bluuebunny/crossref_metadata_2025 huggingface dataset:
The asymmetric effects of local and global network ties on firms’ innovation performance
Authors: Wang Lei , Li Jun , Huang Shaoqing
Published: February 2018

Purpose

The purpose of this paper is to develop and empirically test a theoretical framework examining how local network ties and global network ties affect firms’ innovation performance via their absorptive capacities.

Design/methodology/approach

The conceptual framework is empirically tested in a field study with multi-source data collected from a sample of 297 manufacturing firms located in four. Manufacturing clusters in the south-eastern Yangtze River Delta of China. Hypotheses were tested with the use of path analysis with maximum likelihood robust estimates through the structural equation modelling approach.

Findings

The asymmetry between local network ties (LNT) and global network ties (GNT) in terms of influences on firms’ innovation performance is confirmed by empirical tests. LNT not only significantly and positively contribute to firms’ innovation performance directly but also enhance it indirectly via absorptive capability, whereas GNT exhibit only marginal influence on innovation performance. GNT are shown to boost innovation performance (IP) only indirectly via firms’ absorptive capacities. Knowledge heterogeneity and the difference between domestic and multinational firms’ institutional environment are considered to be the main causes of the asymmetric effects.

Originality/value

While the previous literature either focused on the mediating role of firms’ knowledge absorptive capacities or investigated the effects of social networks separately, this study incorporates both mechanisms into a single analytical framework to better account for the interactions between network effects and absorptive capacities. The results challenge some previous studies positing that GNT are stronger determinants than LNT in shaping a local firm’s innovation capacity in emerging economies, and the findings emphasize the importance of absorptive capacity in helping local enterprises to leverage external linkages to enhance firm’s innovation performance.
Structural and defensive roles of angiosperm leaf venation network reticulation across an Andes–Amazon elevation gradient
Authors: Blonder Benjamin , Salinas Norma , Bentley Lisa Patrick , Shenkin Alexander , Chambi Porroa Percy Orlando , Valdez Tejeira Yolvi , Boza Espinoza Tatiana Erika , Goldsmith Gregory R. , Enrico Lucas , Martin Roberta , Asner Gregory P. , Díaz Sandra , Enquist Brian J. , Malhi Yadvinder
Published: February 2018

The network of minor veins of angiosperm leaves may include loops (reticulation). Variation in network architecture has been hypothesized to have hydraulic and also structural and defensive functions.

We measured venation network trait space in eight dimensions for 136 biomass‐dominant angiosperm tree species along a 3,300 m elevation gradient in southeastern Peru. We then examined the relative importance of multiple ecological and evolutionary predictors of reticulation.

Variation in minor venation network reticulation was constrained to three axes. These axes described reconnecting vs. branching veins, elongated vs. compact areoles compact vs. elongated and low vs. high‐density veins. Variation in the first two axes was predicted by traits related to mechanical strength and secondary compounds, and in the third axis by site temperature.

Synthesis. Defensive and structural factors primarily explain variation in multiple axes of reticulation, with a smaller role for climate‐linked factors. These results suggest that venation network reticulation may be determined more by species interactions than by hydraulic functions.
Enhancing Learning in Emergency Services Organisational Work
Authors: Owen Christine , Brooks Benjamin , Curnin Steven , Bearman Chris
Published: February 2018

The paper aims to assist emergency services organisations to learn how to learn so that managers better understand how to embed effective learning practices and systems into their organisation's culture. Learning in emergency services organisations occurs in a range of contexts. These include after‐action reviews, externally led inquiries, and practice‐led research projects. The paper outlines key themes from the work‐related learning literature and introduces a modified experiential learning framework to ground real‐world experiences. Interviews were conducted with 18 emergency services practitioners. The findings provide examples of the broad challenges that agencies need to manage to enhance and sustain learning. These include shifting value from action post an event, to reflection, focusing on the bigger picture and allowing enough time to effectively embed new practices after an emergency. No organisation can forgo learning. All experiences provide opportunities for learning to occur. A key insight for agencies interested in facilitating improvements in learning is to locate potential weak links in the learning cycle and to develop a better understanding of how to learn.
The Tone from Above: The Effect of Communicating a Supportive Regulatory Strategy on Reporting Quality
Authors: VAN DUIN SANNE R. , DEKKER HENRI C. , WIELHOUWER JACCO L. , MENDOZA JUAN P.
Published: February 2018

In collaboration with the Authority for the Financial Markets in the Netherlands, we manipulate the content of official letters that instruct financial intermediaries to submit a mandatory self‐assessment. As part of the Registered Report Process, we submitted our hypotheses, experimental procedure, and planned statistical analyses before data collection. We predicted that a request indicating a supportive regulatory attitude has a positive effect on reporting quality on average. We also predicted this effect to be stronger for small firms and for firms with a long‐term orientation, and to become negative for firms with a short‐term orientation. Planned analyses show that a supportive letter reduced reporting quality unless firms had a long‐term orientation, supporting the moderating influence of time horizon, but providing no support for the expected average effect or for moderation by firm size.
Impaired Gas Exchange: Prognostic Clinical Indicators of Short‐Term Survival in Children with Acute Respiratory Infection
Authors: Pascoal Lívia Maia , de Oliveira Lopes Marcos Venícios , Chaves Daniel Bruno Resende , Beltrão Beatriz Amorim , Nunes Marília Mendes , da Silva Viviane Martins , de Sousa Freire Vanessa Emille Carvalho
Published: February 2018

PURPOSE

To establish prognostic indicators of survival for impaired gas exchange (IGE) (00030).

METHODS

Secondary analysis of data from an open prospective cohort developed with a group of 136 children with acute respiratory infection (ARI).

FINDINGS

On Day 1, IGE (00030) was present in 42.6% of the sample. New cases arose until the last day of evaluation. With regards to defining characteristics, only hypoxemia and abnormal skin color were associated with a higher risk of developing diagnosis.

CONCLUSIONS

Children with ARI who exhibit hypoxemia and abnormal skin color had a worse prognosis for IGE (00030).

IMPLICATIONS FOR NURSE PRACTICE

Nurses can use the research findings as a predictive marker of the evolution of the patient's health status.
Pre‐eclampsia affects procalcitonin production in placental tissue
Authors: Agostinis Chiara , Rami Damiano , Zacchi Paola , Bossi Fleur , Stampalija Tamara , Mangogna Alessandro , Amadio Leonardo , Vidergar Romana , Vecchi Brumatti Liza , Ricci Giuseppe , Celeghini Claudio , Radillo Oriano , Sargent Ian , Bulla Roberta
Published: February 2018

Problem

Procalcitonin (PCT) is the prohormone of calcitonin which is usually released from neuroendocrine cells of the thyroid gland (parafollicular) and the lungs (K cells). PCT is synthesized by almost all cell types and tissues, including monocytes and parenchymal tissue, upon LPS stimulation. To date, there is no evidence for PCT expression in the placenta both in physiological and pathological conditions.

Method

Circulating and placental PCT levels were analysed in pre‐eclamptic (PE) and control patients. Placental cells and macrophages (PBDM), stimulated with PE sera, were analysed for PCT expression. The effect of anti‐TNF‐α antibody was analysed.

Results

Higher PCT levels were detected in PE sera and in PE placentae compared to healthy women. PE trophoblasts showed increased PCT expression compared to those isolated from healthy placentae. PE sera induced an upregulation of PCT production in macrophages and placental cells. The treatment of PBDM with PE sera in the presence of anti‐TNF‐α completely abrogated the effect induced by pathologic sera.

Conclusion

Trophoblast cells are the main producer of PCT in PE placentae. TNF‐α, in association with other circulating factors present in PE sera, upregulates PCT production in macrophages and normal placental cells, thus contributing to the observed increased in circulating PCT in PE sera.
Utilization of Antiepileptic Medicines in Swedish Children and Adolescents with Different Diagnoses
Authors: Karlsson Lind Linnéa , Wide Katarina , Wettermark Björn , von Euler Mia
Published: February 2018

This study aimed to investigate the utilization of antiepileptic drugs (AEDs) in children and adolescents with epilepsy and other diagnoses in a nationwide population between 2007 and 2014. Data on dispensed prescriptions of AEDs were collected from the Swedish Prescribed Drug Register and linked to diagnosis data from the National Patient Register covering all in‐ and outpatient consultations from Swedish hospitals. Children aged 0–17 years who had received at least one prescription for AEDs were selected. We calculated proportions of patients stratified by indication, sex and type of AED. A total of 18,131 patients (mean age 9.5 years, 50% boys) were initiated on AED treatment between January 2007 and December 2014. Epilepsy was the most frequent diagnosis (46%) recorded within the year prior to the first AED dispensing. Psychiatric and pain diagnoses were more common in girls (sex distribution 70/30 and 59/41, respectively). In epilepsy, the most frequently initiated AED was valproic acid in boys and lamotrigine in girls. Lamotrigine was the most frequently initiated drug in psychiatry, in both boys and girls. This nationwide study provides new knowledge on AED use in children and adolescents. The use of AEDs during the study period was mainly restricted to epilepsy, and the individual AEDs used seems to be in accordance with approved indications. However, the use of AED on non‐epilepsy diagnoses, especially pain disorders, raises concerns.
Generalized Accelerated Recurrence Time Model for Multivariate Recurrent Event Data with Missing Event Type
Authors: Ma Huijuan , Peng Limin , Zhang Zhumin , Lai HuiChuan J.
Published: February 2018

Recurrent events data are frequently encountered in biomedical follow-up studies. The generalized accelerated recurrence time (GART) model (Sun et al., 2016), which formulates covariate effects on the time scale of the mean function of recurrent events (i.e., time to expected frequency), has arisen as a useful secondary analysis tool to provide meaningful physical interpretations. In this article, we investigate the GART model in a multivariate recurrent events setting, where subjects may experience multiple types of recurrent events and some event types may be missing. We propose methods for the GART model that utilize the inverse probability weighting technique or the estimating equation projection strategy to handle event types that are missing at random. The new methods do not require imposing any parametric model for the missing mechanism, and thus are robust; moreover, they enjoy easy and stable implementation. We establish the uniform consistency and weak convergence of the resulting estimators and develop appropriate inferential procedures. Extensive simulation studies and an application to a dataset from Cystic Fibrosis Foundation Patient Registry (CFFPR) illustrate the validity and practical utility of the proposed methods.
The relation between cognitive and metacognitive processing: Building bridges between the SRL, MDL, and SAL domains
Authors: Coertjens Liesje
Published: February 2018

Aim

The main aim of this commentary was to connect the insights from the contributions of the special issue on the intersection between depth and the regulation of strategy use. The seven contributions in this special issue stem from three perspectives: self‐regulated learning (SRL), model of domain learning (MDL), or the student approaches to learning (SAL).

Procedure

Prior to combining insights from different studies, the definition and operationalization of cognitive and metacognitive processing in the seven contributions is described. Subsequently, the grain size and statistical methods used in these contributions are discussed. This information allows us to – albeit cautiously – combine the results from the different studies regarding the relation between cognitive and metacognitive processing.

Conclusion

Deep processing and self‐regulation/monitoring showed a strong correlation, regardless of the theoretical framework or data collection method chosen. The strength of the correlation between surface processing and metacognitive processing differed, however, between the studies. Pathways for future research on students’ cognitive and metacognitive processing are suggested, at the methodological level as well as regarding the conceptualization of unregulated learning and surface processing.
The Earnings Effect of Sexual Orientation: British Evidence from Worker‐Firm Matched Data
Authors: Wang Jing , Gunderson Morley , Wicks David
Published: February 2018

Using the British Workplace Employment Relations Study (WERS) with its preferred self‐identified measure of sexual orientation as well as its organizational‐level variables, we find that gay men earn about the same as heterosexual men and lesbians earn significantly more than heterosexual women. Working in an organization with a diversity and equity management (DEM) policy generally has a positive effect on the earnings of gay men and lesbians, especially if they are single. Implications for theories of diversity management, discrimination and market versus household production are discussed.
Stearate‐to‐palmitate ratio modulates endoplasmic reticulum stress and cell apoptosis in non‐B non‐C hepatoma cells
Authors: Shibasaki Yasushi , Horikawa Makoto , Ikegami Koji , Kiuchi Ryota , Takeda Makoto , Hiraide Takanori , Morita Yoshifumi , Konno Hiroyuki , Takeuchi Hiroya , Setou Mitsutoshi , Sakaguchi Takanori
Published: February 2018

The increased prevalence of hepatocellular carcinoma (HCC) without viral infection, namely, NHCC, is a major public health issue worldwide. NHCC is frequently derived from non‐alcoholic fatty liver (NAFL) and non‐alcoholic steatohepatitis, which exhibit dysregulated fatty acid (FA) metabolism. This raises the possibility that NHCC evolves intracellular machineries to adapt to dysregulated FA metabolism. We herein aim to identify NHCC‐specifically altered FA and key molecules to achieve the adaptation. To analyze FA, imaging mass spectrometry (IMS) was performed on 15 HCC specimens. The composition of saturated FA (SFA) in NHCC was altered from that in typical HCC. The stearate‐to‐palmitate ratio (SPR) was significantly increased in NHCC. Associated with the SPR increase, the ELOVL6 protein level was upregulated in NHCC. The knockdown of ELOVL6 reduced SPR, and enhanced endoplasmic reticulum stress, inducing apoptosis of Huh7 and HepG2 cells. In conclusion, NHCC appears to adapt to an FA‐rich environment by modulating SPR through ELOVL6.
Thromboembolism prophylaxis in patients with Philadelphia‐negative myeloproliferative neoplasms—Clinical practice among Nordic specialists
Authors: Bjerrum Ole Weis , Samuelsson Jan , Ghanima Waleed , Kauppila Marjut , Andersen Christen Lykkegaard ,   the Nordic Myeloproliferative Neoplasm Study Group
Published: February 2018

Background

Patients with Philadelphia chromosome‐negative myeloproliferative neoplasms (MPNs) have higher risks of developing thromboembolisms compared to the general population. International guidelines on the management of MPNs therefore include recommendations concerning thromboembolism prophylaxis. In clinical practice, strict adherence to guidelines may be challenging and dependent on factors such as physician experience, outpatient clinic setting, and access to therapy; however, no data exist on physician adherence or patient compliance to thromboembolism prophylaxis in MPNs.

Objectives

The Nordic Myeloproliferative Neoplasm Study Group (NMPN) performed a survey among Nordic hematology specialists with the aim of documenting the implementation of international recommendations in a region of Northern Europe with similar healthcare systems.

Results

The study showed that Nordic specialists managed their patients in accordance with international guidelines concerning medical intervention, but to a lesser degree regarding the management of additional cardiovascular risk factors. The survey also drew attention to the common clinical dilemma of combining antiaggregatory agents with vitamin K antagonists (VKA), or novel oral anticoagulants (NOAC), as well as phlebotomy limits in female polycythemia vera patients.

Conclusions

The results of this study highlight the importance of considering all risk factors for thrombosis and an optimal collaboration with the primary healthcare sector.
Formulating direction: Navigational instructions in driving lessons
Authors: De Stefani Elwys
Published: February 2018

This contribution focuses on navigational instructions occurring in driving lessons carried out in Italian. It proposes a situated analysis of navigational instructions in their spatio‐temporal and interactional environment with the methods developed in conversation analysis and multimodal interaction analysis. The analytic part of the article first examines the sequential placements of navigational instructions and then zooms in on their turn‐constructional features. The exploration of how interactants coordinate talk with gesture provides a further analytic layer. The article shows that differences in turn format and multimodal delivery of navigational instructions bear on the driving instructor's orientation towards the trainee driver's (putative, assigned) level of competence. Hence, this article contributes to a better understanding of how navigational instructions, as first actions, relate to the overall activity.
Effects of pulsed thermosonication treatment on fungal growth and bioactive compounds of Berberis vulgaris juice
Authors: Hashemi Seyed Mohammad Bagher , Mousavi Khaneghah Amin , Fidelis Marina , Granato Daniel
Published: February 2018

In this study, the single and combined effects of pulsed‐ultrasound amplitude (100 W, 30 kHz with 25 and 50% amplitude levels for up to 30 min) and temperature (65 °C and 75 °C) on fungal growth, total phenolics, flavonoids and antioxidant activity of Berberis vulgaris juice were investigated. The combination of pulsed ultrasound at 50% amplitude for 30 min at temperature of 75 °C as the most effective treatment was resulted in a reduction of about−3.083 ± 0.02, −3.04 ± 0.03, −3.10 ± 0.01 and −2.88 ± 0.02 log (N/N0) on S. cerevisiae, A. flavus, A. versicolor and B. fulva, respectively. Additionally, the highest total phenolics, flavonoids and antioxidant activity were noted for the barberry juice after 30 min of sonication with 50% pulsed‐ultrasound amplitude at either 65 °C or 75 °C. Pulsed thermosonication is a promising technology to extend the shelf life of B. vulgaris fruit juice because of the improvement of antioxidant activity as well as microbial quality.
Defect suppression in CaZrO3‐modified (K, Na)NbO3‐based lead‐free piezoceramic by sintering atmosphere control
Authors: Thong Hao‐Cheng , Li Qi , Zhang Mao‐Hua , Zhao Chunlin , Huang Kevin Xiu , Li Jing‐Feng , Wang Ke
Published: February 2018

During high‐temperature crystal growth, lattice defects will inevitably form inside piezoelectric materials, which can be a hindrance for performance optimization. Through appropriate atmosphere control during sintering, defect levels inside the piezoelectric material can be regulated. Herein, CaZrO3‐modified (K, Na)NbO3‐based lead‐free piezoelectric ceramics with a nominal composition of 0.95(Na0.49K0.49Li0.02)(Nb0.8Ta0.2)O3‐0.05CaZrO3 are produced by sintering in an oxygen‐rich atmosphere. Compared with an air‐sintered sample, the piezoelectric constant of the oxygen‐sintered sample has greatly improved 15% up to 390 pC/N, which is comparable to commercial lead‐based counterparts. In addition, the planar electromechanical coupling factor kp is enhanced from 0.46 to 0.52. A qualitative model related to defect engineering is proposed to support the experimental observations. Our results indicate the feasibility of purposely optimizing the piezoelectric performance by sintering atmosphere control.
Analysis of pancreatic volume in acute‐onset, slowly‐progressive and fulminant type 1 diabetes in a Japanese population
Authors: Sasamori Hiroto , Fukui Tomoyasu , Hayashi Toshiyuki , Yamamoto Takeshi , Ohara Makoto , Yamamoto Saki , Kobayashi Tetsuro , Hirano Tsutomu
Published: February 2018

Aims/Introduction

A decrease in the size of the pancreas is observed in islet autoantibody‐positive non‐diabetic donors and acute‐onset type 1 diabetes irrespective of the diabetes duration. Little is known, however, about the relationship between the size of the pancreas and type 1 diabetes subtypes, including fulminant type 1 diabetes.

Materials and Methods

We examined the pancreatic volume (PV) in 44 adult patients with type 1 diabetes (16 acute‐onset type 1 diabetes, 18 slowly progressive type 1 diabetes and 10 fulminant type 1 diabetes) and 39 age‐ and body mass index‐matched non‐diabetic controls. PV was measured by computed tomography. The ability to secrete insulin was assessed by stimulated C‐peptide after intravenous glucagon administration.

Results

PV was significantly correlated with bodyweight in both control participants and type 1 diabetes patients. The PV index (PVI; PV/bodyweight) was decreased by 39% in type 1 diabetes compared with that in controls. PVI was significantly decreased in acute‐onset type 1 diabetes patients and slowly progressive type 1 diabetes patients (both P < 0.0001), but not in fulminant type 1 diabetes patients (P = 0.10), compared with control participants. In cases patients with recent‐onset type 1 diabetes (0–7 days post‐diagnosis), PVI was significantly decreased in acute‐onset type 1 diabetes patients (n = 8, P = 0.0005), but not in fulminant type 1 diabetes patients (n = 7, P = 0.44), compared with controls. PVI showed no correlations with the diabetes duration, C‐peptide levels, glycated hemoglobin, glutamic acid decarboxylase autoantibody levels, serum amylase or daily total insulin dose in type 1 diabetes subtypes.

Conclusions

The present results show that patients with acute‐onset type 1 diabetes and slowly progressive type 1 diabetes have small pancreases irrespective of the diabetes duration or C‐peptide levels. In contrast to earlier findings on acute‐onset type 1 diabetes, we found no reduction of PVI at the onset of fulminant type 1 diabetes.
Analysis of the effect of seasonal administration on the efficacy of sitagliptin: Subanalysis of the Januvia Multicenter Prospective Trial in Type 2 Diabetes Study
Authors: Sakura Hiroshi , Hashimoto Naotake , Sasamoto Kazuo , Ohashi Hiroshi , Hasumi Sumiko , Ujihara Noriko , Kasahara Tadasu , Tomonaga Osamu , Nunome Hideo , Honda Masashi , Iwamoto Yasuhiko ,   the JAMP Study Investigators
Published: February 2018

Aims/Introduction

Hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus fluctuate throughout the year. However, there are few studies that have evaluated the therapeutic effect of hypoglycemic agents while considering such fluctuations. In a multicenter study (Januvia Multicenter Prospective Trial in Type 2 Diabetes Study), pretreatment patients with type 2 diabetes mellitus were divided into seven groups and given sitagliptin for 1 year. The aim of the present study was to evaluate the differences in the therapeutic effect, and the efficacy of sitagliptin in patients with type 2 diabetes mellitus based on the month the administration of the drug began as a subanalysis of the Januvia Multicenter Prospective Trial in Type 2 Diabetes Study.

Materials and Methods

Patients with type 2 diabetes mellitus were divided into four groups according to the month of initiation of sitagliptin. Changes in HbA1c in each group were compared at 3 and 12 months after administration of sitagliptin. As a negative correlation has been reported between baseline HbA1c and the degree of change after administration of sitagliptin, an analysis using the residual error from the approximate line was carried out.

Results

In the analysis of the degree of change in HbA1c, patients in the group in which administration of sitagliptin was started between August and October had the lowest degree of improvement at 3 months after starting sitagliptin. However, there was no significant intergroup difference in improvement at 12 months after the start of sitagliptin. The same result was also obtained in residual analysis.

Conclusions

The present study suggested that the season of administration of sitagliptin influenced the subsequent hypoglycemic effect even after analysis excluding the influence of HbA1c value at the start of treatment. This study provides possibility, showing that seasonal fluctuations have an effect on the efficacy of antidiabetic drugs.
Does the Association of Comorbidity with 1‐Year Mortality After Hip Fracture Differ According to Gender? The Norwegian Epidemiologic Osteoporosis Studies (NOREPOS)
Authors: L. Riska Brit Solvor , Forsén Lisa , Omsland Tone K. , Søgaard Anne Johanne , Meyer Haakon E. , Holvik Kristin
Published: February 2018

Background/Objectives

Excess mortality after hip fracture is higher in men than in women. The objective was to study whether comorbidity differs in men and women with hip fracture and to what degree differences in comorbidity according to gender may explain the higher excess mortality in men.

Design

Population‐based matched cohort covering the population aged 50 and older in Norway.

Setting

Specialist healthcare (individuals with hip fracture) and general population (controls).

Participants

All individuals with hip fracture aged 50 and older from 2005 to 2008 (n = 32,175) and individuals without hip fracture matched 3:1 to those with hip fracture on gender, age, and county of residence (n = 96,410).

Measurements

Comorbid diagnoses were recorded during the hospital stay. Relative and absolute excess 1‐year mortality in individuals with hip fracture according to gender and Charlson Comorbidity Index (CCI) were investigated using Cox regression and linear regression, respectively.

Results

Despite lower age (mean 78.7 vs 81.7), men had higher comorbidity than women. Compared with controls, women (hazard ratio (HR) = 6.5, 95% confidence interval (CI) = 6.2–6.9) and men (HR = 7.8, 95% CI = 7.3–8.3) with a CCI of 2 or greater were more likely to die. Women with a CCI of 2 or greater had an estimated 1‐year risk of dying of 44%, and controls had an 11% risk; men with a CCI of 2 or greater had an estimated risk of dying of 53%, and controls had a 12% risk. Men were twice as likely as women to die within 1 year (HR = 2.0, 95% CI = 1.9–2.1). When adjusting for comorbidity, the difference was only slightly smaller (HR = 1.8, 95% CI = 1.7–1.8).

Conclusion

Men had greater comorbidity than women, but this did not explain the difference according to gender in excess mortality after hip fracture. Men who fracture a hip are an especially vulnerable subpopulation, even when there is no apparent comorbidity, and warrant special attention in follow‐up and care.
Quality of Hospice Care at Home Versus in an Assisted Living Facility or Nursing Home
Authors: Unroe Kathleen T. , Stump Timothy E. , Effler Shannon , Tu Wanzhu , Callahan Christopher M.
Published: February 2018

Objectives

To describe differences in perceived quality of hospice care for individuals living at home or in a nursing home (NH) or assisted living facility (ALF) through analysis of after‐death surveys of family members.

Design

Retrospective cohort study using hospice medical record data and Family Evaluation of Hospice Care (FEHC) survey data.

Setting

Large, national hospice provider.

Participants

Individuals who died while receiving routine hospice care and family caregivers who completed after‐death quality‐of‐care surveys.

Measurements

Survey results for 7,510 individuals were analyzed using analysis of variance and chi‐square tests. Logistic regression was used to assess relationship between location of care and overall service quality.

Results

The overall survey response rate was 27%; 34.5% of families of individuals in ALFs in hospice, 27.4% of those at home, and 22.9% of those in NHs returned the survey (P < .001). Differences in return rate according to primary diagnosis were significant, although differences were not large. Most (84.3%) respondents reported that hospice referral had occurred at the right time, and 63.4% rated service quality as excellent. Hospice care in the NH was less likely to be perceived as excellent.

Conclusion

There were significant differences in characteristics of individuals whose family members did and did not return surveys, which has implications for use of after‐death surveys to evaluate hospice quality. Lower perceived quality of hospice care in NHs may be related to general dissatisfaction with receiving care in this setting. Survey results have the potential to set priorities for quality improvement, choice of provider, and potentially reimbursement. Underlying causes of differences of perceived quality in different settings of care should be examined.
Nrf2-mediated neuroprotection against oxygen-glucose deprivation/reperfusion injury by emodin via AMPK-dependent inhibition of GSK-3β
Authors: Park Sun Young , Choi Young-Whan , Park Geuntae
Published: February 2018

Objectives

Our study verified the neuroprotective properties of emodin against oxygen-glucose deprivation/reoxygenation (OGD/R) and demonstrated its mechanism.

Methods

Human neuronal SH-SY5Y cells were investigated by analysing cell viability, lactate dehydrogenase levels, expression of molecules related to apoptotic cell death, and using biochemical techniques, flow cytometry and Western blot assays.

Key findings

Emodin reduced OGD/R-lead to neurotoxicity in SH-SY5Y cells. OGD/R significantly increased levels of cleaved poly ADP ribose polymerase, cleaved caspase-3, cleaved caspase-9, p53, p21 and Bax protein. However, emodin treatment effectively inhibited these OGD/R-induced changes. Emodin treatment also increased HO-1 and NQO1 expression in a concentration- and time-dependent manner and caused antioxidant response element (ARE) transcription activity and nuclear Nrf2 accumulation. Emodin phosphorylated AMPK and GSK3β, and pretreatment of cells with an AMPK inhibitor suppressed emodin-induced nuclear Nrf2 accumulation and HO-1 and NQO1 expression. AMPK inhibitor treatment decreased GSK3β phosphorylation, suggesting that AMPK is upstream of GSK3β, Nrf2, HO-1 and NQO1. Emodin's neuroprotective effect was completely blocked by HO-1, NQO1 and Nrf2 knock-down and an AMPK inhibitor, indicating the action of AMPK/GSK3β/Nrf2/ARE in the neuroprotective effect of emodin subjected to OGD/R.

Conclusions

Emodin treatment protected against OGD/R-lead to neurotoxicity by potentiating Nrf2/ARE-regulated neuroprotection through the AMPK/GSK3β pathway, indicating that emodin may be useful for treating neurodegenerative disorders.
Why not to stop antiviral treatment in patients with chronic hepatitis B
Authors: Marciano Sebastián , Gadano Adrián
Published: February 2018

Treatment of chronic hepatitis B with entecavir or tenofovir leads to viral suppression in almost all patients. However, prolonged or lifelong treatment is necessary. At present, there is no consensus among the three major guidelines for the treatment of chronic hepatitis B on whether or not to stop antiviral treatment. One of the main reasons for this controversy is that virological relapse has been well documented in patients with chronic hepatitis B who stop treatment. Relapse rate is particularly high in patients who are HBeAg‐negative when treatment begins, with reported relapse rates of up to 70% 36 months after treatment discontinuation. Moreover, hepatic decompensation, jaundice and death have been described in patients with cirrhosis after treatment discontinuation. The main reason for stopping antiviral treatment is related to cost, however there is no robust evidence to support treatment discontinuation in most patients.
Hepatitis B: Who and when to treat?
Authors: Vlachogiannakos Jiannis , Papatheodoridis George V.
Published: February 2018

As current treatment options almost never achieve eradication of hepatitis B virus (HBV), the most realistic goal for HBV treatment is persistent inhibition of viral replication and ALT normalization. Thus, the decision to start treatment should be based on careful patient selection and individualized decisions. Treatment is generally indicated in chronic hepatitis B patients with HBV DNA >2000 IU/mL, elevated ALT and/or at least moderate histological lesions, while all patients with cirrhosis and detectable HBV DNA should be treated. Patients with HBV DNA >20 000 IU/mL and ALT >2xULN (upper limit of normal), HBV DNA >2000 IU/mL and liver stiffness >9 or >12 kPa in case of normal or ≤5xULN, HBV DNA >2000 IU/mL and a family history of cirrhosis and/or HCC as well as HBeAg‐positive patients with HBV DNA >20 000 IU/mL and over 30 years old can begin treatment whatever the liver histology. Moreover, patients with HBV DNA >2000 IU/mL and at least moderate histological lesions can begin treatment whatever the ALT levels. Prophylactic treatment is indicated in HBV‐related liver transplantation patients to prevent recurrence, in the last trimester of pregnancy in women with high viraemia to prevent vertical transmission and in patients receiving immunosuppression/chemotherapy to prevent the reactivation of HBV. Treatment is also indicated in patients with co‐infections, extrahepatic manifestations and severe acute hepatitis B, or healthcare workers with viraemia. These treatment indications can only change if HBV eradication or at least HBsAg clearance can be achieved in the future in a significant proportion of patients.
Long‐term safety and efficacy of nucleo(t)side analogue therapy in hepatitis B
Authors: Buti Maria , Riveiro‐Barciela Mar , Esteban Rafael
Published: February 2018

Long‐term treatment of chronic hepatitis B (CHB) with nucleos(t)ide analogues is often necessary to achieve durable viral suppression. Therefore, current guidelines recommend the most potent drugs with optimal resistance profiles. Entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are the first‐line monotherapies for CHB. All of these drugs are highly effective in suppressing viral replication but with slightly different safety profiles. This review provides an overview of the long‐term efficacy and safety data that have become available over the 10 years since ETV and TDF were first approved for the treatment of chronic hepatitis, and recent data on TAF in patients with CHB.
Infections complicating cirrhosis
Authors: Piano Salvatore , Brocca Alessandra , Mareso Sara , Angeli Paolo
Published: February 2018

Patients with cirrhosis have a high risk of bacterial infections. Bacterial infections induce systemic inflammation that may lead to organ failure and acute‐on‐chronic liver failure (ACLF) resulting in a high risk of short term mortality. The early diagnosis and treatment of bacterial infections is essential to improve the patient's prognosis. However, in recent years, the spread of multidrug resistant (MDR) bacterial infections has reduced the efficacy of commonly used antibiotics such as third generation cephalosporins. In patients at high risk of MDR bacteria, such as those with nosocomial infections, the early administration of broad spectrum antibiotics has been shown to improve the prognosis. However, early de‐escalation of antibiotics is recommended to reduce a further increase in antibiotic resistance. Strategies to prevent acute kidney injury and other organ failures should be implemented. Although prophylaxis of bacterial infections with antibiotics improves the prognosis in selected patients, their use should be limited to patients at high risk of developing infections. In this article, we review the pathogenesis and management of bacterial infections in patients with cirrhosis.
The next wave of hepatitis C virus: The epidemic of intravenous drug use
Authors: Shiffman Mitchell L.
Published: February 2018

The epidemic of hepatitis C virus (HCV) began in the 1960s when transmission was primarily the result of blood transfusions. By 1990, when HCV was identified and a serologic test for screening donated blood was implemented, 123 million persons had already become infected worldwide and HCV was the most common cause of cirrhosis, hepatocellular carcinoma and the most common indication for liver transplantation. Approximately 75% of persons with HCV are “baby boomers” born between the years 1945 and 1965. The number of new cases of HCV declined precipitously between 1990 and 2005. The next wave of HCV began in 2005, and transmission is primarily the result of an epidemic of intravenous drug use. New cases of HCV have increased three‐fold between 2005 and 2015. Approximately 50% of persons who inject drugs (PWID) have been exposed to HCV, and 25% of these persons are under the age of 25 years. The treatment of chronic HCV in PWID has two goals; treating HCV and preventing the patient from returning to drug use and becoming reinfected. Highly effective oral antiviral agents are now available and can cure HCV in virtually all patients. Treatment can be highly effective in PWID with sustained virologic response rates similar to that observed in a non‐drug‐using population. Preventing the patient from returning to drug use and becoming reinfected with HCV is more difficult and will require that the medical and social problems associated with intravenous drug use be addressed and resolved.
How to improve long‐term outcome after liver transplantation?
Authors: Durand François
Published: February 2018

The outcome of liver transplantation has markedly improved in the last 3 decades. Although early post‐transplantation outcomes have improved over time, this is not true of the long‐term outcome. The majority of late deaths are not related to graft dysfunction, and with the advent of new antiviral agents, recurrence of hepatitis B and hepatitis C after transplantation may no longer represent a source of graft loss and patient's death in the long term. The complications of metabolic syndrome may represent an increasing source of morbidity and mortality after transplantation. This study discusses these modifiable factors associated with late mortality to improve the long‐term results of transplantation.
Diagnosis of non‐alcoholic fatty liver disease/non‐alcoholic steatohepatitis: Why liver biopsy is essential
Authors: Bedossa Pierre
Published: February 2018

The pattern of non‐alcoholic fatty liver disease is complex with an association of several lesions, each of them related to different pathophysiological mechanisms. Despite the progress in non‐invasive tools, liver biopsy remains the only diagnostic procedure that can reliably assess these various patterns, their related severity and associations. The most important difficulties of liver biopsy can be avoided if this procedure is performed by an experienced hepatologist and read by a liver pathologist. However, for obvious reasons, biopsy should be restricted to selected patients, especially in the context of clinical trials. Indeed, liver biopsy is considered mandatory by regulatory authorities as a surrogate to assess drug efficacy in Phase 3 clinical trials. In addition to the clinical diagnosis, liver biopsy can be used to score the various histological patterns of disease (NASH‐CRN, SAF scores) and accurately assess the extent of fibrosis, both of which are useful when follow‐up biopsies are performed. When treatment becomes available in the near future, liver biopsy could remain useful for choosing the most suitable therapeutic option based on the main predominant histological features (activity, steatosis, fibrosis).
Stopping long‐term treatment with nucleos(t)ide analogues is a favourable option for selected patients with HBeAg‐negative chronic hepatitis B
Authors: van Bömmel Florian , Berg Thomas
Published: February 2018

The immune response against the infection is impaired in patients with chronic hepatitis B, and although HBV DNA can effectively be suppressed by nucleos(t)ide analogues (NA), durable immune control is only established in a minority of patients. This especially applies in HBeAg‐negative patients who usually must receive lifelong NA treatment. Calculated withdrawal of NA leads to a relapse of HBV DNA in most patients. There is evidence that this sudden exposure of viral antigens can trigger immune control in some patients which may result in HBsAg loss or a form of immune control, then sustained low HBV DNA levels and normal alanine aminotransferase (ALT). In the first prospective randomized trial investigating tenofovir treatment cessation in HBeAg‐negative patients, most patients did not need retreatment after NA cessation, although all patients showed a transient relapse in HBV DNA. HBsAg loss was identified in almost 20% nearly 3 years after stopping NA. Further confirmation of these findings is needed in larger randomized trials and patients who are most likely to benefit from finite therapy must be identified to individualize NA stopping strategies. However, these results suggest that in patients without risk factors such as cirrhosis or other severe conditions, NA treatment may be stopped, as long as adequate safety rules for retreatment are followed.
The impact of treatment of hepatitis C with DAAs on the occurrence of HCC
Authors: Roche Bruno , Coilly Audrey , Duclos‐Vallee Jean Charles , Samuel Didier
Published: February 2018

Hepatitis C virus infection is a major cause of chronic hepatitis resulting in cirrhosis and hepatocellular carcinoma (HCC). The recent introduction of direct acting antivirals (DAA), results in sustained virological response (SVR) rates of >90% in treated patients whatever the stage of liver fibrosis with an excellent safety profile. This major advancement has allowed treatment of a larger number of patients, some with more advanced liver dysfunction and a higher risk of HCC. An SVR is associated with a reduced risk of hepatic decompensation, the need for liver transplantation and both liver‐related and overall mortality. This high rate of SVR has raised hopes that there would be a significant reduction in the incidence of HCC. However, the impact of DAA‐based regimens on the occurrence of HCC in patients with cirrhosis, and in particular the recurrence of HCC following successful curative treatment is controversial. Published studies suggest that DAA does not increase the risk of de novo HCC following SVR. A more controversial topic is the effect of a DAA‐based SVR on the recurrence of HCC following curative treatment of early HCC. Well‐designed studies with robust comparisons are needed to determine the effect of DAA on the recurrence of HCC. At present, patients with HCV cirrhosis who have undergone resection or ablation for HCC should not be dissuaded from receiving DAA therapy to prevent the progression of liver disease. Monitoring for HCC with liver imaging and AFP should be performed twice a year indefinitely post‐SVR in patients with HCV cirrhosis.
Focus on histological abnormalities of intrahepatic vasculature in chronic viral hepatitis
Authors: Guido Maria , Sarcognato Samantha , Russo Francesco P. , Cardin Romilda , Piciocchi Marika , Colloredo Guido , Farinati Fabio
Published: February 2018

Background & Aims

The histological intrahepatic microvasculature lesions have not been deeply investigated outside the setting of portal hypertension. The aim of this study was to analyse the type and the prevalence of microvasculature abnormalities and their correlation with inflammatory activity, fibrosis stage and tissue markers of fibrogenesis, angiogenesis and oxidative DNA damage in liver biopsies obtained from patients with chronic viral hepatitis.

Methods

Seventy‐four liver biopsies from untreated patients affected by hepatitis B (22 cases) and C (52 cases) were included. The presence of microvascular changes was correlated with (i) the severity of the activity and fibrosis; (ii) immunohistochemical markers of angiogenesis (CD34) and hepatic stellate cells activation (alpha‐smooth muscle actin); (iii) a tissue marker of oxidative damage (8‐OHdG adducts).

Results

Sixty‐five out of 74 biopsies (87.8%) showed vascular lesions. Portal angiomatosis was the most prevalent (62.2%) and it was associated with, on 1 side, the fibrosis stage at both univariate (P < .0001) and multivariate analysis (P = .01, OR = 9.4 [1.6‐54]) and, on the other, with angiogenesis (P = .05) and hepatic stellate cells activation (P = .002). Interestingly, 36/46 cases with portal angiomatosis were at early/intermediate fibrosis stage. The hepatic stellate cells activation was also associated with the presence of aberrant periportal vessels (P = .01).

Conclusions

The histological alterations of intrahepatic microvasculature, usually seen in cirrhosis and portal hypertension, occur in chronic viral hepatitis even at early/intermediate fibrosis stages. Their correlation with angiogenesis and fibrogenesis supports a possible involvement in disease progression.
Multiagent Simulation for Complex Adaptive Modeling of Road Infrastructure Resilience to Sea‐Level Rise
Authors: Batouli Mostafa , Mostafavi Ali
Published: February 2018

Infrastructure systems in coastal areas are exposed to episodic flooding exacerbated by sea‐level rise stressors. To enable assessing the long‐term resilience of infrastructure to such chronic impacts of sea‐level rise, the present study created a novel complex system modeling framework that integrates: (i) stochastic simulation of sea‐level rise stressors, based on the data obtained from downscaled climate studies pertaining to future projections of sea level and precipitation; (ii) dynamic modeling of infrastructure conditions by considering regular decay of infrastructure, as well as structural damages caused by flooding; and (iii) a decision‐theoretic modeling of infrastructure management and adaptation processes based on bounded rationality and regret theories. Using the proposed framework and data collected from a road network in Miami, a multiagent computational simulation model was created to assess the long‐term cost and performance of the road network under various sea‐level rise scenarios, adaptation approaches, and network degradation effects. The results showed the capabilities of the proposed computational model for robust planning and scenario analysis to enhance the resilience of infrastructure systems to sea‐level rise impacts.