bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of high-end ultrasound in the management of a patient with neuroendocrine tumor of the ileum
Authors: Schmidt Tatjana , Schwarz Julia , Steurer Martina , Goetz Martin , Olthof Susann-Cathrin , Malek Nisar , Boozari Bita
Published: November 2017

Diagnostic imaging of jejuno-ileal neuroendocrine tumors (NETs) has been described as challenging. Follow-up requires the detection of metastatic spread as well as screening for local recurrence. Multimodal imaging concepts must often be applied.

We report the case of a 45-year-old man with a history of ileal NET. At 2 points in follow-up of our patient, information provided by high-end ultrasound changed prognosis and treatment considerably: when positron emission tomography/computed tomography newly detected suspected hepatic metastases, contrast-enhanced ultrasound correctly identified the lesions as intrahepatic vascular shunts. Moreover, profound B-mode ultrasound solely detected ileal recurrence, leading to early removal of the tumor.
Is integrated relaxation pressure a promising predictor of effectiveness of peroral endoscopic myotomy for achalasia?
Authors: Jin Hong , Zhao Wei , Zhang Lili , Zheng Zhongqing , Wang Tao , Wu Lanlan , Wang Bangmao
Published: November 2017

Background Peroral endoscopic myotomy (POEM), first introduced in 2010, appears to be an effective therapy with few complications. This study aimed to find an optimal predictor of POEM outcome in achalasia.

Methods We retrospectively assessed 89 patients diagnosed with achalasia who underwent POEM in General Hospital of Tianjin Medical University, from September 2012 to March 2015. Associations of Eckardt score with symptom duration, lower esophageal resting pressure, 4-second integrated relaxation pressure (4s-IRP), and maximum esophageal diameter were assessed before POEM. The most relevant data were progressively grouped to compare symptom improvement after POEM in 85 patients at 1 year follow-up.

Results The most significant correlation was found between 4s-IRP and Eckardt score (p < 0.01). The 85 achalasia patients (1-year follow-up after POEM) were divided into 3 groups according to 4s-IRP values; patients with mean 4s-IRP of 25 – 34 mmHg exhibited significantly greater improvement of clinical symptoms compared with the remaining 2 groups (p < 0.05). No significant postoperative difference was noted between types I and II in all patients according to Chicago classification criteria. The 40 patients with 4s-IRP of 25 – 34 mmHg were further divided into 2 subgroups; the 28 patients with type II achalasia responded better to POEM than the 12 with type I disease (p < 0.05).

Conclusions 4s-IRP, together with achalasia subtypes, may predict treatment outcome after POEM. Patients with type II achalasia and 4s-IRP of 25 – 34 mmHg may experience more satisfactory remission after POEM.
Risk of recurrence after endoscopic resection of early colorectal cancer with positive margins
Authors: Shin Je-Wook , Han Kyung , Hyun Jong , Lee Sang , Kim Bun , Hong Chang , Kim Byung , Sohn Dae , Chang Hee , Kim Min , Park Sung , Oh Jae
Published: November 2017

Background and study aim Additional surgery is recommended if an endoscopically resected T1 colorectal cancer (CRC) specimen shows a positive resection margin. We aimed to investigate the significance of a positive resection margin in endoscopically resected T1 CRC.

Patients and methods We enrolled 265 patients with T1 CRC who underwent endoscopic resection between January 2001 and December 2016. The inclusion criteria were: 1) complete resection by endoscopy, and 2) pathology of a positive margin. Among the 265 patients, 213 underwent additional surgery and 52 did not. In the additional surgery group, various clinicopathological factors were evaluated with respect to the presence or absence of residual tumor. The follow-up results were assessed in the group that did not undergo additional surgery.

Results In the 213 patients who underwent additional surgery, residual tumor was detected in 13 patients (6.1 %), and none of the clinicopathological factors was significantly associated with the presence of residual tumor. Among the 52 patients who did not undergo additional surgery, recurrence was detected in 4 (7.7 %), and all 4 underwent salvage surgery. Among these four patients, three had no risk factors for lymph node metastasis and recurrence was at the previous resection site; pathology was high grade dysplasia, rpT3N0M0, and rpT1N0M0, respectively.

Conclusions A positive resection margin in endoscopically resected T1 CRC is related to a relatively low incidence of residual tumor (6.1 %). Although current guidelines recommend additional surgery for such cases, surveillance and timely salvage surgery could be another option in selected cases.
Medikamentöse Therapie der Zöliakie – „from bench to bedside“
Authors: Stein Jürgen , Schulzke Jörg-Dieter , Schuppan Detlef
Published: November 2017

Die Zöliakie ist eine der weltweit häufigsten Erkrankungen mit einer geschätzten Prävalenz von etwa 0,5 – 1 %. Die Erkrankung entsteht als Folge einer Kombination von Umweltfaktoren (Glutenproteine von Weizen, Roggen oder Gerste) und genetischen Faktoren (hauptsächlich humane Leukozytenantigene HLA-DQ2 oder -DQ8). Aktuell stellt eine strikte glutenfreie Diät (GFD) die einzige Therapiemöglichkeit dar. Allerdings ist die Einhaltung dieser Diät schwierig, nicht zuletzt deshalb, weil Gluten in vielen Fertignahrungsmitteln enthalten ist. Folglich kann die konsequente Vermeidung von Gluten tiefe Einschnitte sowohl in der Nahrungsauswahl als auch im Sozialleben zur Folge haben. Zudem führt die GFD auch bei völlig adhärenten Patienten nicht in jedem Fall zu einer klinischen und histologischen Normalisierung. Deshalb ist das Interesse an (adjunktiven) nicht-diätischen Therapieansätzen für die Zöliakie groß. Ziel dieser Arbeit ist es, basierend auf pathophysiologischen Konzepten zur Zöliakie neueste pharmakologische Therapieansätze vorzustellen und zu diskutieren.
High-visibility in-line fiber-optic optofluidic Fabry–Pérot cavity
Authors: Zhang Qiang , Hao Pengli , Tian Xinzhang , Li Yongmin
Published: November 2017

A high-visibility in-line optofluidic Fabry–Pérot (HVILOFFP) cavity was demonstrated by splicing a silica capillary tube into two standard single mode fibers (SMFs) and polishing the latter SMF. Two size-controllable microfluidic accesses in the sides of the HVILOFFP cavity allow the analyte of interest to smoothly flow into the cavity and directly interact with light without any assisting equipment to direct the analyte into the cavity. Experimental results showed that the fringe visibility of the HVILOFFP cavity was up to 24 dB in both air and water, which is higher than that of most laser-machined in-line fiber-optic Fabry–Pérot cavities because of the smoother end faces of the SMFs. The proposed HVILOFFP cavity was demonstrated by measuring the refractive indices with a sensitivity of 1148.93 nm/RIU in the range of 1.333–1.345. Moreover, the proposed HVILOFFP cavity is economical, compact (<100 μm), robust, and insensitive to temperature. These advantages make it a promising optofluidic platform in biomedical and chemical sensing applications.
On shapes and motion of an elongated bubble in downward liquid pipe flow
Authors: Fershtman A. , Babin V. , Barnea D. , Shemer L.
Published: November 2017

In stagnant liquid, or in a steady upward liquid pipe flow, an elongated (Taylor) bubble has a symmetric shape. The translational velocity of the bubble is determined by buoyancy and the liquid velocity profile ahead of it. In downward flow, however, the symmetry of the bubble nose can be lost. Taylor bubble motion in downward flow is important in numerous applications such as chemical plants and cooling systems that often contain countercurrent gas-liquid flow. In the present study, the relation between the Taylor bubble shape and its translational velocity is investigated experimentally in a vertical pipe for various downward liquid flow rates. At higher downward velocities, the bubble may be forced by the background flow to propagate downward against buoyancy. In order to include those cases as well in our experimental analysis, the bubbles were initially injected into stagnant liquid, whereas the downward flow was initiated at a later stage. This experimental procedure allowed us to identify three distinct modes of translational velocities for a given downward background liquid flow; each velocity corresponds to a different bubble shape. Hydrodynamic mechanisms that govern the transition between the modes observed in the present study are discussed.
Single-photon detectors combining high efficiency, high detection rates, and ultra-high timing resolution
Authors: Esmaeil Zadeh Iman , Los Johannes W. N. , Gourgues Ronan B. M. , Steinmetz Violette , Bulgarini Gabriele , Dobrovolskiy Sergiy M. , Zwiller Val , Dorenbos Sander N.
Published: November 2017

Single-photon detection with high efficiency, high time resolution, low dark counts, and high photon detection rates is crucial for a wide range of optical measurements. Although efficient detectors have been reported before, combining all performance parameters in a single device remains a challenge. Here, we show a broadband NbTiN superconducting nanowire detector with an efficiency exceeding 92%, over 150 MHz photon detection rate, and a dark count rate below 130 Hz operated in a Gifford-McMahon cryostat. Furthermore, with careful optimization of the detector design and readout electronics, we reach an ultra-low system timing jitter of 14.80 ps (13.95 ps decoupled) while maintaining high detection efficiencies (>75%).
Analysis of charging and sudden-discharging characteristics of no-insulation REBCO coil using an electromagnetic coupling model
Authors: Liu Donghui , Yong Huadong , Zhou Youhe
Published: November 2017

No-insulation (NI) high-temperature superconducting (HTS) REBCO coil has been a promising candidate for manufacturing high-field superconducting magnets with high thermal stability and self-protecting features. When NI coil is operated at the external field, it is necessary to analyze charging and sudden-discharging characteristics of NI coil by considering the effect of magnetic field. In addition, the self-field effect has an obvious influence on the critical current for large-scale coil. Thus, an electromagnetic coupling model in which an equivalent circuit axisymmetric model considers the effect of magnetic field is proposed. The results show that when the radial current exists, the coil voltage and central field will tend to be stable faster. In a high field, the decrease of the critical current leads to the increase of radial current and this effect is more obvious for a larger field. And the charging time with the increase of the external field reduces significantly, while the sudden-discharging time is almost unchanged. For NI coils composed of many double-pancake coils, the charging time and sudden-discharging time proportionally increase with the increase of the number of double-pancake coil and turn number of single-pancake coil.
High-performance solar-blind Al0.6Ga0.4N/Al0.5Ga0.5N MSM type photodetector
Authors: Yoshikawa Akira , Ushida Saki , Nagase Kazuhiro , Iwaya Motoaki , Takeuchi Tetsuya , Kamiyama Satoshi , Akasaki Isamu
Published: November 2017

An Al0.6Ga0.4N/Al0.5Ga0.5N metal–semiconductor–metal (MSM) deep-ultraviolet (DUV) photodetector was developed. It possesses both high photosensitivity and high rejection ratios in comparison to photomultiplier tubes (PMTs). The photodetector was designed to have a two-dimensional electron gas layer at the Al0.6Ga0.4N/Al0.5Ga0.5N hetero-interface, which plays an important role in increasing the photosensitivity. Additionally, for reducing the dark current, a V/Al/Mo/Au electrode was employed as a Schottky electrode with an appropriate barrier height. Upon irradiation with 10 μW/cm2, an extremely low dark current (10−11 A) and high photocurrent (5 × 10−5 A) were achieved at a bias voltage of 5 V. The photodetector was true solar-blind with a cut-off wavelength of 280 nm. A high photosensitivity of 106 A/W and a rejection ratio of 106 were realized under the irradiation of 10 nW/cm2 DUV photons. The present results revealed that the AlGaN/AlGaN MSM DUV photodetector is one of the most suitable candidates for an all solid-state photodetector with a performance superior to PMTs.
Local structural behavior of PbZr0.5Ti0.5O3 during electric field application via in situ pair distribution function study
Authors: Zhao Changhao , Hou Dong , Chung Ching-Chang , Yu Yingying , Liu Wenfeng , Li Shengtao , Jones Jacob L.
Published: November 2017

The local structural behavior of PbZr0.5Ti0.5O3 (PZT 50/50) ceramics during application of an electric field was investigated using pair distribution function (PDF) analysis. In situ synchrotron total scattering was conducted, and the PDFs were calculated from the Fourier transform of the total scattering data. The PDF refinement of the zero-field data suggests a local-structure model with [001] Ti-displacement and negligible Zr-displacement. The directional PDFs at different field amplitudes indicate the bond-length distribution of the nearest Pb-B (B = Zr/Ti) pair changes significantly with the field. The radial distribution functions (RDFs) of a model for polarization rotation were calculated. The calculated and the experimental RDFs are consistent. This result suggests the changes in Pb-B bond-length distribution could be dominantly caused by polarization rotation. Peak fitting of the experimental RDFs was also conducted. The peak position trends with increasing field are mostly in agreement with the calculation result of the polarization rotation model. The area ratio of the peaks in the experimental RDFs also changed with field amplitude, indicating that Zr atoms have a detectable displacement driven by the electric field. Our study provides an experimental observation of the behaviors of PZT 50/50 under field at a local scale which supports the polarization rotation mechanism.
Coherent active polarization control without loss
Authors: Ye Yuqian , Hay Darrick , Shi Zhimin
Published: November 2017

We propose a lossless active polarization control mechanism utilizing an anisotropic dielectric medium with two coherent inputs. Using scattering matrix analysis, we derive analytically the required optical properties of the anisotropic medium that can behave as a switchable polarizing beam splitter. We also show that such a designed anisotropic medium can produce linearly polarized light at any azimuthal direction through coherent control of two inputs with a specific polarization state. Furthermore, we present a straightforward design-on-demand procedure of a subwavelength-thick metastructure that can possess the desired optical anisotropy at a flexible working wavelength. Our lossless coherent polarization control technique may lead to fast, broadband and integrated polarization control elements for applications in imaging, spectroscopy, and telecommunication.
Intertidal vermetid reef as a shelter for invasive bivalves in a tropical bay
Authors: Breves A. , Junqueira A. O. R.
Published: November 2017

Vermetid reef building species play an important role as ecosystem engineers modifying the physical environment, creating microhabitats and affecting local hydro-sedimentary patterns. We explore the association of native vermetid reefs (Petaloconchus varians) with the invasive bivalves Isognomon bicolor and Leiosolenus aristatus. We also examined the different utilization of the reef habitat, since L. aristatus is a boring species, comparing their population structure on sheltered and exposed rocky shores. Ten sites (five sheltered, five exposed) were sampled at Ilha Grande Bay (Rio de Janeiro, Brazil). I. bicolor and L. aristatus were the most frequent with mean densities of 20,000 (±3400) and 2100 (±600) ind.m2, respectively. There were no significant differences (t = 1.41; p = 0.17) between sheltered and exposed sites in relation to the densities of I. bicolor. However, there were significant differences (t = 3.14; p = 0.03) in relation to the densities of L. aristatus, with higher values at exposed sites. Mean size of both species was significantly (p < 0.01) higher in sheltered areas where the vermetid weight was significantly higher (t = 2.36; p = 0.02). Although native vermetid reefs act as a shelter for both invasive bivalves on sheltered and exposed rocky shores, they prevent the growth of I. bicolor which reaches smaller sizes in relation to populations outside of the reefs. Our results indicate that the two invasive bivalves might be differently affected by hydrodynamic processes.
Senescence and aging: Causes, consequences, and therapeutic avenues
Authors: McHugh Domhnall , Gil Jesús
Published: November 2017

Aging is the major risk factor for cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. Although we are far from understanding the biological basis of aging, research suggests that targeting the aging process itself could ameliorate many age-related pathologies. Senescence is a cellular response characterized by a stable growth arrest and other phenotypic alterations that include a proinflammatory secretome. Senescence plays roles in normal development, maintains tissue homeostasis, and limits tumor progression. However, senescence has also been implicated as a major cause of age-related disease. In this regard, recent experimental evidence has shown that the genetic or pharmacological ablation of senescent cells extends life span and improves health span. Here, we review the cellular and molecular links between cellular senescence and aging and discuss the novel therapeutic avenues that this connection opens.
Wireless Battery Management System of Electric Transport
Authors: Rahman Ataur , Rahman Mizanur , Rashid Mahbubur
Published: November 2017

Electric vehicles (EVs) are being developed and considered as the future transportation to reduce emission of toxic gas, cost and weight. The battery pack is one of the main crucial parts of the electric vehicle. The power optimization of the battery pack has been maintained by developing a two phase evaporative thermal management system which operation has been controlled by using a wireless battery management system. A large number of individual cells in a battery pack have many wire terminations that are liable for safety failure. To reduce the wiring problem, a wireless battery management system based on ZigBee communication protocol and point-to-point wireless topology has been presented. Microcontrollers and wireless modules are employed to process the information from several sensors (voltage, temperature and SOC) and transmit to the display devices respectively. The WBMS multistage charge balancing system offering more effective and efficient responses for several numbers of series connected battery cells. The concept of double tier switched capacitor converter and resonant switched capacitor converter is used for reducing the charge balancing time of the cells. The balancing result for 2 cells and 16 cells are improved by 15.12% and 25.3% respectively. The balancing results are poised to become better when the battery cells are increased.
7. The happy consciousness
Authors: Bronner Stephen Eric
Published: November 2017

‘The happy consciousness’ explores how happiness precludes progress, and how this can be overcome. For Hegel and the Frankfurt School, conformism and loss of individuality mark the happy consciousness. Only true nonconformists, with an understanding of the constraints of freedom, and therefore an ‘unhappy consciousness’, can effect progress. The Frankfurt School’s members posed many criticisms of modern life and the culture industry. But the danger that advanced industrial society presents to the unhappy consciousness is perhaps the most telling. At stake is the substance of subjectivity and autonomy: the will and ability of the individual to resist external forces intent upon determining the meaning and experience of life.
9. From resignation to renewal
Authors: Bronner Stephen Eric
Published: November 2017

‘From resignation to renewal’ examines where critical theory has gone wrong, and how it can reorient itself for the future. Critical theory was originally intended as an alternative to mainstream metaphysics and materialism. However, after the outbreak of World War II, the liberating alternatives vanished, and resistance became increasingly existential and arbitrary. The preoccupation of critical theorists with abstract preoccupations has left them open to ridicule. Max Horkheimer originally viewed critical theory as a public philosophy. To realise his goal, modern critical theorists must stop trying to express the inexpressible and instead offer practical solutions to the ways society stunts individuality.
10. Unfinished tasks
Authors: Bronner Stephen Eric
Published: November 2017

The Frankfurt School never really thought about the world beyond Europe, the Soviet Union, and the United States. But there exists a global totality in which the most basic principles of solidarity are under attack. Resistance calls for linking liberal cosmopolitan principles with economic class interests. Reinvigorated regulative ideals are necessary. Linkages between liberalism and socialism still need to be drawn; class ideals still await realization; the emancipatory heritage of the past still requires reclaiming; and individual autonomy still remains threatened by religion and authoritarianism. New perspectives in critical theory are required to cultivate transformative prospects within an increasingly global society and, in turn, this calls for subjecting critical theory to ongoing critical interrogation.
Introduction
Authors: Davies Andrew
Published: November 2017

Projects have existed since the earliest agrarian societies. While they may differ in purpose, scale, and scope, each project is established to bring together people with diverse knowledge to complete a temporary assignment, solve a complex problem, or turn a novel idea into reality. The Introduction defines a project as a combination of people and other resources brought together in a temporary organization and process to achieve a specified goal. It considers the role of the project manager, the difference between projects and operations, and a brief history of projects. Traditionally, project performance has been measured by the three constraints of cost, time, and quality, but it is now recognized that project success is multidimensional and varies over time.
Perceptual theories—direct, indirect, and computational
Authors: Rogers Brian
Published: November 2017

‘Perceptual theories—direct, indirect, and computational’ considers three different conceptions of what it means to perceive and the processes involved in each theory. The origins of indirect or constructivist theory can be traced back to Hermann von Helmholtz in the 19th century, who emphasized the importance of experience in shaping our perceptual abilities. It was assumed that the primary purpose of perception was to create subjective experiences. The American psychologist James Gibson first suggested a direct theory—that the primary role of perceptual processes was to guide action. Since the 1960s, there have been many attempts to model the perceptual processes using computer algorithms, with David Marr at MIT being the most influential figure.
1. Troubles
Authors: Fisher Elizabeth
Published: November 2017

Environmental problems are the troubles of politics, economics, and philosophy. They are often bitter troubles, revealing deep divisions in societies over how life should be lived. These divisions concern global environmental problems and also environmental issues that affect specific communities. ‘Troubles’ explains how environmental law is a necessary response to environmental problems providing legislation, case law, international agreements, and regulatory strategies to address the collective nature of environmental problems. It also ensures that collective action in relation to environmental problems is authoritative and consistent with the rule of law and other principles of legitimate action. Environmental law is built on existing legal frameworks, but often requires the development of new legal obligations and doctrine.
Truth functions—or not?
Authors: Priest Graham
Published: November 2017

We are strongly intuitive about the validity of various inferences. This may or may not be hard-wired into us. Intuition gets us into trouble sometimes. ‘Truth functions—or not?’ plays around with the idea of invalid and valid inferences and, using phrases such as ‘or’ or ‘it is not the case that’, shows that chaining valid inferences together doesn’t necessarily result in an invalid inference. People’s intuition can be misleading. Sentences can be true or false. Gottlob Frege called these truth values. If we assume that every sentence is either true or false, but not both, we can predict the conditions in what logicians call a truth table.
Necessity and possibility: what will be must be?
Authors: Priest Graham
Published: November 2017

We often say that something must be so (e.g. ‘It must be going to rain’). We also have ways of saying that, though something may not be the case, it could be (e.g. ‘It could rain tomorrow’). ‘Necessity and possibility: what will be must be?’ considers the notion of things that may happen, things that could happen, and modal operators (it is possible for something to be the case—so it is not necessarily the case that it is false). The argument for fatalism illustrates modal operators. Fatalism is the view that whatever happens must happen. We suppose that every situation comes furnished with a bunch of possibilities, or possible worlds.
Identity and change: is anything ever the same?
Authors: Priest Graham
Published: November 2017

We all think that objects can survive change, but the opposite can be argued. If a person changes their hairstyle, they are both the same person and a different person. ‘Identity and change: is anything ever the same?’ examines problems arising when things change and the identity of objects that change through time. Any change means that the old object no longer exists and is replaced by a different object. Logicians point to the difference between the object and its properties. Is this a language issue? In English, the verb ‘to be’ and its various grammatical forms can be used to express both the object and its properties.
Conceptual and computational framework for logical modelling of biological networks deregulated in diseases
Authors: Montagud Arnau , Traynard Pauline , Martignetti Loredana , Bonnet Eric , Barillot Emmanuel , Zinovyev Andrei , Calzone Laurence
Published: November 2017

Mathematical models can serve as a tool to formalize biological knowledge from diverse sources, to investigate biological questions in a formal way, to test experimental hypotheses, to predict the effect of perturbations and to identify underlying mechanisms. We present a pipeline of computational tools that performs a series of analyses to explore a logical model’s properties. A logical model of initiation of the metastatic process in cancer is used as a transversal example. We start by analysing the structure of the interaction network constructed from the literature or existing databases. Next, we show how to translate this network into a mathematical object, specifically a logical model, and how robustness analyses can be applied to it. We explore the visualization of the stable states, defined as specific attractors of the model, and match them to cellular fates or biological read-outs. With the different tools we present here, we explain how to assign to each solution of the model a probability and how to identify genetic interactions using mutant phenotype probabilities. Finally, we connect the model to relevant experimental data: we present how some data analyses can direct the construction of the network, and how the solutions of a mathematical model can also be compared with experimental data, with a particular focus on high-throughput data in cancer biology. A step-by-step tutorial is provided as a Supplementary Material and all models, tools and scripts are provided on an accompanying website: https://github.com/sysbio-curie/Logical_modelling_pipeline.
MOAT: efficient detection of highly mutated regions with the Mutations Overburdening Annotations Tool
Authors: Lochovsky Lucas , Zhang Jing , Gerstein Mark
Published: November 2017

Identifying genomic regions with higher than expected mutation count is useful for cancer driver detection. Previous parametric approaches require numerous cell-type-matched covariates for accurate background mutation rate (BMR) estimation, which is not practical for many situations. Non-parametric, permutation-based approaches avoid this issue but usually suffer from considerable compute-time cost. Hence, we introduce Mutations Overburdening Annotations Tool (MOAT), a non-parametric scheme that makes no assumptions about mutation process except requiring that the BMR changes smoothly with genomic features. MOAT randomly permutes single-nucleotide variants, or target regions, on a relatively large scale to provide robust burden analysis. Furthermore, we show how we can do permutations in an efficient manner using graphics processing unit acceleration, speeding up the calculation by a factor of ∼250.

Availability and implementation

MOAT is available at moat.gersteinlab.org.

Supplementary information

Supplementary data are available at Bioinformatics online.
PREFMD: a web server for protein structure refinement via molecular dynamics simulations
Authors: Heo Lim , Feig Michael
Published: November 2017

Refinement of protein structure models is a long-standing problem in structural bioinformatics. Molecular dynamics-based methods have emerged as an avenue to achieve consistent refinement. The PREFMD web server implements an optimized protocol based on the method successfully tested in CASP11. Validation with recent CASP refinement targets shows consistent and more significant improvement in global structure accuracy over other state-of-the-art servers.

Availability and implementation

PREFMD is freely available as a web server at http://feiglab.org/prefmd. Scripts for running PREFMD as a stand-alone package are available at https://github.com/feiglab/prefmd.git.

Supplementary information

Supplementary data are available at Bioinformatics online.
Cost-effective and accurate method of measuring fetal fraction using SNP imputation
Authors: Kim Minjeong , Kim Jai-Hoon , Kim Kangseok , Kim Sunshin
Published: November 2017

Motivation

With the discovery of cell-free fetal DNA in maternal blood, the demand for non-invasive prenatal testing (NIPT) has been increasing. To obtain reliable NIPT results, it is important to accurately estimate the fetal fraction. In this study, we propose an accurate and cost-effective method for measuring fetal fractions using single-nucleotide polymorphisms (SNPs).

Results

A total of 84 samples were sequenced via semiconductor sequencing using a 0.3× sequencing coverage. SNPs were genotyped to estimate the fetal fraction. Approximately 900 000 SNPs were genotyped, and 250 000 of these SNPs matched the semiconductor sequencing results. We performed SNP imputation (1000Genome phase3 and HRC v1.1 reference panel) to increase the number of SNPs. The correlation coefficients (R2) of the fetal fraction estimated using the ratio of non-maternal alleles when coverage was reduced to 0.01 following SNP imputation were 0.93 (HRC v1.1 reference panel) and 0.90 (1000GP3 reference panel). An R2 of 0.72 was found at 0.01× sequencing coverage with no imputation performed. We developed an accurate method to measure fetal fraction using SNP imputation, showing cost-effectiveness by using different commercially available SNP chips and lowering the coverage. We also showed that semiconductor sequencing, which is an inexpensive option, was useful for measuring fetal fraction.

Availability and implementation

python source code and guidelines can be found at https://github.com/KMJ403/fetalfraction-SNPimpute.

Supplementary information

Supplementary data are available at Bioinformatics online.
The Topology of Compact Lie Group Actions Through the Lens of Finite Models
Authors: Papadima Stefan , Suciu Alexander I
Published: November 2017

Given a compact, connected Lie group K, we use principal K-bundles to construct manifolds with prescribed finite-dimensional algebraic models. Conversely, let M be a compact, connected, smooth manifold, which supports an almost free K-action. Under a partial formality assumption on the orbit space and a regularity assumption on the characteristic classes of the action, we describe an algebraic model for M with commensurate finiteness and partial formality properties. The existence of such a model has various implications on the structure of the cohomology jump loci of M and of the representation varieties of π1(M). As an application, we show that compact Sasakian manifolds of dimension 2n + 1 are (n − 1)-formal, and that their fundamental groups are filtered-formal. Further applications to the study of weighted-homogeneous isolated surface singularities are also given.
Estimating the causal effects of chronic disease combinations on 30-day hospital readmissions based on observational Medicaid data
Authors: Casucci Sabrina , Lin Li , Hewner Sharon , Nikolaev Alexander
Published: November 2017

Objective

Demonstrate how observational causal inference methods can generate insights into the impact of chronic disease combinations on patients’ 30-day hospital readmissions.

Materials and Methods

Causal effect estimation was used to quantify the impact of each risk factor scenario (ie, chronic disease combination) associated with chronic kidney disease and heart failure (HF) for adult Medicaid beneficiaries with initial hospitalizations in 2 New York State counties. The experimental protocol: (1) created matched risk factor and comparator groups, (2) assessed covariate balance in the matched groups, and (3) estimated causal effects and their statistical significance. Causality lattices summarized the impact of chronic disease comorbidities on readmissions.

Results

Chronic disease combinations were ordered with respect to their causal impact on readmissions. Of disease combinations associated with HF, the combination of HF, coronary artery disease, and tobacco abuse (in that order) had the highest causal effect on readmission rate (+22.3%); of disease combinations associated with chronic kidney disease, the combination of chronic kidney disease, coronary artery disease, and diabetes had the highest effect (+9.5%).

Discussion

Multi-hypothesis causal analysis reveals the effects of chronic disease comorbidities on health outcomes. Understanding these effects will guide the development of health care programs that address unique care needs of different patient subpopulations. Additionally, these insights bring new attention to individuals at high risk for readmission based on chronic disease comorbidities, allowing for more personalized attention and prioritization of care.

Conclusion

Multi-hypothesis causal analysis, a new methodological tool, generates meaningful insights from health care claims data, guiding the design of care and intervention programs.
Introduction
Authors: Oliver Peter , Macklem Patrick , Des Rosiers Nathalie
Published: November 2017

This Handbook is intended to be an authoritative first stop for Canadians and non-Canadians in search of a clear, concise, and critical account of Canadian constitutional law. This Introduction begins by setting out what makes the Canadian Constitution distinctive, before describing the extent to which that Constitution has become a focus for comparative constitutional law. The Introduction concludes by expressing the hope that Canadian readers of this Handbook will find themselves better equipped, and that foreign readers will better understand the types of questions for which Canadians are seeking answers in 2017 and beyond. These include at the very least: decolonization and reconciliation with Indigenous peoples; maintaining a federation and a democracy that works for all its communities and inhabitants; and protecting rights and freedoms in the face of global security, environmental, and other threats.
The British Legal Tradition in Canadian Constitutional Law
Authors: Walters Mark D.
Published: November 2017

This chapter examines the influence of the British legal tradition within Canadian constitutional law. The foundational text of Canada’s constitution, the British North America Act, 1867, was adopted when Canada was still a UK colony, and so it is hardly surprising that this influence would prove to be important—even after Canada emerged as an independent state. Still, the assertion in the preamble to the 1867 Act, that Canada’s constitution is ‘similar in Principle to that of the United Kingdom’, must be approached cautiously. The leading British constitutional scholar A.V. Dicey went so far as to describe this assertion as a piece of ‘official mendacity’. The analysis in Section 2 of this chapter focuses upon institutional structure and design. Here, it will be seen that Dicey was wrong. The analysis in Section 3 of the chapter is on the interpretive ethic or what Dicey called the ‘spirit’ of the constitution.
The Crown in Canada
Authors: Smith Jennifer , Firmini Marcella
Published: November 2017

In Canada, the monarch is habitually, albeit erroneously, considered a figurehead in the nation’s system of government. In fact, in a constitutional monarchy, Her Majesty Queen Elizabeth II’s capacity as head of state means that her position is substantive, not merely superficial. Certainly, the Constitution affirms that all executive authority is vested in her. Therefore, it is important to realize the scope and substance of the sovereign’s authority which is often underappreciated. We trace the development of the Crown in Canada, in particular the changes the institution experienced as the country progressed from remote colonial outpost to independent nation. Most importantly, we assess the Crown’s institutional function by explaining the statutory, prerogative, and reserve powers, and conclude with some reflections on the future of the institution in Canada.
Political Institutions in Canada in a New Era
Authors: Turnbull Lori
Published: November 2017

This chapter examines the meaning and significance of the parliamentary reform package introduced by Prime Minister Justin Trudeau’s government in 2015. The proposed measures address themes that have been part of democratic reform agendas for many years, and most of them can be fairly described as low-hanging fruit. The one that stands out from the rest is the Trudeau government’s approach to appointments. Historically, Prime Ministers have made appointments to the Senate, the Supreme Court, and other positions of profile and authority with little to no restrictions on their discretion. The Trudeau government’s creation of independent advisory boards to preside over appointments throughout federal government institutions, and the identification of specified criteria to guide these appointments, represents a major departure from historic practice and a potentially significant shift away from the concentration of power in the hands of the political Executive.
Courts, Administrative Agencies, and the Constitution
Authors: Sossin Lorne
Published: November 2017

This chapter sets out the constitutional foundation for courts and administrative agencies in Canada. It examines the constitutional foundations for Canadian courts, including Canada’s constitutional texts; unwritten constitutional principles such as judicial independence, access to justice, and the rule of law; quasi-constitutional statutes such as the Supreme Court Act; and the common law Constitution. The chapter next considers the constitutional foundations for administrative agencies, particularly around the extent to which agencies can implement and are subject to the Constitution. Finally, the chapter situates the discussion of administrative agencies against the backdrop of Canada’s separation of powers, including emerging dynamics flowing from Indigenous self-government.
Amending the Constitution of Canada
Authors: Pelletier Benoît
Published: November 2017

In the past, Canadian constitutional reform has been marked by surprising successes and resounding failures. Indeed, the failures were such that constitutional amendment itself, along with the word “Constitution”, became taboo in the eyes of a large part of the Canadian population. This chapter will commence with a brief history of constitutional reform in Canada from the Constitution Act, 1867 to the patriation of 1982, followed by an analysis of the post-patriation constitutional amendment procedures. It will then discuss the political and legal frameworks which further complicate the already strict requirements of modern constitutional amendment in Canada, and will conclude with an overview of the phenomena favouring paraconstitutional adaptation of the Constitution. Finally, it will point out that the full restoration of the word “Constitution” is of utmost importance in ensuring that constitutional reform itself does not simply become a matter of wishful thinking.
Treaties as Constitutional Agreements
Authors: Grammond Sébastien
Published: November 2017

This chapter reviews the history of treaty-making with the Indigenous peoples of Canada. After an initial period of roughly equal relationships, colonial authorities increasingly used treaties as a domestic law concept aimed at securing control over Indigenous land. The practice was continued after Confederation, but there appears to be a major misunderstanding as to the terms of those treaties, in particular as to the purported extinguishment of Aboriginal title. After a 50-year hiatus, treaty-making resumed in 1975 with the signing of ‘land claims agreements’ in most of the Canadian north. These agreements not only provide for the sharing of land, they also contain detailed provisions with respect to co-management of natural resources and, in some cases, self-government. Canadian law now affords statutory and constitutional protection to treaty rights, and courts are prepared to take into account extrinsic and oral evidence in interpreting treaties.
Key Doctrines in Canadian Legal Federalism
Authors: Brouillet Eugénie , Ryder Bruce
Published: November 2017

The division of legislative powers in the Constitution Act, 1867 is the most important textual expression of the federal principle that is at the heart of the Canadian constitutional order. The judiciary has the responsibility of interpreting these provisions and thus of determining the boundaries of the law-making powers of Canadian legislative bodies. In performing this high-stakes task, the courts have developed a rich jurisprudence that draws on text, history, structure, and principle. In recent decades, the Supreme Court has articulated a “modern” or “co-operative” approach that interprets both federal and provincial legislative powers generously, and tolerates a high degree of overlap and interplay between them. Despite this commitment to maximizing the democratic space available to all Canadian legislatures within their respective areas of jurisdiction, some doctrines developed by the courts have had asymmetric effects that favour the federal Parliament.
Constitutional Aspects of Commercial Law
Authors: Anand Anita
Published: November 2017

This chapter describes the constitutional aspects of commercial law and focuses on division-of-powers issues relating to banking, bankruptcy, corporate, and securities law. The chapter makes two important observations. First, the broader jurisdictional lines in commercial law areas are mostly settled. Banking and bankruptcy are areas of federal jurisdiction, for example, whereas the provincial and federal governments have overlapping jurisdiction over corporate law. Securities law is an exception. Although securities law has historically been under provincial control, the appropriate role of the federal government has been the subject of recent controversy and litigation. Second, the chapter explains that although the provincial and federal governments have separate constitutionally protected roles in various areas of commercial law, the role is rarely exclusively assumed (or the field occupied) by one level of government. That is, provincial legislation in one area of law impacts what is otherwise federal constitutional jurisdiction, and vice versa.
The Exploitation of Natural Resources in the Federation
Authors: Walton Luanne A.
Published: November 2017

This chapter traces the evolution of natural resources jurisdictional litigation from Confederation in 1867 until the present. Issues of resource ownership, legislative control, and environmental protection are all explored. In the years immediately following Confederation, the principal focus was establishing resource ownership for all provinces. Once that was established through the Natural Resources Transfer Agreements, legislative jurisdiction over resources became the issue. The caselaw from this period resulted in the resource amendment, which was the only change to the federal-provincial division of powers constitutionally entrenched by the Constitution Act, 1982. Issues of ownership and legislative jurisdiction were settled just in time for the courts to turn their focus to environmental protection. The author demonstrates the way in which litigation and negotiation through the years has led to the current conflict between environmental and resource protection, and the potential profits available in the fossil fuel sector, with special emphasis on pipelines.
The Justification of Rights Violations
Authors: Panaccio Charles-Maxime
Published: November 2017

This chapter is about the interpretation of section 1 of the Canadian Charter of Rights and Freedoms. Section 1 allows ‘limits’ to constitutional rights insofar as they are reasonable and justified in a free and democratic society. It asks the state for moral justification when a right has been infringed by state action. Moral justification has formal and substantive aspects; therefore the application of section 1 deploys a formal framework of proportionality nestled within a thin conception of liberal democratic political morality. The chapter also addresses the relative moral importance of the notion of ‘rights’, as well as the relevance of institutional considerations. It concludes that the section 1 framework follows a standard model of moral justification and cannot be significantly improved upon.
Charter Remedies
Authors: Roach Kent
Published: November 2017

This chapter argues that interpretative remedies have qualified the supremacy clause in section 52(1) of the Constitution Act, 1982 and should only be used when courts can avoid making choices best left to the legislature. It also suggests that suspended declarations of invalidity facilitate dialogue between courts and legislatures but should, as in the recent assisted dying case, be administered so that litigants not suffer irreparable harm during the suspension. Rights may be better enforced and developed in the criminal than the civil trial context because stronger remedies such as exclusion of evidence are available whereas most awards of Charter damages have been modest. Canadian courts prefer declarations or individual remedies such as damages or habeas corpus over the use of injunctions and the retention of jurisdiction. This has impoverished Charter rights relating to conditions of confinement, illustrating how remedies affect and even shape rights.
The Notwithstanding Clause
Authors: Hiebert Janet L.
Published: November 2017

The notwithstanding clause in section 33 has always been the Charter’s most controversial provision. Although rarely invoked, a failure to use this power should not be equated with a willingness to abide by judicial norms about the Charter. This chapter analyses the political life of the notwithstanding clause. It examines the origins of the notwithstanding clause, its uses, its influence on constitutional ideals beyond Canada, and the political consequences associated with a deeply entrenched reticence to invoke the notwithstanding clause. This discussion addresses whether current reluctance to use section 33 is better explained by risk aversion than by legislative compliance with the Charter.