bluuebunny/crossref_metadata_2025 huggingface dataset:
Age over 35 years is associated with increased mortality after pulmonary valve replacement in repaired tetralogy of Fallot: results from the UK National Congenital Heart Disease Audit database
Authors: Dorobantu Dan M , Sharabiani Mansour T A , Taliotis Demetris , Parry Andrew J , Tulloh Robert M R , Bentham James R , Caputo Massimo , van Doorn Carin , Stoica Serban C
Published: February 2020

OBJECTIVES

Many adults with repaired tetralogy of Fallot will require a pulmonary valve replacement (PVR), but there is no consensus on the best timing. In this study, we aim to evaluate the impact of age at PVR on outcomes.

METHODS

This is a national multicentre retrospective study including all patients >15 years of age with repaired tetralogy of Fallot who underwent their first PVR between 2000 and 2013. The optimal age cut-off was identified using Cox regression and classification and regression tree analysis.

RESULTS

A total of 707 patients were included, median age 26 (15–72) years. The mortality rate at 10 years after PVR was 4.2%, and the second PVR rate of 6.8%. Age at PVR of 35 years was identified as the optimal cut-off in relation to late mortality. Patients above 35 years of age had a 5.6 fold risk of death at 10 years compared with those with PVR under 35 years (10.4% vs 1.3%, P < 0.001), more concomitant tricuspid valve repair/replacement (15.1% vs 5.7%, P < 0.001) and surgical arrhythmia treatment (18.4% vs 5.9%, P < 0.001). In those under 50 years, there was an 8.7 fold risk of late death compared with the general population, higher for those with PVR after 35 than those with PVR below 35 years (hazard ratio 9.9 vs 7.4).

CONCLUSIONS

Patients above 35 years of age with repaired tetralogy of Fallot have significantly worse mortality after PVR, compared with younger patients and a higher burden of mortality relative to the general population. This suggests that there are still cases where the timing of initial PVR is not optimal, warranting a re-evaluation of criteria for intervention.
Secondary valve regurgitation in patients with heart failure with preserved ejection fraction, heart failure with mid-range ejection fraction, and heart failure with reduced ejection fraction
Authors: Bartko Philipp E , Hülsmann Martin , Hung Judy , Pavo Noemi , Levine Robert A , Pibarot Philippe , Vahanian Alec , Stone Gregg W , Goliasch Georg
Published: February 2020

Secondary mitral regurgitation and secondary tricuspid regurgitation due to heart failure (HF) remain challenging in almost every aspect: increasing prevalence, poor prognosis, notoriously elusive in diagnosis, and complexity of therapeutic management. Recently, defined HF subgroups according to three ejection fraction (EF) ranges (reduced, mid-range, and preserved) have stimulated a structured understanding of the HF syndrome but the role of secondary valve regurgitation (SVR) across the spectrum of EF remains undefined. This review expands this structured understanding by consolidating the underlying phenotype of myocardial impairment with each type of SVR. Specifically, the current understanding, epidemiological considerations, impact, public health burden, mechanisms, and treatment options of SVR are discussed separately for each lesion across the HF spectrum. Furthermore, this review identifies important gaps in knowledge, future directions for research, and provides potential solutions for diagnosis and treatment. Mastering the challenge of SVR requires a multidisciplinary collaborative effort, both, in clinical practice and scientific approach to optimize patient outcomes.
D-galactose catabolism in archaea: operation of the DeLey–Doudoroff pathway in Haloferax volcanii
Authors: Tästensen Julia-Beate , Johnsen Ulrike , Reinhardt Andreas , Ortjohann Marius , Schönheit Peter
Published: February 2020

The haloarchaeon Haloferax volcanii was found to grow on D-galactose as carbon and energy source. Here we report a comprehensive analysis of D-galactose catabolism in H. volcanii. Genome analyses indicated a cluster of genes encoding putative enzymes of the DeLey–Doudoroff pathway for D-galactose degradation including galactose dehydrogenase, galactonate dehydratase, 2-keto-3-deoxygalactonate kinase and 2-keto-3-deoxy-6-phosphogalactonate (KDPGal) aldolase. The recombinant galactose dehydrogenase and galactonate dehydratase showed high specificity for D-galactose and galactonate, respectively, whereas KDPGal aldolase was promiscuous in utilizing KDPGal and also the C4 epimer 2-keto-3-deoxy-6-phosphogluconate as substrates. Growth studies with knock-out mutants indicated the functional involvement of galactose dehydrogenase, galactonate dehydratase and KDPGal aldolase in D-galactose degradation. Further, the transcriptional regulator GacR was identified, which was characterized as an activator of genes of the DeLey–Doudoroff pathway. Finally, genes were identified encoding components of an ABC transporter and a knock-out mutant of the substrate binding protein indicated the functional involvement of this transporter in D-galactose uptake. This is the first report of D-galactose degradation via the DeLey–Doudoroff pathway in the domain of archaea.
Children ‘born of war’: a role for fathers?
Authors: Oliveira Camile , Baines Erin
Published: February 2020

In this article, we examine exceptional circumstances in which men who father children born as the result of conflict-related sexual violence assume full or partial responsibility for their child's well-being. Children ‘born of war’ are increasingly recognized as a particular victim group in relevant international policy frameworks. Their social status falls somewhere between the victimization of their mother and perpetration of their father. Given the circumstances of their birth, they often experience social rejection and loss of identity with a long-term impact on their well-being. Previous scholarship has primarily documented the challenges faced by their mothers as caregivers and as victims of wartime sexual violence. A discussion on fathers to children ‘born of war’ is absent, attributable not only to their perpetrator status, but also to the assumption that their identity is unknown or that a relationship between father and child is undesired. The article demonstrates this is not always the case. Based on research in northern Uganda between 2016 and 2019 which included interviews and focus group discussions with former male combatants in the rebel group the Lord's Resistance Army, we explore how some fathers seek to maintain a relationship with children born as the result of ‘forced marriage’ and assume partial or full responsibility for their well-being and care.
A Neurofunctional Domains Approach to Evaluate D1/D5 Dopamine Receptor Partial Agonism on Cognition and Motivation in Healthy Volunteers With Low Working Memory Capacity
Authors: Balice-Gordon Rita , Honey Garry D , Chatham Christopher , Arce Estibaliz , Duvvuri Sridhar , Naylor Melissa Graham , Liu Wenlei , Xie Zhiyong , DeMartinis Nicholas , Harel Brian T , Braley Gabriel H , Kozak Rouba , Park Lovingly , Gray David L
Published: February 2020

Background

Dopamine D1 receptor signaling plays key roles in core domains of neural function, including cognition and reward processing; however, many questions remain about the functions of circuits modulated by dopamine D1 receptor, largely because clinically viable, selective agonists have yet to be tested in humans.

Methods

Using a novel, exploratory neurofunctional domains study design, we assessed the safety, tolerability, pharmacodynamics, and pharmacokinetics of PF-06412562, a selective D1/D5R partial agonist, in healthy male volunteers who met prespecified criteria for low working memory capacity. Functional magnetic resonance imaging, electrophysiologic endpoints, and behavioral paradigms were used to assess working memory, executive function, and motivation/reward processing following multiple-dose administration of PF-06412562. A total of 77 patients were assigned PF-06412562 (3 mg twice daily and 15 mg twice daily) or placebo administered for 5 to 7 days. Due to the exploratory nature of the study, it was neither powered for any specific treatment effect nor corrected for multiple comparisons.

Results

Nominally significant improvements from baseline in cognitive endpoints were observed in all 3 groups; however, improvements in PF-06412562–treated patients were less than in placebo-treated participants. Motivation/reward processing endpoints were variable. PF-06412562 was safe and well tolerated, with no serious adverse events, severe adverse events, or adverse events leading to dose reduction or temporary discontinuation except for 1 permanent discontinuation due to increased orthostatic heart rate.

Conclusions

PF-06412562, in the dose range and patient population explored in this study, did not improve cognitive function or motivation/reward processing more than placebo over the 5- to 7-day treatment period.

ClinicalTrials.gov Identifier

NCT02306876
Progress towards a coordinated, national paediatric antimicrobial resistance surveillance programme: Staphylococcus aureus, enterococcal and Gram-negative bacteraemia in Australia
Authors: Campbell Anita J , Daley Denise A , Bell Jan M , Pang Stanley , Coombs Geoffrey W , Carapetis Jonathan R , Bowen Asha C , Blyth Christopher C
Published: February 2020

Background

There is increasing knowledge of antimicrobial usage in children yet limited availability of nationally representative paediatric-specific data on antimicrobial resistance.

Objectives

Paediatric data from this national surveillance programme are presented to explore differences between childhood and adult bloodstream infections and antimicrobial resistance surveillance.

Methods

Using information collected from a prospective coordinated antimicrobial resistance surveillance programme, children ≤18 years and adults >18 years with a positive blood culture for Staphylococcus aureus, Enterococcus spp. or Gram-negative spp. presenting to one of 34 Australian hospitals during 2013–16 were evaluated. Consistent methodologies for key sepsis pathogens were employed and a comparative analysis between children and adults was conducted.

Results

There are stark contrasts between children and adults in this national antimicrobial resistance (AMR) data set. Notable differences include lower rates of AMR, different clinical and molecular phenotypes and lower mortality amongst children. The burden of Gram-negative resistance is disproportionately experienced in children, with higher odds of death with an ESBL versus non-ESBL bacteraemia in comparison with adults.

Conclusions

These data support that children are not just ‘little adults’ in the AMR era, and analyses by age group are important to detect differences in antibiotic susceptibility, clinical phenotype and genetic virulence factors. Antimicrobial surveillance incorporated into routine laboratory practice is vital to inform an array of wider applications including antimicrobial guidelines, stewardship and direction for prioritization of novel antimicrobial development.
Simultaneous Determination of Piracetam and Vincamine by Spectrophotometric and High-Performance Liquid Chromatographic Methods
Authors: El-Saharty Yasser Shaker Ibrahim
Published: February 2020

A mixture of piracetam and vincamine was determined by 3 different methods. The first was the determination of piracetam and vincamine using the ratio-spectra first-derivative (DD1) spectrophotometric technique at 209 and 293 nm in concentration ranges of 1045 and 214 g/mL with mean recoveries of 99.22 0.72 and 99.67 0.79, respectively. The second method was based on the resolution of the 2 components by bivariate calibration depending on a mathematic algorithm that provides simplicity and rapidity. The method depended on quantitative evaluation of the absorbencies at 210 and 225 nm in concentration ranges of 545 and 214 g/mL, with mean recoveries of 100.33 0.54 and 100.44 0.98 for piracetam and vincamine, respectively. The third method was reversed-phase liquid chromatography using 0.05 M potassium dihydrogen phosphatemethanol (50 + 50, v/v) as the mobile phase, with the pH adjusted to 3.5 with phosphoric acid. The eluent was monitored at 215 nm in concentration ranges of 5100 and 2200 g/mL, with mean recoveries of 99.62 0.67 and 99.32 0.85 for piracetam and vincamine, respectively. The suggested procedures were checked using laboratory-prepared mixtures and were successfully applied for the analysis of their pharmaceutical preparation. The methods retained their accuracy and precision when applying the standard addition technique. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by the manufacturer's method.
Comparison of Ion-Selective Electrode and Inductively Coupled Plasma-Mass Spectrometry to Determine Iodine in Milk-Based Nutritional Products
Authors: Hammer Daniel , Andrey Daniel
Published: February 2020

The performances of 2 official methods for iodine analysis based on inductively coupled plasma-mass spectrometry (ICP-MS) and the ion-selective electrode (ISE) method were compared for milk-based products. The aim of the study was to determine the performance characteristics of both methods to check the labeled concentration of iodine. Good precision was found for both methods with highest relative standard deviation of repeatability (RSDr) at 2.3 and 2.7 for ISE and ICP-MS, respectively. Intermediate reproducibility (RSDiR), single laboratory within 6 different days, was also good with the highest values at 7.3 and 8 by ISE and ICP-MS, respectively. Measurement uncertainty was estimated based on the RSDiR data, and it was concluded that both methods were capable of determining iodine concentrations within an uncertainty below 20. The accuracy of the methods was determined by analyzing certified reference materials, in-house proficiency test samples, and commercial products. Both methods returned similar results when applied on freshly opened samples. In samples that had been opened and kept exposed to air during storage, ISE returned lower iodine concentrations than ICP-MS. In commercial samples, the linear regression between both methods was ISE 0.95 ICP-MS 0.060 for freshly opened samples and ISE 0.85 ICP-MS 0.069 for samples exposed to air. The tendency of ISE to return lower results than ICP-MS is explained by the fact that ISE is sensitive to iodide but does not measure iodine that may be bound organically to the matrix. This seems to be more pronounced in samples that were stored longer. Because in most countries iodine is labeled as total iodine, acceptance of an international standard based on the ICP-MS technique which takes all forms of iodine into account, is recommended. This would help to avoid any potential dispute on the accuracy of labeled iodine concentrations in finished products.
Differential Thermal Isomerization: Its Role in the Analysis of Vitamin D3 in Foods
Authors: Gill Brendon D , Abernethy Grant A , Indyk Harvey E , Wood Jackie E , Woollard David C
Published: February 2020

Background

For nutritional purposes, the measurement of vitamin D3 (defined as the sum of vitamin D3 and previtamin D3) is required to obtain an accurate and reliable estimate of its content in foods. An often neglected aspect in the development of methods for the analysis of vitamin D3 is accounting for any potential analytical bias in the results associated with differential thermal isomerization between previtamin D and vitamin D.

Conclusions

For LC-UV methods using a vitamin D2 internal standard, cold saponification, or direct lipid extraction techniques should be avoided, unless chromatographic separation of vitamin D2, vitamin D3, and their previtamin forms is achieved so that UV absorbance corrections can be made. For both LC-UV and LC-MS methods using calciferol internal standards, the simplest solution to avoid analytical bias due to the presence of previtamin D is to utilize heating conditions (typically during saponification) such that previtamin D and vitamin D in the sample and the internal standard reach an equivalent equilibrium state prior to instrumental analysis. Only under such circumstances is the integration of previtamin D unnecessary to obtain accurate results for vitamin D3.

Highlights

A detailed discussion of the quantitation of vitamin D3 in food with concise recommendations for avoiding measurement bias as a consequence of differential thermal isomerization.
Application of homeostatic principles within evolutionary design processes: adaptive urban tissues
Authors: Showkatbakhsh Milad , Makki Mohammed
Published: February 2020

Nature is a repository of dynamic and intertwined processes ready to be analyzed and simulated. Homeostasis, as a scale-free and universal biological process across all species, ensures adaptability to perturbations caused by intrinsic and extrinsic stimuli. Homeostatic processes by which species maintain their stability are strongly present through ontogenetic and phylogenetic histories of living beings. Forms and behaviors of species are imperative to their homeostatic conditions. Although biomimicry has been established for many decades, and has made significant contributions to engineering and architecture, homeostasis has rarely been part of this field of research. The experiments presented in this paper aim to examine the applicability of biological principles of homeostasis into generative design processes in order to evolve urban superblocks with a degree of morphological and behavioral adaptation to environmental changes; the objective is to eventually develop a modus operandi for the design and development of cities with embedded dynamic adaptation attributes.
Nonlocal vibration of carbon/boron-nitride nano-hetero-structure in thermal and magnetic fields by means of nonlinear finite element method
Authors: Sedighi Hamid M , Malikan Mohammad , Valipour Ali , Żur Krzysztof Kamil
Published: February 2020

Hybrid nanotubes composed of carbon and boron-nitride nanotubes have manifested as innovative building blocks to exploit the exceptional features of both structures simultaneously. On the other hand, by mixing with other types of materials, the fabrication of relatively large nanotubes would be feasible in the case of macroscale applications. In the current article, a nonlinear finite element formulation is employed to deal with the nonlocal vibrational behavior of carbon/boron-nitride nano-hetero-tubes in the presence of magneto-thermal environment. Euler–Bernoulli beam model in conjunction with the Eringen’s nonlocal theory of elasticity is adopted to derive the governing equation of motion. In order to conduct a nonlinear frequency analysis, the von-Kármán nonlinearity associated with moderate rotations is also considered. It is well known that temperature gradients can significantly change the dynamic behavior of nanotubes. On the other hand, the coefficients of thermal expansions of carbon and boron-nitride nanotubes are quite different that may affect the structural stability of hybrid nanotubes. Hence, to explore the vibration characteristic of such composite structures, the influence of magneto-thermal environment is also taken into account. Finally, the eigenvalue analysis is performed to exhibit the nonlinear mode shapes and natural frequencies of the system due to initial displacement. It is expected that the recognition of dynamic behavior of such hybrid nanotubes may open the doors to the creative design of next-generation nano-devices.
Invasion of the Brown Marmorated Stink Bug (Hemiptera: Pentatomidae) into the United States: Developing a National Response to an Invasive Species Crisis Through Collaborative Research and Outreach Efforts
Authors: Ludwick Dalton , Morrison William R , Acebes-Doria Angelita L , Agnello Arthur M , Bergh J Christopher , Buffington Matthew L , Hamilton George C , Harper Jayson K , Hoelmer Kim A , Krawczyk Gregory , Kuhar Thomas P , Pfeiffer Douglas G , Nielsen Anne L , Rice Kevin B , Rodriguez-Saona Cesar , Shearer Peter W , Shrewsbury Paula M , Talamas Elijah J , Walgenbach James F , Wiman Nik G , Leskey Tracy C
Published: February 2020

Halyomorpha halys (Stål), the brown marmorated stink bug, is a globally invasive stink bug species. Its first major outbreak was in the United States, where it has caused millions of dollars in damage, threatened livelihoods of specialty crop growers and impacted row crop growers, and become an extreme nuisance pest in and around dwellings. The BMSB IPM Working Group, funded by the Northeastern IPM Center, was central to providing a mechanism to form a multidisciplinary team and develop initial and subsequent research, Extension, regulatory and consumer priorities. Ultimately, a project team consisting of over 50 scientists from 11 institutions in 10 states obtained the largest ever USDA-NIFA Specialty Crop Research Initiative CAP grant, totaling over $10.7 million, to tackle this crisis over a 5-yr period (2011–2016). Researchers and Extension educators integrated stakeholder feedback throughout the course of the project, and priorities evolved according to needs of affected growers and public stakeholders. Initially, the team focused on identification of H. halys, its damage symptoms and crop-specific risks, and short-term mitigation strategies for crop protection. Subsequently, work focused on its biology, ecology, and behavior leading to the development of potential longer-term IPM tactics and landscape level management solutions, including biological control. This work continues under a second SCRI CAP grant (2016–2021). The information from the initial team reached an estimated 22,000 specialty crop stakeholder contacts via Extension efforts, and over 600 million people via mainstream media. We highlight the main lessons learned from coordinating a national response to the threat posed by H. halys to agriculture in the United States.
Using movement ecology to investigate meningeal worm risk in moose, Alces alces
Authors: Ditmer Mark A , McGraw Amanda M , Cornicelli Louis , Forester James D , Mahoney Peter J , Moen Ron A , Stapleton Seth P , St-Louis Véronique , VanderWaal Kimberly , Carstensen Michelle
Published: February 2020

Anthropogenic habitat change and moderating climatic conditions have enabled the northward geographic expansion of white-tailed deer, Odocoileus virginianus, and of the parasitic nematode (meningeal worm) it carries, Parelaphostrongylus tenuis. This expansion can have consequences in dead-end host species for other ungulates because meningeal worm reduces health, causes morbidity or direct mortality, and has been attributed to population declines. In northeastern Minnesota, which marks the southern extent of the bioclimatic range for moose (Alces alces), the moose population has declined more than 50% in the last decade, with studies detecting P. tenuis in 25–45% of necropsied animals. We assessed the factors that most commonly are associated with meningeal worm infection by linking moose movement ecology with known P. tenuis infection status from necropsy. We outfitted moose with GPS collars to assess their space use and cause-specific mortality. Upon death of the subject animal, we performed a necropsy to determine the cause of death and document meningeal worm infection. We then created statistical models to assess the relationship between meningeal worm infection and exposure to hypothesized factors of infection risk based on the space use of each moose by season. Predictors included land cover types, deer space use and density, environmental conditions, and demographics of individual moose (age and sex). Moose with autumn home ranges that included more upland shrub/conifer, and individuals with high proportions of wet environments, regardless of season, had increased infection risk. In contrast, the strongest relationships we found showed that high proportions of mixed and conifer forest within spring home ranges resulted in reduced risk of infection. The spring models showed the strongest relationships between exposure and infection, potentially due to moose foraging on ground vegetation during spring. By incorporating movement of moose into disease ecology, we were able to take a top-down approach to test hypothesized components of infection risk with actual spatial and temporal exposure of individual necropsied moose. The probability of infection for moose was not influenced by deer density, although deer densities did not vary greatly within the study area (2–4 deer/km2), highlighting the importance of also considering both moose space use and environmental conditions in understanding infection risk. We suggest management strategies that use a combination of deer and land management prescriptions designed to limit contact rates in susceptible populations.
Cytomegalovirus (CMV) Shedding in French Day-Care Centers: A Nationwide Study of Epidemiology, Risk Factors, Centers’ Practices, and Parents’ Awareness of CMV
Authors: Alain Sophie , Garnier-Geoffroy Françoise , Labrunie Anaïs , Montané Amélie , Marin Benoit , Gatet Martine , Grosjean Jérôme , Dufour Véronique , Saugeras Mathilde , Postil Deborah , Hantz Sébastien
Published: February 2020

Background

Congenital cytomegalovirus (CMV) remains an important healthcare burden, resulting from primary or secondary infection in pregnant women. Exposure to young children’s saliva is a major risk factor, as prevalence of CMV shedding can reach 34%.

Methods

This cross-sectional, multicenter, nationwide study was conducted in randomly selected day care centers (DCCs), and complemented with a survey among parents and DCCs. All children aged >3 months were eligible. The study measured the CMV shedding prevalence in children’s saliva and described CMV genotypes epidemiology. The risk factors for CMV shedding and high viral load were evaluated using multivariable models.

Results

A total of 93 DCCs participated. Among the 1770 enrolled children with evaluable samples, the CMV shedding prevalence was 40% (713/1770, 95% confidence interval, 34.6–46.1), independently associated with children aged between 12 and 18 months, history of CMV infection in ≥1 parents, a mid-level income. Prevalence increased with DCC staff workload and attending children number. Viral load was ≥5 log-copies CMV/mL in 48% (342/713). Risk factors for higher viral load included children aged between 12 and 18 months, and still being breastfed. The most frequent genotype combinations were gB1-gN4c-gH2 (6.9%), gB1-gN2-gH2 (6.3%), gB4a-gN3a-gH1 (6.3%), and gB1-gN3b-gH2 (5,7%). CMV awareness was low in parents: their serological status was unknown by 72% of mothers and 82% of fathers. Only 41% knew something about CMV.

Conclusions

CMV shedding was independently associated with risk factors related to the children, family and DCC. Some of these risk factors may influence prevention strategies, including through an improved information provided to parents.

Clinical Trials Registration

NCT01704222.
Multiply Robust Bootstrap Variance Estimation in the Presence of Singly Imputed Survey Data
Authors: Chen Sixia , Haziza David , Mashreghi Zeinab
Published: February 2020

Item nonresponse in surveys is usually dealt with through single imputation. It is well known that treating the imputed values as if they were observed values may lead to serious underestimation of the variance of point estimators. In this article, we propose three pseudo-population bootstrap schemes for estimating the variance of imputed estimators obtained after applying a multiply robust imputation procedure. The proposed procedures can handle large sampling fractions and enjoy the multiple robustness property. Results from a simulation study suggest that the proposed methods perform well in terms of relative bias and coverage probability, for both population totals and quantiles.
Redox metabolism: the hidden player in carbon and nitrogen signaling?
Authors: Chaput Valentin , Martin Antoine , Lejay Laurence
Published: February 2020

While decades of research have considered redox metabolism as purely defensive, recent results show that reactive oxygen species (ROS) are necessary for growth and development. Close relationships have been found between the regulation of nitrogen metabolism and ROS in response to both carbon and nitrogen availability. Root nitrate uptake and nitrogen metabolism have been shown to be regulated by a signal from the oxidative pentose phosphate pathway (OPPP) in response to carbon signaling. As a major source of NADP(H), the OPPP is critical to maintaining redox balance under stress situations. Furthermore, recent results suggest that at least part of the regulation of the root nitrate transporter by nitrogen signaling is also linked to the redox status of the plant. This leads to the question of whether there is a more general role of redox metabolism in the regulation of nitrogen metabolism by carbon and nitrogen. This review highlights the role of the OPPP in carbon signaling and redox metabolism, and the interaction between redox and nitrogen metabolism. We discuss how redox metabolism could be an important player in the regulation of nitrogen metabolism in response to carbon/nitrogen interaction and the implications for plant adaptation to extreme environments and future crop development.
The Multi-Tracer Optimal Estimator applied to VIPERS
Authors: Montero-Dorta Antonio D , Abramo L Raul , Granett Benjamin R , de la Torre Sylvain , Guzzo Luigi
Published: February 2020

We use mock galaxy data from the VIMOS Public Extragalactic Redshift Survey (VIPERS) to test the performance of the Multi-Tracer Optimal Estimator (MTOE) of Abramo et al. as a tool to measure the monopoles of the power spectra of multiple tracers of the large-scale structure, $P^{(0)}_\alpha (\mathbf {k})$. We show that MTOE provides more accurate measurements than the standard technique of Feldman, Kaiser & Peacock (FKP), independently of the tracer-selection strategy adopted, on both small and large scales. The largest improvements on individual $P^{(0)}_\alpha (\mathbf {k})$ are obtained on small scales, using a colour–magnitude selection, due to MTOE being naturally better equipped to deal with shot noise: we report an average error reduction with respect to FKP of $\sim 30{{\ \rm per\ cent}}$ at $0.3 \lt k \, [h$ Mpc−1] < 0.5, with improvements exceeding 40–50 ${{\ \rm per\ cent}}$ for some tracers. On large scales (k[h Mpc−1] ≲ 0.1), the gain in accuracy resulting from cosmic-variance cancellation is ∼10 ${{\ \rm per\ cent}}$ for the ratios of $P^{(0)}_\alpha (\mathbf {k})$. We have carried out a Markov chain Monte Carlo analysis to determine the impact of these gains on several quantities derived from $P^{(0)}_\alpha (\mathbf {k})$. If we pushthat the estimated power spectra are themselves the measurement to scales $0.3 \lt k \, [h$ Mpc−1] < 0.5, the average improvements are $\sim 30{{\ \rm per\ cent}}$ for the amplitudes of the monopoles, $\sim 75{{\ \rm per\ cent}}$ for the monopole ratios, and $\sim 20{{\ \rm per\ cent}}$ for the linear galaxy biases. Our results highlight the potential of MTOE to shed light upon the physics that operate both on large and small cosmological scales. The effect of MTOE on cosmological constraints using VIPERS data will be addressed in a separate paper.
Mass outflow of the X-ray emission line gas in NGC 4151
Authors: Kraemer S B , Turner T J , Couto J D , Crenshaw D M , Schmitt H R , Revalski M , Fischer T C
Published: February 2020

We have analysed Chandra/High Energy Transmission Gratings spectra of the X-ray emission line gas in the Seyfert galaxy NGC 4151. The zeroth-order spectral images show extended H- and He-like O and Ne, up to a distance r ∼ 200 pc from the nucleus. Using the first-order spectra, we measure an average line velocity ∼−230 km s−1, suggesting significant outflow of X-ray gas. We generated cloudy photoionization models to fit the first-order spectra; the fit required three distinct emission line components. To estimate the total mass of ionized gas and the mass outflow rates, we applied the model parameters to fit the zeroth-order emission line profiles of Ne ix and Ne x. We determined the total mass of ≈5.4 × 105 M⊙. Assuming the same kinematic profile as that for the [O iii] gas, derived from our analysis of Hubble Space Telescope/Space Telescope Imaging Spectrograph spectra, the peak X-ray mass outflow rate was ≈1.8 M⊙ yr−1, at r ∼ 150 pc. The total mass and mass outflow rates are similar to those determined using [O iii], implying that the X-ray gas is a major outflow component. However, unlike the optical outflows, the X-ray outflow rate does not drop off at r > 100 pc, which suggests that it may have a greater impact on the host galaxy.
A limit on Planck-scale froth with ESPRESSO
Authors: Cooke Ryan , Welsh Louise , Fumagalli Michele , Pettini Max
Published: February 2020

Some models of quantum gravity predict that the very structure of space–time is ‘frothy’ due to quantum fluctuations. Although the effect is expected to be tiny, if these space–time fluctuations grow over a large distance, the initial state of a photon, such as its energy, is gradually washed out as the photon propagates. Thus, in these models, even the most monochromatic light source would gradually disperse in energy due to space–time fluctuations over large distances. In this paper, we use science verification observations obtained with ESPRESSO at the Very Large Telescope to place a novel bound on the growth of space–time fluctuations. To achieve this, we directly measure the width of a narrow Fe ii absorption line produced by a quiescent gas cloud at redshift $z$ ≃ 2.34, corresponding to a comoving distance of ≃5.8 Gpc. Using a heuristic model where the energy fluctuations grow as σE/E = (E/EP)α, where EP ≃ 1.22 × 1028 eV is the Planck energy, we rule out models with α ≤ 0.634, including models where the quantum fluctuations grow as a random walk process (α = 0.5). Finally, we present a new formalism where the uncertainty accrued at discrete space–time steps is drawn from a continuous distribution. We conclude, if photons take discrete steps through space–time and accumulate Planck-scale uncertainties at each step, then our ESPRESSO observations require that the step size must be at least ≳ 1013.2lP, where lP is the Planck length.
Synthetic spectroscopic indices for identifying multiple stellar populations in globular clusters
Authors: Bertone Emanuele , Chávez Miguel , Mendoza J César
Published: February 2020

We present an investigation of synthetic spectroscopic indices that can plausibly help in identifying the presence of multiple stellar populations in globular clusters. The study is based on a new grid of stellar model atmospheres and high-resolution (R  = 500 000) synthetic spectra, that consider chemical partitions that have been singled out in Galactic globular clusters. The data base is composed of 3472 model atmospheres and theoretical spectra calculated with the collection of Fortran codes DFSYNTHE, ATLAS9 and SYNTHE, developed by Robert L. Kurucz. They cover a range of effective temperature from 4300 to 7000 K, surface gravity from 2.0 to 5.0 dex and four different chemical compositions. A set of 19 spectroscopic indices were calculated from a degraded version (R  = 2500) of the theoretical spectra data set. The set includes five indices previously used in the context of globular clusters analyses and 14 indices that we have newly defined by maximizing the capability of differentiating the chemical compositions. We explored the effects of atmospheric parameters on the index values and identified the optimal spectral diagnostics that allow to trace the signatures of objects of different stellar populations, located in the main sequence, the red giant branch and the horizontal branch. We found a suitable set of indices, that mostly involve molecular bands (in particular NH, but also CH and CN), that are very promising for spectroscopically identifying multiple stellar populations in globular clusters.
Children With Spinal Muscular Atrophy With Prior Growth-Friendly Spinal Implants Have Better Results After Definite Spinal Fusion in Comparison to Untreated Patients
Authors: Hell Anna K , Braunschweig Lena , Tsaknakis Konstantinos , von Deimling Urs , Lüders Katja A , Hecker Marina , Lorenz Heiko M
Published: February 2020

BACKGROUND

Almost all children with spinal muscular atrophy (SMA) develop a scoliosis during childhood and adolescence. In the last decades, growth-friendly spinal implants have been established as an interim solution for these patients until definite spinal fusion can be performed. The effect of those implants on the final outcome has yet to be described.

OBJECTIVE

To assess the effect of prior growth-friendly spinal surgical treatment on the outcome after spinal fusion in SMA children in comparison to untreated SMA patients through the prospective study.

METHODS

A total of 28 SMA patients with (n = 14) and without (n = 14) prior surgical treatment with growth-friendly implants were included. Average surgical treatment prior to definite spinal fusion was 4.9 yr. Scoliotic curve angle, pelvic obliquity, spinal length, kyphosis, and lordosis were evaluated for children with prior treatment and before and after dorsal spondylodesis for all children.

RESULTS

The curve angle before definite spinal fusion averaged at 104° for SMA patients without prior treatment and 71° for patients with prior treatment. Spondylodesis reduced the scoliotic curve to 50° and 33°, respectively, which equals a correction of 52% vs 54%. Pelvic obliquity could be improved by spinal fusion in all patients with better results in the pretreated group. Results for spinal length, kyphosis, and lordosis were similar in both groups.

CONCLUSION

These data show the positive effect of prior growth-friendly surgical treatment on radiographic results of spinal fusion in children with SMA. Both scoliotic curve angles and pelvic obliquity showed significantly better values when patients had growth-friendly implants before definite spinal fusion.
Frequency of Potential Drug–Drug Interactions in the Changing Field of HCV Therapy
Authors: Schulte Benjamin , Wübbolding Maximilian , Marra Fiona , Port Kerstin , Manns Michael P , Back David , Cornberg Markus , Stichtenoth Dirk O , Höner zu Siederdissen Christoph , Maasoumy Benjamin
Published: February 2020

Background

With the introduction of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection, drug–drug interactions (DDIs) emerged as significant challenge. Since then, HCV therapy and the infected population have rapidly changed. So far, very limited data are available regarding the clinical relevance of DDIs when using most modern DAA regimens. We aimed to assess how the importance of DDIs has evolved over time.

Methods

From January 2014 to July 2018, 668 consecutive HCV patients were evaluated for their outpatient medication and assessed for DDIs with DAAs. Different time periods were defined based on market approval of key DAAs: A (01/2014–11/2014), B (11/2014–08/2016), and C (08/2016–07/2018).

Results

The frequency of patients with real-world DDIs was highest in period B (A: 37.1%, B: 49.6%, C: 38.8%). The recently approved DAAs (period C) theoretically showed a lower DDI risk profile. However, real-world DDIs were still comparable to period A, as HCV patients’ characteristics changed (eg, age ≥75 years: A: 3.1%, B: 9.8%, C: 5.6%; polypharmacy/patients with ≥8 drugs: A: 11.1%, B: 15.2%, C: 17.2%). Furthermore, although DDIs via CYP 3A4 became less important for some modern regimens, other mechanisms like an altered pH value in the stomach, causing reduced bioavailability, evolved. Relevant DDIs most frequently occurred with proton pump inhibitors, metamizole, statins, and carvedilol.

Conclusions

DDIs during antiviral treatment still affect about 40% of HCV patients. The lower DDI potential of modern DAA regimens is partly counteracted by changing patient characteristics. Therefore, DDIs should not be underestimated.
Preexisting Opioid Use Disorder and Outcomes After Lower Extremity Arthroplasty: A Multistate Analysis, 2007–2014
Authors: Chen Stephanie A , White Robert S , Tangel Virginia , Gupta Soham , Stambough Jeffrey B , Gaber-Baylis Licia K , Weinberg Roniel
Published: February 2020

Objective

The aim of this study was to examine the association of preexisting opioid use disorder and postoperative outcomes in patients undergoing total hip or knee arthroplasty (THA and TKA, respectively) in the overall population and in the Medicare-only population.

Methods

This retrospective cohort study examined data from the State Inpatient Databases of the Healthcare Cost and Utilization Project for the years 2007–2014 from California, Florida, New York, Maryland, and Kentucky. We compared patients with and without opioid use disorders on unadjusted rates and calculated adjusted odds ratios (aORs) of in-hospital mortality, postoperative complications, length of stay, and 30-day and 90-day readmission status; analyses were repeated in a subgroup of Medicare insurance patients only.

Subjects

After applying our exclusion criteria, our study included 1,422,210 adult patients undergoing lower extremity arthroplasties, including 818,931 Medicare insurance patients. In our study, 0.4% of THA patients and 0.3% of TKA patients had present-on-admission opioid use disorder.

Results

Opioid use disorder patients were at higher risk for in-hospital mortality (aOR = 3.10), 30- and 90-day readmissions (aORs = 1.81, 1.81), and pulmonary and infectious complications (aORs = 1.25, 1.96).

Conclusions

Present-on-admission opioid use disorder was a risk factor for worse postoperative outcomes and increased health care utilization in the lower extremity arthroplasty population. Opioid use disorder is a potentially modifiable risk factor for mortality, postoperative complications, and health care utilization, especially in the at-risk Medicare population.
The New Ledoux: Survival Circuits and the Surplus Meaning of ‘Fear’
Authors: Majeed Raamy
Published: February 2020

LeDoux's pioneering work on the neurobiology of fear has played a crucial role in informing debates in the philosophy of emotion. For example, it plays a key part in Griffiths’ argument for why emotions don’t form a natural kind. Likewise, it is employed by Faucher and Tappolet to defend pro-emotion views, which claim that emotions aid reasoning. LeDoux, however, now argues that his work has been misread. He argues that using emotion terms, like ‘fear’, to describe neurocognitive data adds a ‘surplus meaning’: it attributes phenomenal properties to survival circuits which they don’t possess. This paper aims to explore LeDoux's new proposal, and examine the potentially devastating consequences that ensue for the aforementioned views. I end by addressing the worry that these lessons are conditional on LeDoux's own higher-order theory of emotional consciousness being true.
Management of Behcet’s syndrome
Authors: Karadag Omer , Bolek Ertugrul Cagri
Published: February 2020

Behcet’s syndrome (BS) is a variable vessel vasculitis with heterogeneous clinical features. Skin, mucosa and joint involvement can cause impairment of quality of life but do not cause permanent damage whereas untreated eye, vascular, nervous system and gastrointestinal system involvement can cause serious damage and even death. Management of BS as a multidisciplinary team enables a faster and more accurate diagnosis and well-integrated treatment strategies. Corticosteroids are the mainstay of therapy. Colchicine, AZA, ciclosporin-A, cyclophosphamide, IFN alpha, and tumour necrosis factor alpha inhibitors are other agents used as induction and/or maintenance therapy. Although biologic agents have been increasingly used, there are still unmet needs. Head-to-head comparison studies of some therapeutic options (e.g. TNF inhibitors vs IFN alpha in uveitis) are required. Novel therapeutic agents in the pipeline could change the standard of care for BS in the future
Association between depression and anxiety with skin and musculoskeletal clinical phenotypes in systemic lupus erythematosus
Authors: Eldeiry David , Zandy Moe , Tayer-Shifman Oshrat E , Kwan Andrew , Marzouk Sherief , Su Jiandong , Bingham Kathleen , Touma Zahi
Published: February 2020

Objectives

To study the clinical phenotypes, determined based on cumulative disease activity manifestations, and sociodemographic factors associated with depression and anxiety in SLE.

Methods

Patients attending a single centre were assessed for depression and anxiety. SLE clinical phenotypes were based on the organ systems of cumulative 10-year SLE Disease Activity Index 2000 (SLEDAI-2K), prior to visit. Multivariable logistic regression analyses for depression, anxiety, and coexisting anxiety and depression were performed to study associated SLE clinical phenotypes and other factors.

Results

Among 341 patients, the prevalence of anxiety and depression was 34% and 27%, respectively, while 21% had coexisting anxiety and depression. Patients with skin involvement had significantly higher likelihood of anxiety compared with patients with no skin involvement [adjusted odds ratio (aOR) = 1.8; 95% CI: 1.1, 3.0]. Patients with skin involvement also had higher likelihood of having coexisting anxiety and depression (aOR = 2.0, 95% CI: 1.2, 3.9). Patients with musculoskeletal (MSK) (aOR = 1.9; 95% CI: 1.1, 3.5) and skin system (aOR = 1.8; 95% CI: 1.04, 3.2) involvement had higher likelihood of depression compared with patients without skin or musculoskeletal involvement. Employment status and fibromyalgia at the time of the visit, and inception status were significantly associated with anxiety, depression, and coexisting anxiety and depression, respectively.

Conclusion

SLE clinical phenotypes, specifically skin or MSK systems, along with fibromyalgia, employment and shorter disease duration were associated with anxiety or depression. Routine patient screening, especially among patients with shorter disease duration, for these associations may facilitate the diagnosis of these mental health disorders, and allow for more timely diagnosis.
Overlapping but Asymmetrical Relationships Between Schizophrenia and Autism Revealed by Brain Connectivity
Authors: Yoshihara Yujiro , Lisi Giuseppe , Yahata Noriaki , Fujino Junya , Matsumoto Yukiko , Miyata Jun , Sugihara Gen-ichi , Urayama Shin-ichi , Kubota Manabu , Yamashita Masahiro , Hashimoto Ryuichiro , Ichikawa Naho , Cahn Weipke , van Haren Neeltje E M , Mori Susumu , Okamoto Yasumasa , Kasai Kiyoto , Kato Nobumasa , Imamizu Hiroshi , Kahn René S , Sawa Akira , Kawato Mitsuo , Murai Toshiya , Morimoto Jun , Takahashi Hidehiko
Published: February 2020

Although the relationship between schizophrenia spectrum disorder (SSD) and autism spectrum disorder (ASD) has long been debated, it has not yet been fully elucidated. The authors quantified and visualized the relationship between ASD and SSD using dual classifiers that discriminate patients from healthy controls (HCs) based on resting-state functional connectivity magnetic resonance imaging. To develop a reliable SSD classifier, sophisticated machine-learning algorithms that automatically selected SSD-specific functional connections were applied to Japanese datasets from Kyoto University Hospital (N = 170) including patients with chronic-stage SSD. The generalizability of the SSD classifier was tested by 2 independent validation cohorts, and 1 cohort including first-episode schizophrenia. The specificity of the SSD classifier was tested by 2 Japanese cohorts of ASD and major depressive disorder. The weighted linear summation of the classifier’s functional connections constituted the biological dimensions representing neural classification certainty for the disorders. Our previously developed ASD classifier was used as ASD dimension. Distributions of individuals with SSD, ASD, and HCs s were examined on the SSD and ASD biological dimensions. We found that the SSD and ASD populations exhibited overlapping but asymmetrical patterns in the 2 biological dimensions. That is, the SSD population showed increased classification certainty for the ASD dimension but not vice versa. Furthermore, the 2 dimensions were correlated within the ASD population but not the SSD population. In conclusion, using the 2 biological dimensions based on resting-state functional connectivity enabled us to discover the quantified relationships between SSD and ASD.