bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Support Platform: a qualitative research study investigating the feasibility of an internet-based, postdiagnostic support platform for families living with dementia
Authors: Killin Lewis O J , Russ Tom C , Surdhar Sushee Kaur , Yoon Youngseo , McKinstry Brian , Gibson Grant , MacIntyre Donald J
Published: April 2018

Objectives

To establish the feasibility of the Digital Support Platform (DSP), an internet-based, postdiagnostic tool designed for families living with a diagnosis of dementia.

Design

Qualitative methods using normalisation process theory as an analysis framework for semistructured interview transcriptions.

Setting

A community care setting in the South-East Scotland.

Participants

We interviewed 10 dyads of people with Alzheimer’s, vascular or mixed dementia (PWD), and their family carers, who had been given and had used the DSP for at least 2 months.

Results

Our analysis revealed that the DSP was predominantly understood and used by the carers rather than PWD, and was used alongside tools and methods they already used to care for their relative. The DSP was interpreted as a tool that may be of benefit to those experiencing later stages of dementia or with physical care needs. Carers stated that the DSP may be of benefit in the future, reflecting a disinclination to prepare for or anticipate for future needs, rather than focus on those needs present at the time of distribution. PWD spoke positively about an interest in learning to use technology more effectively and enjoyed having their own tablet devices.

Conclusions

The DSP was not wholly appropriate for families living with dementia in its early stages. The views of carers confirmed that postdiagnostic support was valued, but emphasised the importance of tailoring this support to the exact needs and current arrangements of families. There may be a benefit to introducing, encouraging, providing and teaching internet-enabled technology to those PWD who do not currently have access. Training should be provided when introducing new technology to PWD.
What is the cost of palliative care in the UK? A systematic review
Authors: Gardiner Clare , Ryan Tony , Gott Merryn
Published: April 2018

Objectives

Little is known about the cost of a palliative care approach in the UK, and there is an absence of robust activity and unit cost data. The aim of this study was to review evidence on the costs of specialist and generalist palliative care in the UK, and to explore different approaches used for capturing activity and unit cost data.

Methods

A systematic review with narrative synthesis. Four electronic databases were searched for empirical literature on the costs of a palliative care approach in the UK, and a narrative method was used to synthesise the data.

Results

Ten papers met our inclusion criteria. The studies displayed significant variation in their estimates of the cost of palliative care, therefore it was not possible to present an accurate aggregate cost of palliative care in the UK. The majority of studies explored costs from a National Health Service perspective and only two studies included informal care costs. Approaches to estimating activity and costs varied. Particular challenges were noted with capturing activity and cost data for hospice and informal care.

Conclusion

The data are limited, and the heterogeneity is such that it is not possible to provide an aggregate cost of palliative care in the UK. It is notable that the costs of hospice care and informal care are often neglected in economic studies. Further work is needed to address methodological and practical challenges in order to gain a more complete understanding of the costs of palliative care.
Unusual case of suspected recurrent scarlet fever in a UK serviceman
Authors: Phillips Rachel , Martin-Bates A J , Withnall R
Published: April 2018

The UK prevalence of scarlet fever, a Group A streptococcal infection, is increasing. We present an unusual case of suspected recurrent scarlet fever in a member of the UK Armed Forces. Treatments, occupational implication and public health measures to mitigate the risk of disease spread.
DuraGraft vascular conduit preservation solution in patients undergoing coronary artery bypass grafting: rationale and design of a within-patient randomised multicentre trial
Authors: Ben Ali Walid , Voisine Pierre , Olsen Peter Skov , Jeanmart Hugues , Noiseux Nicolas , Goeken Tracy , Satishchandran Vilas , Cademartiri Filippo , Cutter Garry , Veerasingam Dave , Brown Craig , Emmert Maximilian Y , Perrault Louis P
Published: April 2018

Introduction

Saphenous vein grafts (SVGs) remain the most often used conduits in coronary artery bypass grafting (CABG). However, they are prone to vein graft disease (VGD) during follow-up, which may compromise clinical outcomes. Injury to the SVG endothelium during harvesting and storage promotes neointimal hyperplasia that can advance to atherosclerosis characterised by SVG failure. This trial investigates the potential benefit of DuraGraft, a novel, one-time intraoperative graft treatment developed to efficiently protect the structural and functional integrity of the vascular endothelium, on the development and progression of VGD in CABG patients.

Methods and analysis

This ongoing prospective randomised, double-blinded multicentre trial (NCT02272582/NCT02774824) includes patients undergoing isolated CABG requiring at least two SVGs. It compares the impact of DuraGraft, a novel treatment against VGD versus thestandard-of-care(SOC; heparinised saline) using a within-patient randomisation (with one SVG treated with DuraGraft and the other treated with SOC). Besides clinical assessments, patients undergo longitudinal 64-slice or better multidetector CT (MDCT) angiography of paired grafts (within each patient) at 4–6 weeks, 3 months and 12 months. Primary endpoints will be the magnitude of change in mean wall thickness and lumen diameter (stenosis) of paired grafts, at 3 and 12 months, respectively. Besides the evaluation of overall safety, longitudinal assessment of each graft (secondary endpoint) is performed in order to obtain insight into graft behaviour after CABG. Enrolment of 119 patients was successfully completed, and analysis of MDCT angiography follow-up is ongoing with the completed analysis becoming available by end of first quarter of 2018.

Ethics and dissemination

The regional ethics committees have approved the trial. Results will be submitted for publication.

Clinical trial identifier

NCT02272582 andNCT02774824.
Opportunities and challenges for real-world studies on chronic inflammatory joint diseases through data enrichment and collaboration between national registers: the Nordic example
Authors: Chatzidionysiou Katerina , Hetland Merete Lund , Frisell Thomas , Di Giuseppe Daniela , Hellgren Karin , Glintborg Bente , Nordström Dan , Aaltonen Kalle , Törmänen Minna RK , Klami Kristianslund Eirik , Kvien Tore K , Provan Sella A , Guðbjörnsson Bjorn , Dreyer Lene , Kristensen Lars Erik , Jørgensen Tanja Schjødt , Jacobsson Lennart , Askling Johan
Published: April 2018

There are increasing needs for detailed real-world data on rheumatic diseases and their treatments. Clinical register data are essential sources of information that can be enriched through linkage to additional data sources such as national health data registers. Detailed analyses call for international collaborative observational research to increase the number of patients and the statistical power. Such linkages and collaborations come with legal, logistic and methodological challenges. In collaboration between registers of inflammatory arthritides in Sweden, Denmark, Norway, Finland and Iceland, we plan to enrich, harmonise and standardise individual data repositories to investigate analytical approaches to multisource data, to assess the viability of different logistical approaches to data protection and sharing and to perform collaborative studies on treatment effectiveness, safety and health-economic outcomes. This narrative review summarises the needs and potentials and the challenges that remain to be overcome in order to enable large-scale international collaborative research based on clinical and other types of data.
100 years of STIs in the UK: a review of national surveillance data
Authors: Mohammed Hamish , Blomquist Paula , Ogaz Dana , Duffell Stephen , Furegato Martina , Checchi Marta , Irvine Neil , Wallace Lesley A , Thomas Daniel Rhys , Nardone Anthony , Dunbar J Kevin , Hughes Gwenda
Published: April 2018

Objectives

The 1916 Royal Commission on Venereal Diseases was established in response to epidemics of syphilis and gonorrhoea in the UK. In the 100 years since the Venereal Diseases Act (1917), the UK has experienced substantial scientific, economic and demographic changes. We describe historical and recent trends in STIs in the UK.

Methods

We analysed surveillance data derived from STI clinics’ statistical returns from 1917 to 2016.

Results

Since 1918, gonorrhoea and syphilis diagnoses have fluctuated, reflecting social, economic and technological trends. Following spikes after World Wars I and II, rates declined before re-emerging during the 1960s. At that time, syphilis was more common in men, suggestive of transmission within the men who have sex with men (MSM) population. Behaviour change following the emergence of HIV/AIDS in the 1980s is thought to have facilitated a precipitous decline in diagnoses of both STIs in the mid-1980s. Since the early 2000s, gonorrhoea and syphilis have re-emerged as major public health concerns due to increased transmission among MSM and the spread of antimicrobial-resistant gonorrhoea. Chlamydia and genital warts are now the most commonly diagnosed STIs in the UK and have been the focus of public health interventions, including the national human papillomavirus vaccination programme, which has led to substantial declines in genital warts in young people, and the National Chlamydia Screening Programme in England. Since the 1980s, MSM, black ethnic minorities and young people have experienced the highest STI rates.

Conclusion

Although diagnoses have fluctuated over the last century, STIs continue to be an important public health concern, often affecting more marginalised groups in society. Prevention must remain a public health priority and, as we enter a new era of sexual healthcare provision including online services, priority must be placed on maintaining prompt access for those at greatest risk of STIs.
Plastic fingerprint replica: solvent-assisted 3D molding and motion-promoted nano-spherulite formation
Authors: Schultz Clayton W. , Wong Jessica X.H. , Yu Hua-Zhong
Published: April 2018

Fingerprinting is an essential form of identification for both biometric security and forensics today. Herein, we describe the procedure and principle of creating highly resolved, chemically robust, 3D fingerprint physical replicas, which is based on the solvent-assisted molding of transparent plastics and motion-promoted growth of semi-crystalline polymeric nanostructures. Prior to fingerprinting atop, polycarbonate, a commercial polymer with excellent durability and optical transparency, is first swelled and softened with a mild solvent (acetone). The molding motion conforms polymer chains between fingerprint ridges, which facilitates the formation of semi-crystalline spherulites and results in greater opacity between ridges than underneath ridges. Besides being more enduring than digital scanning and ink printed counterparts, the plastic fingerprint replicas can provide additional morphological information (depth of the ridge) and high-level details (distribution of sweat pores).
Extensionality with Respect to Indistinguishability Operators
Authors: Boixader D. , Recasens J.
Published: April 2018

Extensionality is explored form different points of view. Extensional fuzzy subsets from a fuzzy equivalence relation E are considered as observable subsets with respect to the granularity generated by E. Interestingly, they are characterized as the fuzzy subsets that can be obtained as combinations of the fuzzy equivalence classes of E. Extensional mappings are characterized topologically and the set of extensional mappings between two universes are algebraically determined. Specifying the results to fuzzy mappings from a universe X onto [0, 1] an interpretation of type-2 fuzzy subsets of X as fuzzification of its type-1 fuzzy subsets is provided.
An Alternative Approach to Obtaining an Analytical Solution to Dujmovic’s Iterative OWA
Authors: Ahn Byeong Seok
Published: April 2018

Troiano and Díaz presented the analytic solution to the iterative ordered weights averaging (ItOWA) operator weights. Their findings validate Dujmović and Larsen’s conjecture and profoundly contribute to the ItOWA operator due to the closed formula derived. This paper attempts to present another way of deriving the ItOWA operator weights based on other theories. Further, as iterative OWA performs repeated computations for a higher dimension, the orness of the resulting ItOWA operator weights is different from the one initially used in aggregating two input arguments. To resolve this unwanted situation, we suggest some weighting functions that generate the OWA operator weights having a property of constant orness irrespective of the number of input arguments.
Spin Transport in Electric-Barrier-Modulated Ferromagnetic/Normal/Ferromagnetic Monolayer Zigzag MoS2 Nanoribbon Junction
Authors: Xia Y.-Y. , Yuan R.-Y. , Yang Q.-J. , Sun Q. , Zheng J. , Guo Y.
Published: April 2018

In this paper, with the three-band tight-binding model and non-equilibrium Green’s function technique, we investigate spin transport in electric-barrier-modulated Ferromagnetic/Normal/Ferromagnetic (F/N/F) monolayer (ML) zigzag MoS2 nanoribbon junction. The results demonstrate that once the double electric barriers structure emerges, the oscillations of spin conductances become violent, especially for spin-down conductance, the numbers of resonant peaks increase obviously, thus we can obtain [Formula: see text] spin polarization in the low energy region. It is also found that with the intensity of the exchange field enhancement, the resonant peaks of spin-up and spin-down conductances move in the opposite direction in a certain energy region. As a consequence, the spin-down conductance can be filtered out completely. The findings here indicate that the present structure may be considered as a good candidate for spin filter.
The CENDARI Infrastructure
Authors: Boukhelifa Nadia , Bryant Mike , Bulatović Nataša , Čukić Ivan , Fekete Jean-Daniel , Knežević Milica , Lehmann Jörg , Stuart David , Thiel Carsten
Published: April 2018

The CENDARI infrastructure is a research-supporting platform designed to provide tools for transnational historical research, focusing on two topics: medieval culture and World War I. It exposes to the end users modern Web-based tools relying on a sophisticated infrastructure to collect, enrich, annotate, and search through large document corpora. Supporting researchers in their daily work is a novel concern for infrastructures. We describe how we gathered requirements through multiple methods to understand historians’ needs and derive an abstract workflow to support them. We then outline the tools that we have built, tying their technical descriptions to the user requirements. The main tools are the note-taking environment and its faceted search capabilities; the data integration platform including the Data API, supporting semantic enrichment through entity recognition; and the environment supporting the software development processes throughout the project to keep both technical partners and researchers in the loop. The outcomes are technical together with new resources developed and gathered, and the research workflow that has been described and documented.
Workload Characterization for Enterprise Disk Drives
Authors: Kashyap Anil
Published: April 2018

The article presents an analysis of drive workloads from enterprise storage systems. The drive workloads are obtained from field return units from a cross-section of enterprise storage system vendors and thus provides a view of the workload characteristics over a wide spectrum of end-user applications. The workload parameters that have been characterized include transfer lengths, access patterns, throughput, and utilization. The study shows that reads are the dominant workload accounting for 80% of the accesses to the drive. Writes are dominated by short block random accesses while reads range from random to highly sequential. A trend analysis over the period 2010–2014 shows that the workload has remained fairly constant even as the capacities of the drives shipped has steadily increased. The study shows that the data stored on disk drives is relatively cold—on average less than 4% of the drive capacity is accessed in a given 2h interval.
Sympathoexcitation constrains vasodilation in the human skeletal muscle microvasculature during postocclusive reactive hyperemia
Authors: Ichinose Masashi , Nakabayashi Mikie , Ono Yumie
Published: April 2018

We used diffuse correlation spectroscopy to investigate sympathetic vasoconstriction, local vasodilation, and integration of these two responses in the skeletal muscle microvasculature of 20 healthy volunteers. Diffuse correlation spectroscopy probes were placed on the flexor carpi radialis muscle or vastus lateralis muscle, and a blood flow index was derived continuously. We measured hemodynamic responses during sympathoexcitation induced by forehead cooling, after which the effects of the increased sympathetic tone on vasodilatory responses during postocclusive reactive hyperemia (PORH) were examined. PORH was induced by releasing arterial occlusion (3 min) in an arm or leg. To increase sympathetic tone during PORH, forehead cooling was begun 60 s before the occlusion release and ended 60 s after the release. During forehead cooling, mean arterial pressure rose significantly and was sustained at an elevated level. Significant vasoconstriction and decreases in blood flow index followed by gradual blunting of the vasoconstriction also occurred. The time course of these responses is in good agreement with previous observations in animals. The acute sympathoexcitation diminished the peak vasodilation during PORH only in the vastus lateralis muscle, but it hastened the decline in vasodilation after the peak in both the flexor carpi radialis muscle and vastus lateralis muscle. Consequently, the total vasodilatory response assessed as the area of the vascular conductance during the first minute of PORH was significantly diminished in both regions. We conclude that, in humans, the integrated effects of sympathetic vasoconstriction and local vasodilation have an important role in vascular regulation and control of perfusion in the skeletal muscle microcirculation.

NEW & NOTEWORTHY We used diffuse correlation spectroscopy to demonstrate that acute sympathoexcitation constrains local vasodilation in the human skeletal muscle microvasculature during postocclusive reactive hyperemia. This finding indicates that integration of sympathetic vasoconstriction and local vasodilation is importantly involved in vascular regulation and the control of perfusion of the skeletal muscle microcirculation in humans.
RAS–MAPK Reactivation Facilitates Acquired Resistance inFGFR1-Amplified Lung Cancer and Underlies a Rationale for Upfront FGFR–MEK Blockade
Authors: Bockorny Bruno , Rusan Maria , Chen Wankun , Liao Rachel G. , Li Yvonne , Piccioni Federica , Wang Jun , Tan Li , Thorner Aaron R. , Li Tianxia , Zhang Yanxi , Miao Changhong , Ovesen Therese , Shapiro Geoffrey I. , Kwiatkowski David J. , Gray Nathanael S. , Meyerson Matthew , Hammerman Peter S. , Bass Adam J.
Published: April 2018

The FGFR kinases are promising therapeutic targets in multiple cancer types, including lung and head and neck squamous cell carcinoma, cholangiocarcinoma, and bladder cancer. Although several FGFR kinase inhibitors have entered clinical trials, single-agent clinical efficacy has been modest and resistance invariably occurs. We therefore conducted a genome-wide functional screen to characterize mechanisms of resistance to FGFR inhibition in a FGFR1-dependent lung cancer cellular model. Our screen identified known resistance drivers, such as MET, and additional novel resistance mediators including members of the neurotrophin receptor pathway (NTRK), the TAM family of tyrosine kinases (TYRO3, MERTK, AXL), and MAPK pathway, which were further validated in additional FGFR-dependent models. In an orthogonal approach, we generated a large panel of resistant clones by chronic exposure to FGFR inhibitors in FGFR1- and FGFR3-dependent cellular models and characterized gene expression profiles employing the L1000 platform. Notably, resistant clones had enrichment for NTRK and MAPK signaling pathways. Novel mediators of resistance to FGFR inhibition were found to compensate for FGFR loss in part through reactivation of MAPK pathway. Intriguingly, coinhibition of FGFR and specific receptor tyrosine kinases identified in our screen was not sufficient to suppress ERK activity or to prevent resistance to FGFR inhibition, suggesting a redundant reactivation of RAS–MAPK pathway. Dual blockade of FGFR and MEK, however, proved to be a more powerful approach in preventing resistance across diverse FGFR dependencies and may represent a therapeutic opportunity to achieve durable responses to FGFR inhibition in FGFR-dependent cancers. Mol Cancer Ther; 17(7); 1526–39. ©2018 AACR.
Efficient Gene Silencing in Brain Tumors with Hydrophobically Modified siRNAs
Authors: Osborn Maire F. , Coles Andrew H. , Golebiowski Diane , Echeverria Dimas , Moazami Michael P. , Watts Jonathan K. , Sena-Esteves Miguel , Khvorova Anastasia
Published: April 2018

Glioblastoma (GBM) is the most common and lethal form of primary brain tumor with dismal median and 2-year survivals of 14.5 months and 18%, respectively. The paucity of new therapeutic agents stems from the complex biology of a highly adaptable tumor that uses multiple survival and proliferation mechanisms to circumvent current treatment approaches. Here, we investigated the potency of a new generation of siRNAs to silence gene expression in orthotopic brain tumors generated by transplantation of human glioma stem-like cells in athymic nude mice. We demonstrate that cholesterol-conjugated, nuclease-resistant siRNAs (Chol-hsiRNAs) decrease mRNA and silence luciferase expression by 90% in vitro in GBM neurospheres. Furthermore, Chol-hsiRNAs distribute broadly in brain tumors after a single intratumoral injection, achieving sustained and potent (>45% mRNA and >90% protein) tumor-specific gene silencing. This readily available platform is sequence-independent and can be adapted to target one or more candidate GBM driver genes, providing a straightforward means of modulating GBM biology in vivo. Mol Cancer Ther; 17(6); 1251–8. ©2018 AACR.
Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place
Authors: Kotsantis Panagiotis , Petermann Eva , Boulton Simon J.
Published: April 2018

Oncogene activation disturbs cellular processes and accommodates a complex landscape of changes in the genome that contribute to genomic instability, which accelerates mutation rates and promotes tumorigenesis. Part of this cellular turmoil involves deregulation of physiologic DNA replication, widely described as replication stress. Oncogene-induced replication stress is an early driver of genomic instability and is attributed to a plethora of factors, most notably aberrant origin firing, replication–transcription collisions, reactive oxygen species, and defective nucleotide metabolism.

Significance: Replication stress is a fundamental step and an early driver of tumorigenesis and has been associated with many activated oncogenes. Deciphering the mechanisms that contribute to the replication stress response may provide new avenues for targeted cancer treatment. In this review, we discuss the latest findings on the DNA replication stress response and examine the various mechanisms through which activated oncogenes induce replication stress. Cancer Discov; 8(5); 537–55. ©2018 AACR.
Psychosocial, Cognitive, and Physical Impact of Elaborate Consultations and Life Review in Female Patients with Non-Metastasized Breast Cancer
Authors: Thronicke Anja , Kröz Matthias , Merkle Antje , Matthes Harald , Herbstreit Cornelia , Schad Friedemann
Published: April 2018

Background: Elaborate consultations and life review (ECLR) has been regularly applied in patients of various cancer entities and stages within Anthroposophic-integrative oncology concepts. However, a lack of systematic research in this field has been detected. To close this gap of knowledge, we evaluated the impact of ECLR in patients with non-metastasized breast cancer before, during, and after primary oncological treatment. Methods: Patient-reported outcome measures were evaluated by analyzing European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30) in patients with non-metastasized breast cancer who had received either oncological standard therapy alone or in combination with ECLR. Results: 95 female patients were eligible for questionnaire analysis (median age 58 years). Adjusted multivariable linear regression analysis revealed that ECLR was associated with significant improvements in medium-term global health/quality of life and emotional, social, and cognitive functioning. Furthermore, ECLR was associated with significant reductions of short-term appetite loss burden, pain, and short- and medium-term financial difficulties. Subgroup analyses revealed significant improvements in pivotal quality-of-life aspects including fatigue (p = 0.002) in chemotherapy-treated patients after ECLR. Conclusions: 12 months of surveillance of breast cancer patients reveals medium-term recovery of the global health status/quality of life and cognitive and psychosocial well-being associated with ECLR. In addition, our data indicate a possible association between ECLR and reduced short-term fatigue burden, which has to be re-confirmed prospectively in a larger study cohort. As long-term cancer survivors develop psychological symptoms similar to patients with chronic diseases, prospective studies should evaluate the impact of ECLR on the psychosocial well-being in these patients.
Impact of Pathological Fractures on the Prognosis of Primary Malignant Bone Sarcoma in Children and Adults: A Single-Center Retrospective Study of 205 Patients
Authors: Schlegel Miriam , Zeumer Martina  , Prodinger Peter Michael , Woertler Klaus , Steinborn Marc , von Eisenhart-Rothe Rüdiger , Burdach Stefan , Rechl Hans , von Luettichau Irene
Published: April 2018

Background: The purpose of this study was to investigate whether pathological fractures (PF) influence the prognosis of patients with osteosarcoma (OS) or Ewing tumor (ET) regarding 5-year survival, occurrence of metastases, and local recurrence. Methods: We retrospectively analyzed 205 patients with metastatic and nonmetastatic OS or ET. Survival analysis was performed for all patients and differentiated for patients with OS (n = 127) and ET (n = 78) as well as for adults (n = 101) and children (n = 104). Results: Patients with PF showed survival rates of 64% compared to 83% for those without PF (p = 0.023). Local recurrence occurred in 7% of the patients without and in 24% of those with PF (p = 0.023). In patients with ET and in children, survival analysis showed no significant difference between patients with and without PF in survival and local recurrence rates. In patients with OS, survival rate decreased from 83 to 59% (p = 0.024) and local recurrence rate increased from 13 to 30% (p = 0.042). In adults, survival rate decreased from 78 to 51% (p = 0.004) and local recurrence rate increased from 13 to 42% (p < 0.001). In multivariate analysis, age and PF were associated with inferior survival. Conclusion: This study suggests that the occurrence of PF has a negative impact on survival and implicates an increased risk of local recurrence. In children and in patients with ET, PF did not have a prognostic impact.
Activin-A Is a Pro-Inflammatory Regulator in Type-2-Driven Upper Airway Disease
Authors: Chaker Adam M. , Zissler Ulrich Matthias , Poulos Nikolaos , Wagenmann Martin , Bas Murat , Gürth Ferdinand , Xanthou Georgina , Schmidt-Weber Carsten
Published: April 2018

Background: Allergic upper airway disease involves pro-inflammatory type-2 cytokines such as IL-5 and regulatory tissue repair mediators, in particular transforming growth factor (TGF)-β1. The TGF-β-superfamily member activin-A displays multiple biological functions and shares certain signalling pathways with TGF-β1. We aimed to examine the coregulation of mucosal activin-A and TGF-β1 in acute allergic and chronic Th2-driven upper airway disease. Methods: We investigated mucosal cytokine expression profiles and kinetics using RT-PCR after nasal allergen challenges in patients with seasonal allergic rhinitis. Furthermore, we analysed mucosal specimens from patients with chronic upper airway disease with nasal polyps using ELISPOTs and confocal microscopy. In addition, we stimulated nasal mucosa ex vivo from patients with nasal polyps as well as primary nasal cell cultures from healthy donors. Results: Mucosal activin-A expression revealed increasing correlation with IL-5 and TGF-β1 at 0.25, 6, and 24 h, respectively, and was significantly upregulated at 6 h after allergen challenge. The correlated expression was found to be more pronounced in chronic disease with nasal polyps, showing substantially (48-fold) increased activin-A-producing cells in nasal polyps by ELISPOT, while submucosal downstream signalling as determined by confocal microscopy was decreased. Ex vivo stimulations of nasal tissue suggested that activin-A and TGF-β1 mutually regulate each other’s expression at the mRNA level and, when combined, enhance IL-5 expression. Conclusion: Activin-A in allergic upper airway disease acts as a pro-inflammatory mediator and TGF-β1 modifier. Our data in the upper airways oppose the view of potentially anti-inflammatory properties in contrast to lymphatic compartments.
Gray Matter Heterotopia, Mental Retardation, Developmental Delay, Microcephaly, and Facial Dysmorphisms in a Boy with Ring Chromosome 6: A 10-Year Follow-Up and Literature Review
Authors: Liu Shu , Wang Zhiqing , Wei Sisi , Liang Jinqun , Chen Nuan , OuYang Haimei , Zeng Weihong , Chen Liying , Xie Xunjie , Jiang Jianhui
Published: April 2018

Ring chromosome 6, r(6), is an extremely rare cytogenetic abnormality with clinical heterogeneity which arises typically de novo. The phenotypes of r(6) can be highly variable, ranging from almost normal to severe malformations and neurological defects. Up to now, only 33 cases have been reported in the literature. In this 10-year follow-up study, we report a case presenting distinctive facial features, severe developmental delay, and gray matter heterotopia with r(6) and terminal deletions of 6p25.3 (115426-384174, 268 kb) and 6q26-27 (168697778-170732033, 2.03 Mb) encompassing 2 and 15 candidate genes, respectively, which were detected using G-banding karyotyping, FISH, and chromosomal microarray analysis. We also analyzed the available information on the clinical features of the reported r(6) cases in order to provide more valuable information on genotype-phenotype correlations. To the best of our knowledge, this is the first report of gray matter heterotopia manifested in a patient with r(6) in China, and the deletions of 6p and 6q in our case are the smallest with the precise size of euchromatic material loss currently known.
Conchas aos montes: situando os montes artificiais de conchas nos estudos da pré-história brasileira e japonesa
Authors: Reis Silvia , Rodrigues-Carvalho Claudia
Published: April 2018

Sítios arqueológicos marcados pela aparente presença de conchas, nomeados assim por sua característica mais visível, podem ser encontrados em diferentes regiões do mundo. No Brasil, conhecidos principalmente como sambaqui, e no Japão como kaizuka, os estudos de tais montes de conchas estão inseridos em questões locais, regionais e mundiais. Assim, buscamos situar os estudos de montes de conchas em relação aos questionamentos dos quais são objeto e, em uma perspectiva comparada, em que medida estão inseridos em linhas investigativas passíveis de diálogo.
Arqueologia rural galo-romana e ideologia moderna
Authors: Silva Uiran Gebara da
Published: April 2018

O objetivo deste trabalho é avaliar recentes representações historiográficas das regiões rurais da Gália tardo-romana. Com o aumento e a expansão do escopo da arqueologia rural nesse período, em substituição a uma visão de um Império em decadência, passou-se progressivamente a visões que propõem crescimento econômico e comercial nas regiões rurais do Império. Observando o caso específico do norte da Gália tardo-romana, a avaliação dessas representações busca refletir a respeito dos métodos de investigação nos quais se baseiam a arqueologia rural, principalmente o papel da survey archaeology na produção de sítios sub-villa e das interpretações dos achados nesses sítios em termos da criação de mercados locais. Uma vez que essa perspectiva de crescimento econômico se dá no contexto também da reelaboração da perspectiva modernista no estudo da Economia Antiga por meio da aplicação da New Institutional Economics como enquadramento teórico, critica-se os parâmetros modernizantes de interpretação do quadro representado pela documentação material e problematiza-se o uso da ideia de desenvolvimento econômico inspirado em referências de desenvolvimento capitalista. Em contrapartida, busca-se propor formas de lidar com esse quadro documental de forma a elaborar modelos de processos sociais e econômicos mais complexos e dinâmicos do que a historiografia do século XX reconhecia para as regiões rurais da Gália tardo-romana.
O Partenon ateniense: recepção e exposição
Authors: Thomas Katerina
Published: April 2018

Nesse artigo, o Partenon é considerado a partir do contexto de múltiplos significados a ele atribuidos pelo Ocidente. Alterações e danos sofridos ao longo do tempo sáo igualmente incluidos na análise. Eventos fatidicos dentro da turbulenta história da Grécia afetaram tanto o estado de conservação do Partenon como também acrescentaram a um debate que focou esse monumento como a mais importante construção clássica. Foco esse que levou à construção de um fantástico museu em Atenas.
Clinical Events After Discontinuation of β‐Blockers in Patients Without Heart Failure Optimally Treated After Acute Myocardial Infarction
Authors: Neumann Anke , Maura Géric , Weill Alain , Alla François , Danchin Nicolas
Published: April 2018

Background:

β-blockers have been among the first medications shown to improve outcomes after acute myocardial infarction (AMI). With the advent of reperfusion therapy and other secondary-prevention medications, their role has become uncertain, and large-scale experience after AMI in the contemporary era is lacking. In particular, the effect of stopping β-blockers in patients initially treated after AMI is unknown.

Methods and Results:

Using the French healthcare databases, 73 450 patients (<80 years of age), admitted for AMI in 2007 to 2012, without acute coronary syndrome (ACS) in the previous 2 years and no evidence of heart failure, having received optimal treatment with myocardial revascularization and all recommended medications in the 4 months after index admission, and not having discontinued β-blockers before 1 year, were followed for 3.8 years on average. β-Blocker discontinuation was defined as 4 consecutive months without exposure. If β-blocker treatment was resumed later on, follow-up was stopped. Both the risk of the composite outcome of death or admission for ACS and the risk of all-cause mortality were assessed in relation with β-blocker discontinuation during follow-up. Adjusted hazard ratios were estimated using marginal structural models accounting for time-varying confounders affected by previous exposure. A similar analysis was performed with statins. Of 204 592 patient-years, 12 002 (5.9%) corresponded to discontinued β-blocker treatment. For β-blocker discontinuation, the adjusted hazard ratio for death or ACS was 1.17 (95% confidence interval, 1.01–1.35); for all-cause death, the adjusted hazard ratio was 1.13 (95% confidence interval, 0.94–1.36). In contrast, for statin discontinuation, the adjusted hazard ratios for death or ACS and for all-cause death were 2.31 (95% confidence interval, 2.01–2.65) and 2.57 (95% confidence interval, 2.19–3.02), respectively.

Conclusions:

In routine care of patients without heart failure, revascularized and optimally treated after AMI, discontinuation of β-blockers beyond 1 year after AMI was associated with an increased risk of death or readmission for ACS, while statistical significance was not reached for the association with all-cause mortality. A contemporary randomized clinical trial is needed to precise the role of β-blockers in the long-term treatment after AMI.
Frequency of Care and Mortality Following an Incident Diagnosis of Peripheral Artery Disease in the Inpatient or Outpatient Setting: The ARIC (Atherosclerosis Risk in Communities) Study
Authors: Kalbaugh Corey A. , Loehr Laura , Wruck Lisa , Lund Jennifer L. , Matsushita Kunihiro , Bengtson Lindsay G. S. , Heiss Gerardo , Kucharska‐Newton Anna
Published: April 2018

Background

Available health services data for individuals with peripheral artery disease (
PAD
) are often from studies of those eligible for or undergoing intervention. Knowledge of the frequency of care and mortality following an initial
PAD
diagnosis by setting (outpatient versus inpatient) is limited and represents an opportunity to provide new benchmark information.

Methods and Results

The purpose of this study was to characterize the frequency of care and mortality following an incident
PAD
diagnosis in the outpatient or inpatient setting using data from the ARIC (Atherosclerosis Risk in Communities) study cohort linked with Centers for Medicare and Medicaid Services fee‐for‐service claims data (2002–2012). Direct standardization was used to estimate age‐standardized rates of encounters and mortality.
PAD
was defined by billing code in any claim position. We observed 1086 incident
PAD
cases (873 outpatient, 213 inpatient). At 1 year after diagnosis, participants diagnosed in the outpatient setting had 2.15 (95% confidence interval [CI], 2.10–2.21)
PAD
‐related outpatient encounters per person‐year, and 6.4% (95%
CI
, 4.8–8.1) had a
PAD
‐related hospitalization. Conversely, participants diagnosed in the inpatient setting had 1.02 (95%
CI
, 0.94–1.10)
PAD
‐related outpatient encounters per person‐year, and 14.2% (95%
CI
, 9.3–18.7) had a
PAD
‐related rehospitalization. One‐year mortality was 7.1% (95%
CI
, 5.4–8.7) and 16.0% (95%
CI
, 11.0–21.1) among those diagnosed in outpatient and inpatient settings, respectively.

Conclusions

This study provides important data estimating frequency of care and mortality by the setting of initial
PAD
diagnosis. Individuals with
PAD
are frequent users of health care, and those diagnosed in the inpatient setting have high rates of rehospitalization and mortality.
Social Network Trajectories in Myocardial Infarction Versus Ischemic Stroke
Authors: Dhand Amar , Longstreth W. T. , Chaves Paulo H. M. , Dhamoon Mandip S.
Published: April 2018

Background

Changes in social networks are rarely examined before and after various diseases because of insufficient data. CHS (The Cardiovascular Health Study) offers an opportunity to compare social network trajectories surrounding well‐adjudicated myocardial infarction (
MI
) or stroke events. We tested the hypothesis that social networks will be stable after
MI
and decrease after stroke.

Methods and Results

We examined trajectories of the Lubben Social Network Scale score (
LSNS
, range 0–50) before and after vascular events over 11 years. The
LSNS
assesses engagement in family networks, friends’ networks, and social supports. We used a linear mixed model with repeated measures and fixed effects to compare the change in social network score before and after events in 395 people with
MI
and 382 with ischemic stroke. Over a mean of 12.4 years of follow‐up for
MI
and 11.1 years for stroke, we examined an average of 4 social network scores for each participant. We controlled for sociodemographics, baseline cognitive function, and comorbidities. The participants’ mean age was 73.5, 51% were women, and 88% were non‐Hispanic white. After
MI
, the social network trajectory remained stable compared with the baseline trajectory (−0.06 points per year, adjusted
P
=0.2356). After stroke, the social network trajectory declined compared with the baseline trajectory (−0.14 points per year, adjusted
P
=0.0364).

Conclusions

Social networks remained stable after
MI
and declined after stroke. This small and persistent decline after adjustment for potential confounders is notable because it deviates from stable network trajectories found in
CHS
participants and is specific to stroke.
Acute Kidney Injury in Diabetic Patients With Acute Myocardial Infarction: Role of Acute and Chronic Glycemia
Authors: Marenzi Giancarlo , Cosentino Nicola , Milazzo Valentina , De Metrio Monica , Rubino Mara , Campodonico Jeness , Moltrasio Marco , Marana Ivana , Grazi Marco , Lauri Gianfranco , Bonomi Alice , Barbieri Simone , Assanelli Emilio , Dalla Cia Alessia , Manfrini Roberto , Ceriani Roberto , Bartorelli Antonio
Published: April 2018

Background

In acute myocardial infarction, acute hyperglycemia is a predictor of acute kidney injury (
AKI
), particularly in patients without diabetes mellitus. This emphasizes the importance of an acute glycemic rise rather than glycemia level at admission. We investigated whether, in diabetic patients with acute myocardial infarction, the combined evaluation of acute and chronic glycemic levels may have better prognostic value for AKI than admission glycemia.

Methods and Results

At admission, we prospectively measured glycemia and estimated average chronic glucose levels (mg/dL) using glycosylated hemoglobin (HbA
1c
), according to the following formula: 28.7×HbA
1c
(%)−46.7. We evaluated the association with
AKI
of the acute/chronic glycemic ratio and of the difference between acute and chronic glycemia (Δ
A−C
). We enrolled 474 diabetic patients with acute myocardial infarction. Of them, 77 (16%) experienced
AKI
. The incidence of
AKI
increased in parallel with the acute/chronic glycemic ratio (12%, 14%, 22%;
P
=0.02 for trend) and Δ
A−C
(13%, 13%, 23%;
P
=0.01) but not with admission glycemic tertiles (
P
=0.22). At receiver operating characteristic analysis, the acute/chronic glycemic ratio (area under the curve: 0.62 [95% confidence interval, 0.55–0.69];
P
=0.001) and Δ
A−C
(area under the curve: 0.62 [95% confidence interval, 0.54–0.69];
P
=0.002) accurately predicted
AKI
, without difference in the area under the curve between them (
P
=0.53). At reclassification analysis, the addition of the acute/chronic glycemic ratio and Δ
A−C
to acute glycemia allowed proper
AKI
risk prediction in 16% of patients.

Conclusions

In
diabetic
patients with acute myocardial infarction,
AKI
is better predicted by the combined evaluation of acute and chronic glycemic values than by assessment of admission glycemia alone.
Extravascular Blood Augments Myogenic Constriction of Cerebral Arterioles: Implications for Hemorrhage‐Induced Vasospasm
Authors: Deng Wensheng , Kandhi Sharath , Zhang Bin , Huang An , Koller Akos , Sun Dong
Published: April 2018

Background

Subarachnoid hemorrhage is a serious clinical condition that impairs local cerebral blood flow perfusion and consequently initiates neuronal dysfunction. Pressure‐sensitive myogenic vasomotor regulation is an important mechanism involved in the regulation of cerebral blood flow. We hypothesized that extravascular hemolyzed blood enhances arteriolar myogenic constriction, which in vivo may contribute to the reduction of local cerebral blood flow after subarachnoid hemorrhage.

Methods and Results

Arterioles isolated from the middle cerebral artery (
MCA
arterioles) of mice were cannulated in a perfusion chamber. Arteriolar diameters in response to step increases in intraluminal pressure (20–120 mm Hg) were measured in various experimental conditions. In response to increases in intraluminal pressure, all
MCA
arterioles exhibited myogenic vasoconstrictions. Compared with controls, the pressure‐induced constriction was significantly enhanced in arterioles (in vitro) exposed to extravascular hemolyzed blood or different concentrations of extracellular erythrocyte lysate (1%, 10%, and 20%) for different exposure durations (1–6 hours). The magnitude of enhancement was proportional to the lysate concentration and exposure duration. In in vivo experiments, 10 μL of autologous blood lysate were injected into the mouse subarachnoid space on the surface of the left
MCA
. Two hours later,
MCA
arterioles were isolated and left
MCA
arterioles displayed enhanced myogenic responses compared with the right
MCA
. The enhanced myogenic response was prevented by scavenge of superoxide in both in vitro and in vivo experiments.

Conclusions

Extravascular hemolyzed blood, perhaps by promoting vascular production of superoxide, augments myogenic constriction of cerebral arterioles, which plays a crucial role in the subarachnoid hemorrhage–induced cerebral ischemia.
TÜRKİYE'DE YENİLENEBİLİR VE YENİLENEMEYEN ENERJİ TÜKETİMİ, EKONOMİK BÜYÜME VE KARBONDİOKSİT SALINIMI ARASINDAKİ İLİŞKİ: BİR SVAR (YAPISAL VAR) ANALİZİ
Authors: ÇETİN Murat , SEZEN Serhat
Published: April 2018

Bu
çalışmada yenilenebilir ve yenilenemeyen enerji tüketimi, ekonomik büyüme ve
karbondioksit salınımı arasındaki ilişki yapısal VAR (SVAR) analizi ile
araştırılmıştır. Türkiye için 1970-2014 dönemlerini kapsayan çalışmada yıllık
zaman serileri kullanılarak iki farklı yapısal VAR (SVAR) modeli kurulmuştur. Öncelikle
tüm değişkenler birim kök testleriyle sınanmış ve birinci farklarında durağan
hale gelmiştir. Değişkenler arasındaki eşbütünleşme ilişkisinin varlığını
analiz edebilmek için Johansen-Juselius ve Phillips-Ouliaris eşbütünleşme
testleri kullanılmıştır. Analizlerden elde edilen sonuçlar her iki modelde değişkenler
arasında eşbütünleşme ilişkisinin olduğunu göstermiştir. İki farklı yapısal VAR
(SVAR) analizi sonuçları yenilenebilir enerji tüketimindeki şokların
karbondioksit salınımını ve kişi başına reel GSYİH’yı azalttığını, buna
karşılık yenilenemeyen enerji tüketimindeki şokların hem kişi başına GSYİH’yı
hem de karbondioksit salınımını yükselttiğini ortaya koymuştur.
BİREYSEL KREDİLERİN ENFLASYON ÜZERİNDEKİ ETKİSİ: TÜRKİYE ÖRNEĞİ
Authors: KILIÇ Figen
Published: April 2018

Bu çalışma, Türkiye’de enflasyon ile bireysel (tüketici) krediler ve onun önemli alt bileşenleri olan konut kredileri, ihtiyaç kredileri, taşıt kredileri ve bireysel kredi kartları arasındaki ilişkiyi test etmeyi amaçlamaktadır. Çalışmada [2004:11–2015:03] dönemine ait aylık veriler kullanılarak toplam bireysel krediler, konut kredileri, ihtiyaç kredileri, taşıt kredileri ve bireysel kredi kartlarının enflasyon üzerindeki etkisi eşbütünleşme ve Granger nedensellik testi ile analiz edilmiştir. Analiz sonuçlarına göre, bütün değişkenler seviyede durağan çıktığından Johansen eşbütünleşme testinin yapılmasına gerek kalmamıştır. Granger nedensellik testi sonuçlarına göre, bireysel kredi kartları ile enflasyon arasında çift yönlü bir nedensellik, enflasyondan taşıt kredisine, taşıt kredisinden bireysel kredi kartlarına, konut kredisinden bireysel kredi kartlarına ve taşıt kredisine doğru tek yönlü bir nedensellik ilişkisi tespit edilmiştir.