bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Unified Electronic Tool for CPR and Emergency Treatment Escalation Plans Improves Communication and Early Collaborative Decision Making for Acute Hospital Admissions
Authors: Johnson Mae , Whyte Martin , Loveridge Robert , Yorke Richard , Naleem Shairana 
Published: April 2017

The National Confidential Enquiry into Patient Outcomes and Death (NCEPOD) report ‘Time to Intervene’ (2012) stated that in a substantial number of cases, resuscitation is attempted when it was thought a ‘do not attempt cardiopulmonary resuscitation’ (DNACPR) decision should have been in place. Early decisions about CPR status and advance planning about limits of care now form part of national recommendations by the UK Resuscitation Council (2016).Treatment escalation plans (TEP) document what level of treatment intervention would be appropriate if a patient were to become acutely unwell and were not previously formally in place at King's College Hospital. A unifying paper based form was successfully piloted in the Acute Medical Unit, introducing the TEP and bringing together decision making around both treatment escalation and CPR status. Subsequently an electronic order-set for CPR status and treatment escalation was launched in April 2015 which led to a highly visible CPR and escalation status banner on the main screen at the top of the patient's electronic record.Ultimately due to further iterations in the electronic process by December 2016, all escalation decisions for acutely admitted patients now have high quality supporting, explanatory documentation with 100% having TEPs in place.There is now widespread multidisciplinary engagement in the process of defining limits of care for acutely admitted medical patients within the first 14 hours of admission and a strategy for rolling this process out across all the divisions of the hospital through our Deteriorating Patient Group (DPG).The collaborative design with acute medical, palliative and intensive care teams and the high visibility provided by the electronic process in the Electronic Patient Record (EPR) has enhanced communication with these teams, patients, nursing staff and the multidisciplinary team by ensuring clarity through a universally understood process about escalation and CPR.Clarity and openness about these discussions have been welcomed by patient focus groups facilitated via our acute medicine patient experience committee. There has been a shift in medical culture where transparency about limits of care has contributed to improving patient safety and quality of care through reducing unnecessary CPR supported by focus groups of staff.
Direct transfer to angiosuite to reduce door-to-puncture time in thrombectomy for acute stroke
Authors: Ribo Marc , Boned Sandra , Rubiera Marta , Tomasello Alejandro , Coscojuela Pilar , Hernández David , Pagola Jorge , Juega Jesús , Rodriguez Noelia , Muchada Marian , Rodriguez-Luna David , Molina Carlos A 
Published: April 2017

ObjectiveTo evaluate direct transfer to the angiosuite protocol of patients with acute stroke, candidates for endovascular treatment (EVT).MethodsWe studied workflow metrics of all patients with stroke who had undergone EVT in the past 12 months. Patients followed three protocols: direct transfer to emergency room (DTER), CT room (DTCT) or angiosuite (DTAS, only last 6 months if admission National Institute of Health Stroke Scale (NIHSS) score >9 and time from onset <4.5 hours) according to staff/suite availability. DTAS patients underwent cone-beam CT before femoral puncture. Dramatic clinical improvement was defined as 10 NIHSS points drop at 24 hours.Results201 patients were included: 87 DTER (43.3%), 74 DTCT (36.8%), 40 DTAS (19.9%).Ten DTAS patients (25%) did not receive EVT: 3 (7.5%) showed intracranial hemorrhage on cone-beam CT and 7 (17.5%) did not show an occlusion on angiography. Mean door-to-puncture (D2P) time was shorter in DTAS (17±8 min) than DTCT (60±29 min; p<0.01). D2P was longer in DTER (90±53 min) than in the other protocols (p<0.01). For outcome analyses only patients who received EVT were compared; no significant differences in baseline characteristics, including time from symptom-onset to admission, puncture-to-recanalization, or recanalization rate, were seen. However, time from symptom-to-puncture (DTAS: 197±72 min, DTER: 279±156, DTCT: 224±142 min; p=0.01) and symptom-to-recanalization (DTAS: 257±74, DTER: 355±158, DTCT: 279±146 min; p<0.01) were longer in the DTER group. At 24 hours, there were no differences in NIHSS score (p=0.81); however, the rate of dramatic clinical improvement was significantly higher in DTAS: 48.6% (DTER 24.1%, DTCT 27.4%); p=0.01). An adjusted model pointed to shorter onset-to-puncture time as an independent predictor of dramatic improvement (OR=1.23, 95% CI 1.13 to 133; p<0.01)ConclusionIn a subgroup of patients direct transfer and triage in the angiosuite seems feasible, safe, and achieves significant reduction in hospital workflow times.
Cerebral misery perfusion due to carotid occlusive disease
Authors: Maddula Mohana , Sprigg Nikola , Bath Philip M , Munshi Sunil 
Published: April 2017

PurposeCerebral misery perfusion (CMP) is a condition where cerebral autoregulatory capacity is exhausted, and cerebral blood supply in insufficient to meet metabolic demand.We present an educational review of this important condition, which has a range of clinical manifestations.MethodA non-systematic review of published literature was undertaken on CMP and major cerebral artery occlusive disease, using Pubmed and Sciencedirect.FindingsPatients with CMP may present with strokes in watershed territories, collapses and transient ischaemic attacks or episodic movements associated with an orthostatic component. While positron emission tomography is the gold standard investigation for misery perfusion, advanced MRI is being increasingly used as an alternative investigation modality. The presence of CMP increases the risk of strokes. In addition to the devastating effect of stroke, there is accumulating evidence of impaired cognition and quality of life with carotid occlusive disease (COD) and misery perfusion. The evidence for revascularisation in the setting of complete carotid occlusion is weak. Medical management constitutes careful blood pressure management while addressing other vascular risk factors.DiscussionThe evidence for the management of patients with COD and CMP is discussed, together with recommendations based on our local experience. In this review, we focus on misery perfusion due to COD.ConclusionPatients with CMP and COD may present with a wide-ranging clinical phenotype and therefore to many specialties. Early identification of patients with misery perfusion may allow appropriate management and focus on strategies to maintain or improve cerebral blood flow, while avoiding potentially harmful treatment.
Strategies to prevent damage to critical infrastructure due to induced seismicity
Authors: Atkinson Gail M. 
Published: April 2017

There has been a significant increase in the rate of felt earthquakes in western Alberta and eastern British Columbia, which has been associated with hydraulic fracturing and wastewater disposal. The increased rate of seismicity and the potential for localized strong ground motions from very shallow events poses an increased hazard to critical infrastructure such as major dams—particularly for older high-consequence structures. This paper overviews the factors that affect the likelihood of damaging ground motions and examines their implications for hazard assessment and mitigation. A strategy aimed at reducing the likelihood of potentially damaging ground motions to achieve probabilistic targets for critical facilities is developed, comprising elements of both mitigation and avoidance. For critical facilities, an effective strategy includes (i) an exclusion zone having a radius of ∼5 km; and (ii) a monitoring-and-response protocol to track the rate of events at the M > 2 level within 25 km, with adjustment of operational practices if required. An exclusion zone provides a deterministic safety margin to ensure the integrity of those few facilities for which failure consequences are unacceptable. Real-time monitoring tied to a response protocol can be used to control the rate of significant events and thereby limit the hazard more broadly.
Effect of stress concentration on the fatigue strength of A7N01S-T5 welded joints
Authors: Zhang Mingyue , Gou Guoqing , Hang Zongqiu , Chen Hui 
Published: April 2017

Stress concentration is a key factor that affects the fatigue strength of welded joints. In this study, the fatigue strengths of butt joints with and without the weld reinforcement were tested to quantify the effect of stress concentration. The fatigue strength of the welded joints was measured with a high-frequency fatigue machine. The [Formula: see text]–[Formula: see text]–[Formula: see text] curves were drawn under different confidence levels and failure probabilities. The results show that butt joints with the weld reinforcement have much lower fatigue strength than joints without the weld reinforcement. Therefore, stress concentration introduced by the weld reinforcement should be controlled.
Alluvial fans and fluvial fans at the margins of continental sedimentary basins: geomorphic and sedimentological distinction for geo-energy exploration and development
Authors: Moscariello A. 
Published: April 2017

Abstract
Alluvial fans and fluvial fans are the most common depositional landforms along the margins of continental sedimentary basins. Their occurrence is determined by the area, relief and hydrology of the catchment, which ultimately control the relative ratios of sediment v. flow discharge and runoff regimes. Fundamental morphological and process distinctions exist between these two kinds of deposystem, which are seen as essentially different facies associations and internal architectures for the corresponding deposits. Alluvial fans commonly develop over short radial distances (hundreds of metres to a few kilometres) and are constructed by ephemeral, flash flow events that lead to poor organization of the sedimentary facies and overall architecture of the corresponding deposits. By contrast, fluvial (mega)fans are fed by proper river systems, which aggrade much larger volumes of clastic sediment over distances of up to a few hundred kilometres. Distinct channel belt and overbank domains are developed with a marked heterogeneity in the distribution of sedimentary facies, represented by hierarchically well-organized fluvial deposits. The general properties of alluvial and fluvial fans reflect the different potentials for the corresponding successions to host economically attractive oil and gas resources and the different approaches required in exploration and prediction.
Evidence for age-dependent air-space enlargement contributing to loss of lung tissue elastic recoil pressure and increased shear modulus in older age
Authors: Subramaniam K. , Kumar H. , Tawhai M. H. 
Published: April 2017

As a normal part of mature aging, lung tissue undergoes microstructural changes such as alveolar air-space enlargement and redistribution of collagen and elastin away from the alveolar duct. The older lung also experiences an associated decrease in elastic recoil pressure and an increase in specific tissue elastic moduli, but how this relates mechanistically to microstructural remodeling is not well-understood. In this study, we use a structure-based mechanics analysis to elucidate the contributions of age-related air-space enlargement and redistribution of elastin and collagen to loss of lung elastic recoil pressure and increase in tissue elastic moduli. Our results show that age-related geometric changes can result in reduction of elastic recoil pressure and increase in shear and bulk moduli, which is consistent with published experimental data. All elastic moduli were sensitive to the distribution of stiffness (representing elastic fiber density) in the alveolar wall, with homogenous stiffness near the duct and through the septae resulting in a more compliant tissue. The preferential distribution of elastic proteins around the alveolar duct in the healthy young adult lung therefore provides for a more elastic tissue. NEW & NOTEWORTHY We use a structure-based mechanics analysis to correlate air-space enlargement and redistribution of elastin and collagen to age-related changes in the mechanical behavior of lung parenchyma. Our study highlights that both the cause (redistribution of elastin and collagen) and the structural effect (alveolar air-space enlargement) contribute to decline in lung tissue elastic recoil with age; these results are consistent with published data and provide a new avenue for understanding the mechanics of the older lung.
Activation mechanism of a neuromodulator-gated pacemaker ionic current
Authors: Gray Michael , Daudelin Daniel H. , Golowasch Jorge 
Published: April 2017

The neuromodulator-gated current ( IMI) found in the crab stomatogastric ganglion is activated by neuromodulators that are essential to induce the rhythmic activity of the pyloric network in this system. One of these neuromodulators is also known to control the correlated expression of voltage-gated ionic currents in pyloric neurons, as well as synaptic plasticity and strength. Thus understanding the mechanism by which neuromodulator receptors activate IMIshould provide insights not only into how oscillations are initiated but also into how other processes, and currents not directly activated by them, are regulated. To determine what specific signaling molecules are implicated in this process, we used a battery of agonists and antagonists of common signal transduction pathways. We found that the G protein inhibitor GDPβS and the G protein activator GTPγS significantly affect IMIamplitude, suggesting that its activation is mediated by G proteins. Interestingly, when using the more specific G protein blocker pertussis toxin, we observed the expected inhibition of IMIamplitude but, unexpectedly, in a calcium-dependent fashion. We also found that antagonists of calcium- and calmodulin-associated signaling significantly reduce IMIamplitude. In contrast, we found little evidence for the role of cyclic nucleotide signaling, phospholipase C (PLC), or kinases and phosphatases, except two calmodulin-dependent kinases. In sum, these results suggest that proctolin-induced IMIis mediated by a G protein whose pertussis toxin sensitivity is altered by external calcium concentration and appears to depend on intracellular calcium, calmodulin, and calmodulin-activated kinases. In contrast, we found no support for IMIbeing mediated by PLC signaling or cyclic nucleotides.NEW & NOTEWORTHY Neuronal rhythmic activity is generated by either network-based or cell-autonomous mechanisms. In the pyloric network of decapod crustaceans, the activation of a neuromodulator-gated pacemaker current is crucial for the generation of rhythmic activity. This current is activated by several neuromodulators, including peptides and acetylcholine, presumably via metabotropic receptors. We have previously demonstrated a novel extracellular calcium-sensitive voltage-dependence mechanism of this current. We presently report that the activation mechanism depends on intracellular and extracellular calcium-sensitive components.
Clinical Features and Outcomes of Patients with Colorectal Cancers Harboring NRAS Mutations
Authors: Cercek Andrea , Braghiroli Maria Ignez , Chou Joanne F. , Hechtman Jaclyn F. , Kemeny Nancy , Saltz Leonard , Capanu Marinela , Yaeger Rona 
Published: April 2017

Abstract
Purpose: NRAS mutations are now routinely included in RAS testing prior to EGFR inhibitor therapy for metastatic colorectal cancer (mCRC). The clinical implications of NRAS mutation beyond lack of response to anti-EGFR therapy, however, are not known. We undertook this study to determine the clinical features and treatment outcomes of patients with NRAS-mutant mCRC.
Experimental Design: We reviewed clinical characteristics, concurrent mutations, and outcomes for all mCRC cases with NRAS mutations undergoing standard genotyping at our institution from 2008 to 2015. Comparison groups consisted of RAS wild-type and KRAS-mutant mCRC consecutive cases genotyped from 2008 to 2012.
Results: Three percent (87/2764) of mCRC patients had NRAS-mutant tumors (45% exon 2 and 55% exon 3), including three cases with concurrent NRAS and KRAS mutations. Left-sided primary site and African American self-reported race were associated with NRAS mutation (P &lt; 0.01). Resection rate at 12 months was lower for NRAS-mutant mCRC than for RAS wild-type or KRAS-mutant mCRC. Median survival from time of first known metastasis was 33 months for NRAS-mutant, 47 months for KRAS-mutant, and 78 months for RAS wild-type cases (P &lt; 0.001). Multivariate analysis assigned an HR for overall survival of 2.0 for NRAS mutation and 1.5 for KRAS mutation (P &lt; 0.01).
Conclusions: NRAS defines a molecular subset with distinct clinical characteristics from KRAS-mutant and wild-type mCRC. NRAS mutations are enriched in left-sided primary tumors and among African Americans. Mutations in NRAS are associated with poor survival and worse outcomes than either KRAS-mutant or wild-type mCRC. Clin Cancer Res; 23(16); 4753–60. ©2017 AACR.
Risk of Pneumonitis Associated with Programmed Cell Death 1 Inhibitors in Cancer Patients: A Meta-analysis
Authors: Zhang Sheng , Liang Fei , Zhu Ji , Chen Qiang 
Published: April 2017

Abstract
Pneumonitis, a rare but potentially life-threatening adverse event in cancer patients receiving programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors, has been reported in case reports, clinical trials, and retrospective studies. We performed a systematic review and meta-analysis to calculate the RR of pneumonitis associated with the use of PD-1/L1 inhibitors in randomized clinical trials (RCT). We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, trial registers, conference proceedings, review articles, and reference lists of trial publications for all relevant RCTs comparing PD-1/L1 inhibitors to control with available data on pneumonitis. The pooled incidence, RR, and 95% confidence intervals (CI) were calculated using fixed effects or random effects model according to the heterogeneity of included trials. Twelve RCTs were eligible for the meta-analysis, yielding a total of 5,775 patients included in trials evaluating a PD-1 inhibitor; no eligible trials evaluated a PD-L1 inhibitor. The pooled incidence of all-grade pneumonitis for patients treated with PD-1 inhibitors was 3.2% (95% CI, 2.3–4.5), and that of high-grade pneumonitis was 1.1% (95% CI, 0.7–1.7). The RR of all-grade and high-grade pneumonitis was 4.36 (95% CI, 2.58–7.38) and 2.86 (95% CI, 1.30–6.31), respectively. In a sensitivity analysis, PD-1 inhibitors were also associated with significantly increased risk of pneumonitis per person-month (for all grade, RR = 3.37; 95% CI, 1.97–5.76; for high grade, RR = 2.25; 95% CI, 1.03–4.94). PD-1 inhibitors were associated with a significant increase of all-grade and high-grade pneumonitis both per treatment episode and per person-month. Mol Cancer Ther; 16(8); 1588–95. ©2017 AACR.
PAX3–FOXO1 Establishes Myogenic Super Enhancers and Confers BET Bromodomain Vulnerability
Authors: Gryder Berkley E. , Yohe Marielle E. , Chou Hsien-Chao , Zhang Xiaohu , Marques Joana , Wachtel Marco , Schaefer Beat , Sen Nirmalya , Song Young , Gualtieri Alberto , Pomella Silvia , Rota Rossella , Cleveland Abigail , Wen Xinyu , Sindiri Sivasish , Wei Jun S. , Barr Frederic G. , Das Sudipto , Andresson Thorkell , Guha Rajarshi , Lal-Nag Madhu , Ferrer Marc , Shern Jack F. , Zhao Keji , Thomas Craig J. , Khan Javed 
Published: April 2017

Abstract
Alveolar rhabdomyosarcoma is a life-threatening myogenic cancer of children and adolescent young adults, driven primarily by the chimeric transcription factor PAX3–FOXO1. The mechanisms by which PAX3–FOXO1 dysregulates chromatin are unknown. We find PAX3–FOXO1 reprograms the cis-regulatory landscape by inducing de novo super enhancers. PAX3–FOXO1 uses super enhancers to set up autoregulatory loops in collaboration with the master transcription factors MYOG, MYOD, and MYCN. This myogenic super enhancer circuitry is consistent across cell lines and primary tumors. Cells harboring the fusion gene are selectively sensitive to small-molecule inhibition of protein targets induced by, or bound to, PAX3–FOXO1-occupied super enhancers. Furthermore, PAX3–FOXO1 recruits and requires the BET bromodomain protein BRD4 to function at super enhancers, resulting in a complete dependence on BRD4 and a significant susceptibility to BRD inhibition. These results yield insights into the epigenetic functions of PAX3–FOXO1 and reveal a specific vulnerability that can be exploited for precision therapy.
Significance: PAX3–FOXO1 drives pediatric fusion-positive rhabdomyosarcoma, and its chromatin-level functions are critical to understanding its oncogenic activity. We find that PAX3–FOXO1 establishes a myoblastic super enhancer landscape and creates a profound subtype-unique dependence on BET bromodomains, the inhibition of which ablates PAX3–FOXO1 function, providing a mechanistic rationale for exploring BET inhibitors for patients bearing PAX-fusion rhabdomyosarcoma. Cancer Discov; 7(8); 884–99. ©2017 AACR.
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Khorana score and histotype predicts incidence of early venous thromboembolism in non-Hodgkin lymphomas
Authors: Santi Roberto , Ceccarelli Manuela , Bernocco Elisa , Monagheddu Chiara , Evangelista Andrea , Valeri Federica , Monaco Federico , Vitolo Umberto , Cortelazzo Sergio , Cabras Maria , Spina Michele , Baldini Luca , Boccomini Carola , Chiappella Annalisa , Bari Alessia , Luminari Stefano , Visco Carlo , Calabrese Marco , Limberti Giulia , Levis Alessandro , Contino Laura , Ciccone Giovannino , Ladetto Marco 
Published: April 2017

SummaryCurrent data suggests that the risk of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) is comparable to that observed in patients with solid tumours, although more robust confirmatory analyses are required. With that in mind, we investigated the occurrence of VTE in a pooled analysis of 12 “Fondazione Italiana Linfomi” (FIL) prospective clinical studies. Specifically, we wished to assess the cumulative incidence of VTE in NHL patients, evaluate the predictive value of the Khorana Score (KS), and identify other potential risk factors for VTEs. Data for VTE occurrence were retrieved from study databases and pharmacovigilance reports. Our analysis includes 1717 patients from 12 prospective phase II and III trials, including newly diagnosed NHL. We observed 53 VTEs (any grade) in 46 patients, with 20 severe VTEs in 17 patients. The cumulative incidences for „all-grade” or grade ≥3 VTEs were 2.9% (95% CI: 2.1–3.8) and 1.1% (95% CI: 0.6–1.6), respectively. KS categories were positively associated with the risk of VTE of any grade, and with severe events (i. e. grade ≥3; Gray’s test p-values = 0.048 and 0.012, respectively). Among NHL patients, those with diffuse large B-cell lymphoma (DLBCL) showed a greater risk of (any grade) VTE (HR: 3.42, 95% CI: 1.32–8.84, p-value = 0.011). Our study indicates that 1) VTE is a relevant complication for NHL patients, 2) KS is predictive of VTE events and 3) DLBCL histotype is an independent risk factor for VTE incidence, for which preventative interventions could be considered.Supplementary Material to this article is available at www.thrombosis-online.com.