bluuebunny/crossref_metadata_2025_split huggingface dataset:
PP28 ‘They are not silly people – they know the difference’: clinician focus group views on a pilot randomised controlled trial of prehospital continuous positive airway pressure (CPAP)
Authors: Miller Joshua , Keating Samuel , Scott Alex , Fuller Gordon , Goodacre Steve 
Published: September 2019

BackgroundContinuous positive airway pressure (CPAP) is not in widespread use in UK ambulance services, but could benefit patients with acute respiratory failure (ARF). As a new treatment in this context, clinician acceptability is an important factor in the feasibility of conducting definitive research in the prehospital arena.MethodsAs part of a pilot randomised controlled trial (the ACUTE study), nine trial-trained paramedics took part in three semi-structured focus groups. 204 trained staff had been given the opportunity to take part. The sample included six staff who had recruited to the trial, one who had not, and two who had withdrawn from it. Audio-recordings were transcribed and analysed thematically.ResultsParticipants described facilitators to trial participation including: clear eligibility criteria and patient documentation, access to demonstration equipment, training away from the work environment, and repeated patient recruitment. Barriers to taking part included: the lack of protected time for training, inadequate workplace facilities for the electronic learning package used, adverse responses by receiving hospital staff, and infrequent patient exposure. Both paramedics who withdrew cited the inconvenience of carrying packs each shift. Some participants described anxiety and distress when opening packs to find a standard-care mask, and reported patients having similar reactions.ConclusionsFuture researchers could promote improved workplace computing facilities and increased provision of face-to-face training days, which were praised by participants in these focus groups, but limited to a single event distant from some staff. Greater stakeholder engagement by researchers could reduce the difficulties at hospital handover reported by some ambulance staff. Where blinding is not possible, the perceptions of clinicians and patients should be considered carefully, as this study shows both may have adverse emotional responses to being treated with standard care, particularly when prospective consent discussions describe the trial intervention as potentially beneficial.
PP32 Electronic records in ambulances – an observational study (ERA)
Authors: Porter Alison , Black Sarah , Dale Jeremy , Harris-Mayes Robert , Lawrenson Robin , Lyons Ronan , Mason Suzanne , Morrison Zoe , Potts Henry , Siriwardena Niro , Rees Nigel , Snooks Helen , Williams Victoria 
Published: September 2019

BackgroundThe introduction of information technology (IT) in emergency ambulance services to electronically capture, interpret and store patient data can support out of hospital care. Although electronic health records (EHR) in ambulances and other digital technology are encouraged by national policy across the UK, there is considerable variation across services in terms of implementation. We aimed to understand how electronic records can be most effectively implemented in a pre-hospital context, in order to support a safe and effective shift from acute to community-based care.MethodsWe conducted a mixed-methods study with four work packages (WPs): a rapid literature review, a telephone survey of all 13 freestanding UK ambulance services, detailed case studies in four selected sites, and a knowledge sharing workshop.ResultsWe found considerable variation in hardware and software. Services were in a state of constant change, with services transitioning from one system to another, reverting to paper, or upgrading. Ambulance clinicians were dealing with partial or unclear information, which may not fit comfortably with the EHR. Clinicians continued to use indirect data input approaches such as first writing on a glove. The primary function of EHR in all services seemed to be as a store for patient data. There was, as yet, limited evidence of their full potential being realised to transfer information, support decision making or change patient care.ConclusionsRealising the full benefits of EHR requires engagement with other parts of the local health economy, dealing with the challenges of interoperability. Clinicians and data managers are likely to want very different things from a data set, and need to be presented with only the information that they need.
Jeans instability and turbulent gravitational collapse of Bose–Einstein condensate dark matter halos
Authors: Harko Tiberiu 
Published: September 2019

Abstract
We consider the Jeans instability and the gravitational collapse of the rotating Bose–Einstein condensate dark matter halos, described by the zero temperature non-relativistic Gross–Pitaevskii equation, with repulsive interparticle interactions. In the Madelung representation of the wave function, the dynamical evolution of the galactic halos is described by the continuity and the hydrodynamic Euler equations, with the condensed dark matter satisfying a polytropic equation of state with index $$n=1$$n=1. By considering small perturbations of the quantum hydrodynamical equations we obtain the dispersion relation and the Jeans wave number, which includes the effects of the vortices (turbulence), of the quantum pressure and of the quantum potential, respectively. The critical scales above which condensate dark matter collapses (the Jeans radius and mass) are discussed in detail. We also investigate the collapse/expansion of rotating condensed dark matter halos, and we find a family of exact semi-analytical solutions of the hydrodynamic evolution equations, derived by using the method of separation of variables. An approximate first order solution of the fluid flow equations is also obtained. The radial coordinate dependent mass, density and velocity profiles of the collapsing/expanding condensate dark matter halos are obtained by using numerical methods.
Fractured basement play development on the UK and Norwegian rifted margins
Authors: Trice Robert , Hiorth Cecile , Holdsworth Robert 
Published: September 2019

Abstract
Fractured crystalline basement reservoirs (basement) on the UK Continental Shelf (UKCS) and the Norwegian Continental Shelf (NCS) have been underexplored. Over the last 12 years, Hurricane Energy has deliberately set out to explore basement potential by exploring and appraising the Rona Ridge, West of Shetland; and the Rona Ridge Lancaster Field is now being progressed towards being the first UK basement field development. The Norwegian basement play is also recognized as a potentially material resource through serendipitous oil discoveries, with the 16/1-15 well, drilled in 2011, being the first successful full-scale basement test on the NCS. Building on this success, the 2018 Rolvsnes appraisal well (16/1-28 S) has demonstrated the significant basement potential of the extensive Utsira High and confirmed the materiality of a Norwegian basement play. The Rona Ridge and Utsira basement discoveries are used as a comparison with two other, yet to be evaluated, prospective basement plays on the NCS, with the objective of establishing technical subject areas where future UKCS and NCS collaboration would aid in accelerating understanding of the UKCS–NCS basement play.
RNA-Binding Protein ZFP36L1 Suppresses Hypoxia and Cell-Cycle Signaling
Authors: Loh Xin-Yi , Sun Qiao-Yang , Ding Ling-Wen , Mayakonda Anand , Venkatachalam Nachiyappan , Yeo Mei-Shi , Silva Tiago C. , Xiao Jin-Fen , Doan Ngan B. , Said Jonathan W. , Ran Xue-Bin , Zhou Si-Qin , Dakle Pushkar , Shyamsunder Pavithra , Koh Angele Pei-Fern , Huang Ruby Yun-Ju , Berman Benjamin P. , Tan Soo-Yong , Yang Henry , Lin De-Chen , Koeffler H. Phillip 
Published: September 2019

Abstract

ZFP36L1 is a tandem zinc-finger RNA-binding protein that recognizes conserved adenylate-uridylate–rich elements (ARE) located in 3′untranslated regions (UTR) to mediate mRNA decay. We hypothesized that ZFP36L1 is a negative regulator of a posttranscriptional hub involved in mRNA half-life regulation of cancer-related transcripts. Analysis of in silico data revealed that ZFP36L1 was significantly mutated, epigenetically silenced, and downregulated in a variety of cancers. Forced expression of ZFP36L1 in cancer cells markedly reduced cell proliferation in vitro and in vivo, whereas silencing of ZFP36L1 enhanced tumor cell growth. To identify direct downstream targets of ZFP36L1, systematic screening using RNA pull-down of wild-type and mutant ZFP36L1 as well as whole transcriptome sequencing of bladder cancer cells {plus minus} tet-on ZFP36L1 was performed. A network of 1,410 genes was identified as potential direct targets of ZFP36L1. These targets included a number of key oncogenic transcripts such as HIF1A, CCND1, and E2F1. ZFP36L1 specifically bound to the 3′UTRs of these targets for mRNA degradation, thus suppressing their expression. Dual luciferase reporter assays and RNA electrophoretic mobility shift assays showed that wild-type, but not zinc-finger mutant ZFP36L1, bound to HIF1A 3′UTR and mediated HIF1A mRNA degradation, leading to reduced expression of HIF1A and its downstream targets. Collectively, our findings reveal an indispensable role of ZFP36L1 as a posttranscriptional safeguard against aberrant hypoxic signaling and abnormal cell-cycle progression.

Significance:
RNA-binding protein ZFP36L1 functions as a tumor suppressor by regulating the mRNA stability of a number of mRNAs involved in hypoxia and cell-cycle signaling.
Genome-Wide CRISPR-Cas9 Screen Reveals Selective Vulnerability of ATRX-Mutant Cancers to WEE1 Inhibition
Authors: Liang Junbo , Zhao Hong , Diplas Bill H. , Liu Song , Liu Jianmei , Wang Dingding , Lu Yan , Zhu Qing , Wu Jiayu , Wang Wenjia , Yan Hai , Zeng Yi-Xin , Wang Xiaoyue , Jiao Yuchen 
Published: September 2019

Abstract

The tumor suppressor gene ATRX is frequently mutated in a variety of tumors including gliomas and liver cancers, which are highly unresponsive to current therapies. Here, we performed a genome-wide synthetic lethal screen, using CRISPR-Cas9 genome editing, to identify potential therapeutic targets specific for ATRX-mutated cancers. In isogenic hepatocellular carcinoma (HCC) cell lines engineered for ATRX loss, we identified 58 genes, including the checkpoint kinase WEE1, uniquely required for the cell growth of ATRX null cells. Treatment with the WEE1 inhibitor AZD1775 robustly inhibited the growth of several ATRX-deficient HCC cell lines in vitro, as well as xenografts in vivo. The increased sensitivity to the WEE1 inhibitor was caused by accumulated DNA damage–induced apoptosis. AZD1775 also selectively inhibited the proliferation of patient-derived primary cell lines from gliomas with naturally occurring ATRX mutations, indicating that the synthetic lethal relationship between WEE1 and ATRX could be exploited in a broader spectrum of human tumors. As WEE1 inhibitors have been investigated in several phase II clinical trials, our discovery provides the basis for an easily clinically testable therapeutic strategy specific for cancers deficient in ATRX.

Significance:
ATRX-mutant cancer cells depend on WEE1, which provides a basis for therapeutically targeting WEE1 in ATRX-deficient cancers.
See related commentary by Cole, p. 375
Epigenomic Profiling Discovers Trans-lineage SOX2 Partnerships Driving Tumor Heterogeneity in Lung Squamous Cell Carcinoma
Authors: Sato Takashi , Yoo Seungyeul , Kong Ranran , Sinha Abhilasha , Chandramani-Shivalingappa Prashanth , Patel Ayushi , Fridrikh Maya , Nagano Osamu , Masuko Takashi , Beasley Mary Beth , Powell Charles A. , Zhu Jun , Watanabe Hideo 
Published: September 2019

Abstract

Molecular characterization of lung squamous cell carcinoma (LUSC), one of the major subtypes of lung cancer, has not sufficiently improved its nonstratified treatment strategies over decades. Accumulating evidence suggests that lineage-specific transcriptional regulators control differentiation states during cancer evolution and underlie their distinct biological behaviors. In this study, by investigating the super-enhancer landscape of LUSC, we identified a previously undescribed “neural” subtype defined by Sox2 and a neural lineage factor Brn2, as well as the classical LUSC subtype defined by Sox2 and its classical squamous partner p63. Robust protein–protein interaction and genomic cooccupancy of Sox2 and Brn2, in place for p63 in the classical LUSC, indicated their transcriptional cooperation imparting this unique lineage state in the “neural” LUSC. Forced expression of p63 downregulated Brn2 in the “neural” LUSC cells and invoked the classical LUSC lineage with more squamous/epithelial features, which were accompanied by increased activities of ErbB/Akt and MAPK–ERK pathways, suggesting differential dependency. Collectively, our data demonstrate heterogeneous cell lineage states of LUSC featured by Sox2 cooperation with Brn2 or p63, for which distinct therapeutic approaches may be warranted.

Significance:
Epigenomic profiling reveals a novel subtype of lung squamous cell carcinoma with neural differentiation.
Longitudinal Photoacoustic Imaging of the Pharmacodynamic Effect of Vascular Targeted Therapy on Tumors
Authors: Johnson S. Peter , Ogunlade Olumide , Lythgoe Mark F. , Beard Paul , Pedley R. Barbara 
Published: September 2019

Abstract

Purpose:
Photoacoustic imaging (PAI) is a novel noninvasive and nonionizing imaging technique that allows longitudinal imaging of tumor vasculature in vivo and monitoring of response to therapy, especially for vascular targeted chemotherapy agents. In this study, we used a novel high-resolution all-optical PAI scanner to observe the pharmacodynamic response to the vascular-disrupting agent OXi4503.

Experimental Design:
Two models of colorectal carcinoma (SW1222 and LS174T) that possess differing pathophysiologic vascularization were established as subcutaneous tumors in mice. Monitoring of response was performed over a 16-day “regrowth” period following treatment at 40 mg/kg, and at day 2 for a “dose response” study at 40 mg/kg, 10 mg/kg, 1 mg/kg, and sham dose.

Results:
Qualitative and quantitative changes in PA signal are observed, with an initial decrease followed by a plateau and subsequent return of signal indicating regrowth. Both tumor types exhibited a decrease in signal; however, the more vascularized SW1222 tumors show greater response to treatment. Decreasing the dose of OXi4503 led to a decrease in PA signal intensity of 60%, 52%, and 20% in SW1222 tumors and 30%, 26%, and 4% for LS174T tumors.

Conclusions:
We have shown for the first time that PAI can observe the pharmacodynamic response of tumor vasculature to drug treatment both longitudinally and at different dose levels. Assessment of differing response to treatment based on vascular pathophysiologic differences among patients has the potential to provide personalized drug therapy; we have demonstrated that PAI, which is clinically translatable, could be a powerful tool for this purpose.
An Idealized Description for the Diurnal Cycle of the Dry Atmospheric Boundary Layer
Authors: Antoon van Hooft J. , Baas Peter , van Tiggelen Maurice , Ansorge Cedrick , van de Wiel Bas J. H. 
Published: September 2019

Abstract
We present a conceptual model for the diurnal cycle of the dry atmospheric boundary layer (ABL). It may serve as a framework for future numerical studies on the transitional dynamics that characterize the ABL over land. The conceptual model enables us to define expressions for relevant physical scales as a function of the most prominent forcing parameters and the low degree of complexity facilitates a dimensionless description. This is useful to help generalize boundary layer dynamics that occur on a diurnal time scale. Further, the model’s application for numerical studies is illustrated herein with two examples: a single-column-model study that assesses the effect of wind forcing on the main characteristics of the diurnal cycle, and a large-eddy-simulation study on the daily evolution of turbulence under weak-wind-forcing conditions. The results from these studies sketch the general evolution of the present set of diurnal-cycle systems in more detail. We discuss how the setups are able to reproduce well-known dynamical features of the ABL and also highlight limitations, where the simple conceptual system is unable to describe realistic ABL behavior. We conclude that the present conceptual model has an interesting balance between model-system complexity and physical realism, such that it is useful for future idealized studies on the diurnal cycle of the ABL.
Clinical efficacy of laparoscopic modified loop cholecystojejunostomy for the treatment of malignant obstructive jaundice
Authors: Li Jiaxin , Zhuo Shijie , Chen Binghong , Liu Yang , Wu Hong 
Published: September 2019

Objective This study was performed to summarize our experience and investigate the safety and efficacy of laparoscopic modified loop cholecystojejunostomy for the treatment of malignant obstructive jaundice. Methods Thirteen patients with malignant obstructive jaundice who underwent laparoscopic modified loop cholecystojejunostomy from March 2015 to March 2016 were retrospectively reviewed. The patients’ characteristics, operation time, postoperative intestinal recovery time, length of hospital stay, postoperative bilirubin level, and complications were analyzed. Results The patients were followed up as outpatients for 2 years. Nine patients with pancreatic head carcinoma, one patient with periampullary carcinoma, and three patients with distal bile duct carcinoma successfully underwent laparoscopic modified loop cholecystojejunostomy. The mean operation time was 176 ± 45 minutes, and the mean length of hospital stay was 9.5 ± 2.8 days. The serum total bilirubin concentration and gamma-glutamyl transferase concentration significantly decreased on postoperative day 7. The median follow-up time was 7 months. No patients developed bile leakage or required a reoperation. Conclusions Laparoscopic modified loop cholecystojejunostomy is not only safe and minimally invasive, but it is also feasible for patients with malignant obstructive jaundice.
Serum vascular endothelial growth factor level is elevated in patients with impaired glucose tolerance and type 2 diabetes mellitus
Authors: Sun Xiaomeng , Zhang Heng , Liu Jia , Wang Guang 
Published: September 2019

Objective This study was performed to investigate the serum vascular endothelial growth factor (VEGF) levels in Chinese patients with impaired glucose tolerance (IGT) and newly diagnosed type 2 diabetes mellitus (T2DM). Methods A total of 189 subjects (41 controls, 40 patients with IGT, and 108 patients with newly diagnosed T2DM) were recruited. Serum VEGF levels were determined by ELISA; other metabolic parameters were assessed by standard laboratory methods. Results There were significant differences in serum VEGF levels among the T2DM, IGT, and control groups (T2DM vs. controls: 72.00 [45.40, 98.35] pg/mL vs. 53.10 [36.30, 116.25] pg/mL; IGT vs. controls: 78.17 [55.52, 137.25] pg/mL vs. 53.10 [36.30, 116.25] pg/mL). Moreover, serum VEGF levels were positively associated with the homeostasis model assessment for insulin resistance (HOMA-IR) value. Multiple linear regression analysis indicated that the HOMA-IR value was an independent risk factor for elevated serum VEGF level. Conclusions Both IGT and T2DM patients exhibited increased serum VEGF levels, compared with controls; increased serum VEGF level was positively associated with the HOMA-IR value. Therefore, the increased serum VEGF level might partially result from increased insulin resistance in these patients.
Type 2 diabetes and colorectal cancer screening: Findings from the English Longitudinal Study of Ageing
Authors: von Wagner Christian , Cadar Dorina , Hackett Ruth A , Demakakos Panayotes , Beeken Rebecca J , Cooper Bailey Stacy , Wolf Michael , Steptoe Andrew , Renzi Cristina , Stoffel Sandro T 
Published: September 2019

Objectives Type 2 diabetes has been identified as a risk factor for colorectal cancer, but little is known about whether it influences participation in colorectal cancer screening programmes. This study tested the extent to which Type 2 diabetes is negatively associated with colorectal cancer screening uptake. Methods We analysed individual data of screening eligible men and women aged 60–75 without cancer diagnosis from wave 6 of the English Longitudinal Study of Ageing (collected 2012–2013), to investigate whether Type 2 Diabetes influences colorectal cancer screening behaviour independently of demographic characteristics, body mass index, socio-economic status and other chronic diseases. Results Individuals who reported to have Type 2 diabetes or had glycated haemoglobin (HbA1c) levels of 48 mmol/mol or higher were less likely to have ever completed a screening test (faecal occult blood test; 62.8% vs. 75.8%, p < 0.01) or to be up-to-date with their biennial screening invitation (60.2% vs. 72.0%, p < 0.05). The negative associations of Type 2 diabetes on colorectal cancer screening were found both in unadjusted and adjusted regression models. Conclusions Future qualitative and quantitative research should identify reasons for this discrepancy, to inform interventions to increase screening uptake in this high-risk population.
Total Factor Productivity Growth of Indian General Insurance Companies in the Recent Period: A Bootstrapped Approach
Authors: Sinha Ram Pratap 
Published: September 2019

This study estimates Malmquist index of total factor productivity change of 14 major general insurers in India over the period 2009–10 to 2016–17 over 7 annual windows. The study decomposes total factor productivity index into its constituent components, using several approaches including Färe et al. (1989, Productivity Developments in Swedish Hospitals: A Malmquist Output Index Approach. Carbondale: Department of Economics, Southern Illinois University; 1992, Journal of Productivity Analysis 3(1): 85–101), Färe et al. (1994, American Economic Review 84(1): 66–83), Ray and Desli (1997, American Economic Review 87(5): 1033–39) and Wheelock and Wilson (1999, Journal of Money, Credit and Banking 31(2): 212–23). Furthermore, the study uses bootstrap data envelopment analysis (DEA) method to obtain bias-corrected point and interval estimates of Malmquist index and its components. Finally, the study makes a comparison of productivity performance between public and private sector insurers. The results indicate a modest growth in total factor productivity during the period contributed mainly by efficiency changes. The private sector insurers performed better than the public sector in terms of productivity growth. The variations in productivity performance indicate that insurer scale of activity can affect their performance. JEL Classification: G-23, C-61, D-21