bluuebunny/crossref_metadata_2025_split huggingface dataset:
How can consultant-led childbirth care at time of delivery be maximised? A modelling study
Authors: Allen Michael , Villeneuve Emma , Pitt Martin , Thornton Steve 
Published: July 2020

ObjectiveThe Royal College of Obstetricians and Gynaecologists has advised that consolidation of birth centres, where reasonable, into birth centres of at least 6000 admissions per year should allow constant consultant presence. Currently, only 17% of mothers attend such birth centres. The objective of this work was to examine the feasibility of consolidation of birth centres, from the perspectives of birth centre size and travel times for mothers.DesignComputer-based optimisation.SettingHospital-based births.Population or sample1.91 million admissions in 2014–2016.MethodsA multiple-objective genetic algorithm.Main outcome measuresTravel time for mothers and size of birth centres.ResultsCurrently, with 161 birth centres, 17% of women attend a birth centre with at least 6000 admissions per year. We estimate that 95% of women have a travel time of 30 min or less. An example scenario, with 100 birth centres, could provide 75% of care in birth centres with at least 6000 admissions per year, with 95% of women travelling 35 min or less to their closest birth centre. Planning at local level leads to reduced ability to meet admission and travel time targets.ConclusionsWhile it seems unrealistic to have all births in birth centres with at least 6000 admissions per year, it appears realistic to increase the percentage of mothers attending this type of birth centre from 17% to about 75% while maintaining reasonable travel times. Planning at a local level leads to suboptimal solutions.
Cardiac arrest as a reportable condition: a cohort study of the first 6 years of the Norwegian out-of-hospital cardiac arrest registry
Authors: Tjelmeland Ingvild Beathe Myrhaugen , Alm-Kruse Kristin , Andersson Lars-Jøran , Bratland Ståle , Hafstad Arne-Ketil , Haug Bjørn , Langørgen Jørund , Larsen Alf Inge , Lindner Thomas Werner , Nilsen Jan Erik , Olasveengen Theresa M , Soreide Eldar , Skogvoll Eirik , Kramer-Johansen Jo 
Published: July 2020

ObjectivesThe Norwegian Cardiac Arrest Registry (NorCAR) was established in 2013 when cardiac arrest became a mandatory reportable condition. The aim of this cohort study is to describe how the world’s first mandatory, population-based cardiac arrest registry evolved during its first 6 years.SettingNorway has a total population of 5.3 million inhabitants with a population density that varies considerably. All residents are assigned a unique identifier number, giving nationally approved registries access to information about all births and deaths in the country. Data in the registry are entered by data processors; public employees with close links to the emergency medical services. All data processors undergo a standardised training and meet for yearly retraining and updates.ParticipantsAll events of cardiac arrest where bystanders or healthcare professionals have started cardiopulmonary resuscitation or performed defibrillation are included into the NorCAR.Primary and secondary outcome measuresSince the establishment of the registry, the number of reporting health trusts, the number of reported events and the corresponding population at risk were followed year by year. Outcome is measured as changes in inclusion rate, incidence per 100 000 inhabitants and survival to 30 days after cardiac arrest.ResultsIn total, 14 849 cases were registered over 6 years, between 2013 and 2018. The number of health trusts reporting rose steadily from 2013. Within 3 years, all trusts reported to the registry with an increasing number of events reported; going from 1101 to 3400 per year. The prevalence of bystander cardiopulmonary resuscitation increased slightly, but the population incidence of survival did not change.ConclusionDeclaring cardiac arrest as a reportable condition and close follow-up of all reporting areas is essential when building a national registry.
Impact of carbohydrate-reduced nutrition in septic patients on ICU: study protocol for a prospective randomised controlled trial
Authors: Rahmel Tim , Hübner Max , Koos Björn , Wolf Alexander , Willemsen Katrin-Maria , Strauß Gabriele , Effinger David , Adamzik Michael , Kreth Simone 
Published: July 2020

IntroductionSepsis is defined as detrimental immune response to an infection. This overwhelming reaction often abolishes a normal reconstitution of the immune cell homeostasis that in turn increases the risk for further complications. Recent studies revealed a favourable impact of ketone bodies on resolution of inflammation. Thus, a ketogenic diet may provide an easy-to-apply and cost-effective treatment option potentially alleviating sepsis-evoked harm. This study is designed to assess the feasibility, efficiency and safety of a ketogenic diet in septic patients.Methods and analysisThis monocentric study is a randomised, controlled and open-label trial, which is conducted on an intensive care unit of a German university hospital. As intervention enteral nutrition with reduced amount of carbohydrates (ketogenic) or standard enteral nutrition (control) is applied. The primary endpoint is the detection of ketone bodies in patients’ blood and urine samples. As secondary endpoints, the impact on important safety-relevant issues (eg, glucose metabolism, lactate serum concentration, incidence of metabolic acidosis, thyroid function and 30-day mortality) and the effect on the immune system are analysed.Ethics and disseminationThe study has received the following approvals: Ethics Committee of the Medical Faculty of Ruhr-University Bochum (No. 18-6557-BR). Results will be made available to critical care survivors, their caregivers, the funders, the critical care societies and other researchers by publication in a peer-reviewed journal.Trial registration numbersGerman Clinical Trial Register (DRKS00017710); Universal Trial Number (U1111-1237-2493).
Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial
Authors: Liu Fang , Zhu Yuan , Zhang Jing , Li Yiming , Peng Zhiyong 
Published: July 2020

IntroductionThe rapid worldwide spread of COVID-19 has caused a global health crisis. To date, symptomatic supportive care has been the most common treatment. It has been reported that the mechanism of COVID-19 is related to cytokine storms and subsequent immunogenic damage, especially damage to the endothelium and alveolar membrane. Vitamin C (VC), also known as L-ascorbic acid, has been shown to have antimicrobial and immunomodulatory properties. A high dose of intravenous VC (HIVC) was proven to block several key components of cytokine storms, and HIVC showed safety and varying degrees of efficacy in clinical trials conducted on patients with bacterial-induced sepsis and acute respiratory distress syndrome (ARDS). Therefore, we hypothesise that HIVC could be added to the treatment of ARDS and multiorgan dysfunction related to COVID-19.Methods and analysisThe investigators designed a multicentre prospective randomised placebo-controlled trial that is planned to recruit 308 adults diagnosed with COVID-19 and transferred into the intensive care unit. Participants will randomly receive HIVC diluted in sterile water or placebo for 7 days once enrolled. Patients with a history of VC allergy, end-stage pulmonary disease, advanced malignancy or glucose-6-phosphate dehydrogenase deficiency will be excluded. The primary outcome is ventilation-free days within 28 observational days. This is one of the first clinical trials applying HIVC to treat COVID-19, and it will provide credible efficacy and safety data. We predict that HIVC could suppress cytokine storms caused by COVID-19, help improve pulmonary function and reduce the risk of ARDS of COVID-19.Ethics and disseminationThe study protocol was approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (identifiers: Clinical Ethical Approval No. 2020001). Findings of the trial will be disseminated through peer-reviewed journals and scientific conferences.Trial registration numberNCT04264533.
Patient deaths and medical residents: an Asian perspective
Authors: Tan Teresa , Koh Pei Lin , Levetown Marcia , Wong Lisa , Lee Joanne , Yong Woon Chai , Yap Eng Soo 
Published: July 2020

ObjectivesDeath is a significant event that affects healthcare providers emotionally. We aimed to determine internal medicine (IM) and paediatric (PD) residents’ responses and the impact on the residents following patient deaths, and to compare any differences between IM and PD residents. We also aimed to determine whether sufficient resources and measures were in place to support residents through their grief process.MethodsThis is a single-centre, cross-sectional study involving residents from IM and PD programmes from an academic tertiary hospital in Singapore. The residents completed a questionnaire regarding their responses and emotions after experiencing patient deaths.ResultsA total of 122 residents (85 IM and 37 PD, equally distributed between year 1 to year 4 of residency training) participated, with 100% response rate. Only half (57%) felt they would be comfortable treating a dying patient and 66.4% reported feeling sad following their patient’s death. Most (79.5%) were not aware of support resources that were available and 82% agreed that formal bereavement training should be included in the residency curriculum. PD residents had more negative symptoms than IM residents, with poor concentration (PD 35.1% vs IM 16.5%, p=0.02) and lethargy (PD 35.1% vs IM 9.4%, p<0.01) being the most common.ConclusionIn our Asian context, residents are negatively affected by patient deaths, especially the PD residents. There is a need to incorporate relevant bereavement training for all residents.
Predictors of extra-articular manifestations in axial spondyloarthritis and their influence on TNF-inhibitor prescribing patterns: results from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis
Authors: Derakhshan Mohammad H , Dean Linda , Jones Gareth T , Siebert Stefan , Gaffney Karl 
Published: July 2020

ObjectivesExtra-articular manifestations (EAMs) are important systemic features of axial spondyloarthritis (axSpA), which may influence the choice of tumour necrosis factor-inhibitor (TNFi). We examined the cumulative incidence and predictors of EAMs and the influence of these on first TNFi choice in a ‘real-world’ cohort of patients with axSpA.MethodsClinical and patient-reported outcomes of 2420 patients with axSpA from 83 centres were collected by the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis. Lifestyle factors for EAMs (acute anterior uveitis (AAU), inflammatory bowel diseases (IBD), psoriasis) were compared with those without EAMs. Also, the association between pretreatment EAMs and choice of first TNFi (adalimumab, etanercept, certolizumab) was analysed.ResultsAAU was directly associated with human leukocyte antigen (HLA)-B27 (incidence rate ratio (IRR) 1.95, 95% CI 1.40 to 2.73) and inversely associated with ever-smoking (IRR=0.71, 95% CI 0.55 to 0.92). For both psoriasis and IBD, there was an inverse relationship with HLA-B27 (IRR 0.54, 95% CI 0.36 to 0.79 and IRR 0.63, 95% CI 0.43 to 0.91, respectively). A diagnosis of either AAU (OR 3.79, 95% CI 2.11 to 6.80) or IBD (OR 5.50, 95% CI 2.09 to 14.46) was associated with preference for adalimumab versus others. In contrast, a diagnosis of either AAU (OR 0.14, 95% CI 0.06 to 0.33) or IBD (OR 0.17, 95% CI 0.05 to 0.57) was associated with less preference for etanercept over other TNFi.ConclusionThe higher occurrence of AAU and lower occurrence of psoriasis and IBD in HLA-B27-positive patients with axSpA are consistent with current pathophysiology. Patients with previous AAU and IBD are more likely to be prescribed adalimumab and less likely to receive etanercept, consistent with the superior efficacy of monoclonal TNFi for these indications. Future work will determine whether EAMs influence TNFi survival, or effectiveness, and whether this varies between agents.
Delay-Optimal Policies in Partial Fork-Join Systems with Redundancy and Random Slowdowns
Authors: Zubeldia Martin 
Published: July 2020

We consider a large distributed service system consisting of n homogeneous servers with infinite capacity FIFO queues. Jobs arrive as a Poisson process of rate λn/kn (for some positive constant kn and integer kn). Each incoming job consists of ???? identical tasks that can be executed in parallel, and that can be encoded into at least ???? ?replicas" of the same size (by introducing redundancy) so that the job is considered to be completed when any kn replicas associated with it finish their service. Moreover, we assume that servers can experience random slowdowns in their processing rate so that the service time of a replica is the product of its size and a random slowdown.
First, we assume that the server slowdowns are shifted exponential and independent of the replica sizes. In this setting we show that the delay of a typical job is asymptotically minimized (as n - ∞) when the number of replicas per task is a constant that only depends on the arrival rate λ, and on the expected slowdown of servers.
Second, we introduce a new model for the server slowdowns in which larger tasks experience less variable slowdowns than smaller tasks. In this setting we show that, under the class of policies where all replicas start their service at the same time, the delay of a typical job is asymptotically minimized (as n - ∞) when the number of replicas per task is made to depend on the actual size of the tasks being replicated, with smaller tasks being replicated more than larger tasks.
Optimal Data Placement for Heterogeneous Cache, Memory, and Storage Systems
Authors: Zhang Lei , Karimi Reza , Ahmad Irfan , Vigfusson Ymir 
Published: July 2020

New memory technologies are blurring the previously distinctive performance characteristics of adjacent layers in the memory hierarchy. No longer are such layers orders of magnitude different in request latency or capacity. Beyond the traditional single-layer view of caching, we now must re-cast the problem as a data placement challenge: which data should be cached in faster memory if it could instead be served directly from slower memory?
We present Chopt, an offline algorithm for data placement across multiple tiers of memory with asymmetric read and write costs. We show that Chopt is optimal and can therefore serve as the upper bound of performance gain for any data placement algorithm. We also demonstrate an approximation of Chopt which makes its execution time for long traces practical using spatial sampling of requests incurring a small 0.2% average error on representative workloads at a sampling ratio of 1%. Our evaluation of Chopt on more than 30 production traces and benchmarks shows that optimal data placement decisions could improve average request latency by 8.2%-44.8% when compared with the long-established gold standard: Belady and Mattson's offline, evict-farthest-in-the-future optimal algorithms. Our results identify substantial improvement opportunities for future online memory management research.
Logarithmic Communication for Distributed Optimization in Multi-Agent Systems
Authors: London Palma , Vardi Shai , Wierman Adam 
Published: July 2020

Classically, the design of multi-agent systems is approached using techniques from distributed optimization such as dual descent and consensus algorithms. Such algorithms depend on convergence to global consensus before any individual agent can determine its local action. This leads to challenges with respect to communication overhead and robustness, and improving algorithms with respect to these measures has been a focus of the community for decades.
This paper presents a new approach for multi-agent system design based on ideas from the emerging field of local computation algorithms. The frameworkwe develop, LOcal Convex Optimization (LOCO), is the first local computation algorithm for convex optimization problems and can be applied in a wide-variety of settings. We demonstrate the generality of the framework via applications to Network Utility Maximization (NUM) and the distributed training of Support Vector Machines (SVMs), providing numerical results illustrating the improvement compared to classical distributed optimization approaches in each case.
Constituents and Practical Impacts on Civic Engagement of Associations in Contemporary China
Authors: Ji Yingying 
Published: July 2020

Abstract
The analysis in this paper reveals that on the individual level, the institutional framework continues to exert a profound impact on social organizations’ forms and civic engagement in China. The CGSS2012-based analysis leads to the following findings. For a start, political party members and danwei employees demonstrate a higher degree of social organizational involvement and civic engagement. In the meanwhile, the party members’ role in promoting civic engagement is achieved to some extent through mediating effect of social organizations. Next, various types of social organizations have significantly increased civic engagement on a practical level. Finally, income plays a large role to increase the individuals’ organizational involvement, albeit with no obvious influence on civic engagement in practice. These findings are significant in the following ways. First, from an empirical perspective, the current institutional design for social organizations to participate in social governance has delivered the expected results. Second, it confirmed the existence of activists with distinct features in social life as well as the integration of multiple governing networks in social space at grassroots level. Third, in theory, this paper noted that apart from institutional environment of technical governance by bureaucratic government, institutional framework constitutes an important institutional foundation for the development of social organizations, giving rise to the need of further discussions about the interaction mechanism between political parties and society.
Dysregulation of the OGF–OGFr pathway correlates with elevated serum OGF and ocular surface complications in the diabetic rat
Authors: Zagon Ian S , Sassani Joseph W , Purushothaman Indira , McLaughlin Patricia J 
Published: July 2020

Diabetes often presents with ocular surface complications including dry eye, keratopathy, and altered sensitivity, along with systemic disorders. A common theme associated with corneal surface defects is decreased cellular proliferation. The opioid growth factor (OGF)–OGF receptor (OGFr) regulatory axis maintains epithelial homeostasis and can be modulated by naltrexone, an opioid receptor antagonist, to block OGF–OGFr interaction and increase cellular replication. Complete blockade using naltrexone accelerates cell proliferation, increases the rate of re-epithelialization in corneal surface abrasions, reverses dry eye, and restores corneal surface sensitivity in animal models of type 1 and type 2 diabetes. Data on the efficacy of naltrexone in these models suggest that the OGF–OGFr axis is dysregulated in diabetes. In the present study, we investigated the OGF–OGFr axis by assessing serum and tissue levels of OGF and OGFr during the development of streptozotocin-induced hyperglycemia and postulated a mechanism of action. We correlated the dysregulation of the OGF–OGFr axis with the onset and magnitude of corneal surface complications (e.g. tear fluid production, corneal surface sensitivity) in type 1 diabetes (T1D). Serum levels of OGF increased in both uncontrolled T1D and insulin-controlled (T1D-INS) male rats within four weeks of streptozotocin injection. Serum OGFr levels were significantly reduced in diabetic rats on weeks 3 and 8 post streptozotocin. Tear production was significantly reduced, and corneal sensitivity measurements were abnormal in both T1D and T1D-INS animals within four weeks of streptozotocin. Corneal re-epithelialization was delayed in T1D rats, but not in T1D-INS animals; however, expression levels of the inhibitory growth factor OGF and its receptor, OGFr, were elevated in the corneal epithelium more than 2-fold in both diabetic groups. These data demonstrate for the first time that dysregulation of the OGF–OGFr axis in the diabetic cornea is associated with the onset and magnitude of ocular surface complications. Impact statement This research extends our knowledge about the presence and role of the OGF–OGFr regulatory axis in type 1 diabetes (T1D) and demonstrates specific targets within the pathway that are dysregulated. Serum levels of OGF, an inhibitory growth factor, are significantly elevated in male T1D rats, and OGFr serum values are increased in T1D. The onset of elevated OGF corresponds to the onset of ocular surface complications including dry eye, delayed corneal epithelial repair, and abnormal corneal surface sensitivity in T1D. Systemic insulin does not protect against elevated OGF levels or the onset of dry eye and sensitivity. These data are the first to associate some ocular surface defects in T1D with alterations in the OGF–OGFr pathway.
Hybrid phenotype mining method for investigating off-target protein and underlying side effects of anti-tumor immunotherapy
Authors: Zheng Yuyu , Meng Xiangyu , Zweigenbaum Pierre , Chen Lingling , Xia Jingbo 
Published: July 2020

AbstractBackgroundIt is of utmost importance to investigate novel therapies for cancer, as it is a major cause of death. In recent years, immunotherapies, especially those against immune checkpoints, have been developed and brought significant improvement in cancer management. However, on the other hand, immune checkpoints blockade (ICB) by monoclonal antiboties may cause common and severe adverse reactions (ADRs), the cause of which remains largely undetermined. We hypothesize that ICB-agents may induce adverse reactions through off-target protein interactions, similar to the ADR-causing off-target effects of small molecules. In this study, we propose a hybrid phenotype mining approach which integrates molecular level information and provides new mechanistic insights for ICB-associated ADRs.MethodsWe trained a conditional random fields model on the TAC 2017 benchmark training data, then used it to extract all drug-centric phenotypes for the five anti-PD-1/PD-L1 drugs from the drug labels of the DailyMed database. Proteins with structure similar to the drugs were obtained by using BlastP, and the gene targets of drugs were obtained from the STRING database. The target-centric phenotypes were extracted from the human phenotype ontology database. Finally, a screening module was designed to investigate off-target proteins, by making use of gene ontology analysis and pathway analysis.ResultsEventually, through the cross-analysis of the drug and target gene phenotypes, the off-target effect caused by the mutation of gene BTK was found, and the candidate side-effect off-target site was analyzed.ConclusionsThis research provided a hybrid method of biomedical natural language processing and bioinformatics to investigate the off-target-based mechanism of ICB treatment. The method can also be applied for the investigation of ADRs related to other large molecule drugs.