bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using in situ simulation to improve care of the acutely ill patient by enhancing interprofessional working: a qualitative proof of concept study in primary care in England
Authors: Halls Amy , Kanagasundaram Mohan , Lau-Walker Margaret , Diack Hilary , Bettles Simon 
Published: July 2019

ObjectiveAcutely unwell patients in the primary care setting are uncommon, but their successful management requires involvement from staff (clinical and non-clinical) working as a cohesive team. Despite the advantages of interprofessional education being well documented, there is little research evidence of this within primary care. Enhancing interprofessional working could ultimately improve care of the acutely ill patient. This proof of concept study aimed to develop an in situ simulation of a medical emergency to use within primary care, and assess its acceptability and utility through participants’ reported experiences.SettingThree research-active General Practices in south east England. Nine staff members per practice consented to participate, representing clinical and non-clinical professions.MethodsThe intervention of an in situ simulation scenario of a cardiac arrest was developed by the research team. For the evaluation, staff participated in individual qualitative semistructured interviews following the in situ simulation: these focused on their experiences of participating, with particular attention on interdisciplinary training and potential future developments of the in situ simulation.ResultsThe in situ simulation was appropriate for use within the participating General Practices. Qualitative thematic analysis of the interviews identified four themes: (1) apprehension and (un)willing participation, (2) reflection on the simulation design, (3) experiences of the scenario and (4) training.ConclusionsThis study suggests in situ simulation can be an acceptable approach for interdisciplinary team training within primary care, being well-received by practices and staff. This contributes to a fuller understanding of how in situ simulation can benefit both workforce and patients. Future research is needed to further refine the in situ simulation training session.
‘He’s my mate you see’: a critical discourse analysis of the therapeutic role of companion animals in the social networks of people with a diagnosis of severe mental illness
Authors: Brooks Helen , Rushton Kelly , Lovell Karina , McNaughton Rebecca , Rogers Anne 
Published: July 2019

There is increasing recognition of the role pets play in the management of mental health conditions. Evidence suggests that pets promote social interaction and provide secure and intimate relationships which support the management of symptoms. This paper aimed to extend this evidence by exploring the phenomenological understanding of relationships and relationality with companion animals as therapeutic agents in the context of people’s wider social networks.A qualitative study was undertaken incorporating 35 interviews with 12 participants with a diagnosis of severe mental illness who identified a pet as being important in the management of mental health. Participants took part in three in-depth interviews centred on ego network mapping over a 12-month period (baseline, 6 and 12 months). A critical discourse analysis examined therapeutic relationships with pets in relation to mental health and compared these to other types of support over time. Summative discourse analyses were combined with a cross-case thematic analysis to look for commonalities and differences across individuals.Compared with interactions with other therapeutic agents, relationships with pets were free from the obligations and complexities associated with other types of network members and provided an extension and reinforcement to an individual’s sense of self which militated against the negative experiences associated with mental illness. Relationships with human network members were more variable in terms of consistency and capacity to manage demands (eg, network members requiring support themselves) and the emotions of others associated with fluctuations in mental health.This study adds weight to research supporting the inclusion of companion animals in the lexicon of mental health self-management through the therapeutic value attributed to them by participants within a wide personal network of support. The findings point to how consideration might usefully be given to how relationships with companion animals can be incorporated into healthcare planning and delivery.
Changes in cigar sales following implementation of a local policy restricting sales of flavoured non-cigarette tobacco products
Authors: Rogers Todd , Feld Ashley , Gammon Doris G , Coats Ellen M , Brown Elizabeth M , Olson Lindsay T , Nonnemaker James M , Engstrom Martha , McCrae Tarsha , Holder-Hayes Enver , Ross Ashley , Boles Welsh Erin , Guardino Geri , Pearlman Deborah N 
Published: July 2019

IntroductionOn 3 January, 2013, the city of Providence, Rhode Island, began enforcing a restriction on the retail sale of all non-cigarette tobacco products with a characterising flavour other than tobacco, menthol, mint or wintergreen. We assessed the policy impact on cigar sales—which comprise 95% of flavoured non-cigarette tobacco products sold through conventional tobacco retail outlets (eg, convenience stores, supermarkets) in Providence—over time and in comparison to the rest of the state (ROS).MethodsWeekly retail scanner sales data were obtained for January 2012 to December 2016. Cigar sales were categorised into products labelled with explicit-flavour (eg, Cherry) or concept-flavour (eg, Jazz) names. Regression models assessed changes in prepolicy and postpolicy sales in Providence and ROS.ResultsAverage weekly unit sales of flavoured cigars decreased prepolicy to postpolicy by 51% in Providence, while sales increased by 10% in ROS (both p<0.01). The Providence results are due to a 93% reduction in sales of cigars labelled with explicit-flavour names (p<0.01), which did not change significantly in ROS. Sales of cigars labelled with concept-flavour names increased by 74% in Providence and 119% in ROS (both p<0.01). Sales of all cigars—flavoured and otherwise—decreased by 31% in Providence (p<0.01). We detected some evidence of product substitution and cross-border purchasing.ConclusionsThe Providence policy had a city-specific impact on retail sales of flavoured cigars, which was attenuated by an increase in sales of concept flavour-named cigars. Products with concept-flavour names may avoid enforcement agency detection, and their continued sale undermines the intent of the policy.
KCC2 antagonism increases neuronal network excitability but disrupts ictogenesis in vitro
Authors: Chen Li-Yuan , Lévesque Maxime , Avoli Massimo 
Published: July 2019

The potassium-chloride cotransporter 2 (KCC2) plays a role in epileptiform synchronization, but it remains unclear how it influences such a process. Here, we used tetrode recordings in the in vitro rat entorhinal cortex (EC) to analyze the effects of the KCC2 antagonist VU0463271 on 4-aminopyridine (4AP)-induced ictal and interictal activity. During 4AP application, ictal events were associated with significant increases in interneurons and principal cells activities. VU0463271 application transformed ictal discharges to shorter ictal-like events that were not accompanied by significant increases in interneuron or principal cell firing. Interictal events persisted during VU0463271 application at an accelerated frequency of occurrence with significant increases in interneuron and principal cell activity. Further analysis revealed that interneuron and principal cell firing rate during 4AP-induced interictal events were increased after VU0463271 application without changes in synchronicity. Overall, our results demonstrate that in the EC, KCC2 antagonism enhances both interneuron and principal cell excitability, while paradoxically decreasing the ability of neuronal networks to generate structured ictal events. NEW & NOTEWORTHY We are the first to use tetrode recordings in the entorhinal cortex to demonstrate that antagonizing potassium-chloride cotransporter 2 (KCC2) function abolishes ictal discharges and the associated, dynamic changes in single-unit firing in the in vitro 4-aminopyrine model of epileptiform synchronization. Interictal discharges were, however, shorter and more frequent during KCC2 antagonism, while the associated single-unit activity increased, suggesting augmented neuronal excitability. Our findings highlight the complex role of KCC2 in disease pathology.
Between-hand coupling during response inhibition
Authors: Wadsley Corey G. , Cirillo John , Byblow Winston D. 
Published: July 2019

Response inhibition reflects the process of terminating inappropriate preplanned or ongoing movements. When one hand is cued to stop after preparing a bimanual response (Partial trial), there is a substantial delay on the responding side. This delay is termed the interference effect and identifies a constraint that limits selective response inhibition. γ-Aminobutyric acid (GABA)-mediated networks within primary motor cortex (M1) may have distinct roles during response inhibition. In this study we examined whether the interference effect is the consequence of between-hand “coupling” into a unitary response and whether this is reflected in GABAergic intracortical inhibition within M1. Eighteen healthy right-handed participants performed a bimanual synchronous and asynchronous anticipatory response inhibition task. Electromyographic recordings were obtained from the first dorsal interosseous muscle bilaterally. Motor evoked potentials were elicited by single- and paired-pulse transcranial magnetic stimulation over right M1. As expected, Go trial performance was better with the synchronous compared with the asynchronous version of the task. Paradoxically, response delays during Partial trials were longer with the synchronous compared with the asynchronous task. Although task difficulty did not modulate GABAergic intracortical inhibition, there was a trend for between-hand coupling on asynchronous trials to be associated with greater GABAB receptor-mediated inhibition and lesser recruitment of GABAA receptor-mediated inhibition. The novel findings indicate that the interference effect is in part a consequence of between-hand coupling into a unitary response during movement preparation. The ability to respond independently with the two hands may rely on modulation of distinct inhibitory processes. NEW & NOTEWORTHY The temporal dynamics of an anticipated response task were manipulated to effect the difficulty of behavioral stopping and the underlying effects on motor neurophysiology. There were large response delays during trials where a subcomponent of an upcoming bimanual response was cued to stop in conditions where the anticipated action of the hands were synchronous, but not when asynchronous. Response delays reflected the integration of actions of both hands into a unitary response.
Single and population coding of taste in the gustatory cortex of awake mice
Authors: Levitan David , Lin Jian-You , Wachutka Joseph , Mukherjee Narendra , Nelson Sacha B. , Katz Donald B. 
Published: July 2019

Electrophysiological analysis has revealed much about the broad coding and neural ensemble dynamics that characterize gustatory cortical (GC) taste processing in awake rats and about how these dynamics relate to behavior. With regard to mice, however, data concerning cortical taste coding have largely been restricted to imaging, a technique that reveals average levels of neural responsiveness but that (currently) lacks the temporal sensitivity necessary for evaluation of fast response dynamics; furthermore, the few extant studies have thus far failed to provide consensus on basic features of coding. We have recorded the spiking activity of ensembles of GC neurons while presenting representatives of the basic taste modalities (sweet, salty, sour, and bitter) to awake mice. Our first central result is the identification of similarities between rat and mouse taste processing: most mouse GC neurons (~66%) responded distinctly to multiple (3–4) tastes; temporal coding analyses further reveal, for the first time, that single mouse GC neurons sequentially code taste identity and palatability, the latter responses emerging ~0.5 s after the former, with whole GC ensembles transitioning suddenly and coherently from coding taste identity to coding taste palatability. The second finding is that spatial location plays very little role in any aspect of taste responses: neither between- (anterior-posterior) nor within-mouse (dorsal-ventral) mapping revealed anatomic regions with narrow or temporally simple taste responses. These data confirm recent results showing that mouse cortical taste responses are not “gustotopic” but also go beyond these imaging results to show that mice process tastes through time. NEW & NOTEWORTHY Here, we analyzed taste-related spiking activity in awake mouse gustatory cortical (GC) neural ensembles, revealing deep similarities between mouse cortical taste processing and that repeatedly demonstrated in rat: mouse GC ensembles code multiple aspects of taste in a coarse-coded, time-varying manner that is essentially invariant across the spatial extent of GC. These data demonstrate that, contrary to some reports, cortical network processing is distributed, rather than being separated out into spatial subregion.
GnRH Antagonists Have Direct Inhibitory Effects On Castration-Resistant Prostate Cancer Via Intracrine Androgen and AR-V7 Expression
Authors: Cucchiara Vito , Yang Joy C. , Liu Chengfei , Adomat Hans H. , Tomlinson Guns Emma S. , Gleave Martin E. , Gao Allen C. , Evans Christopher P. 
Published: July 2019

Abstract
Hormone therapy is currently the mainstay in the management of locally advanced and metastatic prostate cancer. Degarelix (Firmagon), a gonadotropin-releasing hormone (GnRH) receptor antagonist differs from luteinizing hormone-releasing hormone (LHRH) agonists by avoiding “testosterone flare” and lower follicle-stimulating hormone (FSH) levels. The direct effect of degarelix and leuprolide on human prostate cancer cells was evaluated. In LNCaP, C4-2BMDVR, and CWR22Rv1 cells, degarelix significantly reduced cell viability compared with the controls (P ≤ 0.01). Leuprolide was stimulatory in the same cell lines. In C4-2B MDVR cells, degarelix alone or combined with abiraterone or enzalutamide reduced the AR-V7 protein expression compared with the control group. SCID mice bearing VCaP xenograft tumors were divided into 4 groups and treated with surgical castration, degarelix, leuprolide, or buffer alone for 4 weeks. Leuprolide slightly suppressed tumor growth compared with the vehicle control group (P &gt; 0.05). Tumors in degarelix-treated mice were 67% of those in the leuprolide-treatment group but 170% larger than in surgically castrated ones. Measurements of intratumoral steroids in serum, tumor samples, or treated cell pellets by LC/MS confirmed that degarelix better decreased the levels of testosterone and steroidogenesis pathway intermediates, comparable to surgical castration, whereas leuprolide had no inhibitory effect. Collectively, our results suggested a selective mechanism of action of degarelix against androgen steroidogenesis and AR-variants. This study provides additional molecular insights regarding the mechanism of degarelix compared with GnRH agonist therapy, which may have clinical implications.
Specific RITA Modification Produces Hyperselective Cytotoxicity While Maintaining In Vivo Antitumor Efficacy
Authors: Peyser Brian D. , Hermone Ann , Salamoun Joseph M. , Burnett James C. , Hollingshead Melinda G. , McGrath Connor F. , Gussio Rick , Wipf Peter 
Published: July 2019

Abstract
The preclinical antitumor agent RITA (2,5-bis[5-hydroxymethyl-2-thienyl] furan, NSC 652287), an analog of the natural product α-terthiophene, failed during the development phase due to acute pulmonary toxicity in animal models. A series of synthetic modifications to RITA's heterocyclic scaffold resulted in activity ranging from broadly cytotoxic to highly selective. In the NCI 60-cell line screen, these “hyperselective” agents (e.g., imatinib) are rare. A selectivity index (SI) was developed to quantify this desirable feature, which is 20 for imatinib, whereas RITA's SI is only 0.10. One of the described hyperselective RITA analogs (SI = 7.9) completely lost activity in the presence of a known SULT1A1 inhibitor. These results, coupled with previous evidence that RITA is a SULT1A1 substrate, suggest that carbinol modification by a sulfate leaving group and subsequent formation of a reactive carbocation may explain RITA's broad cytotoxicity. Although SULT1A1 expression is required for susceptibility, hyperselective analogs exhibited reduced association of activity with SULT1A1 mRNA expression compared with RITA, apparently requiring some additional target(s). In support of this hypothesis, there is a strong correlation (P &lt; 0.01, r = 0.95) between quantum mechanically calculated energy barriers for carbocation formation from sulfonated analogs and SI, indicating that hyperselective RITA analogs generate reactive carbocations less readily after sulfate activation. Importantly, narrowing the cytotoxicity profile of RITA did not eliminate its analogs' in vivo antitumor activity, as several new hyperselective agents, NSC 773097 (1), 773392 (2), and 782846 (6), displayed impressive activity against A498 xenografts in mice.
Human Leukocyte Antigen‐Based Risk Stratification in Heart Transplant Recipients—Implications for Targeted Surveillance
Authors: Nilsson Johan , Ansari David , Ohlsson Mattias , Höglund Peter , Liedberg Ann‐Sofie , Smith J. Gustav , Nugues Pierre , Andersson Bodil 
Published: July 2019

Background

Human leukocyte antigen (
HLA
) matching isn't routinely performed in heart transplantation. Novel allograft perfusion methods may make
HLA
matching feasible. The purpose of this study is to reexamine whether
HLA
mismatch may be used in risk stratification to improve outcomes in heart transplantation.

Methods and Results

We analyzed 34 681 recipients undergoing heart transplantation between 1987 and 2013. We used
HLAM
atchmaker to quantify
HLA
eplet mismatches and Cox regression for analysis of time to graft loss. Recipients with 4 mismatched
HLA
‐
DR
/
DQ
alleles and >40 eplets reached an adjusted hazard ratio (
HR)
for graft loss of 1.17 (95%
CI
1.07–1.28) and 1.11 (95%
CI
1.03–1.21), respectively. We found significant interaction between recipient age and numbers of
HLA
‐
DR
/
DQ
allele and eplet mismatches resulting in an adjusted
HR
of 1.78 (95% 1.13–2.80) and 1.82 (95%
CI
, 1.23–2.70), respectively.
HR
for both interaction terms was 0.99 (95%
CI
, 0.98–1.00). Risk of graft loss was more pronounced after 1 year, where recipient <40 years with 4 mismatched
HLA
‐
DR
/
DQ
alleles and >40 eplets had an adjusted
HR
of 1.51 (95%
CI
1.12–2.03) and 1.32 (95%
CI
1.02–1.70), respectively. Pre‐sensitized recipients with panel reactive antibodies >10% had an adjusted
HR
=1.27 (95%
CI
1.16–1.40) for graft loss within 1 year but not thereafter.
HLA
eplet mismatch was independent of panel reactive antibodies on reduction of graft loss within and after 1 year,
P
(interaction)=0.888 and 0.389.

Conclusions

HLA
mismatch may be used in risk stratification for intensified post‐transplant surveillance and therapy.
Magnetic Resonance Imaging Findings Related to Stroke Risk in Japanese Patients With Fabry Disease
Authors: Yagita Yoshiki , Sakai Norio , Miwa Kaori , Ohara Nobuyuki , Tanaka Makiko , Sakaguchi Manabu , Kitagawa Kazuo , Mochizuki Hideki 
Published: July 2019

Background and Purpose—
Stroke is the most frequent severe clinical event in patients with Fabry disease. We aimed to evaluate the cerebral magnetic resonance imaging findings of patients with Fabry disease and assess their association with future stroke risk after enzyme replacement therapy (ERT) induction.

Methods—
We retrospectively reviewed the magnetic resonance imaging findings of 25 patients with Fabry disease. Of these, 12 adult patients without prior stroke or ERT were enrolled to evaluate the association between baseline magnetic resonance imaging findings and stroke occurrence after ERT initiation. We assessed white matter hyperintensities, periventricular hyperintensities, and basilar artery diameter as neuroimaging markers.

Results—

The mean age of participants was 38.8±16.8 years. Fourteen patients (56.0%) were women. White matter hyperintensities and periventricular hyperintensities were observed in 15 and 13 cases, respectively. The mean basilar artery diameter was 3.2±0.55 mm. Two patients demonstrated old infarct lesions. Three of 12 patients in whom ERT was initiated had symptomatic stroke after baseline magnetic resonance imaging. Of these, 2 developed stroke within 6-month post-ERT initiation. The baseline basilar artery diameter was larger in patients who developed stroke than in those who did not (4.0±0.40 versus 2.9±0.49 mm,
P
=0.02).

Conclusions—
Basilar artery diameter may be associated with stroke risk after ERT initiation among Japanese patients with Fabry disease.
Toward an Ontology of the Interface: Identifying the Interface as a Mediation
Entity
Authors: Sá Cristina 
Published: July 2019

Abstract
The interface is more than an assemblage of processes and effects; it is more than a pure relational instance. The interface can be identified as an entity in itself and in relation to other entities. In this article, the author presents an ontological work on the interface, defining what it is and how it exists, and discussing its relation to other entities. The interface is defined both abstractly as a mediation complex—by identifying characteristics present in its multiple instantiations—and in relation to other entities—by observing the case of the human-computer interface.
Stratospheric Gravity Wave Products from Satellite Infrared Nadir Radiances in the Planning, Execution, and Validation of Aircraft Measurements during DEEPWAVE
Authors: Eckermann Stephen D. , Doyle James D. , Reinecke P. Alex , Reynolds Carolyn A. , Smith Ronald B. , Fritts David C. , Dörnbrack Andreas 
Published: July 2019

AbstractGravity wave perturbations in 15-μm nadir radiances from the Atmospheric Infrared Sounder (AIRS) and Cross-Track Infrared Sounder (CrIS) informed scientific flight planning for the Deep Propagating Gravity Wave Experiment (DEEPWAVE). AIRS observations from 2003 to 2011 identified the South Island of New Zealand during June–July as a “natural laboratory” for observing deep-propagating gravity wave dynamics. Near-real-time AIRS and CrIS gravity wave products monitored wave activity in and around New Zealand continuously within 10 regions of scientific interest, providing nowcast guidance and validation for flight planners. A novel technique used these gravity wave products to validate upstream forecasts of nonorographic gravity waves with 1–2-day lead times, providing time to plan flight intercepts as tropospheric westerlies brought forecast source regions into range. Postanalysis verifies the choice of 15μm radiances for nowcasting, since 4.3-μm gravity wave products yielded spurious diurnal cycles, provided no altitude sensitivity, and proved relatively insensitive to deep gravity wave activity over the South Island. Comparisons of DEEPWAVE flight tracks with AIRS and CrIS gravity wave maps highlight successful repeated vectoring of the aircraft into regions of deep orographic and nonorographic gravity wave activity, and how background winds control the amplitude of waves in radiance perturbation maps. We discuss how gravity wave information in AIRS and CrIS radiances might be directly assimilated into future operational forecasting systems.