bluuebunny/crossref_metadata_2025 huggingface dataset:
Onset of natural selection in populations of autocatalytic heteropolymers
Authors: Tkachenko Alexei V. , Maslov Sergei
Published: October 2018

Reduction of information entropy along with ever-increasing complexity is among the key signatures of life. Understanding the onset of such behavior in the early prebiotic world is essential for solving the problem of the origin of life. Here we study a general problem of heteropolymers capable of template-assisted ligation based on Watson-Crick-like hybridization. The system is driven off-equilibrium by cyclic changes in the environment. We model the dynamics of 2-mers, i.e., sequential pairs of specific monomers within the heteropolymer population. While the possible number of them is Z2 (where Z is the number of monomer types), we observe that most of the 2-mers get extinct, leaving no more than 2Z survivors. This leads to a dramatic reduction of the information entropy in the sequence space. Our numerical results are supported by a general mathematical analysis of the competition of growing polymers for constituent monomers. This natural-selection-like process ultimately results in a limited subset of polymer sequences. Importantly, the set of surviving sequences depends on initial concentrations of monomers and remains exponentially large (2L down from ZL for length L) in each of realizations. Thus, an inhomogeneity in initial conditions allows for a massively parallel search of the sequence space for biologically functional polymers, such as ribozymes. We also propose potential experimental implementations of our model in the contexts of either biopolymers or artificial nano-structures.
Exponential parameterization of wave functions for quantum dynamics: Time-dependent Hartree in second quantization
Authors: Madsen Niels Kristian , Hansen Mads Bøttger , Zoccante Alberto , Monrad Kasper , Hansen Mikkel Bo , Christiansen Ove
Published: October 2018

We derive equations for describing the time evolution of variational wave functions in linear and exponential parameterization with a second-quantization (SQ) formulation. The SQ formalism covers time-dependent Hartree (TDH), while exact states and approximate vibrational configuration interaction wave functions are described using state-transfer operators. We present detailed expressions for efficient evaluation of TDH in linear (L-TDH) and exponential (X-TDH) parametrization and an efficient implementation supporting linear scaling with respect to the number of degrees of freedom M when the Hamiltonian operator contains a constant number of terms per mode independently of the size of the system. The computational cost of the X-TDH method is reduced significantly compared to the L-TDH method for systems with many operator terms per mode such as is typical for accurate molecular potential-energy surfaces. Numerical results for L-TDH and X-TDH are presented which confirm the theoretical reduction of the M scaling compared to standard first-quantization formulations. Calculations on Henon-Heiles potentials with more than 105 dimensions and polycyclic aromatic hydrocarbons with up to 264 modes have been performed. Thus, the SQ formulation and the X-TDH method pave the way for studying the time-resolved quantum dynamics of large molecules.
Invited Article: Direct phase mapping of broadband Laguerre-Gaussian metasurfaces
Authors: Faßbender Alexander , Babocký Jiří , Dvořák Petr , Křápek Vlastimil , Linden Stefan
Published: October 2018

We report on the fabrication of metasurface phase plates consisting of gold nanoantenna arrays that generate Laguerre-Gaussian modes from a circularly polarized Gaussian input beam. The corresponding helical phase profiles with radial discontinuities are encoded in the metasurfaces by the orientation of the nanoantennas. A common-path interferometer is used to determine the orbital angular momentum of the generated beams. Additionally, we employ digital holography to record the detailed phase profiles of the Laguerre-Gaussian modes. This method allows a simple and direct quantitative comparison of the measured phase profiles of the generated Laguerre-Gaussian beams with the theoretically expected phase profiles. Experiments with different laser sources demonstrate the broadband operation of the metasurfaces.
Acoustic propagation characteristics of heteromorphic metamaterials
Authors: Han Jianning , Tang Shuai
Published: October 2018

To explore the propagation characteristics of acoustic waves in heterogeneous acoustic materials, we studied the propagation of acoustic waves in resonant phononic crystals. We identified the vibration mechanism of two-dimensional three-component localized resonant phononic crystals. Using the finite element software COMSOL, an acoustic propagation model based on acoustic metamaterials was constructed and the local resonance characteristics of acoustic waves and the original cells were used to simulate multiple acoustic models based on triangular arrays. We found that the planar point-like and linear excitation sources incident from the bottom edge of the triangular array model converge to the focal point at the top corner after being controlled by the model. The low-loss movement effect of the point source could be achieved in a rectangular model with a triangular array. A reversal of the transmission of plane acoustic waves resulted when two or three identical triangular arrays were combined into a parallelogram or a trapezoid. This series of abnormal acoustic phenomena provides new directions for the detection of point sources, low-loss directional transmission of acoustic waves, and acoustic stealth.
Communication: Can excitation energies be obtained from orbital energies in a correlated orbital theory?
Authors: Haiduke Roberto Luiz Andrade , Bartlett Rodney J.
Published: October 2018

This work shows that vertical excitation energies (characterized as single-electron processes) can be expressed in terms of one-particle solutions from a self-consistent field problem built by means of correlated operators. There are two alternative ways of enforcing this proposal for i → a transitions in a system (M): (1) by using only eigenvalues obtained for the cationic species reached after the removal of an electron from orbital i (M+) or (2) by combining these quantities with the eigenvalue associated with orbital i from the neutral M system. We demonstrate that those eigenvalues derived from the equation-of-motion formalism in terms of the coupled cluster approach including single and double substitutions for ionization potentials and electron affinities show excellent performance in reproducing these electronic transition energies by either path, with mean absolute deviations (MADs) between 0.02 and 0.06 eV. Moreover, the Kohn-Sham Density Functional Theory (KS-DFT) methods from the Quantum Theory Project (QTP) family provide nice results in terms of the second approach (MADs from 0.21 to 0.47 eV). However, DFT is not as successful as long as one takes into account only the eigenvalues of M+, although the respective excitation energies from QTP functionals are still reasonable (MADs between 0.55 and 0.74 eV). Ultimately, these relations can be used as a new consistency condition to develop KS-DFT approximations to the correlated orbital theory.
Numerical supersonic flow simulations help improve high-speed engine design
Authors: Johnson-Groh Mara
Published: October 2018

Reducing boundary layer separation in supersonic flows has applications in high-speed engine design. New simulations are revealing underlying physics in the mechanism used to minimize separation.
Does mycorrhizal colonisation vary between maize and sunflower under limitations to radiation source or carbohydrate sink?
Authors: Covacevich Fernanda , Verneri Julieta Martínez , Dosio Guillermo A. A.
Published: October 2018

The aim of this work was to analyse and compare indigenous arbuscular mycorrhizal colonisation (AMC) in relation to growth and total soluble carbohydrates (TSC) in two major, physiologically contrasting crop species: maize (Zea mays L.) and sunflower (Helianthus annuus L.). In order to promote contrasting TSC concentrations, we modified the radiation source by shading and the carbohydrate sink by manipulating reproductive sinks at different phenological stages during the grain-filling period in two field experiments. We assessed plant dry matter, TSC in stems, and root AMC from flowering until final harvest. AMC during the grain-filling period decreased in maize and increased in sunflower. A sink limitation increased AMC in maize, and reduced it in sunflower. A source limitation decreased AMC in both species, especially in sunflower. AMC was positively related to TSC in maize, but negatively in sunflower. The relationship was affected by shading in sunflower, but not in maize. In both species, a different linear model described the relationship between AMC and TSC in plants submitted to the removal of the reproductive organs. The results highlight the role of carbohydrates in mediating mycorrhizal formation, and show for the first time the opposite AMC–TSC relationships in maize and sunflower.
Prescreening in large populations as a tool for identifying elevated CO2-responsive genotypes in plants
Authors: Shimono Hiroyuki , Farquhar Graham , Brookhouse Matthew , Busch Florian A. , O'Grady Anthony , Tausz Michael , Pinkard Elizabeth A.
Published: October 2018

Elevated atmospheric CO2 concentration (e[CO2]) can stimulate the photosynthesis and productivity of C3 species including food and forest crops. Intraspecific variation in responsiveness to e[CO2] can be exploited to increase productivity under e[CO2]. However, active selection of genotypes to increase productivity under e[CO2] is rarely performed across a wide range of germplasm, because of constraints of space and the cost of CO2 fumigation facilities. If we are to capitalise on recent advances in whole genome sequencing, approaches are required to help overcome these issues of space and cost. Here, we discuss the advantage of applying prescreening as a tool in large genome×e[CO2] experiments, where a surrogate for e[CO2] was used to select cultivars for more detailed analysis under e[CO2] conditions. We discuss why phenotypic prescreening in population-wide screening for e[CO2] responsiveness is necessary, what approaches could be used for prescreening for e[CO2] responsiveness, and how the data can be used to improve genetic selection of high-performing cultivars. We do this within the framework of understanding the strengths and limitations of genotype–phenotype mapping.
Improving gout education from patients’ perspectives: a focus group study of Māori and Pākehā people with gout
Authors: Rolston Cassandra J. , Conner Tamlin S. , Stamp Lisa K. , Neha Tia , Pitama Suzanne , Fanning Niamh , Janes Ron , Judd Andrea , Hudson Ben , Hegarty Roisin M. , Treharne Gareth J.
Published: October 2018

ABSTRACT INTRODUCTION Gout is a common form of arthritis that is typically managed in primary care. Gout management guidelines emphasise patient education for successful treatment outcomes, but there is limited literature about the educational experiences of people living with gout in New Zealand, particularly for Māori, who have higher gout prevalence and worse gout outcomes than Pākehā. AIM To explore gout patient education in primary care from the perspectives of Māori and Pākehā people with gout. METHODS In total, 69 people with gout were recruited through primary care providers in three locations across New Zealand. Nine semi-structured focus groups were run with Māori and Pākehā participants in separate groups. RESULTS Thematic analysis yielded two themes in relation to gout education: (i) ‘Multiple sources of gout education’; and (ii) ‘Gaps in gout knowledge’. Participants received education from general practitioners, educational resources, family and friends, and their own experiences. Māori participants preferred information to be kanohi-ki-te-kanohi (face-to-face) and with significant others present where necessary. Participants disclosed gaps in gout’s epidemiology and management. Pākehā and Māori participants reported limited understanding of the genetic basis of gout or the biological underpinnings of the condition and its treatments, but learned treatment adherence through experience. DISCUSSION Despite improved gout patient education, knowledge gaps remain and may contribute to poor medication adherence. Gout patient education interventions need to be tailored to culture and incorporate suitable methods of disseminating information about gout management.
Cross-disciplinary Notes for a Study of Rhythm
Authors: Chesterman Andrew
Published: October 2018

This context brings together three disciplines: Adaptation Studies, Translation Studies, and Semiotics. The question to be considered is the extent to which these disciplines are really ‘saying almost the same thing’. The present paper examines this question from three angles. First, I summarize some ideas concerning the nature of categories in general, and the function of categorization, from which I infer that we can regard a discipline as a kind of category. Second, I outline some examples of research which overlaps the boundaries between our three fields and thus questions the usefulness of holding such boundaries as permanent and universal. And third, I report a small investigation into rhythm, and in particular, the rhythm of a painting and its title, an investigation which merges such categorial boundaries. I present it in illustration of the view that conceptual categories and their boundaries are only tools, to be used or not, as the purpose requires.
Mild Allergic Transfusion Reactions
Authors: Adkins Brian D , Lawicki Shaun , Johnson Mary , Eichbaum Quentin
Published: October 2018

Objectives

Transfusions are often needlessly aborted after occurrence of a mild allergic transfusion reaction (ATR), leading to wastage and reexposure of recipients to additional blood products (with potential alloimmunization). We aimed to determine the symptoms associated with such reactions (along with other parameters) as a possible reason of concern for transfusionists aborting such transfusions.

Methods

We reviewed the symptomology of all mild ATRs (as well as the associated wastage and costs of aborted transfusions) at an academic medical center that occurred over a period of 1 year.

Results

Of the patients, 52.3% had nonatopic-associated symptoms. The most common associated symptom was tachycardia (37.8%), followed by dyspnea (28.9%), hypotension (17.8%), and hypertension (13.3%). More than half of patients (54.7%) required retransfusion. The estimated cost of product wastage was $12,507.

Conclusions

Understanding symptoms associated with mild ATRs may lead to improved management of patients, with fewer unnecessary transfusions and less wastage.
Sex Differences in Hypertension: Where We Have Been and Where We Are Going
Authors: Ramirez Lindsey A , Sullivan Jennifer C
Published: October 2018

While it has been known since the 1940s that men have greater increases in blood pressure (BP) compared with women, there have been intense efforts more recently to increase awareness that women are also at risk for developing hypertension and that cardiovascular diseases (CVDs) are the leading causes of death among both men and women in the United States. With the release of the 2017 Hypertension Clinical Guidelines, 46% of adults in the United States are now classified as hypertensive, and hypertension is the primary modifiable risk factor for the development of CVD. This increase in the prevalence of hypertension is reflected in an increase in prevalence among both men and women across all demographics, although there were greater increases in the prevalence of hypertension among men compared with women. As a result, the well-established gender difference in the prevalence of hypertension is even more pronounced and now extends into the sixth decade of life. The goals of this review are to (i) review the historical clinical trial data and hypertension guidelines from the perspective of both genders and then (ii) review the role of the renin–angiotensin system and T-cell activation in contributing to sex differences in BP control.
DeepHINT: understanding HIV-1 integration via deep learning with attention
Authors: Hu Hailin , Xiao An , Zhang Sai , Li Yangyang , Shi Xuanling , Jiang Tao , Zhang Linqi , Zhang Lei , Zeng Jianyang
Published: October 2018

Motivation

Human immunodeficiency virus type 1 (HIV-1) genome integration is closely related to clinical latency and viral rebound. In addition to human DNA sequences that directly interact with the integration machinery, the selection of HIV integration sites has also been shown to depend on the heterogeneous genomic context around a large region, which greatly hinders the prediction and mechanistic studies of HIV integration.

Results

We have developed an attention-based deep learning framework, named DeepHINT, to simultaneously provide accurate prediction of HIV integration sites and mechanistic explanations of the detected sites. Extensive tests on a high-density HIV integration site dataset showed that DeepHINT can outperform conventional modeling strategies by automatically learning the genomic context of HIV integration from primary DNA sequence alone or together with epigenetic information. Systematic analyses on diverse known factors of HIV integration further validated the biological relevance of the prediction results. More importantly, in-depth analyses of the attention values output by DeepHINT revealed intriguing mechanistic implications in the selection of HIV integration sites, including potential roles of several DNA-binding proteins. These results established DeepHINT as an effective and explainable deep learning framework for the prediction and mechanistic study of HIV integration.

Availability and implementation

DeepHINT is available as an open-source software and can be downloaded from https://github.com/nonnerdling/DeepHINT.

Supplementary information

Supplementary data are available at Bioinformatics online.
Multi-insight visualization of multi-omics data via ensemble dimension reduction and tensor factorization
Authors: Fanaee-T Hadi , Thoresen Magne
Published: October 2018

Motivation

Visualization of high-dimensional data is an important step in exploratory data analysis and knowledge discovery. However, it is challenging, because the interpretation is highly subjective. If we see dimensionality reduction (DR) techniques as the main tool for data visualization, they are like multiple cameras that look into the data from different perspectives or angles. We can hardly prescribe one single perspective for all datasets and problems. One snapshot of data cannot reveal all the relevant aspects of the data in higher dimensions. The reason is that each of these methods has its own specific strategy, normally based on well-established mathematical theories to obtain a low-dimensional projection of the data, which sometimes is totally different from the others. Therefore, relying only on one single projection can be risky, because it can close our eyes to important parts of the full knowledge space.

Results

We propose the first framework for multi-insight data visualization of multi-omics data. This approach, contrary to single-insight approaches, is able to uncover the majority of data features through multiple insights. The main idea behind the methodology is to combine several DR methods via tensor factorization and group the solutions into an optimal number of clusters (or insights). The experimental evaluation with low-dimensional synthetic data, simulated multi-omics data related to ovarian cancer, as well as real multi-omics data related to breast cancer show the competitive advantage over state-of-the-art methods.

Availability and implementation

https://folk.uio.no/hadift/MIV/ [user/pass via hadift@medisin. uio.no]

Supplementary information

Supplementary data are available at Bioinformatics online.
‘Spiritual Risk’: A Parental Perception of Risk for Children in the Ultra-Orthodox Jewish Community
Authors: Nadan Yochay , Gemara Netanel , Keesing Rivka , Bamberger Esther , Roer-Strier Dorit , Korbin Jill
Published: October 2018

This article addresses child protection in close-knit religious communities. Specifically, it presents the findings of a qualitative research project that examined Ultra-Orthodox Jewish parents’ perceptions and ascribed meanings of child risk and protection based on fifty in-depth interviews with parents from Israel and the USA. Here, we hone in on one key theme that emerged from our analysis of the interviews, which the interviewees themselves referred to as ‘spiritual risk’. ‘Spiritual risk’ is a complex construct comprising the following three interrelated dimensions: (i) a decline in observance of the Torah and the commandments, (ii) violation of socio-cultural norms and rules and (iii) a decline in spiritual beliefs, including the sense of connection with G-d. In the eyes of parents, it is decline in these three dimensions that constitutes the ‘spiritual risk’ to the child. ‘Spiritual risk’ can be a consequence of parental maltreatment and can result in children and adolescents moving away from the Ultra-Orthodox religious world and leaving their community. The results of this study advocate context-informed and religious-sensitive prevention and intervention programmes. They also highlight the need to include context and religious competency in the training of professionals working with diverse communities.
Visual and Vestibular Selectivity for Self-Motion in Macaque Posterior Parietal Area 7a
Authors: Avila Eric , Lakshminarasimhan Kaushik J , DeAngelis Gregory C , Angelaki Dora E
Published: October 2018

We examined the responses of neurons in posterior parietal area 7a to passive rotational and translational self-motion stimuli, while systematically varying the speed of visually simulated (optic flow cues) or actual (vestibular cues) self-motion. Contrary to a general belief that responses in area 7a are predominantly visual, we found evidence for a vestibular dominance in self-motion processing. Only a small fraction of neurons showed multisensory convergence of visual/vestibular and linear/angular self-motion cues. These findings suggest possibly independent neuronal population codes for visual versus vestibular and linear versus angular self-motion. Neural responses scaled with self-motion magnitude (i.e., speed) but temporal dynamics were diverse across the population. Analyses of laminar recordings showed a strong distance-dependent decrease for correlations in stimulus-induced (signal correlation) and stimulus-independent (noise correlation) components of spike-count variability, supporting the notion that neurons are spatially clustered with respect to their sensory representation of motion. Single-unit and multiunit response patterns were also correlated, but no other systematic dependencies on cortical layers or columns were observed. These findings describe a likely independent multimodal neural code for linear and angular self-motion in a posterior parietal area of the macaque brain that is connected to the hippocampal formation.
Role of Early De-escalation of Antimicrobial Therapy on Risk of Clostridioides difficile Infection Following Enterobacteriaceae Bloodstream Infections
Authors: Seddon Megan M , Bookstaver P Brandon , Justo Julie Ann , Kohn Joseph , Rac Hana , Haggard Emily , Mediwala Krutika N , Dash Sangita , Al-Hasan Majdi N
Published: October 2018

Background

There is a paucity of data on the effect of early de-escalation of antimicrobial therapy on rates of Clostridioides difficile infection (CDI). This retrospective cohort study evaluated impact of de-escalation from antipseudomonal β-lactam (APBL) therapy within 48 hours of Enterobacteriaceae bloodstream infections (BSIs) on 90-day risk of CDI.

Methods

Adult patients hospitalized for >48 hours for treatment of Enterobacteriaceae BSI at Palmetto Health hospitals in Columbia, South Carolina, from 1 January 2011 through 30 June 2015 were identified. Multivariable Cox proportional hazards regression was used to examine time to CDI in patients who received >48 hours or ≤48 hours of APBL for empirical therapy of Enterobacteriaceae BSI after adjustment for the propensity to receive >48 hours of APBL.

Results

Among 808 patients with Enterobacteriaceae BSI, 414 and 394 received >48 and ≤48 hours of APBL, respectively. Incidence of CDI was higher in patients who received >48 hours than those who received ≤48 hours of APBL (7.0% vs 1.8%; log-rank P = .002). After adjustment for propensity to receive >48 hours of APBL and other variables in the multivariable model, receipt of >48 hours of APBL (hazard ratio [HR], 3.56 [95% confidence interval {CI}, 1.48–9.92]; P = .004) and end-stage renal disease (HR, 4.27 [95% CI, 1.89–9.11]; P = .001) were independently associated with higher risk of CDI.

Conclusions

The empirical use of APBL for >48 hours was an independent risk factor for CDI. Early de-escalation of APBL using clinical risk assessment tools or rapid diagnostic testing may reduce the incidence of CDI in hospitalized adults with Enterobacteriaceae BSIs.
Hybrid coronary computed tomography angiography and positron emission tomography myocardial perfusion imaging in evaluation of recurrent symptoms after coronary artery bypass grafting
Authors: Maaniitty Teemu , Jaakkola Samuli , Saraste Antti , Knuuti Juhani
Published: October 2018

Aims

Recurrent chest pain after coronary artery bypass grafting (CABG) poses a diagnostic challenge. We hypothesized that combining anatomy of bypass grafts and native coronary arteries with ischaemia detection by hybrid imaging could be used to gain valuable and complementary information in patients with recurrent symptoms after CABG.

Methods and results

We analysed 36 consecutive patients (67 ± 9 years, 81% male) who had undergone hybrid imaging using coronary computed tomography angiography (CCTA) and [15O]H2O positron emission tomography (PET) myocardial perfusion imaging due to recurrent symptoms after CABG. Coronary tree and left ventricular myocardium were divided into three main territories, yielding a total of 108 coronary territories in 36 patients. The presence of obstructive (≥50%) stenosis and the patency of grafts were evaluated by CCTA, while myocardial ischaemia was assessed by quantitative adenosine-stress PET. Altogether 28 (78%) of the 36 study patients presented with matched PET/CCTA abnormalities. Forty-one coronary territories were supplied by non-obstructed bypass grafts or native coronary arteries (protected territory). However, 12 (29%) of these presented with a perfusion defect. In six cases, the perfusion defect involved myocardium distal to the graft-coronary anastomosis, as interpreted on the PET/CCTA fusion images. In turn, in 48 coronary territories the supplying artery was obstructed on CCTA (unprotected territory). Of these, 41 (85%, P < 0.001 vs. protected) presented with abnormal perfusion, involving myocardium distal to the anastomosis in 29 cases.

Conclusion

Hybrid imaging provides complementary information on the presence and localization of atherosclerotic lesions and myocardial perfusion abnormalities in symptomatic patients with previous CABG.
Mesenchymal Stem Cells for Periodontal Tissue Regeneration in Elderly Patients
Authors: Ledesma-Martínez Edgar , Mendoza-Núñez Víctor Manuel , Santiago-Osorio Edelmiro
Published: October 2018

Mesenchymal stem cell (MSC) grafting is a highly promising alternative strategy for periodontal regeneration in periodontitis, which is one of the primary causes of tooth loss in the elderly. However, aging progressively decreases the proliferative and differentiation potential of MSCs and diminishes their regenerative capacity, which represents a limiting factor for their endogenous use in elderly patients. Therefore, tissue regeneration therapy with MSCs in this age group may require a cellular source without the physiological limitations that MSCs exhibit in aging. In this sense, exogenous or allogeneic MSCs could have a better chance of success in regenerating periodontal tissue in elderly patients. This review examines and synthesizes recent data in support of the use of MSCs for periodontal regenerative therapy in patients. Additionally, we analyze the progress of the therapeutic use of exogenous MSCs in humans.
Effect of Food Predictability on Life Span in Male Mice
Authors: Rowland Neil E , Robertson Kimberly L , Minaya Dulce , Minervini Vanessa , Cervantez Melissa , Kaiser Kathryn A , Allison David B
Published: October 2018

The purpose of this study is to compare the effect of unpredictable (U) or predictable (P) food delivery on health and longevity in mice. From 2 months of age until end of life, singly-housed male C57BL/6 mice were fed a semisynthetic diet either ad libitum (AL), or as imposed meals delivered as small pellets at either P or U times, frequencies, or amounts. The total daily food consumed by all groups was the same. The AL group gained body weight faster than either P or U groups, and had ~12% shorter median life span compared with either P or U groups. Bimonthly noninvasive body composition determinations showed that the differences in body weights were due to differences in fat and lean mass. Postmortem examinations revealed that the organ pathologies were similar in all groups, but a larger fraction of P and U mice were euthanized due to end-of-life suffering. There were no systematic differences in outcome measures between P and U groups suggesting that, within the range studied, the temporal pattern of food delivery did not have a significant metabolic effect.
The demand-pull effect of public procurement on innovation and industrial renewal
Authors: Crespi Francesco , Guarascio Dario
Published: October 2018

This article empirically analyzes the link between public procurement (PP) and innovation activities, by taking into account the moderating effect played by import penetration on PP. Using industry-level information on patent applications for 24 countries over the period 1995–2012, we test the impact of PP on innovation activities and whether and in which direction import penetration on PP impacts on patenting. The econometric analysis relies on Poisson regression techniques aiming to investigate the correlation between patent counts, supply- as well as demand-side determinants, and controlling for country and sector heterogeneity. The obtained results confirm our main hypotheses. The dynamics of patenting is positively affected by the PP, while a high degree of import penetration reduces the innovation enhancing effect exerted by public demand. Our results suggest that public demand may represent an effective tool for industrial policy to stimulate innovative activities, shape the transformation of production systems, and foster industrial renewal. Moreover, the empirical evidence shows that the strategy regarding the degree of openness in PP toward nondomestic firms is a crucial policy choice capable of affecting the innovative potential of public demand.
Habitual sleep quality, plasma metabolites and risk of coronary heart disease in post-menopausal women
Authors: Huang Tianyi , Zeleznik Oana A , Poole Elizabeth M , Clish Clary B , Deik Amy A , Scott Justin M , Vetter Céline , Schernhammer Eva S , Brunner Robert , Hale Lauren , Manson JoAnn E , Hu Frank B , Redline Susan , Tworoger Shelley S , Rexrode Kathryn M
Published: October 2018

Background

Epidemiologic studies suggest a strong link between poor habitual sleep quality and increased cardiovascular disease risk. However, the underlying mechanisms are not entirely clear. Metabolomic profiling may elucidate systemic differences associated with sleep quality that influence cardiometabolic health.

Methods

We explored cross-sectional associations between sleep quality and plasma metabolites in a nested case–control study of coronary heart disease (CHD) in the Women’s Health Initiative (WHI; n = 1956) and attempted to replicate the results in an independent sample from the Nurses’ Health Study II (NHSII; n = 209). A sleep-quality score (SQS) was derived from self-reported sleep problems asked in both populations. Plasma metabolomics were assayed using LC–MS with 347 known metabolites. General linear regression was used to identify individual metabolites associated with continuous SQS (false-discovery rate <0.05). Using least absolute shrinkage and selection operator (LASSO) algorithms, a metabolite score was created from replicated metabolites and evaluated with CHD risk in the WHI.

Results

After adjusting for age, race/ethnicity, body mass index (BMI) and smoking, we identified 69 metabolites associated with SQS in the WHI (59 were lipids). Of these, 16 were replicated in NHSII (15 were lipids), including 6 triglycerides (TAGs), 4 phosphatidylethanolamines (PEs), 3 phosphatidylcholines (PCs), 1 diglyceride (DAG), 1 lysophosphatidylcholine and N6-acetyl-L-lysine (a product of histone acetylation). These metabolites were consistently higher among women with poorer sleep quality. The LASSO selection resulted in a nine-metabolite score (TAGs 45: 1, 48: 1, 50: 4; DAG 32: 1; PEs 36: 4, 38: 5; PCs 30: 1, 40: 6; N6-acetyl-L-lysine), which was positively associated with CHD risk (odds ratio per SD increase in the score: 1.16; 95% confidence interval: 1.05, 1.28; p = 0.0003) in the WHI after adjustment for matching factors and conventional CHD risk factors.

Conclusions

Differences in lipid metabolites may be an important pathogenic pathway linking poor habitual sleep quality and CHD risk.
A mathematical model of white blood cell dynamics during maintenance therapy of childhood acute lymphoblastic leukemia
Authors: Le Thuy T T , Jost Felix , Raupach Thomas , Zierk Jakob , Rauh Manfred , Suttorp Meinolf , Stanulla Martin , Metzler Markus , Sager Sebastian
Published: October 2018

Acute lymphoblastic leukemia is the most common malignancy in childhood and requires prolonged oral maintenance chemotherapy to prevent disease relapse after remission induction with intensive intravenous chemotherapy. In maintenance therapy, drug doses of 6-mercaptopurine (6-MP) and methotrexate (MTX) are adjusted to achieve sustained antileukemic activity without excessive myelosuppression. However, uncertainty exists regarding timing and extent of drug dose responses and optimal dose adaptation strategies. We propose a novel comprehensive mathematical model for 6-MP and MTX pharmacokinetics, pharmacodynamics and myelosuppression in acute lymphoblastic maintenance therapy. We personalize and cross-validate the mathematical model using clinical data and propose a real-time algorithm to predict chemotherapy responses with a clinical decision support system as a potential future application.
Picard Groups of Moduli Spaces of Curves with Symmetry
Authors: Kordek Kevin
Published: October 2018

We study the Picard groups of moduli spaces of smooth complex projective curves that have a group of automorphisms with a prescribed topological action. One of our main tools is the theory of symmetric mapping class groups. In the 1st part of the paper, we show that, under mild restrictions, the moduli spaces of smooth curves with an abelian group of automorphisms of a fixed topological type have finitely generated Picard groups. In certain special cases, we are able to compute them exactly. In the 2nd part of the paper, we show that finite abelian level covers of the hyperelliptic locus in the moduli space of smooth curves have finitely generated Picard groups. We also compute the Picard groups of the moduli spaces of hyperelliptic curves of compact type.
Codimension One Holomorphic Distributions on the Projective Three-space
Authors: Calvo-Andrade Omegar , Corrêa Maurício , Jardim Marcos
Published: October 2018

We study codimension one holomorphic distributions on the projective three-space, analyzing the properties of their singular schemes and tangent sheaves. In particular, we provide a classification of codimension one distributions of degree at most 2 with locally free tangent sheaves and show that codimension one distributions of arbitrary degree with only isolated singularities have stable tangent sheaves. Furthermore, we describe the moduli space of distributions in terms of Grothendieck’s Quot-scheme for the tangent bundle. In certain cases, we show that the moduli space of codimension one distributions on the projective space is an irreducible, nonsingular quasi-projective variety. Finally, we prove that every rational foliation and certain logarithmic foliations have stable tangent sheaves.
Physical Activity and Colorectal Cancer Prognosis According to Tumor-Infiltrating T Cells
Authors: Koh Hideo , Hamada Tsuyoshi , Song Mingyang , Liu Li , Cao Yin , Nowak Jonathan A , da Silva Annacarolina , Twombly Tyler , Morikawa Teppei , Kim Sun A , Masugi Yohei , Kosumi Keisuke , Shi Yan , Gu Mancang , Li Wanwan , Du Chunxia , Chen Yang , Li Wenbin , Liu Hongli , Li Chenxi , Wu Kana , Nosho Katsuhiko , Inamura Kentaro , Hanyuda Akiko , Zhang Xuehong , Giannakis Marios , Chan Andrew T , Fuchs Charles S , Nishihara Reiko , Meyerhardt Jeffrey A , Ogino Shuji
Published: October 2018

Background

Evidence suggests that high-level physical activity may potentially reduce cancer mortality through its immune enhancement effect. We therefore hypothesized that survival benefits associated with physical activity might be stronger in colorectal carcinomas with lower immune reaction at diagnosis.

Methods

Using molecular pathological epidemiology databases of 470 colon and rectal carcinoma cases in the Nurses’ Health Study and the Health Professionals Follow-up Study, we assessed the prognostic association of postdiagnosis physical activity in strata of densities of CD3+ cells, CD8+ cells, CD45RO (PTPRC)+ cells, or FOXP3+ cells in tumor tissue. Cox proportional hazards regression model was used to adjust for potential confounders, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation, KRAS, BRAF, and PIK3CA mutations, and expression of CTNNB1 (beta-catenin), PTGS2 (cyclooxygenase-2), and IRS1.

Results

The association of postdiagnosis physical activity with colorectal cancer-specific mortality differed by CD3+ cell density (Pinteraction < .001). Multivariable-adjusted colorectal cancer-specific mortality hazard ratios for a quartile-unit increase in physical activity were 0.56 (95% confidence interval = 0.38 to 0.83) among cases with the lowest quartile of CD3+ cell density compared with 1.14 (95% confidence interval = 0.79 to 1.65) in cases with the highest quartile. We observed no differential survival association of physical activity by densities of CD8+ cells, CD45RO+ cells, or FOXP3+ cells.

Conclusions

The association between postdiagnosis physical activity and colorectal cancer survival appeared stronger for carcinomas with lower T cell infiltrates, suggesting an interactive effect of exercise and immunity on colorectal cancer progression.
Change in Survival in Metastatic Breast Cancer with Treatment Advances: Meta-Analysis and Systematic Review
Authors: Caswell-Jin Jennifer L , Plevritis Sylvia K , Tian Lu , Cadham Christopher J , Xu Cong , Stout Natasha K , Sledge George W , Mandelblatt Jeanne S , Kurian Allison W
Published: October 2018

Background

Metastatic breast cancer (MBC) treatment has changed substantially over time, but we do not know whether survival post-metastasis has improved at the population level.

Methods

We searched for studies of MBC patients that reported survival after metastasis in at least two time periods between 1970 and the present. We used meta-regression models to test for survival improvement over time in four disease groups: recurrent, recurrent estrogen (ER)-positive, recurrent ER-negative, and de novo stage IV. We performed sensitivity analyses based on bias in some studies that could lead earlier cohorts to include more aggressive cancers.

Results

There were 15 studies of recurrent MBC (N = 18 678 patients; 3073 ER-positive and 1239 ER-negative); meta-regression showed no survival improvement among patients recurring between 1980 and 1990, but median survival increased from 21 (95% confidence interval [CI] = 18 to 25) months to 38 (95% CI = 31 to 47) months from 1990 to 2010. For ER-positive MBC patients, median survival increased during 1990–2010 from 32 (95% CI = 23 to 43) to 57 (95% CI = 37 to 87) months, and for ER-negative MBC patients from 14 (95% CI = 11 to 19) to 33 (95% CI = 21 to 51) months. Among eight studies (N = 35 831) of de novo stage IV MBC, median survival increased during 1990–2010 from 20 (95% CI = 16 to 24) to 31 (95% CI = 24 to 39) months. Results did not change in sensitivity analyses.

Conclusion

By bridging studies over time, we demonstrated improvements in survival for recurrent and de novo stage IV MBC overall and across ER-defined subtypes since 1990. These results can inform patient-doctor discussions about MBC prognosis and therapy.
History and Current Trends in the Electronic Cigarette Retail Marketplace in the United States: 2010–2016
Authors: Cantrell Jennifer , Huang Jidong , Greenberg Marisa , Willett Jeffrey , Hair Elizabeth , Vallone Donna
Published: October 2018

Introduction

The US market for electronic nicotine delivery systems (ENDS) has grown rapidly in the last decade. There is limited published evidence examining changes in the ENDS marketplace prior to the US Food and Drug Administration’s (FDA) deeming rule in 2016. This study describes US ENDS retail market trends from 2010 to 2016.

Methods

National data were obtained from Nielsen retail scanners for five product types: (1) disposables, (2) rechargeables, (3) cartridge replacements, (4) e-liquid bottle refills, and (5) specialty vapor products. We examined dollar sales, volume, price, brand, and flavor.

Results

Adjusted national sales increased from $11.6 million in 2010 to $751.2 million in 2016. The annual rate of sales growth rapidly increased before slowing through 2015. The rate of growth spiked in 2016. Market share for menthol products and other assorted flavors increased from 20% in 2010 to 52.1% by 2016. NJOY’s early market dominance shifted as tobacco industry brands entered the market and eventually captured 87.8% of share by 2016. Rechargeables and accompanying products comprised an increased proportion of total volume sold over time while disposable volume declined. Specialty vapor products appeared at retail in 2015.

Conclusions

Findings show strong early growth in the ENDS retail market followed by considerable slowing over time, despite a slight uptick in 2016. Trends reflect shifts to flavored products, newer generation “open-system” devices, lower prices, and tobacco industry brands. This study provides a baseline against which to compare the impact of FDA’s 2016 deeming rule and future actions on the ENDS marketplace.

Implications

This study uses market scanner data from US retail outlets to describe trends in the ENDS retail market from 2010 to 2016, providing a baseline against which to compare the impact of FDA’s 2016 deeming rule and future actions on the ENDS marketplace. Understanding historical market trends is valuable in assessing how future regulatory efforts and advances in ENDS technology may impact industry response and consumer uptake and use.
Childhood Trauma and Neurocognition in Adults With Psychotic Disorders: A Systematic Review and Meta-analysis
Authors: Vargas Teresa , Lam Phoebe H , Azis Matilda , Osborne K Juston , Lieberman Amy , Mittal Vijay A
Published: October 2018

Background

Characterizing the link between childhood trauma and adult neurocognitive function in psychosis is crucial for improving the fields understanding of how early environmental risk factors impact the presentation of the disorder. To date, the literature has been inconsistent: meta-analytic synthesis is lacking, and it is unclear whether specific cognitive functions are affected.

Methods

A meta-analysis was performed on a total of 3315 subjects with a psychotic disorder. The links between childhood trauma, overall neurocognitive function, and four cognitive subdomains (working memory, executive function, verbal/visual memory, and attention/processing speed) were examined. Relevant sample characteristics and methodological moderators were tested. The strength of the association between trauma and overall neurocognition in individuals with psychotic disorders was also compared to that of healthy controls.

Results

Among individuals with psychotic disorders, there was a significant association between overall cognition and childhood trauma, r = −.055; 95% CI = −0.09, −0.02, P = .002. There was also a modest, negative relationship between childhood trauma and working memory, r = −.091; 95% CI = −0.15, −0.03, P = .002. Moderators did not have a significant effect on these analyses. Further, the association between childhood trauma and neurocognition was significantly stronger in healthy controls compared to patients with a psychotic disorder.

Conclusion

A small negative association was found between overall cognition and childhood trauma in individuals with psychotic disorders. Results suggest the association is less strong for individuals with a psychotic disorder compared to healthy populations. Findings are informative for prominent etiological models of psychosis.
‘Candidatus Liberibacter asiaticus’ and Its Vector, Diaphorina citri, Augment the Tricarboxylic Acid Cycle of Their Host via the γ-Aminobutyric Acid Shunt and Polyamines Pathway
Authors: Nehela Yasser , Killiny Nabil
Published: October 2018

Huanglongbing (HLB), a destructive citrus disease, is associated with ‘Candidatus Liberibacter asiaticus’, which is transmitted by the Asian citrus psyllid Diaphorina citri. Both ‘Ca. L. asiaticus’ and its vector manipulate the host metabolism for their benefit, to meet their nutritional needs and neutralize the host defense responses. We used a targeted gas chromatography-mass spectrometry–based method to explore the connection between the tricarboxylic acid (TCA) cycle, γ-aminobutyric acid (GABA) shunt, and polyamines (PAs) pathways in citrus. ‘Ca. L. asiaticus’ and D. citri accelerated the conversion of α-ketoglutarate to glutamate, then to GABA, causing an accumulation of GABA in the cytosol. In silico analysis showed that the citrus genome possesses a putative GABA permease that connects the GABA shunt with the TCA cycle and supports the accumulation of succinate, fumarate, and citrate. Additionally, the PAs biosynthetic pathway might be connected directly to the TCA cycle, through the production of fumarate, or indirectly, via enhancement of GABA shunt. Taken together, we suggest that GABA shunt and PAs pathways are alternative pathways that contribute to the flux toward succinate rather than an intact TCA cycle in citrus. Both ‘Ca. L. asiaticus’ and its vector enhance these pathways. This study provides more insights into citrus responses to the HLB pathosystem and could be a further step toward clues for understanding the nutritional needs of ‘Ca. L. asiaticus’, which could help in culturing ‘Ca. L. asiaticus’.
Enhanced recovery after cardiac surgery program to improve patient outcomes
Authors: McConnell Gina , Woltz Patricia , Bradford William T. , Ledford J. Erin , Williams Judson B.
Published: October 2018

This article details the obstacles of implementing a cardiac-specific enhanced recovery after surgery (ERAS) program in a 919-bed not-for-profit community-based health system and the benefits of ERAS programs for different patient populations.
The C. difficile puzzle
Authors: Chapman Christie , Foley Catherine
Published: October 2018

This article explores Clostridium difficile infection (CDI) versus colonization, regulations surrounding CDI reporting, the varied types of CDI testing methods available, and the important role nurses have in thoughtful submission of stool specimens for C. difficile testing.