bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of locally advanced rectal cancer (LARC) to
radiochemotherapy: DW-MRI and multiparametric PET/CT in correlation with
histopathology
Authors: Cerny Milena , Dunet Vincent , Rebecchini Caterina , Hahnloser Dieter , Prior John , Sempoux Christine , Schmidt Sabine
Published: February 2019

Aim To prospectively evaluate histological significance and predictive
value of changes in apparent diffusion coefficient (ADC) and 18F-FDG
PET/CT parameters in locally advanced rectal cancer (LARC) after neoadjuvant
radiochemotherapy (RCT).

Methods Twenty-one patients with untreated LARC underwent pre-RCT and
post-RCT 18F-FDG PET/CT and diffusion-weighted magnetic resonance
imaging (DW-MRI), followed by surgery. For both datasets, two readers measured
the tumor SUVmax, SUVmean, MTV, TLG, ADCmin, ADCmean, and respective differences
(∆SUVmax, ∆SUVmean, ∆MTV, ∆TLG, ∆ADCmin, ∆ADCmean) for the whole tumor. Tumor
regression grade according to Mandard (TRGm), percentage of residual tumor cells
and fibrosis were estimated by two pathologists in consensus. Relationship
between parameters was assessed on stepwise multivariate regression analysis and
ROC curve analysis to evaluate their performance and predict the treatment
response.

Results Eighteen LARCs were analyzed. SUVmax and SUVmean decreased from
21.3 ± 8.9 to 9.3 ± 5.5 g/mL, (p = 0.0002) and 12.3 ± 5.1 to 5.4 ± 3.1 g/mL,
(p = 0.0002), respectively, after RCT, whereas ADCmin and ADCmean increased from
396 ± 269 to 573 ± 313×10–6 mm2/s (p = 0.014) and
1159 ± 212 to 1355 ± 194×10–6 mm2/s (p = 0.0008),
respectively. TRGm and percentage of residual tumor cells independently
correlated with post-RCT SUVmean (β = 0.73 and β = 0.76, p < 0.001) and
post-RCT SUVmax (β = 0.72 and β = 0.78, p < 0.001), whereas percentage of
fibrosis independently correlated with ∆ADCmean (β = 0.38, p = 0.008). Post-RCT,
SUVmax and SUVmean performed well in predicting TRGm < 3 and residual tumor
cells ≤ 20 %. ΔADCmean predicted fibrosis > 70 % well.

Conclusion Post-RCT SUVmean, SUVmax and ∆ADCmean are complementary
parameters for respectively evaluating residual tumor burden and amount of
fibrosis in LARC. However, only SUV independently correlated with TRGm.
Klinische Überlegungen bezüglich der
wundheilungsphasenadaptierten und gewebespezifischen Dosierung in der Manuellen
Therapie
Authors: Koller Thomas
Published: February 2019

„Gebrauch bestimmt die Funktion“! Für eine funktionelle Ausrichtung
(Mechanotransduktion) reichen wahrscheinlich schon minimale Kräfte von außen
aus. Der zweite Bindegewebewiderstand (R2) scheint klinisch ein guter
Anhaltspunkt für die adäquate Dosierung in der Proliferationsphase zu sein und
somit einer potenziellen Überdosierung entgegenzuwirken.
Overview of Primary Malignant Tumors Affecting the Hip
Authors: Gianakos Arianna , Patel Jay , Miller Justin , Wittig James
Published: February 2019

Malignancy within the hip joint can present with nonspecific symptoms such as a limp, joint stiffness, and pain. While malignant disease within the hip joint is not as common as in other areas of the body, its recognition is important, as a delay in proper diagnosis may be detrimental to patient outcomes. The authors present an overview of several malignant disease processes involving the hip joint as well as the senior author's preferred technique for endoprosthetic reconstruction in treating these conditions.
A gas source declaration scheme based on a tetrahedral sensor structure in three-dimensional airflow environments
Authors: Hou Hui-Rang , Tong Yuan , Ren Chao , Meng Qing-Hao
Published: February 2019

A gas source declaration scheme based on a tetrahedral sensor structure in three-dimensional airflow environments is proposed. First, a tetrahedral sensor structure was established. Based on the tetrahedral structure, the gas source declaration problem was converted into a two-class classification issue. Then a classification algorithm combining an extreme learning machine (ELM, a fast neural network classifier) with a gas mass flux criterion is proposed. A novel calculation method for the mass flux through a closed tetrahedral surface is presented, and a mass flux criterion was developed which acts as a training sample filter for the ELM. The source declaration scheme was validated by using both regular and irregular tetrahedron experiments.
Velocity dispersion in rocks: A laboratory technique for direct measurement of P-wave modulus at seismic frequencies
Authors: Lozovyi Serhii , Bauer Andreas
Published: February 2019

Fluid saturated rocks exhibit a dependence of acoustic velocities on frequency, which is called velocity dispersion. For some rocks, e.g., shales, velocity dispersion is rather strong and has to be taken into account when interpreting and comparing data from seismic surveys, sonic logs, and ultrasonic measurements on core plugs in the laboratory. In this work, a new laboratory technique has been developed that allows the direct measurement of the P-wave modulus at seismic frequencies from which the P-wave velocities can be derived. Together with ultrasonic velocity measurements that are carried out simultaneously, the P-wave velocity dispersion between seismic and ultrasonic frequencies is obtained.
An algebraic method to calculate parameter regions for constrained steady-state distribution in stochastic reaction networks
Authors: Vu Tan Van , Hasegawa Yoshihiko
Published: February 2019

Steady state is an essential concept in reaction networks. Its stability reflects fundamental characteristics of several biological phenomena such as cellular signal transduction and gene expression. Because biochemical reactions occur at the cellular level, they are affected by unavoidable fluctuations. Although several methods have been proposed to detect and analyze the stability of steady states for deterministic models, these methods cannot be applied to stochastic reaction networks. In this paper, we propose an algorithm based on algebraic computations to calculate parameter regions for constrained steady-state distribution of stochastic reaction networks, in which the means and variances satisfy some given inequality constraints. To evaluate our proposed method, we perform computer simulations for three typical chemical reactions and demonstrate that the results obtained with our method are consistent with the simulation results.
Ex situ
metrology and data analysis for optimization of beamline performance of aspherical pre-shaped x-ray mirrors at the advanced light source
Authors: Yashchuk Valeriy V. , Lacey Ian , Gevorkyan Gevork S. , McKinney Wayne R. , Smith Brian V. , Warwick Tony
Published: February 2019

Super high quality aspherical x-ray mirrors with a residual slope error of ∼100 nrad (root-mean-square) and a height error of ∼1-2 nm (peak-to-valley), and even lower, are now available from a number of the most advanced vendors utilizing deterministic polishing techniques. The mirror specification for the fabrication is based on the simulations of the desired performance of the mirror in the beamline optical system and is normally given with the acceptable level of deviation of the mirror figure and finish from the desired ideal shape. For example, in the case of aspherical x-ray mirrors designed for the Advanced Light Source (ALS) QERLIN beamline, the ideal shape is defined with the beamline application (conjugate) parameters and their tolerances. In this paper, we first discuss an original procedure and dedicated software developed at the ALS X-Ray Optics Laboratory (XROL) for optimization of beamline performance of pre-shaped hyperbolic and elliptical mirrors. The optimization is based on results of ex situ surface slope metrology and consists in minimization of the mirror shape error by determining the conjugate parameters of the best-fit ideal shape within the specified tolerances. We describe novel optical metrology instrumentation, measuring techniques, and analytical methods used at the XROL for acquisition of surface slope data and optimization of the optic’s beamline performance. The high efficacy of the developed experimental methods and data analysis procedures is demonstrated in results of measurements with and performance optimization of hyperbolic and elliptical cylinder mirrors designed and fabricated for the ALS QERLIN beamline.
Electronic ground state analysis of Eu(II)-doped alkali-earth sulfide phosphors for photoluminescence properties
Authors: Nakano Hiroshi , Oh-e Masahito
Published: February 2019

Theoretically probing the physics underlying the photoluminescence of phosphors and predicting their thermal quenching properties are significant issues in the field of phosphor research. The electronic ground states of a series of Eu(II)-doped alkali-earth sulfide phosphors, i.e., MS:Eu2+ (M = Mg, Ca, Sr, Ba), have been analyzed using density functional theory calculations to characterize and analyze their photoluminescence properties in terms of quantum efficiency and its thermal decay tendency. Anderson’s impurity model to MS:Eu2+ enables devising a physical picture of how the electronic ground states |ψEu−5d⟩ representing the Eu(II)-5d orbitals are mixed with those of the conduction bands (CBs) of host materials. The focus is on quantitatively deducing the electron delocalization nature of |ψEu−5d⟩ over |CB〉, especially ∑k|ψkM−dk⟩, which represents the bands formed by the d orbitals of M atoms. The ratio of the probability amplitudes of |ψEu−5d⟩ and ∑k|ψkM−dk⟩, i.e., CEu−5d/CM−d, proves to be correlated with the electron localization nature of |ψEu−5d⟩, thereby suggesting that this ratio can be an effective parameter for evaluating the thermal quenching tendency of photoluminescence without more precise information on the electronic excited states. Energetically small gaps and large spatial overlaps between |ψEu−5d⟩ and |CB〉 delocalize electrons in a hybridized state, which gives these electrons the tendency to dissipate without luminescence. The results explain the rankings of the quantum yield and its temperature dependence in the MS:Eu2+ (M = Ca, Sr, Ba) systems, which follow the Dorenbos thermal quenching model, while MgS:Eu2+ does not have the same mechanistic origin.
Stochastic coupled map model of subcellular calcium cycling in cardiac cells
Authors: Romero Luis , Alvarez-Lacalle Enric , Shiferaw Yohannes
Published: February 2019

In this study, we analyze a nonlinear map model of intracellular calcium (Ca) and voltage in cardiac cells. In this model, Ca release from the sarcoplasmic reticulum (SR) occurs at spatially distributed dyadic junctions that are diffusively coupled. At these junctions, release occurs with a probability that depends on key variables such as the SR load and the diastolic interval. Using this model, we explore how nonlinearity and stochasticity determine the spatial distribution of Ca release events within a cardiac cell. In particular, we identify a novel synchronization transition, which occurs at rapid pacing rates, in which the global Ca transient transitions from a period 2 response to a period 1 response. In the global period 2 response dyadic junctions fire in unison, on average, on alternate beats, while in the period 1 regime, Ca release at individual dyads is highly irregular. A close examination of the spatial distribution of Ca reveals that in the period 1 regime, the system coarsens into spatially out-of-phase regions with a length scale much smaller than the system size, but larger than the spacing between dyads. We have also explored in detail the coupling to membrane voltage. We study first the case of positive coupling, where a large Ca transient promotes a long action potential duration (APD). Here, the coupling to voltage synchronizes Ca release so that the system exhibits a robust period 2 response that is independent of initial conditions. On the other hand, in the case of negative coupling, where a large Ca transient tends to shorten the APD, we find a multitude of metastable states which consist of complex spatially discordant alternans patterns. Using an analogy to equilibrium statistical mechanics, we show that the spatial patterns observed can be explained by a mapping to the Potts model, with an additional term that accounts for a global coupling of spin states. Using this analogy, we argue that Ca cycling in cardiac cells exhibits complex spatiotemporal patterns that emerge via first or second order phase transitions. These results show that voltage and Ca can interact in order to induce complex subcellular responses, which can potentially lead to heart rhythm disorders.
Experimental determination of the relationship between the elements of a back-to-back diode model for organic photovoltaic cells’ S-shaped I-V characteristics and cell structure
Authors: Sesa Elisa , Darwis Darmawati , Zhou Xiaojing , Belcher Warwick J. , Dastoor Paul C.
Published: February 2019

Equivalent circuit models are becoming increasingly important for the development of large scale demonstrations of organic photovoltaics. The ‘S’ shaped profile is a common feature of OPV current-voltage (I-V) curves and consequently equivalent circuit models that replicate these features are urgently required. In this paper we prepare a case study based on ITO/PEDOT-PSS/P3HT:PCBM/Al devices whose I-V profiles transition from ‘S’ shape to ‘J’ shape with increasing aluminium thickness prepared using low evaporation rates. We show that the new back-to-back diode model (B2BDM) not only faithfully models these I-V profiles but, more importantly, that the specific circuit elements in the model directly correlate with the physical structures in OPV devices that determine the ‘S’ shaped character. On the basis of these observations, the physical interpretation of the B2BDM is discussed.
Correction of beam hardening in X-ray radiograms
Authors: Baur Manuel , Uhlmann Norman , Pöschel Thorsten , Schröter Matthias
Published: February 2019

The intensity of a monochromatic X-ray beam decreases exponentially with the distance it has traveled inside a material; this behavior is commonly referred to as Beer-Lambert’s law. Knowledge of the material-specific attenuation coefficient μ allows us to determine the thickness of a sample from the intensity decrease the beam has experienced. However, classical X-ray tubes emit a polychromatic bremsstrahlung-spectrum. And the attenuation coefficients of all materials depend on the photon energy: photons with high energy are attenuated less than photons with low energy. In consequence, the X-ray spectrum changes while traveling through the medium; due to the relative increase in high energy photons, this effect is called beam hardening. For this varying spectrum, the Beer-Lambert law only remains valid if μ is replaced by an effective attenuation coefficient μeff which depends not only on the material but also on its thickness x and the details of the X-ray setup used. We present here a way to deduce μeff(x) from a small number of auxiliary measurements using a phenomenological model. This model can then be used to determine an unknown material thickness or in the case of a granular media its volume fraction.
Analysis, design and implement of asymmetric coupled wireless power transfer systems for unmanned aerial vehicles
Authors: Yang Chuankai , He Yuanjian , Qu Haoyue , Wu Jingfeng , Hou Zhe , Lin Zhongzheng , Cai Changsong
Published: February 2019

To solve the problem of short operating time of UAVs, this paper designs an asymmetric coupled wireless power transfer (WPT) system with optimized coupling structures and parameters, which effectively improves horizontal tolerance and performance for UAVs’ charging. Expressions of receiving power and transfer efficiency are derived to guide the design of parameters by modeling and analyzing the WPT systems. Structures and parameters of coupling coils are optimized to improve the quality factor and horizontal tolerance by simulations and comparison. System characteristics are further calculated and optimized with compensation topology. A prototype platform is implemented to verify the analysis and design, and experimental results show that it can achieve 64.87 W power transfer for UAVs with 57.94 % transfer efficiency, and the system is tolerant to horizontal misalignments of coupling coils. The analysis, design and implementation of asymmetric coupled WPT systems provides an important reference for the application of WPT technology in UAVs’ charging.
Route to chaos in the weakly stratified Kolmogorov flow
Authors: Gargano F. , Ponetti G. , Sammartino M. , Sciacca V.
Published: February 2019

We consider a two-dimensional fluid exposed to Kolmogorov’s forcing cos(ny) and heated from above. The stabilizing effects of temperature are taken into account using the Boussinesq approximation. The fluid with no temperature stratification has been widely studied and, although relying on strong simplifications, it is considered an important tool for the theoretical and experimental study of transition to turbulence. In this paper, we are interested in the set of transitions leading the temperature stratified fluid from the laminar solution [U∝cos(ny),0, T ∝ y] to more complex states until the onset of chaotic states. We will consider Reynolds numbers 0 < Re ≤ 30, while the Richardson numbers shall be kept in the regime of weak stratifications (Ri ≤ 5 × 10−3). We shall first review the non-stratified Kolmogorov flow and find a new period-tripling bifurcation as the precursor of chaotic states. Introducing the stabilizing temperature gradient, we shall observe that higher Re are required to trigger instabilities. More importantly, we shall see new states and phenomena: the newly discovered period-tripling bifurcation is supercritical or subcritical according to Ri; more period-tripling and doubling bifurcations may depart from this new state; strong enough stratifications trigger new regions of chaotic solutions and, on the drifting solution branch, non-chaotic bursting solutions.
Ultrafast molecular photophysics in the deep-ultraviolet
Authors: Chergui Majed
Published: February 2019

In the landscape of ultrafast spectroscopic tools, the deep- and near-ultraviolet ranges (200–400 nm) have lagged behind due to the lack of tunability of both the pump and the probe pulses in this range. With the advent of novel nonlinear optical methods, this has now become possible. In this perspective, I will review some of the recent studies in the 250–400 nm range on (bio)chemical systems in order to stress the capabilities of ultrafast deep-UV spectroscopy to unravel new phenomena. This will serve as a basis to dwell on the promise and the new directions not only for molecular systems but also materials in solid or nanostructured form.
Defect annealing kinetics in ZnO implanted with Zn substituting elements: Zn interstitials and Li redistribution
Authors: Azarov Alexander , Aarseth Bjørn L. , Vines Lasse , Hallén Anders , Monakhov Edouard , Kuznetsov Andrej
Published: February 2019

It is known that the behavior of residual Li in ion implanted ZnO depends on the preferential localization of the implants, in particular, forming characteristic Li depleted or Li pile-up regions for Zn or O sublattice occupation of the implants due to the corresponding excess generation of Zn and O interstitials in accordance with the so-called “+1 model.” However, the present study reveals that conditions for the radiation damage annealing introduce additional complexity into the interpretation of the Li redistribution trends. Specifically, four implants residing predominantly in the Zn-sublattice, but exhibiting different lattice recovery routes, were considered. Analyzing Li redistribution trends in these samples, it is clearly shown that Li behavior depends on the defect annealing kinetics which is a strong function of the implanted fluence and ion species. Thus, Li depleted and Li pile-up regions (or even combinations of the two) were observed and correlated with the defect evolution in the samples. It is discussed how the observed Li redistribution trends can be used for better understanding a thermal evolution of point defects in ZnO and, in particular, energetics and migration properties of Zn interstitials.
Automatic thermal conductivity measurements with 3-omega technique
Authors: Chernodoubov D. A. , Inyushkin A. V.
Published: February 2019

This article describes an improvement of the 3-omega thermal conductivity measurement system facilitating automatic mode measurement. The use of the electrical circuit with negative feedback to compensate the first harmonic in the voltage signal on the heater-thermometer eliminates manual resistance tuning. To test the procedure, measurements of the thermal conductivity of single crystal sapphire Al2O3 were made. The experimental thermal conductivity value is in a good agreement with the reference data.
Climate-driven variation in mosquito density predicts the spatiotemporal dynamics of dengue
Authors: Li Ruiyun , Xu Lei , Bjørnstad Ottar N. , Liu Keke , Song Tie , Chen Aifang , Xu Bing , Liu Qiyong , Stenseth Nils C.
Published: February 2019

Significance

Using extensive data on dengue fever and mosquito density, we demonstrate that local weather conditions, through their impact on the variation of mosquito abundance, are a driver of dengue dynamics in China. We believe that this mechanism can be applied to explain dengue dynamics in other places as well. We furthermore conjecture that our integrative approach would be applicable to other vector-borne diseases, such as Zika, malaria, and chikungunya.
Five computational developability guidelines for therapeutic antibody profiling
Authors: Raybould Matthew I. J. , Marks Claire , Krawczyk Konrad , Taddese Bruck , Nowak Jaroslaw , Lewis Alan P. , Bujotzek Alexander , Shi Jiye , Deane Charlotte M.
Published: February 2019

Significance

Immunogenicity, instability, self-association, high viscosity, polyspecificity, or poor expression can all preclude an antibody from becoming a therapeutic. Early identification of these negative characteristics is essential. Akin to the Lipinski guidelines, which measure druglikeness in small molecules, our Therapeutic Antibody Profiler highlights antibodies that possess characteristics that are rare/unseen in clinical-stage mAb therapeutics. The only required input is the variable domain sequence. We show examples where our approach would have advised against manufacturing antibodies that were found to aggregate or have poor expression.
Mitochondrial small heat shock protein mediates seed germination via thermal sensing
Authors: Ma Wei , Guan Xueying , Li Jie , Pan Ronghui , Wang Luyao , Liu Fengjun , Ma Hongyu , Zhu Shuijin , Hu Jin , Ruan Yong-Ling , Chen Xiaoya , Zhang Tianzhen
Published: February 2019

Significance

The propagation of most flowering plant species is determined by the success of seed germination, which is of both economic and ecologic importance. Mitochondria are the energy resource and crucial organelles for plant seed germination. Studying the underlying mechanism is important for us to understand the basic principles of plant development and improve crop yields. Here we identify HSP24.7 as a central activator for temperature-dependent seed germination. HSP24.7 modulates cytochrome C/C
1
production in the mitochondrial electron transport chain and induces the generation of reactive oxygen species, which accelerates seed germination. Our work provides a comprehensive framework of how mitochondria regulate seed germination in response to the dynamics of environmental temperature.
WNK4 kinase is a physiological intracellular chloride sensor
Authors: Chen Jen-Chi , Lo Yi-Fen , Lin Ya-Wen , Lin Shih-Hua , Huang Chou-Long , Cheng Chih-Jen
Published: February 2019

Significance

The existence of intracellular Cl
−
sensors has long been postulated and sought after. Recent structural and in vitro results support that with-no-lysine (WNK) kinases, particularly WNK4, may function as Cl
−
sensors. Here, we demonstrate that knockin mice carrying Cl
−
-insensitive WNK4 mutant phenocopy Mendelian disease and a previous mouse model caused by gain-of-function mutations of WNK4. Furthermore, Cl
−
-insensitive WNK4 knockin mice lose the expected WNK4-mediated stimulation of sodium-chloride cotransporter caused by hypokalemia-induced decreases in the intracellular concentration of Cl
−
. Thus, WNK4 is a bona fide physiological intracellular Cl
−
sensor. The results shed light on the pathophysiology of hypertension in potassium deficiency.
MAP7 family proteins regulate kinesin-1 recruitment and activation
Authors: Hooikaas Peter Jan , Martin Maud , Mühlethaler Tobias , Kuijntjes Gert-Jan , Peeters Cathelijn A.E. , Katrukha Eugene A. , Ferrari Luca , Stucchi Riccardo , Verhagen Daan G.F. , van Riel Wilhelmina E. , Grigoriev Ilya , Altelaar A.F. Maarten , Hoogenraad Casper C. , Rüdiger Stefan G.D. , Steinmetz Michel O. , Kapitein Lukas C. , Akhmanova Anna
Published: February 2019

Kinesin-1 is responsible for microtubule-based transport of numerous cellular cargoes. Here, we explored the regulation of kinesin-1 by MAP7 proteins. We found that all four mammalian MAP7 family members bind to kinesin-1. In HeLa cells, MAP7, MAP7D1, and MAP7D3 act redundantly to enable kinesin-1–dependent transport and microtubule recruitment of the truncated kinesin-1 KIF5B-560, which contains the stalk but not the cargo-binding and autoregulatory regions. In vitro, purified MAP7 and MAP7D3 increase microtubule landing rate and processivity of kinesin-1 through transient association with the motor. MAP7 proteins promote binding of kinesin-1 to microtubules both directly, through the N-terminal microtubule-binding domain and unstructured linker region, and indirectly, through an allosteric effect exerted by the kinesin-binding C-terminal domain. Compared with MAP7, MAP7D3 has a higher affinity for kinesin-1 and a lower affinity for microtubules and, unlike MAP7, can be cotransported with the motor. We propose that MAP7 proteins are microtubule-tethered kinesin-1 activators, with which the motor transiently interacts as it moves along microtubules.
A 40-year review of food–energy–water nexus literature and its application to the urban scale
Authors: Newell Joshua P , Goldstein Benjamin , Foster Alec
Published: February 2019

Essential for society to function, the production and consumption of food, energy, and water (FEW) are deeply intertwined, leading to calls for a nexus approach to understand and manage the complex tradeoffs and cascading effects. What research exists to date on this FEW nexus? How have scholars conceptualized these interactions at the urban scale? What are some promising approaches? Where are the research gaps? To answer these questions, we conducted a quantitative review of the academic literature on the FEW nexus (1399 publications) over more than four decades (1973–2017), followed by in-depth analysis of the most influential papers using an evaluation matrix that examined four components: 1) modeling approach; 2) scale; 3) nexus ‘trigger’; and 4) governance and policy. Scholars in the fields of environmental science predominated, while social science domains were under-represented. Most papers used quantitative rather than qualitative approaches, especially integrated assessment and systems dynamics modeling although spatial scale was generally recognized, explicit consideration of multi-scalar interactions was limited. Issues of institutional structure, governance, equity, resource access, and behavior were also underdeveloped. Bibliometric analysis of this literature revealed six distinct research communities, including a nascent urban FEW community. We replicated the analysis for this urban group, finding it to be just emerging (80% of papers have been published since 2010) and dominated by scholars in industrial ecology. These scholars focus on quantifying FEW flows of the urban metabolism in isolation rather than as a nexus, largely ignoring the political and socio-economic factors shaping these flows. We propose the urban FEW metabolism as a boundary object to draw in diverse scholarly and practitioner communities. This will advance research on complex FEW systems in four key areas: (1) integration of heterogeneous models and approaches; (2) scalar linkages between urban consumption and trans-boundary resource flows; (3) how actors and institutions shape resource access, distribution and use; and (4) co-production of knowledge with stakeholders.
SUBSTRA: Supervised Bayesian Patient Stratification
Authors: Khakabimamaghani Sahand , Kelkar Yogeshwar D , Grande Bruno M , Morin Ryan D , Ester Martin , Ziemek Daniel
Published: February 2019

Motivation

Patient stratification methods are key to the vision of precision medicine. Here, we consider transcriptional data to segment the patient population into subsets relevant to a given phenotype. Whereas most existing patient stratification methods focus either on predictive performance or interpretable features, we developed a method striking a balance between these two important goals.

Results

We introduce a Bayesian method called SUBSTRA that uses regularized biclustering to identify patient subtypes and interpretable subtype-specific transcript clusters. The method iteratively re-weights feature importance to optimize phenotype prediction performance by producing more phenotype-relevant patient subtypes. We investigate the performance of SUBSTRA in finding relevant features using simulated data and successfully benchmark it against state-of-the-art unsupervised stratification methods and supervised alternatives. Moreover, SUBSTRA achieves predictive performance competitive with the supervised benchmark methods and provides interpretable transcriptional features in diverse biological settings, such as drug response prediction, cancer diagnosis, or kidney transplant rejection.

Availability and implementation

The R code of SUBSTRA is available at https://github.com/sahandk/SUBSTRA.

Supplementary information

Supplementary data are available at Bioinformatics online.
Health Care Transition Outcomes in Inflammatory Bowel Disease: A Multinational Delphi Study
Authors: van den Brink Gertrude , van Gaalen Martha A C , de Ridder Lissy , van der Woude C Janneke , Escher Johanna C
Published: February 2019

Background

Transition programmes are designed to prepare adolescent inflammatory bowel disease [IBD] patients for transfer to adult care. It is still unclear which outcome parameters define ‘successful transition’. Therefore, this study aimed to identify outcomes important for success of transition in IBD.

Methods

A multinational Delphi study in patients, IBD nurses, and paediatric and adult gastroenterologists was conducted. In stage 1, panellists commented on an outcome list. In stage 2, the refined list was graded from 1 to 9 [least to very important], by an expert and a patient panel. In stage 3, the expert panel ranked important outcomes from 1 to 10 [least to most important]. Descriptive statistics and Mann–Whitney U-tests were performed.

Results

The final item list developed in stage 1 was tested by the expert [n = 74 participants, 52.7% paediatric] and patient panel [n = 61, aged 16–25 years, 49.2% male]. Respectively, ten and 11 items were found to be important by the expert and patient panel. Both panels agreed on eight of these items, of which six reflected self-management skills. In stage 3, the expert panel formed a top-ten list. The three most important items were: decision-making regarding IBD [mean score 6.7], independent communication [mean score 6.3] and patient satisfaction [mean score 5.8].

Conclusion

This is the first study identifying outcomes that IBD healthcare providers and patients deem important factors for successful transition. Self-management skills were considered more important than IBD-specific items. This is a first step to further define success of transition in IBD and subsequently evaluate the efficacy of different transition models.
E-cigarettes and Smoking Cessation in the United States According to Frequency of E-cigarette Use and Quitting Duration: Analysis of the 2016 and 2017 National Health Interview Surveys
Authors: Farsalinos Konstantinos E , Niaura Raymond
Published: February 2019

Introduction

The purpose of this study was to examine the association between electronic cigarette (e-cigarette) use and smoking cessation among US adults. Duration of smoking cessation was taken into consideration because e-cigarette awareness and use were low in the United States before 2010.

Methods

A pooled analysis of the 2016 and 2017 National Health Interview Surveys on current (N = 9935) and former smokers (N = 14 754) was performed. Adjusted prevalence ratios (aPRs), for sociodemographic factors, were calculated.

Findings

Current e-cigarette use was reported by 10.5% (95% CI = 9.8% to 11.3%) of current smokers and 4.5% (95% CI = 4.0% to 5.0%) of former smokers. Prevalence was high in former smokers of less than 1 year (16.8%, 95% CI = 13.9% to 20.2%), 1–3 years (15.0%, 95% CI = 13.0% to 17.3%), and 4–6 years (10.5%, 95% CI = 8.6% to 12.7%), and very low in former smokers of more than 6 years (0.7%, 95% CI = 0.5% to 0.9%). Similar patterns were observed for daily e-cigarette use. Current e-cigarette use was negatively associated with being a former smoker when quit duration was ignored (aPR = 0.64, 95% CI = 0.59 to 0.69) but was positively associated with being a former smoker of less than 1 year (aPR = 1.44, 95% CI = 1.12 to 1.84) and 1–3 years (aPR = 1.21, 95% CI = 1.03 to 1.42). Daily e-cigarette use was not associated with being a former smoker when quit duration was ignored but was positively associated with being a former smoker of less than 1 year (aPR = 3.44, 95% CI = 2.63 to 4.49), 1–3 years (aPR = 2.51, 95% CI = 2.13 to 2.95), and 4–6 years (aPR = 1.84, 95% CI = 1.49 to 2.26).

Conclusions

Daily e-cigarette use is strongly associated with recent smoking cessation (≤6 years) among US adults. Frequency of e-cigarette use and smoking cessation duration are important parameters when analyzing the effects of e-cigarettes in population surveys.

Implications

There is controversy on whether e-cigarettes promote or prevent smoking cessation. This study presents a detailed analysis of the association between e-cigarette use and smoking cessation in the United States considering frequency of e-cigarette use and duration of smoking cessation. The latter was considered appropriate because e-cigarette awareness and use were low in the United States before 2010. Daily e-cigarette use is strongly associated with recent (≤6 years) smoking cessation in the United States. Both frequency of e-cigarette use and duration of smoking cessation are important factors in determining the effects of e-cigarettes in population studies.
Capturing the complexity of mental disorders in the medically ill: the network approach on behavioral medicine
Authors: van der Lee Marije L , Schellekens Melanie P J
Published: February 2019

Since Descartes introduced dualism, body and mind have been seen as separate entities. The latent disease model, the view that symptoms are caused by an underlying disease, was possible within the dualistic paradigm. This paradigm, although successful in some aspects of medicine, is also assumed to underlie psychiatric disorders. As an alternative to the latent disease model, the network approach conceptualizes disorders as complex networks of causally connected symptoms. It offers a new way of understanding psychiatric disorders by directing attention away from the underlying cause and towards the symptoms and their functional interconnectedness, making the distinction between mental and physical symptoms obsolete. This article discusses how the network perspective helps us to overcome some of the problems we have faced when diagnosing and treating psychopathology in the medically ill. Furthermore, we describe how the network perspective can stimulate new research to better understand psychopathology in medically ill patients and how it can help deliver the most suitable treatment to the individual patient.
Obstructive Sleep Apnea in Pregnant Women: A Review of Pregnancy Outcomes and an Approach to Management
Authors: Dominguez J.E. , Krystal A.D. , Habib A.S.
Published: February 2019

(Anesth Analg. 2018;127:1167–1177)

Sleep-disordered breathing (SDB) is often comorbid with obesity; among obese pregnant women, 15% to 20% have obstructive sleep apnea (OSA), and prevalence increases with body mass index (BMI). Untreated OSA has been associated with a range of cardiovascular, pulmonary, and metabolic comorbidities. The authors of this review discussed pregnancy as a vulnerable period for the development or worsening of OSA, associations between OSA and adverse maternal and fetal outcomes, current screening modalities for OSA in pregnancy, and current recommendations regarding peripartum management of OSA.
Neonatal Morbidity Associated With Vaginal Delivery of Noncephalic Second Twins
Authors: Schmitz T. , Korb D. , Battie C. , Cordier A.G. , de Carne Carnavalet C. , Chauleur C. , Equy V. , Haddad B. , Lemercier D. , Poncelet C. , Rigonnot L. , Goffinet F.
Published: February 2019

(Am J Obstet Gynecol. 2018;218:449.e1–e13)

The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine have recommended vaginal deliveries be attempted in women with cephalic/cephalic and cephalic/noncephalic presenting twins. However, survey data revealed >40% of US practitioners are reluctant to perform breech extractions in noncephalic second twins and prefer to perform cesarean deliveries. A national prospective Jumeaux Mode d’Accouchement (JUMODA) study was conducted to evaluate the management of twin deliveries and assess neonatal mortality and morbidity according to second twin presentation after vaginal birth of the first twin at ≥32 weeks of gestation. This was a planned secondary analysis of the JUMODA cohort.
Embracing Multiple Stakeholder Perspectives in Defining Trainee Competence
Authors: Lundsgaard Kristine Sarauw , Tolsgaard Martin G. , Mortensen Ole Steen , Mylopoulos Maria , Østergaard Doris
Published: February 2019

Purpose

To explore how multiple stakeholder groups contribute to the understanding of trainee competence.

Method

The authors conducted a constructivist qualitative study in 2015 using focus group discussions to explore the perceptions of different stakeholder groups (patients, nurses/nurse practitioners, supervisors/senior physicians, leaders/administrators, trainees) regarding trainee competence in the emergency department. The authors used a conventional content analysis, a comparative analysis of supervisors’/senior physicians’ versus other stakeholders’ perspectives, and a directed analysis informed by stakeholder theory to analyze the focus group transcripts.

Results

Forty-six individuals participated in nine focus groups. Four categories of competence were identified: Core Clinical Activities, Patient Centeredness, Aligning Resources, and Code of Conduct. Stakeholders generally agreed in their overall expectations regarding trainee competence. Within individual categories, each stakeholder group identified new considerations, details, and conflicts, which were a replication, elaboration, or complication of a previously identified theme. All stakeholders stressed those aspects of trainee competence that were relevant to their work or values. Trainees were less aware of the patient perspective than that of the other stakeholder groups.

Conclusions

Considering multiple stakeholder perspectives enriched the description and conceptualization of trainee competence. It also can inform the development of curricula and assessment tools and guide learning about inter- and intradisciplinary conflicts. Further research should explore how trainees’ perceptions of value are influenced by their organizational context and, in particular, how trainees adapt their learning goals in response to the divergent demands of key stakeholders.
Immune Checkpoint Inhibition in Sepsis: A Phase 1b Randomized, Placebo-Controlled, Single Ascending Dose Study of Antiprogrammed Cell Death-Ligand 1 Antibody (BMS-936559)*
Authors: Hotchkiss Richard S. , Colston Elizabeth , Yende Sachin , Angus Derek C. , Moldawer Lyle L. , Crouser Elliott D. , Martin Greg S. , Coopersmith Craig M. , Brakenridge Scott , Mayr Florian B. , Park Pauline K. , Ye June , Catlett Ian M. , Girgis Ihab G. , Grasela Dennis M.
Published: February 2019

Objectives:

To assess for the first time the safety and pharmacokinetics of an antiprogrammed cell death-ligand 1 immune checkpoint inhibitor (BMS-936559; Bristol-Myers Squibb, Princeton, NJ) and its effect on immune biomarkers in participants with sepsis-associated immunosuppression.

Design:

Randomized, placebo-controlled, dose-escalation.

Setting:

Seven U.S. hospital ICUs.

Study Population:

Twenty-four participants with sepsis, organ dysfunction (hypotension, acute respiratory failure, and/or acute renal injury), and absolute lymphocyte count less than or equal to 1,100 cells/μL.

Interventions:

Participants received single-dose BMS-936559 (10–900 mg; n = 20) or placebo (n = 4) infusions. Primary endpoints were death and adverse events; key secondary endpoints included receptor occupancy and monocyte human leukocyte antigen-DR levels.

Measurements and Main Results:

The treated group was older (median 62 yr treated pooled vs 46 yr placebo), and a greater percentage had more than 2 organ dysfunctions (55% treated pooled vs 25% placebo); other baseline characteristics were comparable. Overall mortality was 25% (10 mg dose: 2/4; 30 mg: 2/4; 100 mg: 1/4; 300 mg: 1/4; 900 mg: 0/4; placebo: 0/4). All participants had adverse events (75% grade 1–2). Seventeen percent had a serious adverse event (3/20 treated pooled, 1/4 placebo), with none deemed drug-related. Adverse events that were potentially immune-related occurred in 54% of participants; most were grade 1–2, none required corticosteroids, and none were deemed drug-related. No significant changes in cytokine levels were observed. Full receptor occupancy was achieved for 28 days after BMS-936559 (900 mg). At the two highest doses, an apparent increase in monocyte human leukocyte antigen-DR expression (> 5,000 monoclonal antibodies/cell) was observed and persisted beyond 28 days.

Conclusions:

In this first clinical evaluation of programmed cell death protein-1/programmed cell death-ligand 1 pathway inhibition in sepsis, BMS-936559 was well tolerated, with no evidence of drug-induced hypercytokinemia or cytokine storm, and at higher doses, some indication of restored immune status over 28 days. Further randomized trials on programmed cell death protein-1/programmed cell death-ligand 1 pathway inhibition are needed to evaluate its clinical safety and efficacy in patients with sepsis.
Latino Health Perceptions in Rural Montana
Authors: Nitzinger Violeta , Held Suzanne , Kevane Bridget , Eudave Yanet
Published: February 2019

The primary purposes of this study were to use photovoice with Facebook to explore health perceptions and health needs among promotores living in rural Montana and to build community among geographically dispersed promotores. Seven promotores participated in a photovoice project where they uploaded photographs and shared comments in a private Facebook group. Emergent themes based on the promotores' health perceptions, discussions, and interviews were transcribed and coded. Findings of this study will be used to assess health perceptions and needs of the promotores and Latino community in rural Montana.
Promoting Health Equity Through Trauma-Informed Care
Authors: Levy-Carrick Nomi C. , Lewis-O'Connor Annie , Rittenberg Eve , Manosalvas Kiara , Stoklosa Hanni M. , Silbersweig David A.
Published: February 2019

Trauma-informed care has emerged as an important model to address the pervasiveness of traumatic experiences across the life cycle and their association with significant adverse medical and psychiatric consequences. To achieve health equity, in which all people have the opportunity for health, it is crucial for physicians to become comfortable with a neurobiopsychosocial understanding of trauma and how to provide optimal trauma-informed care. Given the pervasiveness of trauma exposure, and its impact on individual and community health, this paradigm shift in adult health care delivery systems requires physician engagement at every stage of development and implementation.
Treatment of Hypothermic Cardiac Arrest in the Pediatric Drowning Victim, a Case Report, and Systematic Review
Authors: Bauman Brent D. , Louiselle Amanda , Nygaard Rachel M. , Vakayil Victor , Acton Robert , Hess Donavan , Saltzman Daniel , Kreykes Nathaniel , Fischer Gwenyth , Louie Jeffrey , Segura Bradley
Published: February 2019

Objectives

Drowning is the second leading cause of death in children. Extracorporeal membrane oxygenation (ECMO) has become the criterion standard therapy to resuscitate the hypothermic drowning victim in cardiac arrest. We present our own experience treating 5 children with hypothermic cardiac arrest in conjunction with a systematic review to analyze clinical features predictive of survival.

Methods

Our search resulted in 55 articles. Inclusion criteria were as follows: (1) younger than 18 years, (2) ECMO therapy, and (3) drowning. Ten articles met our inclusion criteria. We included studies using both central and peripheral ECMO and salt or fresh water submersions. We compared clinical features of survivors to nonsurvivors.

Results

A total of 29 patients from the 10 different studies met our criteria. Data analyzed included presenting cardiac rhythm, time to initiation of ECMO, submersion time, pH, potassium, lactate, duration of chest compressions, and survival. There was a significant increase in mortality for presenting rhythm of asystole and with hyperkalemia (P < 0.05).

Conclusions

Extracorporeal membrane oxygenation is an important resuscitation tool for the hypothermic drowning victim. Hyperkalemia and presenting cardiac rhythm correlate with survival although they are not reasons to end resuscitation. More studies are needed to compare the outcomes in using ECMO for the hypothermic drowning victim.