, and progressive expansion of aorta. The goal of this study was to develop drug candidates for AAA and other disease conditions involving cell death and inflammation. We screened 1141 kinase inhibitors for their ability to block necroptosis using the RIP1 inhibitor Necrostatin-1s (Nec-1s) as a selection baseline. Positive compounds were further screened for cytotoxicity and virtual binding to RIP3. A cluster of top hits, represented by GSK2593074A (GSK’074), displayed structural similarity to the established RIP3 inhibitor GSK’843. In multiple cell types including mouse SMCs, fibroblasts (L929), bone marrow derived macrophages (BMDM), and human colon epithelial cells (HT29), GSK’074 inhibited necroptosis with an IC50 of ~3 nM. Furthermore, GSK’074, but not Nec-1s, blocked cytokine production by SMCs. Biochemical analyses identified both RIP1 and RIP3 as the biological targets of GSK’074. Unlike GSK’843 which causes profound apoptosis at high doses (>3 µM), GSK’074 showed no detectable cytotoxicity even at 20 µM. Daily intraperitoneal injection of GSK’074 at 0.93 mg/kg significantly attenuated aortic expansion in two mouse models of AAA (calcium phosphate: DMSO 66.06 ± 9.17% vs GSK’074 27.36 ± 8.25%, P < 0.05; Angiotensin II: DMSO 85.39 ± 15.76% vs GSK’074 36.28 ± 5.76%, P < 0.05). Histologically, GSK’074 treatment diminished cell death and macrophage infiltration in aneurysm-prone aortae. Together, our data suggest that GSK’074 represents a new class of necroptosis inhibitors with dual targeting ability to both RIP1 and RIP3. The high potency and minimum cytotoxicity make GSK’074 a desirable drug candidate of pharmacological therapies to attenuate AAA progression and other necroptosis related diseases.