bluuebunny/crossref_metadata_2025 huggingface dataset:
PKC-dependent regulation of Kv7.5 channels by the bronchoconstrictor histamine in human airway smooth muscle cells
Authors: Haick Jennifer M. , Brueggemann Lioubov I. , Cribbs Leanne L. , Denning Mitchell F. , Schwartz Jeffrey , Byron Kenneth L.
Published: March 2017

Kv7 potassium channels have recently been found to be expressed and functionally important for relaxation of airway smooth muscle. Previous research suggests that native Kv7 currents are inhibited following treatment of freshly isolated airway smooth muscle cells with bronchoconstrictor agonists, and in intact airways inhibition of Kv7 channels is sufficient to induce bronchiolar constriction. However, the mechanism by which Kv7 currents are inhibited by bronchoconstrictor agonists has yet to be elucidated. In the present study, native Kv7 currents in cultured human trachealis smooth muscle cells (HTSMCs) were observed to be inhibited upon treatment with histamine; inhibition of Kv7 currents was associated with membrane depolarization and an increase in cytosolic Ca2+ ([Ca2+]cyt). The latter response was inhibited by verapamil, a blocker of L-type voltage-sensitive Ca2+ channels (VSCCs). Protein kinase C (PKC) has been implicated as a mediator of bronchoconstrictor actions, although the targets of PKC are not clearly established. We found that histamine treatment significantly and dose-dependently suppressed currents through overexpressed wild-type human Kv7.5 (hKv7.5) channels in cultured HTSMCs, and this effect was inhibited by the PKC inhibitor Ro-31-8220 (3 µM). The PKC-dependent suppression of hKv7.5 currents corresponded with a PKC-dependent increase in hKv7.5 channel phosphorylation. Knocking down or inhibiting PKCα, or mutating hKv7.5 serine 441 to alanine, abolished the inhibitory effects of histamine on hKv7.5 currents. These findings provide the first evidence linking PKC activation to suppression of Kv7 currents, membrane depolarization, and Ca2+ influx via L-type VSCCs as a mechanism for histamine-induced bronchoconstriction.
Cell-Cycle Regulation Accounts for Variability in Ki-67 Expression Levels
Authors: Sobecki Michal , Mrouj Karim , Colinge Jacques , Gerbe François , Jay Philippe , Krasinska Liliana , Dulic Vjekoslav , Fisher Daniel
Published: March 2017

The cell proliferation antigen Ki-67 is widely used in cancer histopathology, but estimations of Ki-67 expression levels are inconsistent and understanding of its regulation is limited. Here we show that cell-cycle regulation underlies variable Ki-67 expression in all situations analyzed, including nontransformed human cells, normal mouse intestinal epithelia and adenomas, human cancer cell lines with or without drug treatments, and human breast and colon cancers. In normal cells, Ki-67 was a late marker of cell-cycle entry; Ki-67 mRNA oscillated with highest levels in G2 while protein levels increased throughout the cell cycle, peaking in mitosis. Inhibition of CDK4/CDK6 revealed proteasome-mediated Ki-67 degradation in G1. After cell-cycle exit, low-level Ki-67 expression persisted but was undetectable in fully quiescent differentiated cells or senescent cells. CDK4/CDK6 inhibition in vitro and in tumors in mice caused G1 cell-cycle arrest and eliminated Ki-67 mRNA in RB1-positive cells but had no effect in RB1-negative cells, which continued to proliferate and express Ki-67. Thus, Ki-67 expression varies due to cell-cycle regulation, but it remains a reliable readout for effects of CDK4/CDK6 inhibitors on cell proliferation. Cancer Res; 77(10); 2722–34. ©2017 AACR.
A Model-Based Personalized Cancer Screening Strategy for Detecting Early-Stage Tumors Using Blood-Borne Biomarkers
Authors: Hori Sharon Seiko , Lutz Amelie M. , Paulmurugan Ramasamy , Gambhir Sanjiv Sam
Published: March 2017

An effective cancer blood biomarker screening strategy must distinguish aggressive from nonaggressive tumors at an early, intervenable time. However, for blood-based strategies to be useful, the quantity of biomarker shed into the blood and its relationship to tumor growth or progression must be validated. To study how blood biomarker levels correlate with early-stage viable tumor growth in a mouse model of human cancer, we monitored early tumor growth of engineered human ovarian cancer cells (A2780) implanted orthotopically into nude mice. Biomarker shedding was monitored by serial blood sampling, whereas tumor viability and volume were monitored by bioluminescence imaging and ultrasound imaging. From these metrics, we developed a mathematical model of cancer biomarker kinetics that accounts for biomarker shedding from tumor and healthy cells, biomarker entry into vasculature, biomarker elimination from plasma, and subject-specific tumor growth. We validated the model in a separate set of mice in which subject-specific tumor growth rates were accurately predicted. To illustrate clinical translation of this strategy, we allometrically scaled model parameters from mouse to human and used parameters for PSA shedding and prostate cancer. In this manner, we found that blood biomarker sampling data alone were capable of enabling the detection and discrimination of simulated aggressive (2-month tumor doubling time) and nonaggressive (18-month tumor doubling time) tumors as early as 7.2 months and 8.9 years before clinical imaging, respectively. Our model and screening strategy offers broad impact in their applicability to any solid cancer and associated biomarkers shed, thereby allowing a distinction between aggressive and nonaggressive tumors using blood biomarker sampling data alone. Cancer Res; 77(10); 2570–84. ©2017 AACR.
Validation of Noninvasive Measurement of Cardiac Output Using Inert Gas Rebreathing in a Cohort of Patients With Heart Failure and Reduced Ejection Fraction
Authors: Hassan Mohamed , Wagdy Kerolos , Kharabish Ahmed , Selwanos Peter Philip , Nabil Ahmed , Elguindy Ahmed , ElFaramawy Amr , Elmahdy Mahmoud F. , Mahmoud Hani , Yacoub Magdi H.
Published: March 2017

Background—

Cardiac output (CO) is a key indicator of cardiac function in patients with heart failure. No completely accurate method is available for measuring CO in all patients. The objective of this study was to validate CO measurement using the inert gas rebreathing (IGR) method against other noninvasive and invasive methods of CO quantification in a cohort of patients with heart failure and reduced ejection fraction.

Methods and Results—

The study included 97 patients with heart failure and reduced ejection fraction (age 42±15.5 years; 64 patients (65.9%) had idiopathic dilated cardiomyopathy and 21 patients (21.6%) had ischemic heart disease). Median left ventricle ejection fraction was 24% (10%–36%). Patients with atrial fibrillation were excluded. CO was measured using 4 methods (IGR, cardiac magnetic resonance imaging, cardiac catheterization, and echocardiography) and indexed to body surface area (cardiac index [CI]). All studies were performed within 48 hours. Median CI measured by IGR was 1.75, by cardiac magnetic resonance imaging was 1.82, by cardiac catheterization was 1.65, and by echo was 1.7 L·min
−1
·m
−2
. There were significant modest linear correlations between IGR-derived CI and cardiac magnetic resonance imaging–derived CI (
r
=0.7;
P
<0.001), as well as cardiac catheterization–derived CI (
r
=0.6;
P
<0.001). Using Bland–Altman analysis, the agreement between the IGR method and the other methods was as good as the agreement between any 2 other methods with each other.

Conclusions—

The IGR method is a simple, accurate, and reproducible noninvasive method for quantification of CO in patients with advanced heart failure. The prognostic value of this simple measurement needs to be studied prospectively.
Independent Modular Filter for Embolic Protection in Carotid Stenting
Authors: Scheinert Dierk , Reimers Bernhard , Cremonesi Alberto , Schmidt Andrej , Sievert Horst , Rohde Stefan , Schofer Joachim , Mudra Harald G. , Bosiers Marc , Zeller Thomas , Pacchioni Andrea , Rosenschein Uri
Published: March 2017

Background—

Embolic protection during carotid artery stenting reduces the rate of thromboembolic events. The Wirion Embolic Protection System is used to deploy an independent distal filter using any 0.014″ guidewire. WISE study (Wirion Study Europe) evaluated the safety and performance of Wirion Embolic Protection System in patients undergoing carotid artery stenting.

Methods and Results—

A prospective, multicenter, nonrandomized, open-label, single-arm study of carotid artery stenting in high surgical risk patients was performed. The primary end point, a composite of death, stroke, and myocardial infarction at 30 days, was compared with performance goal derived from historical controls. Secondary end points were components of the primary end point and the device, angiographic, procedural, and clinical success rates. Preplanned interim analysis was performed on the first 120 patients. At interim analysis, the primary end point was significantly lower for the Wirion Embolic Protection System group, compared with historical data (3.3% versus 6.3%, respectively;
P
value =0.0008). Analysis of primary end point components in the WISE group, compared with the historical control group, shows numerically lower mortality (0% versus 1.7%, respectively;
P
=0.21), stroke (2.5% versus 4.6%, respectively;
P
=0.18), and myocardial infarction (0.8% versus 1.5%, respectively;
P
=0.50). Device, angiographic, procedural, and clinical success was achieved in 99.2%, 99.1%, 98.3%, and 96.6% of cases, respectively.

Conclusions—

The data suggest that independent modular filter use in carotid artery stenting in high surgical risk patients is safe and effective. The outcomes suggest that use of an independent modular filter may be associated with a lower rate of embolic complications associated with carotid stent placement.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01783639.
Timely Reperfusion in Stroke and Myocardial Infarction Is Not Correlated
Authors: Sauser Zachrison Kori , Levine Deborah A. , Fonarow Gregg C. , Bhatt Deepak L. , Cox Margueritte , Schulte Phillip , Smith Eric E. , Suter Robert E. , Xian Ying , Schwamm Lee H.
Published: March 2017

Background—

Timely reperfusion is critical in acute ischemic stroke (AIS) and ST-segment–elevation myocardial infarction (STEMI). The degree to which hospital performance is correlated on emergent STEMI and AIS care is unknown. Primary objective of this study was to determine whether there was a positive correlation between hospital performance on door-to-balloon (D2B) time for STEMI and door-to-needle (DTN) time for AIS, with and without controlling for patient and hospital differences.

Methods and Results—

Prospective study of all hospitals in both Get With The Guidelines-Stroke and Get With The Guidelines-Coronary Artery Disease from 2006 to 2009 and treating ≥10 patients. We compared hospital-level DTN time and D2B time using Spearman rank correlation coefficients and hierarchical linear regression modeling. There were 43 hospitals with 1976 AIS and 59 823 STEMI patients. Hospitals’ DTN times for AIS did not correlate with D2B times for STEMI (ρ=−0.09;
P
=0.55). There was no correlation between hospitals’ proportion of eligible patients treated within target time windows for AIS and STEMI (median DTN time <60 minutes: 21% [interquartile range, 11–30]; median D2B time <90 minutes: 68% [interquartile range, 62–79]; ρ=−0.14;
P
=0.36). The lack of correlation between hospitals’ DTN and D2B times persisted after risk adjustment. We also correlated hospitals’ DTN time and D2B time data from 2013 to 2014 using Get With The Guidelines (DTN time) and Hospital Compare (D2B time). From 2013 to 2014, hospitals’ DTN time performance in Get With The Guidelines was not correlated with D2B time performance in Hospital Compare (n=546 hospitals).

Conclusions—

We found no correlation between hospitals’ observed or risk-adjusted DTN and D2B times. Opportunities exist to improve hospitals’ performance of time-critical care processes for AIS and STEMI in a coordinated approach.
Baseline Hemodynamic Impairment and Future Stroke Risk in Adult Idiopathic Moyamoya Phenomenon
Authors: Derdeyn Colin P. , Zipfel Gregory J. , Zazulia Allyson R. , Davis Patricia H. , Prabhakaran Shyam , Ivan Cristina S. , Aiyagari Venkatesh , Sagar James R. , Hantler Nancy , Shinawi Lina , Lee John J. , Jafri Hussain , Grubb Robert L. , Miller J. Philip , Dacey Ralph G.
Published: March 2017

Background and Purpose—

The purpose was to test the hypothesis that increased oxygen extraction fraction (OEF), a marker of severe hemodynamic impairment measured by positron emission tomography, is an independent risk factor for subsequent ischemic stroke in this population.

Methods—

Adults with idiopathic moyamoya phenomena were recruited between 2005 and 2012 for a prospective, multicenter, blindly adjudicated, longitudinal cohort study. Measurements of OEF were obtained on enrollment. Subjects were followed up for the occurrence of ipsilateral ischemic stroke at 6-month intervals. Patients were censored at the time of surgical revascularization or at last follow-up. The primary analysis was time to ischemic stroke in the territory of the occlusive vasculopathy.

Results—

Forty-nine subjects were followed up during a median of 3.7 years. One of 16 patients with increased OEF on enrollment had an ischemic stroke and another had an intraparenchymal hemorrhage. Three of 33 patients with normal OEF had an ischemic stroke. On a per-hemisphere basis, 21 of 79 hemispheres with moyamoya vasculopathy had increased OEF at baseline. No ischemic strokes and one hemorrhage occurred in a hemisphere with increased OEF (n=21). Sixteen patients (20 hemispheres), including 5 with increased OEF at enrollment, were censored at a mean of 5.3 months after enrollment for revascularization surgery.

Conclusions—

The risk of new or recurrent stroke was lower than expected. The low event rate, low prevalence of increased OEF, and potential selection bias introduced by revascularization surgery limit strong conclusions about the association of increased OEF and future stroke risk.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00629915.
Intraoperative Completion Studies, Local Anesthesia, and Antiplatelet Medication Are Associated With Lower Risk in Carotid Endarterectomy
Authors: Knappich Christoph , Kuehnl Andreas , Tsantilas Pavlos , Schmid Sofie , Breitkreuz Thorben , Kallmayer Michael , Zimmermann Alexander , Eckstein Hans-Henning
Published: March 2017

Background and Purpose—

In Germany, all surgical and endovascular procedures on the carotid bifurcation must be documented in a statutory nationwide quality assurance database. We aimed to analyze the association between procedural and perioperative variables and in-hospital stroke or death rates after carotid endarterectomy.

Methods—

Between 2009 and 2014, overall 142 074 elective carotid endarterectomy procedures for asymptomatic or symptomatic carotid artery stenosis were documented in the database. The primary outcome of this secondary data analysis was in-hospital stroke or death. Major stroke or death, stroke, and death, each until discharge were secondary outcomes. Adjusted relative risks (RRs) were assessed by multivariable multilevel regression analyses.

Results—

The primary outcome occurred in 1.8% of patients, with a rate of 1.4% in asymptomatic and 2.5% in symptomatic patients, respectively. In the multivariable analysis, lower risks of stroke or death were independently associated with local anesthesia (versus general anesthesia: RR, 0.85; 95% confidence interval [CI], 0.75–0.95), carotid endarterectomy with patch plasty compared with primary closure (RR, 0.71; 95% CI, 0.52–0.97), intraoperative completion studies by duplex ultrasound (RR, 0.74; 95% CI, 0.63–0.88) or angiography (RR, 0.80; 95% CI, 0.71–0.90), and perioperative antiplatelet medication (RR, 0.83; 95% CI, 0.71–0.97). No shunting and a short cross-clamp time were also associated with lower risks; however, these are suspected to be confounded.

Conclusions—

Local anesthesia, patch plasty compared with primary closure, intraoperative completion studies by duplex ultrasound or angiography, and perioperative antiplatelet medication were independently associated with lower in-hospital stroke or death rates after carotid endarterectomy.
Individual and System Contributions to Race and Sex Disparities in Thrombolysis Use for Stroke Patients in the United States
Authors: Faigle Roland , Urrutia Victor C. , Cooper Lisa A. , Gottesman Rebecca F.
Published: March 2017

Background and Purpose—

Intravenous thrombolysis (IVT) is underutilized in ethnic minorities and women. To disentangle individual and system-based factors determining disparities in IVT use, we investigated race/sex differences in IVT utilization among hospitals serving varying proportions of minority patients.

Methods—

Ischemic stroke admissions were identified from the Nationwide Inpatient Sample between 2007 and 2011. Hospitals were categorized based on the percentage of minority patients admitted with stroke (<25% minority patients [white hospitals], 25% to 50% minority patients [mixed hospitals], or >50% minority patients [minority hospitals]). Logistic regression was used to evaluate the association between race/sex and IVT use within and between the different hospital strata.

Results—

Among 337 201 stroke admissions, white men had the highest odds of IVT among all race/sex groups in any hospital strata, and the odds of IVT for white men did not differ by hospital strata. For white women and minority men, the odds of IVT were significantly lower in minority hospitals compared with white hospitals (odds ratio, 0.83; 95% confidence interval, 0.71–0.97, for white women; and odds ratio, 0.82; 95% confidence interval, 0.69–0.99, for minority men). Race disparities in IVT use among women were observed in white hospitals (odds ratio, 0.88; 95% confidence interval, 0.78–0.99, in minority compared with white women), but not in minority hospitals (odds ratio, 0.94, 95% confidence interval, 0.82–1.09). Sex disparities in IVT use were observed among whites but not among minorities.

Conclusions—

Minority men and white women have significantly lower odds of IVT in minority hospitals compared with white hospitals. IVT use in white men does not differ by hospital strata.
Predictive Value of RAPID Assessed Perfusion Thresholds on Final Infarct Volume in SWIFT PRIME (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment)
Authors: Mokin Maxim , Levy Elad I. , Saver Jeffrey L. , Siddiqui Adnan H. , Goyal Mayank , Bonafé Alain , Cognard Christophe , Jahan Reza , Albers Gregory W.
Published: March 2017

Background and Purpose—

Computed tomography perfusion imaging can estimate the size of the ischemic core, which can be used for the selection of patients for endovascular therapy. The relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) thresholds chosen to identify ischemic core influence the accuracy of prediction. We aimed to analyze the accuracy of various rCBV and rCBF thresholds for predicting the 27-hour infarct volume using RAPID automated analysis software from the SWIFT PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment) data.

Methods—

Patients from the SWIFT PRIME study who achieved complete reperfusion based on time until the residue function reached its peak >6 s perfusion maps obtained at 27 hours were included. Patients from both the intravenous tissue-type plasminogen activator only and endovascular groups were included in analysis. Final infarct volume was determined on magnetic resonance imaging (fluid-attenuated inversion recovery images) or computed tomography scans obtained 27 hours after symptom onset. The predicted ischemic core volumes on rCBV and rCBF maps using thresholds ranging between 0.2 and 0.8 were compared with the actual infarct volume to determine the most accurate thresholds.

Results—

Among the 47 subjects, the following baseline computed tomography perfusion thresholds most accurately predicted the actual 27-hour infarct volume: rCBV=0.32, median absolute error (MAE)=9 mL; rCBV=0.34, MAE=9 mL; rCBF=0.30, MAE=8.8 mL; rCBF=0.32, MAE=7 mL; and rCBF=0.34, MAE=7.3.

Conclusions—

Brain regions with rCBF 0.30 to 0.34 or rCBV 0.32 to 0.34 thresholds provided the most accurate prediction of infarct volume in patients who achieved complete reperfusion with MAEs of ≤9 mL.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01657461.
Organizational Knowledge Creation in the Context of a Professional Development Program: Mixed-Methods Longitudinal Results From the ALPS Study
Authors: Richard Lucie , Chiocchio François , Morales Hudon Anahi , Fortin-Pellerin Laurence , Litvak Éric , Beaudet Nicole
Published: March 2017

In Quebec (Canada), the 2004 health system reform brought new challenges for organizations and professionals. To support the reform, the Regional Public Health Directorate of Montreal designed a professional development pilot program, the Health Promotion Laboratory, a strategy to develop and improve health promotion practices and competencies in local health and social services centers. This article reports the results of an analysis of two laboratory sites using a mixed-methods approach and a multiple case study design; the aim was to describe the creation of knowledge through the laboratory and its dissemination in the organization, as well as to identify influencing factors. In-depth semistructured interviews were conducted to collect data on the knowledge creation process and organizational context. Self-administered questionnaires were used four times over the course of each laboratory to measure active participation, commitment, psychological safety, innovation, and satisfaction. Our findings showed that knowledge acquired through participation in the laboratory was disseminated in the host organizations, both through externalization, combination, and, to a lesser extent, internalization. It is highly plausible that team processes and outcomes such as commitment, satisfaction, and innovation influenced this process, as well as contextual factors such as participant turnover, university affiliation, and internal team dynamics. These results show the potential of the laboratory for improving professional practices. They also suggest useful avenues for managers and decision makers interested in implementing such an initiative. Future work should consider the inclusion of other constructs derived from the literature on team effectiveness such as group learning, communication, and skill development.
Millennial Student Preference of Audience Response System Technology
Authors: Firsing Stephen L. , Yannessa John F. , McGough Fredanna A. D. , Delport John , Po Mariel C. , Brown Kaitlyn
Published: March 2017

Previous research studies have found that audience response systems or “clickers” provide significant classroom, learning, and assessment benefits in higher education. However, there are few to no research studies that have pitted popular clicker systems against each other using data collected from a sample of millennial students in public health–related professions. As a result, the purpose of this study was to compare two popular audience response systems in the college classroom with undergraduate students, specifically those studying public health. The study was implemented using a mixed methods quasi-experimental crossover design with three observation points over one academic year. Both qualitative and quantitative data were collected. Findings suggest that undergraduate students prefer using a dedicated “clicker” system to respond to questions from an audience response system than a system that requires them to use their personal cell phones.
Leveraging increased cytoplasmic nucleoside kinase activity to target mtDNA and oxidative phosphorylation in AML
Authors: Liyanage Sanduni U. , Hurren Rose , Voisin Veronique , Bridon Gaëlle , Wang Xiaoming , Xu ChangJiang , MacLean Neil , Siriwardena Thirushi P. , Gronda Marcela , Yehudai Dana , Sriskanthadevan Shrivani , Avizonis Daina , Shamas-Din Aisha , Minden Mark D. , Bader Gary D. , Laposa Rebecca , Schimmer Aaron D.
Published: March 2017

Key Points

AML cells have increased cytoplasmic nucleoside kinase expression, which functionally contribute to mtDNA biosynthesis. AML cells preferentially activated the nucleoside analog ddC, which inhibited mtDNA replication, oxphos, and induced anti-AML effects.
An intracytoplasmic β3 Leu718 deletion in a patient with a novel platelet phenotype
Authors: Nurden Paquita , Bordet Jean-Claude , Pillois Xavier , Nurden Alan T.
Published: March 2017

Key Points

A novel heterozygous ITGB3 Leu718del shows loss of synchronization between the intracytoplasmic tail of β3 with that of αIIb. Decreased activation of αIIbβ3 accompanies enlarged platelets that contain giant granules and give a poor aggregation response.
Candidemia in a major regional tertiary referral hospital – epidemiology, practice patterns and outcomes
Authors: Teo Jocelyn Qi-Min , Candra Samuel Rocky , Lee Shannon Jing-Yi , Chia Shannon Yu-Hng , Leck Hui , Tan Ai-Ling , Neo Hui-Peng , Leow Kenneth Wei-Liang , Cai Yiying , Ee Rachel Pui-Lai , Lim Tze-Peng , Lee Winnie , Kwa Andrea Lay-Hoon
Published: March 2017

Background

Candidemia is a common cause of nosocomial bloodstream infections, resulting in high morbidity and mortality. This study was conducted to describe the epidemiology, species distribution, antifungal susceptibility patterns and outcomes of candidemia in a large regional tertiary referral hospital.

Methods

A retrospective surveillance study of patients with candidemia was conducted at Singapore General Hospital between July 2012 and December 2015. In addition, incidence densities and species distribution of candidemia episodes were analysed from 2008 to 2015.

Results

In the period of 2012 to 2015, 261 candidemia episodes were identified. The overall incidence was 0.14/1000 inpatient-days. C. glabrata (31.4%), C. tropicalis (29.9%), and C. albicans (23.8%) were most commonly isolated. The incidence of C. glabrata significantly increased from 2008 to 2015 (Coefficient 0.004, confidence interval 0–0.007, p = 0.04). Fluconazole resistance was detected primarily in C. tropicalis (16.7%) and C. glabrata (7.2%). fks mutations were identified in one C. albicans and one C. tropicalis. Candidemia episodes caused by C. tropicalis were more commonly encountered in patients with haematological malignancies (p = 0.01), neutropenia (p < 0.001) and higher SAPS II scores (p = 0.02), while prior exposure to echinocandins was associated with isolation of C. parapsilosis (p = 0.001). Echinocandins (73.3%) were most commonly prescribed as initial treatment. The median (range) time to initial treatment was 1 (0–9) days. The 30-day in-hospital mortality rate was 49.8%. High SAPS II score (Odds ratio, OR 1.08; 95% confidence interval, CI 1.05–1.11) and renal replacement therapy (OR 5.54; CI 2.80–10.97) were independent predictors of mortality, while drain placement (OR 0.44; CI 0.19–0.99) was protective.

Conclusions

Decreasing azole susceptibilities to C. tropicalis and the emergence of echinocandin resistance suggest that susceptibility patterns may no longer be sufficiently predicted by speciation in our institution. Candidemia is associated with poor outcomes. Strategies optimising antifungal therapy, especially in the critically-ill population, should be explored.
Surveying the historical landscape: the evaluative voice of history textbooks
Authors: Myskow Gordon
Published: March 2017

Much attention has been devoted to understanding the rhetorical features of history texts and how they position readers to take up particular views toward the past. One useful taxonomy for investigating evaluative meaning from the systemic-functional tradition is the Appraisal framework. Voice Theory extends this framework to account for the particular combinations of Appraisal resources that tend to occur in different genres and at specific stages within them, showing how authors take up various evaluative postures or ‘voices’ when communicating with their audiences. The Voices of History framework identifies a variety of such voices including Recorder and Interpreter that describe the particular configurations of Appraisal found in different history genres. Recent research, however, has shown that the types of Appraisal resources that commonly occur in history textbooks do not fit neatly with the existing Voices of History framework—a set of resources that was initially developed to describe the voices of written school history genres. This paper elaborates the Voices of History framework by proposing a new voice called Surveyor Voice to account for the types of Appraisal commonly deployed in history textbooks. It also discusses the modified framework in the context of broader disciplinary issues in historiography, including the underlying epistemological principles of historical knowledge construction.
Diagnostic Evaluation of Nontraumatic Chest Pain in Athletes
Authors: Moran Byron , Bryan Sean , Farrar Ted , Salud Chris , Visser Gary , Decuba Raymond , Renelus Deborah , Buckley Tyler , Dressing Michael , Peterkin Nicholas , Coris Eric
Published: March 2017

This article is a clinically relevant review of the existing medical literature relating to the assessment and diagnostic evaluation for athletes complaining of nontraumatic chest pain. The literature was searched using the following databases for the years 1975 forward: Cochrane Database of Systematic Reviews; CINAHL; PubMed (MEDLINE); and SportDiscus. The general search used the keywords chest pain and athletes. The search was revised to include subject headings and subheadings, including chest pain and prevalence and athletes. Cross-referencing published articles from the databases searched discovered additional articles. No dissertations, theses, or meeting proceedings were reviewed. The authors discuss the scope of this complex problem and the diagnostic dilemma chest pain in athletes can provide. Next, the authors delve into the vast differential and attempt to simplify this process for the sports medicine physician by dividing potential etiologies into cardiac and noncardiac conditions. Life-threatening causes of chest pain in athletes may be cardiac or noncardiac in origin, which highlights the need for the sports medicine physician to consider pathology in multiple organ systems simultaneously. This article emphasizes the importance of ruling out immediately life threatening diagnoses, while acknowledging the most common causes of noncardiac chest pain in young athletes are benign. The authors propose a practical algorithm the sports medicine physician can use as a guide for the assessment and diagnostic work-up of the athlete with chest pain designed to help the physician arrive at the correct diagnosis in a clinically efficient and cost-effective manner.
Management of Suspected Fluid Balance Issues in Participants of Wilderness Endurance Events
Authors: Hoffman Martin D. , Joslin Jeremy , Rogers Ian R.
Published: March 2017

Dehydration and exercise-associated hyponatremia (EAH) are both relatively common conditions during wilderness endurance events. Whereas dehydration is treated with fluids, EAH is appropriately managed with fluid restriction and a sodium bolus but can worsen with isotonic or hypotonic fluids. Therefore, caution is recommended in the provision of postevent rehydration in environments where EAH is a potential consideration because accurate field assessment of hydration status can be challenging, and measurement of blood sodium concentration is rarely possible in the wilderness. Dehydration management with oral rehydration is generally adequate and preferred to intravenous rehydration, which should be reserved for athletes with sustained orthostasis or inability to tolerate oral fluid ingestion after some rest. In situations where intravenous hydration is initiated without known blood sodium concentration or hydration status, an intravenous concentrated sodium solution should be available in the event of acute neurological deterioration consistent with the development of EAH encephalopathy.
Identifying and managing dehydration in care homes
Authors: Murray Sophie
Published: March 2017

Until there are nationally adopted standards for hydration, dehydration in the care home will remain an area of concern. In this article, Sophie Murray examines the importance of, and provides tips for, actively promoting hydration for residents
Implementing the Care Certificate in a residential setting
Authors: Ashurst Adrian
Published: March 2017

The Care Certificate sets a national standard that care support workers must follow, by giving everyone the same structured training. Adrian Ashurst offers his thoughts on this system and how he has seen it impact on the way older people are cared for in the UK
Improving 24-hour nursing care: an outcome audit
Authors: Bond Kirsten , Nadeem Kiran , Oyón Alexander
Published: March 2017

Older people are prone to episodes of illness requiring emergency medical interventions. Kirsten Bond, Kiran Nadeem and Alexander Oyon discuss the outcomes of an audit to reduce the number of episodes requiring unplanned medical treatment at a nursing home
Tribunals: the price of discrimination in the care home
Authors: Bernstein Adam
Published: March 2017

Discrimination in the workplace can have serious and expensive repercussions. In this article Adam Bernstein explains how and where discrimination can occur, and what can be done to protect the care home from falling foul of equality laws
Buying commercial assets: high value and high stakes
Authors: Williams James
Published: March 2017

All sales contracts carry a degree of risk; the bigger the asset, the higher the risk. In this article, James Williams outlines what a home should be doing to minimise the risk of being left without ownership of commercial assets, after a sale has gone through
Key CQC inspection questions: is your care home outstanding?
Authors: Bernstein Adam
Published: March 2017

The CQC asks five key questions when assessing whether a care home meets their standards. In this article, Adam Bernstein offers a round-up of what inspectors are looking for, including how to achieve an outstanding rating on the inspection report
Regulating care for with people with learning disabilities
Authors: Frankova Helena
Published: March 2017

CQC's policy on their changed approach towards regulating services for people with learning disabilities was launched in December 2016. In this article, Helena Frankova examines what this means for care providers and commissioners
An overview of the revalidation process for care home nurses
Authors: Ashurst Adrian
Published: March 2017

Revalidation is something that all care home nurses must go through in order to renew their registration with the Nursing & Midwifery Council. In the first article of a new series, Adrian Ashurst looks at the factors that need to be considered by the home
How to … develop a personal learning and development plan
Authors: Ashurst Adrian
Published: March 2017

Continuous professional development is a core aspect of keeping staff at their best. In this article, Adrian Ashurst discusses the importance of supporting staff in their professional development, and gives advice on how this can be achieved
Utilization of Reflex Testing for Direct Bilirubin in the Early Recognition of Biliary Atresia
Authors: Lam Leo , Musaad Samarina , Kyle Campbell , Mouat Stephen
Published: March 2017

BACKGROUND

Delayed diagnosis of biliary atresia is an important cause of pediatric end-stage liver failure and liver transplantation. We sought to determine whether direct bilirubin is underutilized by retrospectively reviewing patients with biliary atresia. Further, we aimed to determine the role of reflex testing for direct bilirubin in patients suspected for jaundice.

METHODS

The time intervals between total bilirubin and direct bilirubin measurements were retrospectively reviewed in patients with biliary atresia. We also audited the results of two major laboratories that had implemented reflex testing for direct bilirubin. We evaluated the clinical impact and cost of reflex testing in infants with increased direct bilirubin (>1.5 mg/dL; >25 μmol/L).

RESULTS

In patients with known biliary atresia, an isolated total bilirubin measurement preceded direct bilirubin measurement in 46% (40/87) of patients; with a median delay of 19 days (interquartile range 3–44 days). In the community setting, direct bilirubin had a higher clinical specificity for biliary atresia than in the hospital setting. Reporting direct bilirubin results in 1591 infants younger than 2 weeks of age in the community was associated with three admissions to the hospital, one of whom was diagnosed with biliary atresia. The cost for the two laboratories for direct-bilirubin testing was estimated at US$3200 (NZ$4600) for each newly diagnosed case of biliary atresia.

CONCLUSIONS

We identified underutilization of direct bilirubin as a cause of delay in the recognition of biliary atresia and show that reflex testing for direct bilirubin in jaundiced infants is a cost-effective solution.
Ga-La-S-Se glass for visible and thermal imaging
Authors: Ravagli Andrea , Craig Christopher , Lincoln John , Hewak Daniel W.
Published: March 2017

Chalcogenide glasses are emerging as important enabling materials for low-cost infrared imaging by virtue of their transparency in the key short-wave infrared (SWIR) to long-wave infrared (LWIR) bands and the ability to be mass produced and molded into near-net shape lenses. In this paper, we introduce a new family of chalcogenide glasses, which offer visible as well as infrared transmission and improved thermal and mechanical properties. These glasses are based on Ga2S3-La2S3 with added Ga2Se3-up to complete the substitution of Ga2S3 for Ga2Se3. The samples are prepared via the melt-quench method in an argon-purged atmosphere. All the studied compositions showed a lower glass transition temperature and an extended transmission window. Particularly, the LWIR transmission was extended from about 9 μm for gallium lanthanum sulfide (Ga-La-S) glass to about 15 μm for Se-added Ga-La-S retaining visible transmission from around 463 nm. The thermal and mechanical properties were investigated to prove the suitability of these novel materials for the production of optical components such as visible to LWIR lenses. Their suitability for drawing into optical fibers is also discussed.
Determination of working states of the rotating cutting assembly in forage harvesters by artificial neural networks
Authors: Walther Christian , Wenzel Andreas , Beneke Frank , Hensel Oliver , Huster Jochen
Published: March 2017

This work describes an algorithm which is able to determine the working states of a rotating cutting assembly
automatically. The approach was validated at a self-propelled forage harvester under different environmental and harvest
conditions. Data were recorded throughout different field trials near the cutting assembly using two built-in vibration
sensors. The working states of the cutting assembly were divided into processing, neutral and
grinding. The analysis was performed using evolutionary optimized Artificial Neural Networks. The generated
models for classification are able to determine the working states robustly for this type of a rotating cutting
assembly. Case-specific and sensor-specific confusion matrices are presented for performance evaluation. As a conclusion
vibration data is suitable for automatic and robust classification in this context.
Order of experimentation and advisability of corner measurements
Authors: Belz Julian , Nelles Oliver
Published: March 2017

Basically two questions are examined regarding the design of
experiments. First, for what settings is the placement of design
points in the corners of the input space advisable in order to achieve
a good generalization performance. And second, what order of
experimentation leads to the best model quality in early stages of the
measurement process. The effect of the explicit addition of corner
measurements to three space-filling experimental designs is
investigated. It turns out that for most cases the incorporation of
corner points harms the model quality. Two new methods to determine
the order of experimentation are compared to one active learning
strategy and a simple randomization of the measurement sequence. Both
order determination methods prove to outperform the random sequences
significantly and are only slightly inferior to the active learning
strategy.
Prognose für preisbeeinflusstes Verbrauchsverhalten
Authors: Klaiber Stefan , Waczowicz Simon , Konotop Irina , Westermann Dirk , Mikut Ralf , Bretschneider Peter
Published: March 2017

Durch die Beeinflussung des elektrischen Verbrauchs mittels Preiszeitreihen (Demand Response) können zusätzliche
Flexibilitätspotentiale für die Energieversorgung erschlossen werden. Durch die Einführung von Demand Response
ergeben sich jedoch neue Anforderungen an die Lastprognose. Dieser Beitrag befasst sich mit der Modellierung von
preisbeeinflusstem Verbrauchsverhalten (PVV) und stellt einen neuen Prognoseansatz vor.
DaMoQ: Eine Open-Source-MATLAB-Toolbox zur Bewertung von Daten- und Modellqualität in Regressionen
Authors: Doneit Wolfgang , Mikut Ralf , Gröll Lutz , Pychynski Tim , Reischl Markus
Published: March 2017

In diesem Beitrag wird DaMoQ vorgestellt, eine Erweiterung zur MATLAB-Toolbox SciXMiner, um die Datenqualität von
Eingangsdaten für Regressionen zu bewerten. Bei SciXMiner handelt es sich um eine Open-Source-MATLAB-Toolbox zur
automatisierten Bild- und Datenanalyse. In DaMoQ werden verschiedene Muster ungleichmäßiger Verteilungen in Datensätzen
quantifiziert und visualisiert. Während die Visualisierungen dem Anwender einen schnellen Einblick in den vorliegenden
Datensatz geben, wird die Quantifizierung für eine aggregierte Bewertung der einzelnen Eingangsgrößen sowie des
Datensatzes genutzt. Anhand Benchmark-Datensätze und einer Anwendung für Labyrinthdichtungen wird gezeigt, dass die
Kriterien und Visualisierungen von DaMoQ nicht nur ähnliche Ergebnisse wie eine visuelle Analyse der Streuwolkendiagramme
liefern, sondern auch visuell schwer erkennbare Phänomene identifizieren.
Introduction To U.S. Free Trade Agreements
Authors: Gantz David A.
Published: March 2017

This introduction explores the historical changes in the trade policies of the United States (U.S.), namely, the shift from the support of multilateral rules to the embracement of regional trade agreements and provides an overview of the political and economic considerations behind the conclusion of the major U.S. free trade agreements.
Transatlantic Trade and Investment Partnership (TTIP): The Devil in Disguise or a Golden Opportunity to Build a Transatlantic Marketplace?
Authors: Pitschas Christian
Published: March 2017

The European Union (EU) and the United States are currently negotiating a free-trade agreement, the so-called Transatlantic Trade and Investment Partnership (TTIP). These negotiations have to be seen in perspective, since a number of other - bilateral and plurilateral - trade deals are being pursued at the same time. All these negotiations point to a worrisome aspect: the World Trade Organisation’s failure to come to a meaningful agreement in the Doha-round negotiations, in terms of market access, new rules and development. Like the Trans-Pacific Partnership (TPP), TTIP would stand out among the crowd of trade agreements because of the sheer volume of trade and investment flows across the Atlantic and the declared intention to boost regulatory cooperation and compatibility which is expected to bring the bulk of TTIP’s economic benefits. However, the prospect of concluding such a transatlantic agreement raises many concerns; the public in the European Union and the United States fears that TTIP could undermine existing levels of protection in areas such as health and the environment and impinge on either side’s “right to regulate”. Moreover, questions are being posed as to what TTIP would mean for the multilateral trading system and how it would affect third countries, especially developing countries. Against this backdrop, this article addresses the following issues in relation to TTIP: the vision underlying the negotiations; the European Commission’s negotiating mandate; the structure of the negotiations and their state of play; the Union’s competence for concluding TTIP and whether it is shared with EU Member States; and finally TTIP’s impact on the multilateral trading system and developing countries.
Challenges For Countries In Trade In Services’ Negotiations With The Nafta Approach: The Experience Of Chile In The Free Trade Agreement With The United States
Authors: Monardes V Rodrigo
Published: March 2017

The negotiation of trade in services in the context of a free trade agreement is particularly challenging for developing countries in view of the diverse nature of the services sector, the broad regulation applicable to the supply of services, the different modes of supply and the different approaches available for the adoption of the rules governing bilateral trade in services. Two main approaches are available for these negotiations, the General Agreement on Trade in Services (GATS) model or positive list approach, and the North American Free Trade Agreement (NAFTA) model or negative list approach. Even though these two models are similar with respect to the substantive obligations covering the conditions for supplying services, they differ significantly with respect to the manner and the structure of commitments.

Chile faced significant challenges in concluding a free trade agreement with the United States. The importance of the trading partner and its market for Chilean exports meant that Chile had to adopt a number of unfamiliar features, particularly in relation to financial services and e-commerce, in order to facilitate and consolidate the process of opening its market. This article focuses on the chapters of the United States-Chile Free Trade Agreement addressing trade in services, i.e. cross-border trade in services, financial services, telecommunications, temporary entry of business persons and some provisions on e-commerce. Some investment issues will also be address, particularly those interacting with cross-border trade in services. Finally, the article explains the relevance of this approach as a model or basis for bilateral and plurilateral negotiations on trade in services for the Pacific Rim countries and as the preferred model for services trade liberalization for the Latin American countries.