bluuebunny/crossref_metadata_2025_split huggingface dataset:
PP14 Development of a prehospital assessment to identify stroke mimic conditions
Authors: McClelland Graham , Rodgers Helen , Flynn Darren , Price Chris 
Published: September 2017

BackgroundDespite routine use of pre-hospital identification instruments, approximately 30% of suspected stroke admissions are stroke mimics (SM). Early identification may allow “false positive” SM patients to be directed to appropriate care and improve healthcare resource utilisation.MethodsA retrospective database of ambulance records containing a paramedic impression of stroke was linked to hospital specialist diagnosis data from 01/06/13 to 31/05/16. Logistic regression identified clinical features predictive of SM. An assessment score was constructed prioritising specificity over sensitivity.Results1650 patients (mean age 75.3, 47% male, 40% SM) were included. 1520 (92%) were Face Arm Speech Test (FAST) positive. Table 1 describes the characteristics in the SM assessment. Each characteristic scores 1 point if present.Table 1Stroke mimic characteristicsCharacteristicStroke patients(n=982)Mimic patients (n=668)Diagnostic Odds Ratio(95% CI)Systolic blood pressure<95 mmHg3136 (2–13)Temperature>38.0°C AND heart rate>90bpm21814 (3–59)History of epilepsy AND seizures01118 (2–138)*Age<40 years4249 (3–26)History of migraine AND headache2129 (2–40)*Approximated86% (66/77) of suspected stroke patients scoring 1 were SM. 100% (6/6) of patients scoring >1 characteristic were SM. A score ≥1 identified SM with 11% (95% CI, 8–13) sensitivity, 99% (95% CI, 98–99) specificity, positive predictive value of 87% (95% CI, 79–94), negative predictive value of 62% (95% CI, 60–64) and a diagnostic odds ratio of 11 (95% CI, 6–20, p<0.0001).ConclusionsAmongst ambulance patients with suspected stroke, a small number of SM can be identified with a high degree of certainty. This simple tool needs further validation, prospective testing in the pre-hospital environment with characteristics systematically recorded and consideration of potential clinical impact.
02 A pilot study to assess the feasibility of paramedics delivering antibiotic treatment to ‘red flag’ sepsis patients
Authors: Chippendale Jonathan , Lloyd Adele , Payne Tanya , Dunmore Sally , Stoddart Bethan 
Published: September 2017

BackgroundSepsis is associated with a 36% mortality rate rising up to 50% for septic shock. Currently when an East Midlands Ambulance Service (EMAS) clinician recognises ‘red flag’ sepsis, only the oxygen and fluid elements of the ‘Sepsis 6’ care bundle are delivered, omitting the antibiotic therapy. Each hour antibiotics are delayed there is an increased risk of septic shock which is associated with a 7.6% greater risk of death. Ambulance clinicians are therefore appropriately placed to assess and commence treatment at the earliest point of recognition. The aim of this pilot was to assess the feasibility of paramedic training in recognising ‘red flag’ sepsis, obtaining blood cultures and administering a broad spectrum antibiotic to patients in the pre-hospital environment.MethodsA prospective six month feasibility pilot evaluation was introduced in May 2016. Paramedics were trained and given access to a broad spectrum antibiotic along with a patient group directive (PGD) to administer the antibiotic to ‘red flag’ sepsis patients. Training included sepsis recognition, taking of blood cultures and PGD compliance.Results20 paramedics volunteered and successfully completed the training. Of the patients that were identified as ‘red flag’ sepsis (n=113) 93% (n=107) were confirmed as infected by hospital record. 98 blood samples were harvested of which only 7.14% (n=7) were reported contaminated compared to an overall 8.48% of those taken in ED during the same time period. 80% (n=90) of patients assessed by paramedics met the criteria and were treated with meropenem. PGD compliance was 100%.ConclusionEMAS paramedics were accurate and reliable in their recognition of identifying ‘red flag’ sepsis and able to administer meropenem safely in accordance with the PGD. EMAS paramedic blood sample contamination rate was lower than those taken in the ED.
03 Data linkage across ambulance services and acute trusts: challenges and opportunities
Authors: Clark Sophie , Porter Alison , Halter Mary , Dorning Holly 
Published: September 2017

BackgroundMost callers to 999 ambulance services are transported to hospital emergency departments (EDs), but ambulance services receive no information on patient outcomes. PHED Data is a two-year mixed-methods observational study of the process and potential benefits of linking data from EDs with ambulance service data to allow analysis of patient outcomes. We report on our first aim, to examine the potential opportunities and challenges to routinely linking these data.MethodsWe approached six acute trusts, selected to give a range of performance, location and size, from an English metropolitan area. We used a structured learning log to collect data on the process, time input and reflections. We analysed these data with descriptive statistics, and qualitatively for themes.ResultsAll six trusts we approached agreed to participate. Data were linked using an algorithm based on date, time and patient demographics. We achieved a dataset of 7 75 018 records covering 2012–2016, and a linkage rate of 81%.We identified five stages of the process: senior approval; exploring data availability; information governance agreement; data transfer and linking.The most intensive phases were; negotiating senior approval (mean research team input per trust of 8 hours 5 min [SD 8 hours 3 min] plus additional time from acute trusts), and data linkage (mean research team input per trust 12 hours 40 min [SD 7 hours 4 min]).The stage which took the longest was information governance (mean 19 weeks).Key themes included the positive attitudes of trusts to participating, the range of decision-makers involved, and the need for sustained input from the research team.ConclusionsWe have found the process of data linkage to be feasible, but requires dedicated time from research and trust staff, over a prolonged period, in order to achieve initial set up. Linked data are now being analysed.
Randomised controlled trial of two advanced and extended cardiac rehabilitation programmes
Authors: Sunamura Madoka , ter Hoeve Nienke , van den Berg-Emons Rita J G , Geleijnse Marcel L , Haverkamp Mirjam , Stam Henk J , Boersma Eric , van Domburg Ron T 
Published: September 2017

ObjectiveThe OPTICARE (OPTImal CArdiac REhabilitation) randomised controlled trial compared two advanced and extended cardiac rehabilitation (CR) programmes to standard CR for patients with acute coronary syndrome (ACS). These programmes were designed to stimulate permanent adoption of a heart-healthy lifestyle. The primary outcome was the SCORE (Systematic COronary Risk Evaluation) 10-year cardiovascular mortality risk function at 18 months follow-up.MethodsIn total, 914 patients with ACS (age, 57 years; 81% men) were randomised to: (1) 3 months standard CR (CR-only); (2) standard CR including three additional face-to-face active lifestyle counselling sessions and extended with three group fitness training and general lifestyle counselling sessions in the first 9 months after standard CR (CR+F); or (3) standard CR extended for 9 months with five to six telephone general lifestyle counselling sessions (CR+T).ResultsIn an intention-to-treat analysis, we found no difference in the SCORE risk function at 18 months between CR+F and CR-only (3.30% vs 3.47%; p=0.48), or CR+T and CR-only (3.02% vs 3.47%; p=0.39). In a per-protocol analysis, two of three modifiable SCORE parameters favoured CR+F over CR-only: current smoking (13.4% vs 21.3%; p<0.001) and total cholesterol (3.9 vs 4.3 mmol/L; p<0.001). The smoking rate was also lower in CR+T compared with the CR-only (12.9% vs 21.3%; p<0.05).ConclusionsExtending CR with extra behavioural counselling (group sessions or individual telephone sessions) does not confer additional benefits with respect to SCORE parameters. Patients largely reach target levels for modifiable risk factors with few hospital readmissions already following standard CR.Trial registration numberClinicalTrials.gov NCT01395095; results.
Magnetic resonance imaging to detect local tissue reactions after vaccination in sheep in vivo
Authors: Bernau Maren , Kremer‐Rücker Prisca Valerie , Kreuzer Lena Sophie , Schwanitz Sebastian , Cussler Klaus , Hoffmann Andreas , Scholz Armin Manfred 
Published: September 2017

ObjectivesVaccination is one of the most effective methods to keep up the health status in humans and in livestock. Therefore, farm animals are vaccinated several times during their lifetime. Although vaccines are being checked regarding their local reactogenicity, side effects occur frequently—especially in the case of the application of adjuvanted products. Many reports exist about local reactions in sheep. The present study aimed at testing MRI as a method to document injection site reactions three‐dimensionally.DesignTwo groups of Merino lambs (n=16 each) were vaccinated subcutaneously into the left neck side. Two different, licensed inactivated vaccines were used. Both groups of lambs were anaesthetised and scanned using MRI at days 1, 3, 8, 15, 22 and 29 after vaccination.SettingThe study was performed on a commercial‐like farm.ParticipantsThirty‐two Merino lambs entered the experiment, 16 male and 16 female ones (one animal died at day 22 after vaccination). At first examination day they were approximately three months old.Primary and secondary outcome measuresVolume differences were measured between vaccination and control neck side to evaluate the time pattern of local tissue reactions.ResultsLocal tissue reactions were visible on the skin surface and also appeared in deeper tissue layers on MRI. These deeper reactions would not have been found without MRI or, alternatively, without sacrificing the animals. Some of these extensive local reactions lasted for more than 29 days.ConclusionsThe in vivo MRI results proved suitable to record local tissue reactions in terms of three‐dimensional extent over a longer period of time in large farm animals without the need to sacrifice test animals. A three‐dimensional MRI examination of the injection site during regulatory licensing studies offers an objective evaluation that could be used in a benefit‐risk assessment of veterinary vaccines.Trial registration numberDistrict Government of Upper Bavaria:55.2‐1‐54‐2532‐2‐13.
Systemic Antitumor Immunity by PD-1/PD-L1 Inhibition Is Potentiated by Vascular-Targeted Photodynamic Therapy of Primary Tumors
Authors: O'Shaughnessy Matthew J. , Murray Katie S. , La Rosa Stephen P. , Budhu Sadna , Merghoub Taha , Somma Alexander , Monette Sebastien , Kim Kwanghee , Corradi Renato Beluco , Scherz Avigdor , Coleman Jonathan A. 
Published: September 2017

AbstractPurpose: PD-1/PD-L1 pathway inhibition is effective against advanced renal cell carcinoma, although results are variable and may depend on host factors, including the tumor microenvironment. Vascular-targeted photodynamic (VTP) therapy with the photosensitizer WST11 induces a defined local immune response, and we sought to determine whether this could potentiate the local and systemic antitumor response to PD-1 pathway inhibition.Experimental Design: Using an orthotopic Renca murine model of renal cell carcinoma that develops lung metastases, we treated primary renal tumors with either VTP alone, PD-1/PD-L1 antagonistic antibodies alone, or a combination of VTP and antibodies and then examined treatment responses, including immune infiltration in primary and metastatic sites. Modulation of PD-L1 expression by VTP in human xenograft tumors was also assessed.Results: Treatment of renal tumors with VTP in combination with systemic PD-1/PD-L1 pathway inhibition, but neither treatment alone, resulted in regression of primary tumors, prevented growth of lung metastases, and prolonged survival in a preclinical mouse model. Analysis of tumor-infiltrating lymphocytes revealed that treatment effect was associated with increased CD8+:regulatory T cell (Treg) and CD4+FoxP3-:Treg ratios in primary renal tumors and increased T-cell infiltration in sites of lung metastasis. Furthermore, PD-L1 expression is induced following VTP treatment of human renal cell carcinoma xenografts.Conclusions: Our results demonstrate a role for local immune modulation with VTP in combination with PD-1/PD-L1 pathway inhibition for generation of potent local and systemic antitumor responses. This combined modality strategy may be an effective therapy in cancers resistant to PD-1/PD-L1 pathway inhibition alone. Clin Cancer Res; 24(3); 592–9. ©2017 AACR.
The Driver Mutational Landscape of Ovarian Squamous Cell Carcinomas Arising in Mature Cystic Teratoma
Authors: Cooke Susanna L. , Ennis Darren , Evers Lisa , Dowson Suzanne , Chan Mei Yen , Paul James , Hirschowitz Lynn , Glasspool Rosalind M. , Singh Naveena , Bell Sarah , Day Elizabeth , Kochman Agata , Wilkinson Nafisa , Beer Philip , Martin Sancha , Millan David , Biankin Andrew V. , McNeish Iain A. 
Published: September 2017

Abstract
Purpose: We sought to identify the genomic abnormalities in squamous cell carcinomas (SCC) arising in ovarian mature cystic teratoma (MCT), a rare gynecological malignancy of poor prognosis.
Experimental design: We performed copy number, mutational state, and zygosity analysis of 151 genes in SCC arising in MCT (n = 25) using next-generation sequencing. The presence of high-/intermediate-risk HPV genotypes was assessed by quantitative PCR. Genomic events were correlated with clinical features and outcome.
Results: MCT had a low mutation burden with a mean of only one mutation per case. Zygosity analyses of MCT indicated four separate patterns, suggesting that MCT can arise from errors at various stages of oogenesis. A total of 244 abnormalities were identified in 79 genes in MCT-associated SCC, and the overall mutational burden was high (mean 10.2 mutations per megabase). No SCC was positive for HPV. The most frequently altered genes in SCC were TP53 (20/25 cases, 80%), PIK3CA (13/25 cases, 52%), and CDKN2A (11/25 cases, 44%). Mutation in TP53 was associated with improved overall survival. In 8 of 20 cases with TP53 mutations, two or more variants were identified, which were bi-allelic.
Conclusions: Ovarian SCC arising in MCT has a high mutational burden, with TP53 mutation the most common abnormality. The presence of TP53 mutation is a good prognostic factor. SCC arising in MCT share similar mutation profiles to other SCC. Given their rarity, they should be included in basket studies that recruit patients with SCC of other organs. Clin Cancer Res; 23(24); 7633–40. ©2017 AACR.
Henry Ford HEART Score Randomized Trial
Authors: Frisoli Tiberio M. , Nowak Richard , Evans Kaleigh L. , Harrison Michael , Alani Maath , Varghese Saira , Rahman Mehnaz , Noll Samantha , Flannery Katherine R. , Michaels Alex , Tabaku Mishel , Jacobsen Gordon , McCord James 
Published: September 2017

Background—
Hospital evaluation of patients with chest pain is common and costly. The HEART score risk stratification tool that merges troponin testing into a clinical risk model for evaluation emergency department patients with possible acute myocardial infarction (AMI) has been shown to effectively identify a substantial low-risk subset of patients possibly safe for early discharge without stress testing, a strategy that could have tremendous healthcare savings implications.

Method and Results—

A total of 105 patients evaluated for AMI in the emergency departments of 2 teaching hospitals in the Henry Ford Health System (Detroit and West Bloomfield, MI), between February 2014 and May 2015, with a modified HEART score ≤3 (which includes cardiac troponin I <0.04 ng/mL at 0 and 3 hours) were randomized to immediate discharge (n=53) versus management in an observation unit with stress testing (n=52). The primary end points were 30-day total charges and length of stay. Secondary end points were all-cause death, nonfatal AMI, rehospitalization for evaluation of possible AMI, and coronary revascularization at 30 days. Patients randomized to early discharge, compared with those who were admitted for observation and cardiac testing, spent less time in the hospital (median 6.3 hours versus 25.9 hours;
P
<0.001) with an associated reduction in median total charges of care ($2953 versus $9616;
P
<0.001). There were no deaths, AMIs, or coronary revascularizations in either group. One patient in each group was lost to follow-up.

Conclusions—
Among patients evaluated for possible AMI in the emergency department with a modified HEART score ≤3, early discharge without stress testing as compared with transfer to an observation unit for stress testing was associated with significant reductions in length of stay and total charges, a finding that has tremendous potential national healthcare expenditure implications.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT03058120
Relationship between pine wilt-tolerance rankings of Pinus thunbergii trees and the number of Bursaphelenchus xylophilus passing through branch sections
Authors: Menéndez-Gutiérrez María , Matsunaga Koji , Togashi Katsumi 
Published: September 2017

To establish a simple, time-saving method for selecting Pinus tree candidates tolerant to the infection of Bursaphelenchus xylophilus, the causative agent of pine wilt disease, three experiments were conducted. When two virulent isolates Sc-9 and T-4 were inoculated on cut ends of branch sections, more nematodes were inhibited from passing through P. taeda branch sections than P. thunbergii sections. Sc-9 tended to pass through P. thunbergii sections more easily than T-4. The probability of nematodes passing through 5-cm-long P. thunbergii branch sections was greater when 200 nematodes were inoculated. When 200 Sc-9 nematodes were inoculated on 5-, 10- or 15-cm-long branch sections of P. taeda trees and P. thunbergii clones of different tolerance classes in late August, an insignificant correlation was found between the tolerance class of P. thunbergii clones and the number of nematodes passing through 5-cm-long branch sections, although nematode dispersal ability could distinguish between tolerant and susceptible pine clones in mid-August, suggesting it was a helpful method for selecting tolerant tree candidates. Abrupt seasonal increases in tolerance level suggested that weather conditions, such as hot temperatures and drought, may have disrupted the tolerance mechanism of resistant species of P. taeda.
Azerbaijan’s Perspectives on the osce Minsk Group
Authors: Shiriyev Zaur 
Published: September 2017

The Organization for Security and Co-operation in Europe (osce) led Minsk Group – the principal mediator tasked with the resolution of the Nagorno-Karabakh conflict, is often criticised by Azerbaijan, due to the stalemate in negotiations. The intensive period of engagement between 2006 and 2009 brought first the initial and then the “updated” Madrid Principles. This was the chief working document that set forth the basic principles for peaceful resolution. The inactivity of the Minsk Group is often conceded as the result of maintaining “minimalist goals” – preventing full scale war and trying to bring conflict parties to the negotiating table. The April war in 2016 tested the fragility of the first goal: preventing skirmishes from leading to larger scale conflict. Similarly, after the April 2016 war, the attempt to revitalise the second goal – i.e. bringing the parties to the negotiating table – also collapsed, due to the increased mistrust between the parties after the war.
The article will evaluate the geopolitical changes and their impact on the Minsk Group’s work since 2008, the reasons for the demands to change the format of the Minsk Group, and finally Azerbaijan’s perspectives on the limitations of the Minsk Group’s current mandate and mechanisms.
Using an Isohaline Flux Analysis to Predict the Salt Content in an Unsteady Estuary
Authors: Rayson Matthew D. , Gross Edward S. , Hetland Robert D. , Fringer Oliver B. 
Published: September 2017

AbstractAn estuary is classified as unsteady when the salinity adjustment time is longer than the forcing time scale. Predicting salt content or salt intrusion length using scaling arguments based on a steady-state relationship between flow and salinity is inaccurate in these systems. In this study, a time-dependent salinity box model based on an unsteady Knudsen balance is used to demonstrate the effects of river flow, inward total exchange flow (tidal plus steady), and the salinity difference between inflow and outflow on the salt balance. A key component of the box model is a relationship that links the normalized difference between inflowing and outflowing salinity at the mouth and the mean salinity content. The normalized salinity difference is shown to be proportional to the mean salinity squared, based on theoretical arguments from the literature. The box model is validated by hindcasting 5 years of mean salinity in Galveston Bay (estimated from coarse observations) in response to highly variable river discharge. It is shown that this estuary typically has a long adjustment time relative to the forcing time scales, and, therefore, the volume-averaged salinity rarely reaches equilibrium. The box model highlights the reasons why the adjustment time in a large, partially mixed estuary like Galveston Bay is slower when the mean salt content is higher. Furthermore, it elucidates why the salt content in the estuary is more responsive to changes in river flow than in landward exchange flow at the estuary mouth, even though the latter quantity is usually several times larger.
Comments on “A Combined Derivation of the Integrated and Vertically Resolved, Coupled Wave–Current Equations”
Authors: Ardhuin Fabrice , Suzuki Nobuhiro , McWilliams James C. , Aiki Hidenori 
Published: September 2017

AbstractSeveral equivalent equations for the evolution of the wave-averaged current momentum have been proposed, implemented, and used. In contrast, the equation for the total momentum, which is the sum of the current and wave momenta, has not been widely used because it requires a less practical wave forcing. In an update on previous derivations, Mellor proposed a new formulation of the wave forcing for the total momentum equation. Here, the authors show that this derivation misses a leading-order term that has a zero depth-integrated value. Corrected for this omission, the wave forcing is equivalent to that in the first paper by Mellor. When this wave forcing effect on the currents is approximated it leads to an inconsistency. This study finally repeats and clarifies that the vertical integration of several various forms of the current-only momentum equations are consistent with the known depth-integrated equations for the mean flow momentum obtained by subtracting the wave momentum equation from the total momentum equation. Several other claims in prior Mellor manuscripts are discussed.