bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS‐III—Omics
Authors: D'Alessandro Angelo , Culp‐Hill Rachel , Reisz Julie A. , Anderson Mikayla , Fu Xiaoyun , Nemkov Travis , Gehrke Sarah , Zheng Connie , Kanias Tamir , Guo Yuelong , Page Grier , Gladwin Mark T. , Kleinman Steve , Lanteri Marion , Stone Mars , Busch Michael , Zimring James C. ,   for the Recipient Epidemiology and Donor Evaluation Study‐III (REDS‐III)
Published: October 2018

BACKGROUND

Biological and technical variability has been increasingly appreciated as a key factor impacting red blood cell (RBC) storability and, potentially, transfusion outcomes. Here, we performed metabolomics analyses to investigate the impact of factors other than storage duration on the metabolic phenotypes of stored RBC in a multicenter study.

STUDY DESIGN AND METHODS

Within the framework of the REDS‐III (Recipient Epidemiology and Donor Evaluation Study‐III) RBC‐Omics study, 13,403 donors were enrolled from four blood centers across the United States and tested for the propensity of their RBCs to hemolyze after 42 days of storage. Extreme hemolyzers were recalled and donated a second unit of blood. Units were stored for 10, 23, and 42 days prior to sample acquisition for metabolomics analyses.

RESULTS

Unsupervised analyses of metabolomics data from 599 selected samples revealed a strong impact (14.2% of variance) of storage duration on metabolic phenotypes of RBCs. The blood center collecting and processing the units explained an additional 12.2% of the total variance, a difference primarily attributable to the storage additive (additive solution 1 vs. additive solution 3) used in the different hubs. Samples stored in mannitol‐free/citrate‐loaded AS‐3 were characterized by elevated levels of high‐energy compounds, improved glycolysis, and glutathione homeostasis. Increased methionine metabolism and activation of the transsulfuration pathway was noted in samples processed in the center using additive solution 1.

CONCLUSION

Blood processing impacts the metabolic heterogeneity of stored RBCs from the largest multicenter metabolomics study in transfusion medicine to date. Studies are needed to understand if these metabolic differences influenced by processing/storage strategies impact the effectiveness of transfusions clinically.
LTAD Model Active Beginning Stage Adaptation in Judo Basic Education Program (Ukemi, Tachiwaza & Newaza Basic Drills) for 4-6 Aged Kids
Authors: Demiral Sengul
Published: October 2018

Early childhood is known as a critical period in acquisition of development and basic mobility skills. In this period, physical education and judo education contribute to development of general body, hand-eye and foot-eye coordination, 5 motor skills, static and dynamic balance. Moreover, the sub-structure of lifelong sport habits is being prepared by teaching values with respect to judo, kindness, self-determination, solidarity, honesty, friendship, patience, courage and modesty. As a result, due to basic education of judo such as 'Ukemi, Tachi Waza and Newaza Basic Drills', children learn much more than movement skills. In this study, importance of physical education and judo activities in pre-school period has been considered in practice. The results showed Judo has an impact on pre-service and in-service training in practice of pre-school physical education and judo activities. It is inevitable that these activities contribute to almost all targeted development areas of a child, in addition to contributing to training of large group of children in first phase of long-term athlete development model in our country.
La contabilidad financiera como motor de la redefinición de la concepción de empresa
Authors: Pardo López Steven , Peña Cortés Ángela Rocio
Published: October 2018

El predominio de la financiarización económica ha otorgado prevalencia a un concepto de empresa según el cual el accionista, la gestión financiera y la generación de valor emergen como elementos determinantes de las relaciones entabladas entre los agentes organizacionales. La reproducción de esta concepción en economías que carecen de estructuras financieras robustas constituye el centro de estudio del presente artículo. En este sentido, el trabajo explora el declive del sector industrial y el ascenso del sector financiero en Colombia. Asimismo, se identifica el surgimiento de tensiones entre la realidad organizacional y el ambiente institucional, por cuenta del ascenso de la concepción financiera de la empresa, en detrimento de la concepción orgánica de esta. El estudio concluye que estas tensiones son superadas con la ayuda de un isomorfismo institucional en el que las modernizaciones contables interpretan un papel central, puesto que insertan a la realidad organizacional un conjunto de técnicas y racionalidades afines a actividades especulativas.
Estrutura de capital na perspectiva da teoria Pecking Order e Assimetria da Informação nas empresas brasileiras, chilenas e mexicanas no período de 1999 a 2013
Authors: Fiirst Clóvis , Chaves Cunha Leila , Da Silva Tarcísio Pedro
Published: October 2018

O presente trabalho tem por objetivo identificar a estrutura de capital das empresas de capital aberto do Brasil, Chile e México, na perspectiva da Teoria Pecking Order e da Assimetria da Informação, no período de 1999 a 2013. A pesquisa quanto aos objetivos caracteriza-se como descritiva, quanto aos procedimentos, documental e quanto a abordagem do problema, quantitativa. Para o tratamento dos dados são utilizadas técnicas de correlação linear, regressão linear múltipla, com dados em painel. A amostra é composta por 40 empresas brasileiras, 39 empresas chilenas e 23 empresas mexicanas, com 1.530 observações. Os determinantes que apresentam resultados significantes para a estrutura de capital das empresas são evidenciados a partir de indicadores de nível de endividamento contábil e financeiro. Os resultados demonstram que as empresas brasileiras apresentam a maior oscilação e incremento no endividamento total contábil no período pesquisado (1999-2013), seguida do Chile e por fim México e que a rentabilidade das empresas brasileiras, chilenas e mexicanas diminui com o passar do tempo. Conclui-se que a estrutura de capital das empresas brasileiras, chilenas e mexicanas, nesse lapso temporal de 15 anos, é explicada, principalmente, pela teoria Pecking Order, mas também pela Assimetria da Informação, com menor ênfase. Sugere-se para futuras pesquisas a comparabilidade com painel dinâmico.
Política de dividendos e reputação nas empresas mais responsáveis e com melhor governança corporativa
Authors: Sousa da Silva Emanoel Mamede , Carvalho de Vasconcelos Alessandra , Nobre Parente Paulo Henrique , Mendes De Luca Márcia Martins
Published: October 2018

O presente estudo investiga a correlação entre a política de dividendos e a reputação das empresas brasileiras listadas no ranking Merco 2014 das empresas mais responsáveis e com melhor governança corporativa. Os dados foram coletados nas demonstrações financeiras e nos formulários de referência de 39 empresas listadas na BM&FBovespa, do ano 2013. Estes foram analisados para testar as hipóteses de que a política de dividendos –interpretada como um sinal de rentabilidade e redução da assimetria informacional– está correlacionada com a reputação corporativa. Os resultados foram submetidos à análise de homogeneidade, correspondência e correlação. Estes mostraram que (a) as empresas distribuem dividendos principalmente sob a forma de juros sobre capital próprio, (b) empresas familiares tendem a ter uma fraca política de dividendos e baixa reputação corporativa e (c) a política de dividendos está positivamente associada com a reputação corporativa. Assim, à luz da teoria da sinalização, pode-se concluir que a política de dividendos foi positivamente associada à reputação corporativa nas empresas incluídas na amostra.
El uso de los métodos deductivo e inductivo para aumentar la eficiencia del procesamiento de adquisición de evidencias digitales
Authors: Prieto Castellanos Bayron José
Published: October 2018

El presente artículo tiene como propósito mostrar la aplicación de los métodos de investigación deductivo e inductivo en el ámbito de la optimización del procesamiento de evidencias digitales. Dicha pesquisa tiene como base un esquema de adquisición estructurada de la información, y se desarrolla con la finalidad de aumentar la eficiencia de los procesos descritos, en el contexto de la práctica informática forense. Según lo anterior, el autor define dichos métodos filosóficos, en tanto que son útiles en otras áreas del conocimiento, y presenta la aplicación de ambos mecanismos de acuerdo con el marco general de obtención y análisis de evidencias digitales E-Discovery, así como con el proceso de adquisición, procesamiento, puesta a disposición e investigación (APPI), que es definido y desarrollado también en el presente estudio. Asimismo, el autor presenta todos estos conceptos bajo el lente de los lineamientos que constan en las leyes 527 de 1999 —Ley de Comercio Electrónico— y 906 de 2004, al igual que bajo el rasero del Decreto Reglamentario 1747 de 2000 y la norma ISO 27 001.
Using Flight-Time to Contextualize Radiological Dose
Authors: Stahmer Ulf
Published: October 2018

During every moment of our lives, we are surrounded by radiation from natural and manmade sources. Our bodies contain radionuclides from which we receive radiation. Radionuclides are found in the foods we eat and in the ground we walk on. We receive cosmic radiation from space. Radionuclides are also found in the airborne particles we breathe. The radiological dose from all these sources is termed background dose. Many of us are unaware of the radiation around us. Radiation is as much a part of our daily lives as air and water. In this article, time spent flying in an airplane is used as an analogy to contextualize radiological dose.
Context integration deficit in tone perception in Cantonese speakers with congenital amusia
Authors: Shao Jing , Zhang Caicai
Published: October 2018

Congenital amusia is a neuro-developmental disorder of pitch processing. This study investigated how this deficit affects lexical tone perception with and without context. Twenty-three Cantonese-speaking amusics and 23 controls were tested on the identification of high-variation tone stimuli in isolation vs in a carrier sentence. The controls generally achieved a higher accuracy with context than in isolation, suggesting that speech context facilitated tone identification. In contrast, amusics generally failed to benefit from the context, despite some variation among different tones. These findings provide insights into the underlying deficits of amusia, revealing a context integration deficit of tone perception in amusia.
Data clustering analysis of early reflections in small room
Authors: Zhang Zhaoqi , Zhu Ge , Shen Yong
Published: October 2018

It is common to increase the number of measurement points to improve the robustness of multipoint room equalization. However, the measurement of numerous points is extremely time-consuming and laborious. This letter analyzes the early reflections extracted from a large amount of room impulse responses using a K-means clustering algorithm, revealing that the spatial distribution of early reflections in the same cluster is not disorganized but regular and predictable. Furthermore, the results of the Monte Carlo simulation suggest that the appropriate selection of measurement positions can reduce the number of measurement points without compromising the robustness of multipoint room equalization.
Uncovering the psychoactivity of a cannabinoid from liverworts associated with a legal high
Authors: Chicca A. , Schafroth M. A. , Reynoso-Moreno I. , Erni R. , Petrucci V. , Carreira E. M. , Gertsch J.
Published: October 2018

Pharmacology on cannabinoids originating from convergent evolution in bryophytes was enabled by total synthesis.
Pre-Clovis projectile points at the Debra L. Friedkin site, Texas—Implications for the Late Pleistocene peopling of the Americas
Authors: Waters Michael R. , Keene Joshua L. , Forman Steven L. , Prewitt Elton R. , Carlson David L. , Wiederhold James E.
Published: October 2018

Stemmed projectile points are ~13,500 to ~15,500 years old and lie stratigraphically below ~13,000-year-old Clovis artifacts.
Lsm12 Mediates Deubiquitination of DNA Polymerase η To Help
Saccharomyces cerevisiae
Resist Oxidative Stress
Authors: Yao Rui , Shi Liujia , Wu Chengjin , Qiao Weihua , Liu Liming , Wu Jing
Published: October 2018

Polη was shown to be critical for cell growth in the yeast
Saccharomyces cerevisiae
, and deletion of its corresponding gene
RAD30
caused a severe growth defect under exposure to oxidative stress with 2 mM H
2
O
2
. Furthermore, we found that Lsm12 physically interacts with Polη and promotes Polη deubiquitination and recruitment. Overall, these findings indicate Lsm12 is a novel regulator mediating Polη deubiquitination that regulates its recruitment in response to DNA damage induced by oxidative stress.
A Cyclic Metabolic Network in Pseudomonas protegens Pf-5 Prioritizes the Entner-Doudoroff Pathway and Exhibits Substrate Hierarchy during Carbohydrate Co-Utilization
Authors: Wilkes Rebecca A. , Mendonca Caroll M. , Aristilde Ludmilla
Published: October 2018

Species of the
Pseudomonas
genus thrive in various nutritional environments and have strong biocatalytic potential due to their diverse metabolic capabilities. Carbohydrate substrates are ubiquitous both in environmental matrices and in feedstocks for engineered bioconversion. Here, we investigated the metabolic network for carbohydrate metabolism in
Pseudomonas protegens
Pf-5. Metabolic flux quantitation revealed the relative involvement of different catabolic routes in channeling carbohydrate carbons through a cyclic metabolic network. We also uncovered that mannose catabolism was similar to fructose catabolism, despite the annotation of a different pathway in the genome. Elucidation of the constitutive metabolic network in
P. protegens
is important for understanding its innate carbohydrate processing, thus laying the foundation for targeting metabolic engineering of this untapped
Pseudomonas
species.
PCR Detection of Respiratory Pathogens in Asymptomatic and Symptomatic Adults
Authors: Sundell Nicklas , Andersson Lars-Magnus , Brittain-Long Robin , Sundvall Pär-Daniel , Alsiö Åsa , Lindh Magnus , Gustavsson Lars , Westin Johan
Published: October 2018

The frequency of viral respiratory pathogens in asymptomatic subjects is poorly defined. The aim of this study was to explore the prevalence of respiratory pathogens in the upper airways of asymptomatic adults, compared with a reference population of symptomatic patients sampled in the same centers during the same period.
Low-pH Endocytic Entry of the Porcine Alphaherpesvirus Pseudorabies Virus
Authors: Miller Jonathan L. , Weed Darin J. , Lee Becky H. , Pritchard Suzanne M. , Nicola Anthony V.
Published: October 2018

PRV is a pathogen of great economic and animal welfare importance in many parts of the world. PRV causes neurological, respiratory, and reproductive disorders, often resulting in mortality of young and immunocompromised animals. Mortality, decreased production, and trade restrictions result in significant financial losses for the agricultural industry. Understanding the molecular mechanisms utilized by PRV to enter host cells is an important step in identifying novel strategies to prevent infection and spread. A thorough understanding of these mechanisms will contribute to a broader understanding of alphaherpesvirus entry. Here, we demonstrate PRV entry into multiple model cell lines via a low-pH endocytosis pathway. Together, these results provide a framework for elucidating the early events of the PRV replicative cycle.
Biogenesis of Extracellular Vesicles during Herpes Simplex Virus 1 Infection: Role of the CD63 Tetraspanin
Authors: Dogrammatzis Christos , Deschamps Thibaut , Kalamvoki Maria
Published: October 2018

Intercellular communication, especially in neurons, largely relies on EVs, and modulation of EVs is known to impact physiological processes. Here, we present evidence that HSV-1 infection causes major alterations in the biogenesis of EVs, including an increase in their number and an increase in the CD63-positive population of EVs. These alterations result in an enrichment of the milieu of infection with EVs carrying signatures from infected cells. In addition to changes in the origin and type, EVs released by infected cells have differences in cargo, as they carry viral and host factors determined by the virus. The tetraspanin CD63 negatively impacts the infection, as demonstrated by CD63-knockdown and overexpression assays. A proposed mechanism involves the activation of antiviral responses in cells receiving CD63-positive EVs released by infected cells. Overall, HSV-1 causes major alterations in EVs that could contribute to HSV-1 persistence and pathogenesis.
High-Quality Draft Genome Sequence of Xanthomonas arboricola pv. juglandis CPBF 1521, Isolated from Leaves of a Symptomatic Walnut Tree in Portugal without a Past of Phytosanitary Treatment
Authors: Fernandes Camila , Blom Jochen , Pothier Joël F. , Tavares Fernando
Published: October 2018

Here, we report the draft genome sequence of
Xanthomonas arboricola
pv. juglandis CPBF 1521, isolated from symptomatic leaves of an ornamental walnut in a public site in Portugal without any record of phytosanitary treatment.
Complete Genome Sequence of a Boa (
Boa constrictor
)-Specific Papillomavirus Type 1 Isolate
Authors: Kubacki Jakub , Ramsauer Anna Sophie , Bachofen Claudia , Favrot Claude , Nicolier Alexandra , Fraefel Cornel , Tobler Kurt
Published: October 2018

We present the full-length genome sequence of a new papillomavirus detected in skin lesions collected from a boa (
Boa constrictor
). Based on the nucleotide sequence analysis, we propose to designate the newly identified virus as
Boa constrictor
papillomavirus type 1
(BcPV1), a new species in the genus
Dyomupapillomavirus
.
Draft Genome Sequence of Trebouxiophyceae sp. Strain KSI-1, Isolated from an Island Hot Spring
Authors: Takahashi Hiro , Tanaka Satoshi , Hayashi Shuhei , Miyaki Shido , Takahashi Anna , Onai Shinnosuke , Fukuyoshi Shuichi , Miyasaka Hitoshi
Published: October 2018

Trebouxiophyceae sp. KSI-1 is a green alga isolated from a seashore hot spring on Satsuma Iōjima in Kagoshima, Japan, and is highly tolerant to oxidative stress.
Complete Genome Sequence of Cluster A1 Mycobacterium smegmatis Bacteriophage Arlo
Authors: Stewart Brittany , Adams Megan , Fuentes Miranda , Hanson Leeila , Sandoval Esperanza , Tovar Mario , Trautman Camille , Willis Bianca , Emmert Keith , Edwards Julie , Meik Jesse , Pierce James , Edwards Dustin
Published: October 2018

Mycobacteriophage Arlo is a newly isolated
Siphoviridae
bacteriophage isolated from soil samples collected in Bluff Dale, Texas. Mycobacteriophage Arlo has a 52,960 base-pair double-stranded DNA genome that is predicted to contain 96 protein-coding genes.
Complete Genome Sequence of the Arcobacter ellisii Type Strain LMG 26155
Authors: Miller William G. , Yee Emma , Bono James L.
Published: October 2018

Arcobacter
spp. are highly prevalent in contaminated environmental waters and have been recovered from both freshwater and seawater, with several species isolated from shellfish.
Genome Sequence of the Extremely Acidophilic Fungus Acidomyces richmondensis FRIK2901
Authors: Rosienski Matthew D. , Lee Mi-Kyung , Yu Jae-Hyuk , Kaspar Charles W. , Gibbons John G.
Published: October 2018

Acidomyces richmondensis
is an extremophilic fungal species found in warm, acidic, and metal-rich environments. To improve upon the existing reference genome, we used PacBio and Illumina sequencing to assemble a highly contiguous 29.3-Mb genome of
A. richmondensis
FRIK2901.
Two-year follow-up of mineralocorticoid receptor antagonists for chronic central serous chorioretinopathy
Authors: Zola Marta , Daruich Alejandra , Matet Alexandre , Mantel Irmela , Behar-Cohen Francine
Published: October 2018

Aims

To evaluate the long-term oral mineralocorticoid receptor antagonist (MRa) treatment in chronic central serous chorioretinopathy (CSC).

Methods

Patients with chronic non-resolving CSC (defined as foveal subretinal fluid (SRF) lasting >4 months with retinal pigment epithelium (RPE) alterations) treated with MRa only (eplerenone or spironolactone) for at least 6 months were retrospectively included. Clinical and imaging characteristics were recorded during visits at baseline, 6, 12, 18 and 24 months.

Results

Sixteen eyes of 16 patients were included (mean age 53±11 years; 14 men, 2 women). Mean duration of SRF before treatment initiation was 11.2±19.7 months. MRa treatment was administered during 21.0±5.1 months (range, 10–24 months). There was a progressive improvement of visual acuity (p=0.05), a decrease of foveal SRF height (p=0.011), central macular thickness (p=0.004) and subfoveal choroidal thickness (p=0.002) over 24 months. Changes in SRF were correlated with subfoveal choroidal thickness at 24 months (p=0.006, Spearman r=065). The mean time to complete foveal SRF resolution was 10.5±8.0 months after treatment initiation. At 24 months, foveal SRF resolution was achieved in 13 eyes (81%). Minor side effects occurred in five patients (31%) and resolved after switching between MRa.

Conclusion

The visual and anatomical benefit of MRa treatment prolonged for 6 months or more in chronic, non-resolving CSC appeared to be maintained over a 24-month period. These results suggest that MRa can be proposed as an alternative therapy in severe CSC with advanced RPE alterations.
Risk selection in primary care: a cross-sectional fixed effect analysis of Swedish individual data
Authors: Isaksson David , Blomqvist Paula , Pingel Ronnie , Winblad Ulrika
Published: October 2018

Objective

To assess socioeconomic differences between patients registered with private and public primary healthcare centres.

Design

Population-based cross-sectional study controlling for municipality and household.

Setting

Swedish population-based socioeconomic data collected from Statistics Sweden linked with individual registration data from all 21 Swedish regions.

Participants

All individuals residing in Sweden on 31 December 2015 (n=9 851 017) were included in the study.

Primary outcome measures

Registration with private versus public primary healthcare centres.

Results

After controlling for municipality and household, individuals with higher socioeconomic status were more likely to be registered with a private primary healthcare provider. Individuals in the highest income quantile were 4.9 percentage points (13.7%) more likely to be registered with a private primary healthcare provider compared with individuals in the lowest income quantile. Individuals with 1–3 years of higher education were 4.7 percentage points more likely to be registered with a private primary healthcare provider compared with those with an incomplete primary education.

Conclusions

The results show that there are notable differences in registration patterns, indicating a skewed distribution of patients and health risks between private and public primary healthcare providers. This suggests that risk selection behaviour occurs in the reformed Swedish primary healthcare system, foremost through location patterns.
Combining brief contact interventions (BCI) into a decision-making algorithm to reduce suicide reattempt: the VigilanS study protocol
Authors: Duhem Stéphane , Berrouiguet Sofian , Debien Christophe , Ducrocq François , Demarty Anne Laure , Messiah Antoine , Courtet Philippe , Jehel Louis , Thomas Pierre , Deplanque Dominique , Danel Thierry , Walter Michel , Notredame Charles-Edouard , Vaiva Guillaume
Published: October 2018

Introduction

The early postattempt period is considered to be one of the most at-risk time windows for suicide reattempt or completion. Among the postcrisis prevention programmes developed to compensate for this risk, brief contact interventions (BCIs) have been proven to be efficient but not equally for each subpopulation of attempters. VigilanS is a region-wide programme that relies on an algorithmic system to tailor surveillance and BCI provisions to individuals discharged from the hospital after a suicide attempt.

Aim

VigilanS’ main objective is to reduce suicide and suicide reattempt rates both at the individual level (patients included in VigilanS) and at the populational level (inhabitants of the Nord–Pas-de-Calais region).

Methods and analysis

At discharge, every attempter coming from a participating centre is given a crisis card with an emergency number to contact in case of distress. Patients are then systematically recontacted 6 months later. An additional 10-day call is also given if the index suicide attempt is not the first one. Depending on the clinical evaluation during the phone call, thecall teammay carry out proportionated crisis interventions. Personalised postcards are sent whenever patients are unreachable by phone or in distress. On the populational level, mean suicide and suicide attempt rates in Nord–Pas-de-Calais will be compared before and after the implementation of the programme. Here/there cross-sectional comparisons with a control region will test the spatial specificity of the observed fluctuations, while time-series analyses will be performed to corroborate the temporal plausibility of imputing these fluctuations to the implementation of the programme. On the individual level, patients entered in VigilanS will be prospectively compared with a matched control cohort by means of survival analyses (survival curve comparisons and Cox models).

Discussion

VigilanS interventional components fall under the ordinary law care regime, and the individuals’ general rights as patients apply with no addendums or restrictions for their participation in the programme. The research section received authorisation from the Ethical Committee of Lille Nord-Ouest under the caption ‘Study aimed at evaluating routine care’ and is registered in ‘Clinical Trials’. The French Ministry of Health plans to extend the experimentation to other regions and probe the relevance of this type of ‘bottom–up’ territorial prevention policy at the national level.

Trial registration number

NCT03134885.
Protocol for evaluating and implementing a pragmatic value-based healthcare management model for patients with inflammatory arthritis: a Danish population-based regional cohort and qualitative implementation study
Authors: Jørgensen Tanja Schjødt , Lykkegaard Jens Jørgen , Hansen Annette , Schrøder Heidi Morsø , Stampe Betina , Sweeney Anne-Marie Tetsche , Appel Esbensen Bente , Bech Bianca , Christensen Katja , Friis-Mikkelsen Ellen , Røgind Henrik , Lundbak Tine , Taylor Peter C , Petersson Ingemar F , Wæhrens Eva Ejlersen , Kjellberg Jakob , Gudbergsen Henrik , Kristensen Lars Erik
Published: October 2018

Introduction

The provision of healthcare for patients with inflammatory arthritis occurs in the context of somewhat conflicting targets, values and drivers. Therefore, there is a need for introducing ‘value-based healthcare’ defined as the value of patient relevant health outcomes in relation to costs. This term is a central part of tomorrow’s healthcare sector, especially for rheumatic diseases, yet the transition is a huge challenge, as it will impact the development, delivery and assessment of healthcare.

Aims

The aim of this study is to compare medical and patient evaluated impact of the traditional settlement and financing production (DAGS) controlled healthcare setting with a value-based and patient-centred adjunctive to standard care.

Methods and analysis

Patients with inflammatory arthritis receiving treatment in routine care at the outpatient clinics in the Capital Region of Denmark will prospectively and consecutively be enrolled in a Non-Intervention-Study framework providing a pragmatic value-based management model. A Danish reference cohort, used for comparison will be collected as part of routine clinical care. The enrolment period will be from 1 June 2018 until 31December 2023. Baseline and follow-up visits will be according to routine clinical care. Registry data will be obtained directly from patients and include personal, clinical and outcomes information. The study results will be reported in accordance with the STROBE statement.

Ethics and dissemination

The study has been notified to the Danish Data Protection Agency and granted authorisation for the period June 2018 to January 2025 (pending). Informed consent will be obtained from all patients before enrolment in the study. The study is approved by the ethics committee, Capital Region of Denmark (H-18013158). Results of the study will be disseminated through publication in international peer-reviewed journals.
Neurite density is reduced in the presymptomatic phase ofC9orf72disease
Authors: Wen Junhao , Zhang Hui , Alexander Daniel C , Durrleman Stanley , Routier Alexandre , Rinaldi Daisy , Houot Marion , Couratier Philippe , Hannequin Didier , Pasquier Florence , Zhang Jiaying , Colliot Olivier , Le Ber Isabelle , Bertrand Anne
Published: October 2018

Objective

To assess the added value of neurite orientation dispersion and density imaging (NODDI) compared with conventional diffusion tensor imaging (DTI) and anatomical MRI to detect changes in presymptomatic carriers of chromosome 9 open reading frame 72 (C9orf72) mutation.

Methods

The PREV-DEMALS (Predict to Prevent Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis) study is a prospective, multicentre, observational study of first-degree relatives of individuals carrying theC9orf72mutation. Sixty-seven participants (38 presymptomaticC9orf72mutation carriers (C9+) and 29 non-carriers (C9−)) were included in the present cross-sectional study. Each participant underwent one single-shell, multishell diffusion MRI and three-dimensional T1-weighted MRI. Volumetric measures, DTI and NODDI metrics were calculated within regions of interest. Differences in white matter integrity, grey matter volume and free water fraction betweenC9+andC9−individuals were assessed using linear mixed-effects models.

Results

Compared withC9−,C9+demonstrated white matter abnormalities in 10 tracts with neurite density index and only 5 tracts with DTI metrics. Effect size was significantly higher for the neurite density index than for DTI metrics in two tracts. No tract had a significantly higher effect size for DTI than for NODDI. For grey matter cortical analysis, free water fraction was increased in 13 regions inC9+, whereas 11 regions displayed volumetric atrophy.

Conclusions

NODDI provides higher sensitivity and greater tissue specificity compared with conventional DTI for identifying white matter abnormalities in the presymptomaticC9orf72carriers. Our results encourage the use of neurite density as a biomarker of the preclinical phase.

Trial registration number

NCT02590276.
Phosgene use in World War 1 and early evaluations of pathophysiology
Authors: Nicholson-Roberts T C
Published: October 2018

World War 1 ended 100 years ago. The aftermath included the consolidation of significant advances in medical care of casualties. Some of these advances were made in the care of chemical casualties, in particular the mechanisms of toxicity and treatment of phosgene exposure. Phosgene, or carbonyl chloride, is an extremely poisonous vapour that was used to devastating effect during World War 1. Observations made of acutely poisoned casualties formed the basis of much research in the early post-World War 1 era. Some extremely elegant experiments, some at the nascent Porton Down research facility, further evaluated the toxin and defences against it. Researchers drew on knowledge that was later forgotten and has since been relearnt later in the 20th century and made many correct assumptions. Their work is the bedrock of our understanding of phosgene toxicity that survives to this day. The horrors of chemical warfare prompted the Geneva Protocol of 1925, prohibiting the use of chemical agents in warfare, and chemical warfare on this scale has not been repeated. The ease with which phosgene can be synthesised requires healthcare providers to be familiar with its effects.
Cataplexy
Authors: Reading Paul
Published: October 2018

Remarkably and almost invariably, the clinical phenomenon of cataplexy results from the loss of around 40 000 hypocretin-containing neurones in the lateral hypothalamus in the context of narcolepsy type 1. Cataplexy reflects the dysregulation of rapid-eye-movement (REM) sleep, such that REM-sleep atonia intrudes inappropriately into wakefulness as brief episodes of either focal or total paralysis of voluntary muscle. The semiology of cataplexy differs between adults and children. A defining and enigmatic aspect is that certain emotional stimuli usually trigger the episodes. Cataplexy can be the most disabling symptom of the narcolepsy syndrome, severely limiting normal activities of daily living. Antidepressant drug therapy at relatively low doses is the traditional treatment; these most likely work through inhibiting REM sleep, predominantly by increasing brain monoamine concentrations. Sodium oxybate is probably the most effective drug for severe cataplexy, taken before overnight sleep and once through the night; its precise mechanism of action remains obscure. Pitolisant is a new agent for treating the excessive daytime sleepiness of narcolepsy that also helps cataplexy control by increasing histamine concentrations in the hypothalamus. Further understanding of the neurobiology of cataplexy and how it relates to hypocretin deficiency should improve our understanding of the brain’s emotional processing and provide insights into REM sleep and its control.
Constant rate of strain consolidation testing of soft clays and fibrous peats
Authors: Mesri Gholamreza , Feng Tao-Wei
Published: October 2018

The constant rate of strain (CRS) oedometer test, using an imposed vertical strain rate [Formula: see text] equal to 10 times the end-of-primary (EOP) vertical strain rate [Formula: see text], requiring a test duration of about 2 days produces reliable information on both the e versus log[Formula: see text] relation and e versus logkvrelation of soft clays and fibrous peats. An empirical correction for the strain rate effect on preconsolidation pressure leads to the EOP e versus log[Formula: see text] relation and EOP [Formula: see text]. The imposed vertical strain rate [Formula: see text] produces excess pore-water pressures at the impervious bottom of the specimen, corresponding to [Formula: see text] values in the range of 3%–15% and allows, use of the Darcy flow equation, a reliable calculation of the coefficient of permeability. Compressibility and permeability data are from CRS and incremental loading (IL) oedometer tests on specimen quality designation (SQD) A samples of seven soft clays and two fibrous peats are presented in this paper.
Analytical resolution of the Poisson–Boltzmann equation for a cylindrical polyion immersed in an electrolyte solution: using the optimal linearization method
Authors: Djebbara Leila , Habchi Mohammed , Boussaid Abdalhak
Published: October 2018

By using the optimal linearization method (OLM), the potential of the electrical double layer created by a highly charged cylindrical polyion immersed in an electrolyte reservoir, which is represented by the so-called Poisson–Boltzmann equation (PBE), has been solved analytically under general potential conditions. For this system, three regions must be considered. The first one is in the near-neighborhood of the polyion and it is deprived of coions because of the repulsion phenomenon between the polyion and the coions, as proposed by Fuoss et al. (Proc. Natl. Acad. Sci. 37, 579 (1951). doi: 10.1073/pnas.37.9.579 ). For the second region, where the potential is slightly lower, we propose an OLM for solving the PBE. In the last region, where the potential is sufficiently low, the approximation of Debye–Hückel is adopted. This method allowed us to overcome some shortcomings in the analytical calculation of the electrostatic potential created by a polyion in an electrolyte solution.
Functional characterization of a reproductive tissue specific promoter fromEucalyptus camaldulensis
Authors: Unnikrishnan Boby Vattekkattu , Shankaranarayana Gurumurthy Demlapura
Published: October 2018

SWEET proteins are essential for the maintenance of nectar production, as well as seed and pollen development, in plants. A search within the Eucalyptus genome identified 52 putative genes belonging to the SWEET gene family based on sequence similarity. The expression of two of these genes, EcSWEET2 and EcSWEET5, was analyzed in vegetative and reproductive tissues of Eucalyptus camaldulensis. The expression of EcSWEET5 was specific to male reproductive tissues, and transcripts were detected only at certain stages of flower development. Tobacco Rattle Virus (TRV)-mediated suppression of EcSWEET5 resulted in a significant reduction in pollen germination percentage in Nicotiana benthamiana without adverse effect on vegetative growth. A promoter sequence 1 kb upstream of the start codon of EcSWEET5 contained many elements suggestive of pollen specificity of the promoter. This specificity was confirmed in transgenic tobacco lines harboring a GUS gene whose expression was controlled by the EcSWEET5 gene promoter. GUS expression was limited to pollen alone in transgenic tobacco as evidenced by histochemical staining. The expression of a cytotoxic gene, barnase under the control of the EcSWEET5 gene promoter, showed pollen ablation in transgenic tobacco with normal vegetative growth.
Constraining quantum collapse inflationary models with current data: The semiclassical approach
Authors: Piccirilli María Pía , León Gabriel , Landau Susana J. , Benetti Micol , Sudarsky Daniel
Published: October 2018

The hypothesis of the self-induced collapse of the inflaton wave function was introduced as a candidate for the physical process responsible for the emergence of inhomogeneity and anisotropy at all scales. In particular, we consider different proposal for the precise form of the dynamics of the inflaton wave function: (i) the GRW-type collapse schemes proposals based on spontaneous individual collapses which generate nonvanishing expectation values of various physical quantities taken as ansatz modifications of the standard inflationary scenario; (ii) the proposal based on a Continuous Spontaneous Localization (CSL) type modification of the Schrödinger evolution of the inflaton wave function, based on a natural choice of collapse operator. We perform a systematic analysis within the semi-classical gravity approximation, of the standing of those models considering a full quasi-de Sitter expansion scenario. We note that the predictions for the Cosmic Microwave Background (CMB) temperature and polarization spectrum differ slightly from those of the standard cosmological model. We also analyze these proposals with a Bayesian model comparison using recent CMB and Baryonic Acoustic Oscillations (BAO) data. Our results show a moderate preference of the joint CMB and BAO data for one of the studied collapse schemes model over the [Formula: see text]CDM one, while there is no preference when only CMB data are considered. Additionally, analysis using CMB data provide the same Bayesian evidence for both the CSL and Standard Models, i.e. the data have no preference between the simplicity of the LCDM model and the complexity of the collapse scenario.
Cosmological perfect-fluids in f(R) gravity
Authors: Capozziello Salvatore , Mantica Carlo Alberto , Molinari Luca Guido
Published: October 2018

We show that an [Formula: see text]-dimensional generalized Robertson–Walker (GRW) space-time with divergence-free conformal curvature tensor exhibits a perfect fluid stress–energy tensor for any [Formula: see text] gravity model. Furthermore, we prove that a conformally flat GRW space-time is still a perfect fluid in both [Formula: see text] and quadratic gravity where other curvature invariants are considered.
Global convergence properties of the BBB conjugate gradient method
Authors: Boumediene Amina , Benzine Rachid , Belloufi Mohammed
Published: October 2018

Nonlinear conjugate gradient (CG) methods are widely used for solving large scale unconstrained optimization problems. Many studies have been devoted to develop and improve these methods. In this paper, we aim to study the global convergence of the BBB conjugate gradient method with exact line search.
Synthesis of micro-mesoporous glass-analcime composite structure with soda–lime–silica glass as raw material
Authors: Lin Cunlong , Wang Deping , Ye Song
Published: October 2018

The micro-mesoporous composite phase structure of the analcime and the glass phase was successfully synthesized at 200∘C by using hydrothermal method, in which the soda–lime–silica glass was used as the silica source and the sodium hydroxide and aluminum oxide were used as additive. The TEM and SEM results showed that the obtained rod-shaped analcime was growing on the surface of glass particles. Thermogravimetric analysis indicated that they are stable and the adsorption isotherm shape indicated the coexistence of micropores and mesopores.
An Overview of the Stratospheric Observatory for Infrared Astronomy Since Full Operation Capability
Authors: Ennico Kimberly , Becklin Eric E. , Le Jeanette , Rangwala Naseem , Reach William T. , Rhodes Alan , Roellig Thomas L. , Sarver George , Temi Pasquale , Yorke Harold W. , Zavala Eddie
Published: October 2018

The Stratospheric Observatory for Infrared Astronomy (SOFIA), a joint project between NASA and the German Aerospace Center DLR, provides access to observations of the infrared and sub-millimeter universe. As its development timeline is unique compared to all other NASA astrophysics missions, a milestone called the Full Operation Capability (FOC) was defined to identify the start of science operations. SOFIA reached this in February 2014. With a wide range of imagers, spectrometers and a new polarimeter, SOFIA provides unique scientific results that cannot be obtained with a ground-based facility and any spacecraft expected in the next decade. The airborne platform has continued to mature its mission systems as part of a planned spiral development approach, particularly with upgradable instrumentation that opens up new science directions for the Observatory. A third generation instrument is planned for commissioning in 2019. This paper summarizes the current state of the Observatory with emphasis on the science and instrumentation updates since FOC.
EXES: The Echelon-cross-echelle Spectrograph for SOFIA
Authors: Richter M. J. , DeWitt C. N. , McKelvey M. , Montiel E. , McMurray R. , Case M. E.
Published: October 2018

The Echelon-cross-echelle spectrograph (EXES) is a high spectral resolution, mid-infrared spectrograph designed for and operated on the Stratospheric Observatory for Infrared Astronomy (SOFIA). EXES has multiple operational modes, but is optimized for high spectral resolution. The heart of the instrument is a one meter long, diamond-machined echelon grating. EXES also uses a 10242 Si:As detector optimized for low-background flux. We will discuss the design, operation and performance of EXES.
Diffusion analysis
Authors: Kim Mira , Hayakawa Masahiro
Published: October 2018

Graph is a widely used scheme for representing complex datasets in terms of graphical illustration comprised of nodes and edges. Diffusion is a paradigm of propagating or transmitting substances or knowledge pieces from nodes to nodes. Diffusion analysis takes a slightly different approach from the reachability-based graph analysis; it takes the phenomenon as diffusion problems. In this paper, we present a technical survey on literatures of diffusion analysis.
MadMax: surviving out-of-gas conditions in Ethereum smart contracts
Authors: Grech Neville , Kong Michael , Jurisevic Anton , Brent Lexi , Scholz Bernhard , Smaragdakis Yannis
Published: October 2018

Ethereum is a distributed blockchain platform, serving as an ecosystem for smart contracts: full-fledged inter-communicating programs that capture the transaction logic of an account. Unlike programs in mainstream languages, a gas limit restricts the execution of an Ethereum smart contract: execution proceeds as long as gas is available. Thus, gas is a valuable resource that can be manipulated by an attacker to provoke unwanted behavior in a victim's smart contract (e.g., wasting or blocking funds of said victim). Gas-focused vulnerabilities exploit undesired behavior when a contract (directly or through other interacting contracts) runs out of gas. Such vulnerabilities are among the hardest for programmers to protect against, as out-of-gas behavior may be uncommon in non-attack scenarios and reasoning about it is far from trivial.

In this paper, we classify and identify gas-focused vulnerabilities, and present MadMax: a static program analysis technique to automatically detect gas-focused vulnerabilities with very high confidence. Our approach combines a control-flow-analysis-based decompiler and declarative program-structure queries. The combined analysis captures high-level domain-specific concepts (such as "dynamic data structure storage" and "safely resumable loops") and achieves high precision and scalability. MadMax analyzes the entirety of smart contracts in the Ethereum blockchain in just 10 hours (with decompilation timeouts in 8% of the cases) and flags contracts with a (highly volatile) monetary value of over $2.8B as vulnerable. Manual inspection of a sample of flagged contracts shows that 81% of the sampled warnings do indeed lead to vulnerabilities, which we report on in our experiment.
ShareJIT: JIT code cache sharing across processes and its practical implementation
Authors: Xu Xiaoran , Cooper Keith , Brock Jacob , Zhang Yan , Ye Handong
Published: October 2018

Just-in-time (JIT) compilation coupled with code caching are widely used to improve performance in dynamic programming language implementations. These code caches, along with the associated profiling data for the hot code, however, consume significant amounts of memory. Furthermore, they incur extra JIT compilation time for their creation. On Android, the current standard JIT compiler and its code caches are not shared among processes—that is, the runtime system maintains a private code cache, and its associated data, for each runtime process. However, applications running on the same platform tend to share multiple libraries in common. Sharing cached code across multiple applications and multiple processes can lead to a reduction in memory use. It can directly reduce compile time. It can also reduce the cumulative amount of time spent interpreting code. All three of these effects can improve actual runtime performance.

In this paper, we describe ShareJIT, a global code cache for JITs that can share code across multiple applications and multiple processes. We implemented ShareJIT in the context of the Android Runtime (ART), a widely used, state-of-the-art system. To increase sharing, our implementation constrains the amount of context that the JIT compiler can use to optimize the code. This exposes a fundamental tradeoff: increased specialization to a single process’ context decreases the extent to which the compiled code can be shared. In ShareJIT, we limit some optimization to increase shareability. To evaluate the ShareJIT, we tested 8 popular Android apps in a total of 30 experiments. ShareJIT improved overall performance by 9% on average, while decreasing memory consumption by 16% on average and JIT compilation time by 37% on average.