bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innovation responses of Japanese firms to Chinese import competition
Authors: Yamashita Nobuaki , Yamauchi Isamu 
Published: June 2019

AbstractThis paper examines innovation responses of a panel of Japanese firms to the intensified import competition from China in the period 1995–2005. We build a comprehensive firm‐level dataset linking patents and R&D merged to cross‐industry measures of Chinese import competition. Accounting for a simultaneity bias between innovation and importing and the possible heterogeneous effects across firms, we found that patenting has increased in response to an influx of Chinese imports, but it has adversely affected the quality of innovation, measured by forward citations received. These effects are only observed for globally engaged firms, not for firms focusing on the domestic market.
A novel form of glycolytic metabolism‐dependent cardioprotection revealed by PKCα and β inhibition
Authors: Brennan Sean , Chen Shen , Makwana Samir , Martin Christopher A. , Sims Mark W. , Alonazi Asma S.A. , Willets Jonathan M , Squire Iain B. , Rainbow Richard D. 
Published: June 2019

Key points
Acute hyperglycaemia at the time of a heart attack worsens the outcome for the patient.
Acute hyperglycaemia is not limited to diabetic patients and can be due to a stress response in non‐diabetics.
This study suggests that the damaging cardiac effects of hyperglycaemia can be reversed by selective PKC inhibition.
If PKCα/β isoforms are inhibited, then high glucose itself becomes protective against ischaemic damage.
Selective PKC inhibition may therefore be a useful therapeutic tool to limit the damage that can occur during a heart attack by stress-induced hyperglycaemia.
AbstractHyperglycaemia has a powerful association with adverse prognosis for patients with acute coronary syndromes (ACS). Previous work shows that high glucose prevents ischaemic preconditioning and causes electrical and mechanical disruption via protein kinase C α/β (PKCα/β) activation. The present study aimed to: (i) determine whether the adverse clinical association of hyperglycaemia in ACS can be replicated in preclinical cellular models of ACS and (ii) determine the importance of PKCα/β activation to the deleterious effect of glucose. Freshly isolated rat, guinea pig or rabbit cardiomyocytes were exposed to simulated ischaemia after incubation in the presence of normal (5 mm) or high (20 mm) glucose in the absence or presence of small molecule or tat‐peptide‐linked PKCαβ inhibitors. In each of the four conditions, the following hallmarks of cardioprotection were recorded using electrophysiology or fluorescence imaging: cardiomyocyte contraction and survival, action potential stability and time to failure, intracellular calcium and ATP, mitochondrial depolarization, ischaemia‐sensitive leak current, and time to Kir6.2 opening. High glucose alone resulted in decreased cardiomyocyte contraction and survival; however, it also imparted cardioprotection in the presence of PKCα/β inhibitors. This cardioprotective phenotype displayed improvements in all of the measured parameters and decreased myocardium damage during whole heart coronary ligation experiments. High glucose is deleterious to cellular and whole‐heart models of simulated ischaemia, in keeping with the clinical association of hyperglycaemia with an adverse outcome in ACS. PKCαβ inhibition revealed high glucose to show a cardioprotective phenotype in this setting. The results of the present study suggest the potential for the therapeutic application of PKCαβ inhibition in ACS associated with hyperglycaemia.
Endogenous AT1 receptor–protein kinase C activity in the hypothalamus augments glutamatergic input and sympathetic outflow in hypertension
Authors: Ma Huijie , Chen Shao‐Rui , Chen Hong , Pan Hui‐Lin 
Published: June 2019

Key points
The angiotensin AT1 receptor expression and protein kinase C (PKC)‐mediated NMDA receptor phosphorylation levels in the hypothalamus are increased in a rat genetic model of hypertension.
Blocking AT1 receptors or PKC activity normalizes the increased pre‐ and postsynaptic NMDA receptor activity of hypothalamic presympathetic neurons in hypertensive animals.
Inhibition of AT1 receptor–PKC activity in the hypothalamus reduces arterial blood pressure and sympathetic nerve discharges in hypertensive animals.
AT1 receptors in the hypothalamus are endogenously activated to sustain NMDA receptor hyperactivity and elevated sympathetic outflow via PKC in hypertension.
AbstractIncreased synaptic N‐methyl‐d‐aspartate receptor (NMDAR) activity in the hypothalamic paraventricular nucleus (PVN) plays a major role in elevated sympathetic output in hypertension. Although exogenous angiotensin II (AngII) can increase NMDAR activity in the PVN, whether endogenous AT1 receptor–protein kinase C (PKC) activity mediates the augmented NMDAR activity of PVN presympathetic neurons in hypertension is unclear. Here we show that blocking AT1 receptors with losartan or inhibiting PKC with chelerythrine significantly decreased the frequency of NMDAR‐mediated miniature excitatory postsynaptic currents (mEPSCs) and the amplitude of puff NMDA currents of retrogradely labelled spinally projecting PVN neurons in spontaneously hypertensive rats (SHRs). Also, treatment with chelerythrine abrogated the potentiating effect of AngII on mEPSCs and puff NMDA currents of labelled PVN neurons in SHRs. In contrast, neither losartan nor chelerythrine had any effect on mEPSCs or puff NMDA currents in labelled PVN neurons in Wistar–Kyoto (WKY) rats. Furthermore, levels of AT1 receptor mRNA and PKC‐mediated NMDAR phosphorylation in the PVN were significantly higher in SHRs than in WKY rats. In addition, microinjection of losartan or chelerythrine into the PVN substantially reduced blood pressure and renal sympathetic nerve discharges in SHRs but not in WKY rats. Chelerythrine blocked sympathoexcitatory responses to AngII microinjected into the PVN. Our findings suggest that endogenous AT1 receptor–PKC activity is essential for presynaptic and postsynaptic NMDAR hyperactivity of PVN presympathetic neurons and for the augmented sympathetic outflow in hypertension. This information advances our mechanistic understanding of the interplay between angiotensinergic and glutamatergic excitatory inputs in hypertension.
Smokers’ strategies across social grades to minimise the cost of smoking in a period with annual tax increases: evidence from a national survey in England
Authors: Kuipers Mirte AG , Partos Timea , McNeill Ann , Beard Emma , Gilmore Anna B , West Robert , Brown Jamie 
Published: June 2019

ObjectivesTo assess associations between smokers’ strategies to minimise how much their smoking costs and cost of smoking among smokers across three social grades during a period of annual tax increases in England.DesignRepeat cross-sectional.SettingEngland, May 2012–December 2016.Participants16 967 adult smokers in 56 monthly surveys with nationally representative samples.Measures and analysisWeighted generalised additive models assessed associations between four cost-minimising strategies (factory-made and roll-your-own (RYO) cigarette consumption levels, illicit and cross-border purchases) and cost of smoking (£/week). We adjusted for inflation rate, age, gender and secular and seasonal trends.ResultsCost of smoking did not increase above the rate of inflation. Factory-made cigarette consumption decreased, while proportion of RYO and, to a much lesser extent, illicit and cross-border purchases increased. These trends were only evident in lowest social grade. Cost of smoking was 12.99% lower with consumption of 10 fewer factory-made cigarettes (95% CI −13.18 to −12.80) and 5.86% lower with consumption of 10 fewer RYO cigarettes (95% CI −5.66 to −6.06). Consumption levels accounted for 60% of variance in cost. Cross-border and illicit tobacco purchases were associated with 9.64% (95% CI −12.94 to −6.33) and 9.47% (95% CI −12.74 to −6.20) lower costs, respectively, but due to low prevalence, accounted for only 0.2% of variation. Associations were similar across social grades, although weaker for illicit and cross-border purchases and stronger for consumption in higher social grades compared with lower social grades.ConclusionDuring a period of annual tax increases, the weekly cost of smoking did not increase above inflation. Cost-minimising strategies increased, especially among more disadvantaged smokers. Reducing cigarette consumption and switching to RYO tobacco explained a large part of cost variation, while use of illicit and cross-border purchasing played only a minor role.
Healthcare provision, functional ability and quality of life after proximal femoral fracture - ’ProFem': Study protocol of a population-based, prospective study based on individually linked survey and statutory health insurance data
Authors: Andrich Silke , Ritschel Michaela , Meyer Gabriele , Hoffmann Falk , Stephan Astrid , Baltes Marion , Blessin Juliane , Jobski Kathrin , Fassmer Alexander M , Haastert Burkhard , Gontscharuk Veronika , Arend Werner , Theunissen Lena , Colley Denise , Hinze Raoul , Thelen Simon , Fuhrmann Petra , Sorg Christian G G , Windolf Joachim , Rupprecht Christoph J , Icks Andrea 
Published: June 2019

IntroductionProximal femoral fractures (PFF) are among the most frequent fractures in older people. However, the situation of people with a PFF after hospital discharge is poorly understood. Our aim is to (1) analyse healthcare provision, (2) examine clinical and patient-reported outcomes (PROs), (3) describe clinical and sociodemographic predictors of these and (4) develop an algorithm to identify subgroups with poor outcomes and a potential need for more intensive healthcare.Methods and analysisThis is a population-based prospective study based on individually linked survey and statutory health insurance (SHI) data. All people aged minimum 60 years who have been continuously insured with the AOK Rheinland/Hamburg and experience a PFF within 1 year will be consecutively included (SHI data analysis). Additionally, 700 people selected randomly from the study population will be consecutively invited to participate in the survey. Questionnaire data will be collected in the participants’ private surroundings at 3, 6 and 12 months after hospital discharge. If the insured person considers themselves to be only partially or not at all able to take part in the survey, a proxy person will be interviewed where possible. SHI variables include healthcare provision, healthcare costs and clinical outcomes. Questionnaire variables include information on PROs, lifestyle characteristics and socioeconomic status. We will use multiple regression models to estimate healthcare processes and outcomes including mortality and cost, investigate predictors, perform non-responder analysis and develop an algorithm to identify vulnerable subgroups.Ethics and disseminationThe study was approved by the ethics committee of the Faculty of Medicine, Heinrich-Heine-University Düsseldorf (approval reference 6128R). All participants including proxies providing written and informed consent can withdraw from the study at any time. The study findings will be disseminated through scientific journals and public information.Trial registration numberDRKS00012554.
Better Use of Data to improve parent Satisfaction (BUDS): protocol for a prospective before-and-after pilot study employing mixed methods to improve parent experience of neonatal care
Authors: Sakonidou Susanna , Andrzejewska Izabela , Kotzamanis Sophia , Carnegie Wendy , Nakubulwa Mable , Woodcock Thomas , Modi Neena , Bell Derek , Gale Chris 
Published: June 2019

IntroductionHaving a baby that requires neonatal care is stressful and traumatic. Parents often report dissatisfaction with communication of clinical information. In the UK neonatal care data are recorded daily using electronic patient record systems (EPR), from which deidentified data form the National Neonatal Research Database (NNRD). We aim to evaluate the impact of sharing neonatal EPR data with parents, on parent-reported satisfaction, parent–staff interactions, staff workload and data completeness.MethodsA prospective, before-and-after, mixed-method study. Participants are parents of inpatient babies (maximum 90) and staff in a tertiary neonatal intensive care unit, London, UK. The intervention was developed by former neonatal parents, neonatologists and neonatal nurses: a communication tool for parents comprising individualised, written, daily infant updates for parents, derived from EPR data. The intervention will be provided to parents over 6 weeks. Plan-Do-Study-Act cycles will inform the tool’s iterative development and improvement. The tool’s impact will be measured using a validated parent survey, staff survey, data completeness measures and interviews.AnalysisPrimary outcome: parent satisfaction ‘with communication of clinical information and involvement in care’. Secondary outcomes: parent–staff interactions, staff workload, data completeness. Baseline survey data will be obtained from clinical service evaluation preceding the intervention. Baseline data completeness will be derived from the NNRD. During the intervention, surveys will be administered biweekly and data completeness assessed daily. We will analyse outcomes using run charts and partially paired statistical tests. Parent and staff interviews will explore information exchange and the communication tool’s impact.DiscussionThis study will evaluate the impact of a parent co-designed intervention on communication with parents in neonatal care and the completeness of routinely recorded electronic clinical data. Better use of routinely recorded clinical data provides the opportunity to improve parent satisfaction and increase the research utility of such data, benefiting clinical care.Ethics and disseminationReviewed and approved by the West Midlands—South Birmingham REC (18/WM/0175).Registration numberISRCTN62718241.
Family carer support in home and hospital: a cross-sectional survey of specialised palliative care
Authors: Vermorgen Maarten , De Vleminck Aline , Leemans Kathleen , Van den Block Lieve , Van Audenhove Chantal , Deliens Luc , Cohen Joachim 
Published: June 2019

ObjectivesTo evaluate: (1) to what extent family carers of people supported by specialised palliative care services felt they had been provided with information, support and aftercare and (2) how this varied by type of palliative care service, length of enrolment and characteristics of deceased.MethodsA cross-sectional postal survey was conducted using a structured questionnaire with nine items on information, support and aftercare provided by specialised palliative care services to family carers. Flemish family carers of people who had made use of specialised palliative care services at home or in hospital were contacted.ResultsOf all primary family carers (response rate of 53.5% resulting in n=1504), 77.7% indicated they were asked frequently by professionals how they were feeling. Around 75% indicated they had been informed about specific end-of-life topics and around 90% felt sufficiently supported before and immediately after the death. Family carers of people who had died in a palliative care unit, compared with other types of specialised palliative care services, indicated having received more information, support and aftercare.ConclusionsFamily carers evaluate the professional assistance provided more positively when death occurred in a palliative care unit. Policy changes might be needed to reach the same level of care across all specialised palliative care services.
Identifying and de-risking near-field opportunities through reliable pre-stack broadband attributes: examples from the Paleocene North Sea (UK–Norway) injectites play
Authors: Pernin Noémie , Feuilleaubois Laurent , Bird Tim , Reiser Cyrille 
Published: June 2019

Abstract

Tertiary injectites, which are re-mobilized sandstones, represent commercially attractive targets for near-field, long-reach tie-backs to existing field infrastructure above and adjacent to producing reservoirs. Injectites exhibit exceptional porosity–permeability and productivity, such that discoveries can add incremental reserves and lift production decline in mature fields. Abundant injectites are visible on seismic data in the Tertiary of the Viking Graben, but, as some disappointing wells have established, not all are hydrocarbon-charged. The challenge is to reliably distinguish hydrocarbon-filled high porosity–permeability features from tight or dry reservoirs in a cost-effective way. Regional rock physics analysis of injectite reservoirs, using well data from fields in Norway and the UK, reveals that a combination of elastic attributes can effectively discriminate lithology and hydrocarbon presences in these reservoirs. After pre-stack conditioning, broadband seismic data correlate reliably with wells, giving confidence that pre-stack seismic is faithfully imaging the elastic properties of the subsurface in lower Tertiary target intervals. Informed by rock physics analysis, a combination of broadband seismic elastic attributes is used to predict sand presence and de-risk hydrocarbon presence in reservoirs v. water-wet targets. Hydrocarbon sand distribution predicted from relative acoustic impedance and
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matches to known accumulations and identifies remaining near-field opportunities.
One North Sea fairway analysis: revealing opportunities through data integration across scales
Authors: Roberts Paul , Jordan Oliver , Steen Øyvind , Leppard Christopher , Janssen Jose Salvadores , Baudia Emmanuelle , Ramm Alice , Helgesen Geir 
Published: June 2019

Abstract
While the North Sea has many well-established prolific plays, the downwards trend of annual discovered resources has cast doubt on the continued ability of the stratigraphy to provide world-class future discoveries. However, despite this downwards trend, significant discoveries can still be made, such as Johan Sverdrup (Norwegian North Sea in 2010). Furthermore, new sub-plays within this petroleum system and new unproven plays with alternative source rocks are still being tested, although often with associated higher perceived pre-drill subsurface risk (Pg) and/or lower volume potential. There is room for new optimism, however, as new approaches and technologies are deployed, which could lead to future success. The analysis of regionally extensive integrated datasets allows for the interpretation of ‘One North Sea’ fairway maps that honour detailed observations from the prospect scale through to the play scale and beyond. By integrating source-rock maturity, hydrocarbon expulsion and migration, well shows, seismically defined gas chimneys, and direct hydrocarbon indications onto regional fairway maps, hydrocarbons can be traced from the source kitchens to the traps. By utilizing a zoom-in/zoom-out methodology, models can be developed, tested and applied across the basin, allowing new ideas to emerge, de-risk established prospects and reveal under-appreciated hydrocarbon volumetric upsides.
Deletion of organic cation transporter Oct3 promotes hepatic fibrosis via upregulation of TGFβ
Authors: Vollmar Johanna , Kim Yong Ook , Marquardt Jens U. , Becker Diana , Galle Peter R. , Schuppan Detlef , Zimmermann Tim 
Published: June 2019

Organic cation transporters (OCT) are responsible for the intracellular uptake and detoxification of a broad spectrum of endogenous and exogenous substrates. OCTs are downregulated in cholestasis, fibrosis, and hepatocellular carcinoma, but the underlying molecular mechanisms and downstream effects of OCT deletion are unknown. Oct3-knockout ( Oct3−/−; FVB.Slc22a3tm10pb) and wild-type (WT; FVB) mice were subject to escalating doses of carbon tetrachloride (CCl4) or thioacetamide (TAA) for 6 wk to induce advanced parenchymal liver fibrosis. Secondary biliary fibrosis was generated by bile duct ligation. Liver fibrosis was assessed by hydroxyproline determination, quantitative Sirius red morphometry, and quantitative real-time PCR for fibrosis and inflammation-related genes. Ductular reaction was assessed by bile duct count per field of view in hematoxylin and eosin staining. General gene expression analyses were performed in liver tissue from untreated Oct3−/− and WT mice. Finally, primary murine hepatocytes were treated with the nonselective OCT inhibitor quinine, and transforming growth factor-β1 ( Tgfβ1) protein expression was quantified by quantitative real-time PCR and Western blot. Oct3−/− mice developed significantly more fibrosis after bile duct ligation and CCl4 treatment compared with WT mice. Ductular reaction was enhanced in the long-term model. Concomitantly, Oct1 mRNA expression was downregulated during cholestatic and chemically (TAA and CCl4) induced fibrogenesis. The downregulation of Oct1 mRNA in fibrotic liver tissue reversed within 4 wk after TAA cessation. Gene expression analysis by next-generation sequencing revealed an enrichment of Tgfβ1 target genes in Oct3−/− mice. Tgfβ1 mRNA expression was significantly upregulated after chemically induced fibrosis ( P < 0.001) in Oct3−/− compared with WT mice. Accordingly, in primary murine hepatocytes functional inhibition of OCT led to an upregulation of Tgfβ1 mRNA expression. Loss of Oct3 promotes fibrogenesis by affecting Tgfβ-mediated homeostasis in mice with chronic biliary and parenchymal liver damage and fibrosis. NEW & NOTEWORTHY We show for the first time that organic cation transporter 3 (Oct3) is not only downregulated in fibrosis but loss of Oct3 also leads to an upregulation of transforming growth factor-β contributing to fibrosis progression.
Spike-field Granger causality for hybrid neural data analysis
Authors: Gong Xiajing , Li Wu , Liang Hualou 
Published: June 2019

Neurotechnological innovations allow for simultaneous recording at various scales, ranging from spiking activity of individual neurons to large neural populations’ local field potentials (LFPs). This capability necessitates developing multiscale analysis of spike-field activity. A joint analysis of the hybrid neural data is crucial for bridging the scales between single neurons and local networks. Granger causality is a fundamental measure to evaluate directional influences among neural signals. However, it is mainly limited to inferring causal influence between the same type of signals—either LFPs or spike trains—and not well developed between two different signal types. Here we propose a model-free, nonparametric spike-field Granger causality measure for hybrid data analysis. Our measure is distinct from existing methods in that we use “binless” spikes (precise spike timing) rather than “binned” spikes (spike counts within small consecutive time windows). The latter clearly distort the information in the mixed analysis of spikes and LFP. Therefore, our spectral estimate of spike trains is directly applied to the neural point process itself, i.e., sequences of spike times rather than spike counts. Our measure is validated by an extensive set of simulated data. When the measure is applied to LFPs and spiking activity simultaneously recorded from visual areas V1 and V4 of monkeys performing a contour detection task, we are able to confirm computationally the long-standing experimental finding of the input-output relationship between LFPs and spikes. Importantly, we demonstrate that spike-field Granger causality can be used to reveal the modulatory effects that are inaccessible by traditional methods, such that spike→LFP Granger causality is modulated by the behavioral task, whereas LFP→spike Granger causality is mainly related to the average synaptic input. NEW & NOTEWORTHY It is a pressing question to study the directional interactions between local field potential (LFP) and spiking activity. In this report, we propose a model-free, nonparametric spike-field Granger causality measure that can be used to reveal directional influences between spikes and LFPs. This new measure is crucial for bridging the scales between single neurons and neural networks; hence it represents an important step to explicate how the brain orchestrates information processing.