bluuebunny/crossref_metadata_2025 huggingface dataset:
Recrystallization of VO2 films into (011)-oriented micrometer-sized grains on Al2O3 (001) in biased reactive sputtering
Authors: Azhan Nurul Hanis , Okimura Kunio , Matsuoka Kohei , Zaghrioui Mustapha , Sakai Joe
Published: October 2017

The authors report on recrystallization of VO2 films on Al2O3 (001) single crystalline substrates into (011)-oriented large grains. In the VO2 films deposited by biased reactive sputtering, (011)-oriented micrometer-sized grains were found to coexist with commonly observed (010)-oriented nanometer-sized grains. Characteristic maps of oxygen concentrations observed using an electron probe microanalyzer for areas with and without (011)-oriented grains suggest recrystallization phenomena of (020)-oriented grains in the existence of VOx (x > 2) phases, where the growth mode in the Thornton model is able to enter the recrystallization zone in which the ratio of substrate temperature (Ts) to melting temperature (Tm) exceeds 0.7. Accordingly, rapid grain boundary migrations and bulk diffusions would occur during sputtering deposition and result in the occurrence of the recrystallization phenomena. Recrystallized (011)-oriented micrometer-sized grains underwent structural phase transition (SPT) through the intermediate M2 phase, suggesting a significant role of crystalline orientation and size, in addition to the elongation of the V–V distance along the cR-axis. Micro-Raman mapping showed that (011)-oriented grains possess characteristic features in crystallinity compared to (020)-oriented grains, giving the possibility for controlling SPT of VO2 on Al2O3 (001) in the present study.
Localization of complex sounds is modulated by behavioral relevance and sound category
Authors: Derey Kiki , Rauschecker Josef P. , Formisano Elia , Valente Giancarlo , de Gelder Beatrice
Published: October 2017

Meaningful sounds represent the majority of sounds that humans hear and process in everyday life. Yet studies of human sound localization mainly use artificial stimuli such as clicks, pure tones, and noise bursts. The present study investigated the influence of behavioral relevance, sound category, and acoustic properties on the localization of complex, meaningful sounds in the horizontal plane. Participants localized vocalizations and traffic sounds with two levels of behavioral relevance (low and high) within each category, as well as amplitude-modulated tones. Results showed a small but significant effect of behavioral relevance: localization acuity was higher for complex sounds with a high level of behavioral relevance at several target locations. The data also showed category-specific effects: localization biases were lower, and localization precision higher, for vocalizations than for traffic sounds in central space. Several acoustic parameters influenced sound localization performance as well. Correcting localization responses for front-back reversals reduced the overall variability across sounds, but behavioral relevance and sound category still had a modulatory effect on sound localization performance in central auditory space. The results thus demonstrate that spatial hearing performance for complex sounds is influenced not only by acoustic characteristics, but also by sound category and behavioral relevance.
A multiscale analytical model of bronchial airway acoustics
Authors: Henry Brian , Royston Thomas J.
Published: October 2017

Sound transmission and resulting airway wall vibration in a complex multiscale viscoelastic model of the subglottal bronchial tree was calculated using a modified one-dimensional (1D) branching acoustic waveguide approach. This is an extension of previous work to enable use of complex airway trees that are partially derived from subject-specific medical images, without the need for self-similarity in the geometric structure. The approach was validated numerically for simplified airway geometries, as well as experimentally by comparison to previous studies. A comprehensive conducting airway tree with about 60 000 branches was then modified to create fibrotic, bronchoconstrictive, and pulmonary infiltrate conditions. The fibrotic case—systemic increase in soft tissue stiffness—increased the Helmholtz resonance frequency due to the increased acoustic impedance. Bronchoconstriction, with geometric changes in small conducting airways, decreased acoustic energy transmission to the peripheral airways due in part to the increased impedance mismatch between airway orders. Pulmonary infiltrate significantly altered the local acoustic field in the affected lobe. Calculation of acoustic differences between healthy versus pathologic cases can be used to enhance the understanding of vibro-acoustic changes correlated to pathology, and potentially provide improved tools for the diagnosis of pulmonary diseases that uniquely alter the acoustics of the airways.
Inhibition of the oncogenic fusion protein EWS-FLI1 causes G
2
-M cell cycle arrest and enhanced vincristine sensitivity in Ewing’s sarcoma
Authors: Zöllner Stefan K. , Selvanathan Saravana P. , Graham Garrett T. , Commins Ryan M. T. , Hong Sung Hyeok , Moseley Eric , Parks Sydney , Haladyna Jessica N. , Erkizan Hayriye V. , Dirksen Uta , Hogarty Michael D. , Üren Aykut , Toretsky Jeffrey A.
Published: October 2017

A drug sensitizes Ewing’s sarcoma cells to chemotherapy by inducing mitotic arrest and priming the cells for apoptosis.
Immunohistochemical Investigations of Treatment with Ro 13-3978, Praziquantel, Oxamniquine, and Mefloquine in Schistosoma mansoni-Infected Mice
Authors: Panic Gordana , Ruf Marie-Thérèse , Keiser Jennifer
Published: October 2017

To date, there is only one drug in use, praziquantel, to treat more than 250 million people afflicted with schistosomiasis, a debilitating parasitic disease. The aryl hydantoin Ro 13-3978 is a promising drug candidate within vivoactivity superior to that of praziquantel against both adult and juvenileSchistosoma mansoniorganisms. Given the drug's contrasting low activityin vitroand the timing of its onset of actionin vivo, it was postulated that immune-assisted parasite clearance could contribute to the drug'sin vivoactivity. We undertook histopathological studies to investigate this hypothesis. Infected mice were treated with an effective dose of Ro 13-3978 (100 mg/kg of body weight) and were dissected before and after the drug'sin vivoonset of action. The veins and livers were excised, paraffin-embedded, and sectioned, and macrophages (IBA-1), neutrophils (Neutro), B cells (CD45R), and T cells (CD3) were stained by immunohistochemistry. For comparison, samples from infected untreated mice and mice treated with effective doses of praziquantel (400 mg/kg), oxamniquine (200 mg/kg), and mefloquine (200 mg/kg) were examined. At 24 h after treatment with Ro 13-3978, significant macrophage recruitment to the veins was observed, along with a modest increase in circulating B cells, and at 48 h, neutrophils and T cells are also present. Treatment with praziquantel and oxamniquine showed similar patterns of recruitment but with comparatively higher cellular levels, whereas mefloquine treatment resulted in minimal cell recruitment until 3 days posttreatment. Our study sheds light on the immediate immune responses to antischistosomal treatment in mice and provides further insight into immune effector mechanisms of schistosome clearance.
Pharmacokinetic Interactions between Simeprevir and Ledipasvir in Treatment-Naive Hepatitis C Virus Genotype 1-Infected Patients without Cirrhosis Treated with a Simeprevir-Sofosbuvir-Ledipasvir Regimen
Authors: Bourgeois Stefan , Horsmans Yves , Nevens Frederik , van Vlierberghe Hans , Moreno Christophe , Beumont Maria , Vijgen Leen , van Eygen Veerle , Luo Donghan , Hillewaert Vera , Van Remoortere Pieter , van de Logt Jolanda , Ouwerkerk-Mahadevan Sivi
Published: October 2017

Interactions between simeprevir (hepatitis C virus [HCV] NS3/4A protease inhibitor) and ledipasvir (HCV NS5A replication complex inhibitor) were investigated in treatment-naive HCV genotype 1-infected patients without cirrhosis, treated with simeprevir-sofosbuvir-ledipasvir in a two-panel, phase 2, open-label study. Patients had stable background treatment with sofosbuvir (400 mg once daily [QD]). In panel 1 (
n
= 20), the effect of ledipasvir (90 mg QD) on simeprevir (150 mg QD) was studied. Patients received simeprevir and sofosbuvir from days 1 to 14; steady-state pharmacokinetics (PK) of simeprevir was assessed (day 14). On day 15, ledipasvir was added and steady-state PK of simeprevir in the combination was evaluated (day 28). In panel 2 (
n
= 20), the effect of simeprevir on ledipasvir was investigated. From days 1 to 14, patients received ledipasvir and sofosbuvir and steady-state PK of ledipasvir was assessed (day 14). On day 15, simeprevir was added and a full PK profile was obtained (day 28). The least-squares mean maximum plasma concentration and area under the concentration-time curve (90% confidence interval) increased 2.3-fold (2.0- to 2.8-fold) and 3.1-fold (2.4- to 3.8-fold) for simeprevir, respectively (panel 1), and 1.6-fold (1.4- to 1.9-fold) and 1.7-fold (1.6- to 2.0-fold) for ledipasvir, respectively (panel 2), in the presence versus the absence of the other drug. All patients achieved sustained virologic responses 12 weeks after treatment end. Adverse events, mainly grade 1/2, occurred in 80% of patients; the most common was photosensitivity (45%). Due to the magnitude of interaction and the limited amount of safety data available, the use of this treatment combination is not recommended. (This study has been registered at ClinicalTrials.gov under registration no. NCT02421211.)
Role of Alanine Racemase Mutations in Mycobacterium tuberculosis
d
-Cycloserine Resistance
Authors: Nakatani Yoshio , Opel-Reading Helen K. , Merker Matthias , Machado Diana , Andres Sönke , Kumar S. Siva , Moradigaravand Danesh , Coll Francesc , Perdigão João , Portugal Isabel , Schön Thomas , Nair Dina , Devi K. R. Uma , Kohl Thomas A. , Beckert Patrick , Clark Taane G. , Maphalala Gugu , Khumalo Derrick , Diel Roland , Klaos Kadri , Aung Htin Lin , Cook Gregory M. , Parkhill Julian , Peacock Sharon J. , Swaminathan Soumya , Viveiros Miguel , Niemann Stefan , Krause Kurt L. , Köser Claudio U.
Published: October 2017

A screening of more than 1,500 drug-resistant strains of
Mycobacterium tuberculosis
revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling,
in vitro
MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to
d
-cycloserine.
New Variant of
mcr-3
in an Extensively Drug-Resistant Escherichia coli Clinical Isolate Carrying
mcr-1
and
bla
NDM-5
Authors: Liu Lu , Feng Yu , Zhang Xiaoxia , McNally Alan , Zong Zhiyong
Published: October 2017

A colistin- and carbapenem-resistant
Escherichia coli
clinical isolate was found to carry two plasmid-borne colistin-resistant genes,
mcr-1
and the newly identified
mcr-3
, and a carbapenemase gene,
bla
NDM-5
.
mcr-3
is a new variant (
mcr-3.5
) in the isolate and encodes three amino acid substitutions compared with the original MCR-3.
mcr-3
was carried by a Tn
As3
-like transposon on a self-transmissible IncP plasmid in the isolate, highlighting that
mcr-3
may have widely spread.
Transmission of Methicillin-Resistant Staphylococcus aureus to Human Volunteers Visiting a Swine Farm
Authors: Angen Øystein , Feld Louise , Larsen Jesper , Rostgaard Klaus , Skov Robert , Madsen Anne Mette , Larsen Anders Rhod
Published: October 2017

Transmission of methicillin-resistant
Staphylococcus aureus
(MRSA) from animals to humans is of great concern due to the implications for human health and the health care system. The objective was to investigate the frequency and duration of MRSA carriage in human volunteers after a short-term exposure in a swine farm. The experimental study included 34 human volunteers staying 1 h in a MRSA-positive swine farm in four trials. In two of the trials, the influence of farm work involving pig contact was studied using a crossover design. The quantities of MRSA in nasal swabs, throat swabs, and air samples were measured at different time points and analyzed in relation to relevant covariates. This investigation showed that, overall, 94% of the volunteers acquired MRSA during the farm visit. Two hours after the volunteers left the stable, the nasal MRSA count had declined to unquantifiable levels in 95% of the samples. After 48 h, 94% of the volunteers were MRSA-negative. Nasal MRSA carriage was positively correlated to personal exposure to airborne MRSA and farm work involving pig contact and negatively correlated to smoking. No association was observed between MRSA carriage and face touching behavior, nasal methicillin-susceptible
Staphylococcus aureus
(MSSA) carriage, age, or gender. The increase in human MRSA carriage among the volunteers with pig contact seems to be dependent on the increased concentration of airborne MRSA of the surrounding air and not directly on physical contact with pigs. MRSA was not detected in any of the throat samples.

IMPORTANCE
The experimental approach made it possible to elucidate the contributions of airborne MRSA levels and farm work to nasal MRSA carriage in a swine farm. Short-term exposure to airborne MRSA poses a substantial risk for farm visitors to become nasal carriers, but the carriage is typically cleared within hours to a few days. The risk for short-term visitors to cause secondary transmissions of MRSA is most likely negligible due to the observed decline to unquantifiable levels in 95% of the nasal samples after only 2 h. The MRSA load in the nose was highly correlated to the amount of MRSA in the air and interventions to reduce the level of airborne MRSA or the use of face masks might consequently reduce nasal contamination.
Expression of a Peptidoglycan Hydrolase from Lytic Bacteriophages Atu_ph02 and Atu_ph03 Triggers Lysis of Agrobacterium tumefaciens
Authors: Attai Hedieh , Rimbey Jeanette , Smith George P. , Brown Pamela J. B.
Published: October 2017

To provide food security, innovative approaches to preventing plant disease are currently being explored. Here, we demonstrate that lytic bacteriophages and phage lysis proteins are effective at triggering lysis of the phytopathogenAgrobacterium tumefaciens. Phages Atu_ph02 and Atu_ph03 were isolated from wastewater and induced lysis of C58-derived strains ofA. tumefaciens. The coinoculation ofA. tumefacienswith phages on potato discs limited tumor formation. The genomes of Atu_ph02 and Atu_ph03 are nearly identical and are ∼42% identical to those of T7 supercluster phages.In silicoattempts to find a canonical lysis cassette were unsuccessful; however, we found a putativephagepeptidoglycanhydrolase (PPH), which contains a C-terminal transmembrane domain. Remarkably, the endogenous expression ofpphin the absence of additional phage genes causes a block in cell division and subsequent lysis ofA. tumefacienscells. When the presumed active site of theN-acetylmuramidase domain carries an inactivating mutation, PPH expression causes extensive cell branching due to a block in cell division but does not trigger rapid cell lysis. In contrast, the mutation of positively charged residues at the extreme C terminus of PPH causes more rapid cell lysis. Together, these results suggest that PPH causes a block in cell division and triggers cell lysis through two distinct activities. Finally, the potent killing activity of this single lysis protein can be modulated, suggesting that it could be engineered to be an effective enzybiotic.

IMPORTANCEThe characterization of bacteriophages such as Atu_ph02 and Atu_ph03, which infect plant pathogens such asAgrobacterium tumefaciens, may be the basis of new biocontrol strategies. First, cocktails of diverse bacteriophages could be used as a preventative measure to limit plant diseases caused by bacteria; a bacterial pathogen is unlikely to simultaneously develop resistances to multiple bacteriophage species. The specificity of bacteriophage treatment for the host is an asset in complex communities, such as in orchards where it would be detrimental to harm the symbiotic bacteria in the environment. Second, bacteriophages are potential sources of enzymes that efficiently lyse bacterial cells. These phage proteins may have a broad specificity, but since proteins do not replicate as phages do, their effect is highly localized, providing an alternative to traditional antibiotic treatments. Thus, studies of lytic bacteriophages that infectA. tumefaciensmay provide insights for designing preventative strategies against bacterial pathogens.
Akinetes May Be Representative of Past Nostocalean Blooms: a Case Study of Their Benthic Spatiotemporal Distribution and Potential for Germination in a Eutrophic Lake
Authors: Legrand Benjamin , Le Jeune Anne-Hélène , Colombet Jonathan , Thouvenot Antoine , Latour Delphine
Published: October 2017

Monitoring of water and surface sediment in a French eutrophic lake (Lake Aydat) was carried out over a 2-year period in order to determine whether akinetes in sediment could be representative of the most recent bloom and to estimate their germination potential. Sediment analysis revealed two akinete species,
Dolichospermum macrosporum
and
Dolichospermum
flos-aquae
, present in the same proportions as observed for the pelagic populations. Moreover, similar spatial patterns observed for vegetative cells in the water column and akinete distributions in the sediment suggest that akinetes in the sediment may be representative of the previous bloom. However, the relationship between akinetes in the sediment and vegetative cells in the water column was not linear, and other factors may interfere. For example, our results highlighted horizontal transport of akinetes during the winter. The benthic overwinter phase did not seem to influence the percentages of intact akinetes, which remained stable at approximately 7% and 60% for
D. macrosporum
and
D. flos-aquae
, respectively. These percentages may thus be the result of processes that occurred in the water column. The intact overwintering akinetes showed germination rates of up to 90% after 72 h for
D. flos-aquae
or 144 h for
D. macrosporum
. The difference in akinete germination rates between these two species demonstrates different ecological strategies, which serve to expand the window for germination in time and space and thus optimize colonization of the water column by nostocalean cyanobacteria.

IMPORTANCE
Cyanobacteria have the ability to proliferate and to form blooms. These blooms can then affect the local ecology, health, and economy. The akinete, a resistant cell type that persists in sediment, is an important intermediate phase between previous and future blooms. We monitored the water column and the surface sediment of a French eutrophic lake (Lake Aydat) to investigate the relationship between vegetative cells in the water column and akinetes in the sediment. This study focused on the characterization of spatiotemporal akinete distributions, cellular integrity, and germination potential. Species-specific ecological strategies were highlighted and may partly explain the temporal succession of species in the water column. Akinetes may also be used to understand past nostocalean blooms and to predict future ones.
Extracorporeal membrane oxygenation for neonatal collapse caused by enterovirus myocarditis
Authors: Cortina Gerard , Best Derek , Deisenberg Markus , Chiletti Roberto , Butt Warwick
Published: October 2017

Objective

To describe the effect of extracorporeal membrane oxygenation (ECMO) on survival and cardiac outcome of neonates with myocardial failure secondary to severe enterovirus (EV) myocarditis.

Design

Retrospective case series.

Setting

A 15-bed cardiac paediatric intensive care unit (ICU).

Patients

We describe the clinical presentations, cardiac findings, ECMO characteristics and outcome of seven neonates with severe EV myocarditis. Additionally, 35 previously reported cases of EV myocarditis supported with ECMO are presented.

Interventions

Extracorporeal membrane oxygenation.

Results

Seven neonates presented with cardiovascular collapse within the first 10 days after birth and required ECMO support. Echocardiography showed left ventricular dysfunction in all and additional right ventricular dysfunction in four patients. ECG showing widespread ST changes as well as elevated troponin I indicated myocardial damage. All patients were cannulated onto ECMO shortly after ICU admission. None of the patients suffered cardiac arrest prior to ECMO initiation. Four patients survived ECMO and three survived to hospital discharge. All three survivors showed complete cardiac recovery after a median follow-up of 34 months. The survival rate in 35 previously reported cases was 34% (12/35) and including our seven cases 36% (15/42).

Conclusions

In this case series, ECMO initiation prevented further deterioration and cardiac arrest in neonates with severe EV myocarditis and not responding to conventional medical therapies. Moreover, complete cardiac recovery occurred in survivors. However, these neonates may need long ECMO runs and are at increased risk for mechanical complications. Furthermore, mortality remains high due to greater disease severity.
Sensory exposure of neonates in single-room environments (SENSE): an observational study of light
Authors: Best Kobi , Bogossian Fiona , New Karen
Published: October 2017

Objectives

To measure the internal and external light exposure of incubators and open cots in an Australian single-room configured neonatal unit and compare findings to current recommendations.

Methods

Light meters were placed in the internal and external environment of incubators and open cots within occupied single rooms in a tertiary-level neonatal unit between 15 September and 28 October 2015. Data were recorded in one-second increments over a minimum of 48 hours per room.

Results

Internal median light in incubators and open cots predominantly fell below 50 lux, with low amplitude diurnal cycling. Incubator covers substantially reduced external light exposure, contributing to very low light conditions (<10 lux). Periodically, light inside incubators peaked six times greater than the maximum recommendation of 600 lux. Overall, internal incubator and open cot lighting in the neonatal unit met American Academy of Pediatrics and American College of Obstetricians and Gynecologists recommendations for 65.1% of the time during the day and 25.6% overnight. Australasian Health Infrastructure Alliance recommendations were met for 6.7% of the time during the day and 2.4% overnight.

Conclusions

Overall, light levels fell predominantly below 50 lux with peak periods of extreme light exposure. Low amplitude cyclic light was evident, but it remains unknown if this is sufficient to produce an effect on circadian entrainment, especially in preterm neonates. Current guidelines do not stipulate optimal cyclic light levels in neonatal units to promote circadian rhythms in the newborn population. Further research to determine well-defined lighting parameters for neonates of different gestations is paramount.
Always a burden? Healthcare providers’ perspectives on moral distress
Authors: Prentice Trisha M , Gillam Lynn , Davis Peter G , Janvier Annie
Published: October 2017

Background

Current conceptualisations of moral distress largely portray a negative phenomenon that leads to burnout, reduced job satisfaction and poor patient care.

Objective

To explore clinical experiences, perspectives and perceptions of moral distress in neonatology.

Design

An anonymous questionnaire was distributed to medical and nursing providers within two tertiary level neonatal intensive care units (NICUs)—one surgical and one perinatal—seeking their understanding of the term and their experience of it. Open-ended questions were analysed using qualitative methodology.

Results

A total of 345 healthcare providers from two NICUs participated (80% response rate): 286 nurses and 59 medical providers. Moral distress was correctly identified as constrained moral judgement resulting in distress by 93% of participants. However, in practice the term moral distress was also used as an umbrella term to articulate different forms of distress. Moral distress was experienced by 72% of providers at least once a month. Yet despite the negative sequelae of moral distress, few (8% medical, 21% nursing providers) thought that moral distress should be eliminated from the NICU. Open-ended responses revealed that while interventions were desired to decrease the negative impacts of moral distress, moral distress was also viewed as an essential component of the caring profession that prompts robust discussion and acts as an impetus for medical decision-making.

Conclusions

Moral distress remains prevalent within NICUs. While the harmful aspects of moral distress need to be mitigated, moral distress may have a positive role in advocating for and promoting the interests of the neonatal population.
Choroidal neovascularisation triggered multiple evanescent white dot syndrome (MEWDS) in predisposed eyes
Authors: Mathis Thibaud , Delaunay Benoit , Cahuzac Armelle , Vasseur Vivien , Mauget-Faÿsse Martine , Kodjikian Laurent
Published: October 2017

Background

Multiple evanescent white dot syndrome (MEWDS) is an inflammatory disease that can be associated with choroidalneovascularisation (CNV). However, few studies in the literature have described the occurrence of MEWDS in association with CNV. This paper discusses whether CNV can trigger MEWDS in a predisposed eye.

Methods

A retrospective multicentric case series of six eyes in six patients with acute onset of MEWDS and evidence of previous CNV was conducted between January 2015 and January 2017. All patients underwent ophthalmic examination including multimodal imaging at baseline and during follow-up.

Results

The mean age was 32.2±12.2 years. The majority of patients were women (5/1). In each case, MEWDS was diagnosed during a recurrence or occurrence of CNV secondary to choriocapillaritis, central serous chorioretinopathy or atrophic scar, presumably due to congenital toxoplasmosis. All patients were treated with intravitreal injections of antivascular endothelial growth factor (anti-VEGF) with good anatomical and functional responses (mean gain of 0.3±0.31logMAR). The mean duration of follow-up was 13.5±10.65 months.

Conclusion

This study highlights a sequence in the development of MEWDS, following the occurrence or recurrence of CNV. CNV may trigger MEWDS, possibly due to the proinflammatory environment created by the retinal tissue surrounding the CNV.
Development of a trigger tool to identify adverse events and no-harm incidents that affect patients admitted to home healthcare
Authors: Lindblad Marléne , Schildmeijer Kristina , Nilsson Lena , Ekstedt Mirjam , Unbeck Maria
Published: October 2017

Background

Adverse events (AEs) and no-harm incidents are common and of great concern in healthcare. A common method for identification of AEs is retrospective record review (RRR) using predefined triggers. This method has been used frequently in inpatient care, but AEs in home healthcare have not been explored to the same extent. The aim of this study was to develop a trigger tool (TT) for the identification of both AEs and no-harm incidents affecting adult patients admitted to home healthcare in Sweden, and to describe the methodology used for this development.

Methods

The TT was developed and validated in a stepwise manner, in collaboration with experts with different skills, using (1) literature review and interviews, (2) a five-round modified Delphi process, and (3) two-stage RRRs. Ten trained teams from different sites in Sweden reviewed 600 randomly selected records.

Results

In all, triggers were found 4031 times in 518 (86.3%) records, with a mean of 6.7 (median 4, range 1–54) triggers per record with triggers. The positive predictive values (PPVs) for AEs and no-harm incidents were 25.4% and 16.3%, respectively, resulting in a PPV of 41.7% (range 0.0%–96.1% per trigger) for the total TT when using 38 triggers. The most common triggers were unplanned contact with physician and/or registered nurse, moderate/severe pain, moderate/severe worry, anxiety, suffering, existential pain and/or psychological pain. AEs were identified in 37.7% of the patients and no-harm incidents in 29.5%.

Conclusion

This study shows that adapted triggers with definitions and decision support, developed to identify AEs and no-harm incidents that affect patients admitted to home healthcare, may be a valid method for safety and quality improvement work in home healthcare.
Impact of out-of-hours admission on patient mortality: longitudinal analysis in a tertiary acute hospital
Authors: Han Lu , Sutton Matt , Clough Stuart , Warner Richard , Doran Tim
Published: October 2017

Background

Emergency hospital admission on weekends is associated with an increased risk of mortality. Previous studies have been limited to examining single years and assessing day—not time—of admission. We used an enhanced longitudinal data set to estimate the ‘weekend effect’ over time and the effect of night-time admission on all-cause mortality rates.

Methods

We examined 246 350 emergency spells from a large teaching hospital in England between April 2004 and March 2014. Outcomes included 7-day, 30-day and in-hospital mortality rates. We conducted probit regressions to estimate the impact on the absolute difference in the risk of mortality of two key predictors: (1) admission on weekends (19:00 Friday to 06:59 Monday); and (2) night-time admission (19:00 to 06:59). Logistic regressions were used to estimate ORs for relative mortality risk differences.

Results

Crude 30-day mortality rate decreased from 6.6% in 2004/2005 to 5.2% in 2013/2014. Adjusted mortality risk was elevated for all out-of-hours periods. The highest risk was associated with admission on weekend night-times: 30-day mortality increased by 0.6 percentage points (adjusted OR: 1.17, 95% CI 1.10 to 1.25), 7-day mortality by 0.5 percentage points (adjusted OR: 1.23, 95% CI 1.12 to 1.34) and in-hospital mortality by 0.5 percentage points (adjusted OR: 1.14, 95% CI 1.08 to 1.21) compared with admission on weekday daytimes. Weekend night-time admission was associated with increased mortality risk in 9 out of 10 years, but this was only statistically significant (p<0.05) in 5 out of 10 years.

Conclusions

There is an increased risk of mortality for patients admitted as emergencies both on weekends and during the night-time. These effects are additive, so that the greatest risk of mortality occurs in patients admitted during the night on weekends. This increased risk appears to be consistent over time, but the effects are small and are not statistically significant in individual hospitals in every year.
Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia
Authors: Singhi Aatur D , McGrath Kevin , Brand Randall E , Khalid Asif , Zeh Herbert J , Chennat Jennifer S , Fasanella Kenneth E , Papachristou Georgios I , Slivka Adam , Bartlett David L , Dasyam Anil K , Hogg Melissa , Lee Kenneth K , Marsh James Wallis , Monaco Sara E , Ohori N Paul , Pingpank James F , Tsung Allan , Zureikat Amer H , Wald Abigail I , Nikiforova Marina N
Published: October 2017

Objective

DNA-based testing of pancreatic cyst fluid (PCF) is a useful adjunct to the evaluation of pancreatic cysts (PCs). Mutations in KRAS/GNAS are highly specific for intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), while TP53/PIK3CA/PTEN alterations are associated with advanced neoplasia. A prospective study was performed to evaluate preoperative PCF DNA testing.

Design

Over 43-months, 626 PCF specimens from 595 patients were obtained by endoscopic ultrasound (EUS)-fine needle aspiration and assessed by targeted next-generation sequencing (NGS). Molecular results were correlated with EUS findings, ancillary studies and follow-up. A separate cohort of 159 PCF specimens was also evaluated for KRAS/GNAS mutations by Sanger sequencing.

Results

KRAS/GNAS mutations were identified in 308 (49%) PCs, while alterations in TP53/PIK3CA/PTEN were present in 35 (6%) cases. Based on 102 (17%) patients with surgical follow-up, KRAS/GNAS mutations were detected in 56 (100%) IPMNs and 3 (30%) MCNs, and associated with 89% sensitivity and 100% specificity for a mucinous PC. In comparison, KRAS/GNAS mutations by Sanger sequencing had a 65% sensitivity and 100% specificity. By NGS, the combination of KRAS/GNAS mutations and alterations in TP53/PIK3CA/PTEN had an 89% sensitivity and 100% specificity for advanced neoplasia. Ductal dilatation, a mural nodule and malignant cytopathology had lower sensitivities (42%, 32% and 32%, respectively) and specificities (74%, 94% and 98%, respectively).

Conclusions

In contrast to Sanger sequencing, preoperative NGS of PCF for KRAS/GNAS mutations is highly sensitive for IPMNs and specific for mucinous PCs. In addition, the combination of TP53/PIK3CA/PTEN alterations is a useful preoperative marker for advanced neoplasia.
A comparison of the resection rate for cold and hot snare polypectomy for 4–9 mm colorectal polyps: a multicentre randomised controlled trial (CRESCENT study)
Authors: Kawamura Takuji , Takeuchi Yoji , Asai Satoshi , Yokota Isao , Akamine Eisuke , Kato Minoru , Akamatsu Takuji , Tada Kazuhiro , Komeda Yoriaki , Iwatate Mineo , Kawakami Ken , Nishikawa Michiko , Watanabe Daisuke , Yamauchi Atsushi , Fukata Norimasa , Shimatani Masaaki , Ooi Makoto , Fujita Koichi , Sano Yasushi , Kashida Hiroshi , Hirose Satoru , Iwagami Hiroyoshi , Uedo Noriya , Teramukai Satoshi , Tanaka Kiyohito
Published: October 2017

Objective

To investigate the success rate of cold snare polypectomy (CSP) for complete resection of 4–9 mm colorectal adenomatous polyps compared with that of hot snare polypectomy (HSP).

Design

A prospective, multicentre, randomised controlled, parallel, non-inferiority trial conducted in 12 Japanese endoscopy units. Endoscopically diagnosed sessile adenomatous polyps, 4–9 mm in size, were randomly assigned to the CSP or HSP group. After complete removal of the polyp using the allocated technique, biopsy specimens from the resection margin after polypectomy were obtained. The primary endpoint was the complete resection rate, defined as no evidence of adenomatous tissue in the biopsied specimens, among all pathologically confirmed adenomatous polyps.

Results

A total of 796 eligible polyps were detected in 538 of 912 patients screened for eligibility between September 2015 and August 2016. The complete resection rate for CSP was 98.2% compared with 97.4% for HSP. The non-inferiority of CSP for complete resection compared with HSP was confirmed by the +0.8% (90% CI −1.0 to 2.7) complete resection rate (non-inferiority p<0.0001). Postoperative bleeding requiring endoscopic haemostasis occurred only in the HSP group (0.5%, 2 of 402 polyps).

Conclusions

The complete resection rate for CSP is not inferior to that for HSP. CSP can be one of the standard techniques for 4–9 mm colorectal polyps. (Study registration: UMIN000018328)
International development and validation of a classification system for the identification of Barrett’s neoplasia using acetic acid chromoendoscopy: the Portsmouth acetic acid classification (PREDICT)
Authors: Kandiah Kesavan , Chedgy Fergus J Q , Subramaniam Sharmila , Longcroft-Wheaton Gaius , Bassett Paul , Repici Alessandro , Sharma Prateek , Pech Oliver , Bhandari Pradeep
Published: October 2017

Background

Barrett’s oesophagus is an established risk factor for developing oesophageal adenocarcinoma. However, Barrett’s neoplasia can be subtle and difficult to identify. Acetic acid chromoendoscopy (AAC) is a simple technique that has been demonstrated to highlight neoplastic areas but lesion recognition with AAC remains a challenge, thereby hampering its widespread use.

Objective

To develop and validate a simple classification system to identify Barrett’s neoplasia using AAC.

Design

The study was conducted in four phases: phase 1—development of component descriptive criteria; phase 2—development of a classification system; phase 3—validation of the classification system by endoscopists; and phase 4—validation of the classification system by non-endoscopists.

Results

Phases 1 and 2 led to the development of a simplified AAC classification system based on two criteria: focal loss of acetowhitening and surface patterns of Barrett’s mucosa. In phase 3, the application of PREDICT (Portsmouth acetic acid classification) by endoscopists improved the sensitivity and negative predictive value (NPV) from 79.3% and 80.2% to 98.1% and 97.4%, respectively (p<0.001). In phase 4, the application of PREDICT by non-endoscopists improved the sensitivity and NPV from 69.6% and 75.5% to 95.9% and 96.0%, respectively (p<0.001).

Conclusion

We developed and validated a classification system known as PREDICT for the diagnosis of Barrett’s neoplasia using AAC. The improvement seen in the sensitivity and NPV for detection of Barrett’s neoplasia in phase 3 demonstrates the clinical value of PREDICT and the similar improvement seen among non-endoscopists demonstrates the potential for generalisation of PREDICT once proven in real time.
Cost-effectiveness of a risk-stratified approach to cardiac resynchronisation therapy defibrillators (high versus low) at the time of generator change
Authors: Claridge Simon , Sebag Frederic A , Fearn Steven , Behar Jonathan M , Porter Bradley , Jackson Tom , Sieniewicz Benjamin , Gould Justin , Webb Jessica , Chen Zhong , O’Neill Mark , Gill Jaswinder , Leclercq Christophe , Rinaldi Christopher A
Published: October 2017

Objective

Responders to cardiac resynchronisation therapy whose device has a defibrillator component and who do not receive a therapy in the lifetime of the first generator have a very low incidence of appropriate therapy after box change. We investigated the cost implications of using a risk stratification tool at the time of generator change resulting in these patients being reimplanted with a resynchronisation pacemaker.

Methods

A decision tree was created using previously published data which had demonstrated an annualised appropriate defibrillator therapy risk of 2.33%. Costs were calculated at National Health Service (NHS) national tariff rates (2016–2017). EQ-5D utility values were applied to device reimplantations, admissions and mortality data, which were then used to estimate quality-adjusted life-years (QALYs) over 5 years.

Results

At 5 years, the incremental cost of replacing a resynchronisation defibrillator device with a second resynchronisation defibrillator versus resynchronisation pacemaker was £5045 per patient. Incremental QALY gained was 0.0165 (defibrillator vs pacemaker), resulting in an incremental cost-effectiveness ratio (ICER) of £305 712 per QALYs gained. Probabilistic sensitivity analysis resulted in an ICER of £313 612 (defibrillator vs pacemaker). For reimplantation of all patients with a defibrillator rather than a pacemaker to yield an ICER of less than £30 000 per QALY gained (current NHS cut-off for approval of treatment), the annual arrhythmic event rate would need to be 9.3%. The budget impact of selective replacement was a saving of £2 133 985 per year.

Conclusions

Implanting low-risk patients with a resynchronisation defibrillator with the same device at the time of generator change is not cost-effective by current NHS criteria. Further research is required to understand the impact of these findings on individual patients at the time of generator change.
Histopathological abnormalities in the central arteries and veins of Fontan subjects
Authors: Hays Brandon S , Baker Michael , Laib Annie , Tan Wei , Udholm Sebastian , Goldstein Bryan H , Sanders Stephen P , Opotowsky Alexander R , Veldtman Gruschen R
Published: October 2017

Objective

Fontan circulations have obligatory venous hypertension, depressed cardiac output and abnormal arterial elastance. Ventriculovascular coupling is known to be abnormal, but the underlying mechanisms are poorly defined. We aim to describe the histopathological features of vascular remodelling encountered in the central arteries and veins in the Fontan circulation as a possible underlying pathological representation of abnormal ventriculovascular coupling.

Methods

Postmortemvasculature (inferior vena cava (IVC), superior vena cava (SVC), pulmonary artery (PA), pulmonary vein (PV) and aorta) of 13 patients with a Fontan circulation (mean age 29.9 years, range 9.0–59.8 years) and 2 biventricular controls (ages 17.9 and 30.2 years) was examined.

Results

IVC and SVC: Eccentric and variable intimal fibromuscular proliferation occurred in 11 Fontan subjects. There was variable loss of medial smooth muscle bundles with reciprocal replacement with dense collagenous tissue.

PA: Similar intimal fibromuscular proliferation was seen; however, these intimal changes were accompanied by medial thinning rather than expansion, medial myxoid degeneration and elastic alteration.

PV: The PVs demonstrated intimal fibroproliferation and disorganisation of the muscular media.

Aorta: The aortic lamina intima was thickened, with associated fibromuscular proliferation and elasticisation. There was also moderate lymphocytic inflammation in the aortic wall.

Conclusions

Vascular architectural remodelling is common in Fontan patients. The central veins demonstrate profound changes of eccentric intimal expansion and smooth muscle replacement with collagen. The pulmonary demonstrated abnormal intimal proliferation, and aortic remodelling was characterised by intima lamina thickening and a moderate degree of aortic wall inflammation.
Safe Kids Week: Analysis of gender bias in a national child safety campaign, 1997–2016
Authors: Bauer Michelle E E , Brussoni Mariana , Giles Audrey R , Fuselli Pamela
Published: October 2017

Background and PurposeChild safety campaigns play an important role in disseminating injury prevention information to families. A critical discourse analysis of gender bias in child safety campaign marketing materials can offer important insights into how families are represented and the potential influence that gender bias may have on uptake of injury prevention information.

MethodsOur approach was informed by poststructural feminist theory, and we used critical discourse analysis to identify discourses within the poster materials. We examined the national Safe Kids Canada Safe Kids Week campaign poster material spanning twenty years (1997-2016). Specifically, we analyzed the posters’ typeface, colour, images, and language to identify gender bias in relation to discourses surrounding parenting, safety, and societal perceptions of gender.

ResultsThe findings show that there is gender bias present in the Safe Kids Week poster material. The posters represent gender as binary, mothers as primary caregivers, and showcase stereotypically masculine sporting equipment among boys and stereotypically feminine equipment among girls. Interestingly, we found that the colour and typeface of the text both challenge and perpetuate the feminization of safety.

DiscussionIt is recommended that future child safety campaigns represent changing family dynamics, include representations of children with non-traditionally gendered sporting equipment, and avoid the representation of gender as binary. This analysis contributes to the discussion of the feminization of safety in injury prevention research and challenges the ways in which gender is represented in child safety campaigns.
Could the rise in mortality rates since 2015 be explained by changes in the number of delayed discharges of NHS patients?
Authors: Green Mark A , Dorling Danny , Minton Jonathan , Pickett Kate E
Published: October 2017

Background

2015 saw the largest annual spike of mortality rates in England in almost 50 years. We examine whether these changes in mortality rates are associated with an indicator of poor functioning of health and social care: delay in hospital discharges.

Methods

Office for National Statistics monthly data of death counts and mortality rates for the period August 2010–March 2016 were compared with delays in discharges from National Health Service (NHS) England data on transfers of care for acute and non-acute patients in England. Autoregressive Integrated Moving Average regression models were used in the analysis.

Results

We estimate that each additional day an acute admission was late being discharged was associated with an increase in 0.394 deaths (95% CIs 0.220 to 0.569). For each additional acute patient delayed being discharged, we found an increase of 7.322 deaths (95% CIs 1.754 to 12.890). Findings for non-acute admissions were mixed.

Conclusion

The increased prevalence of patients being delayed in discharge from hospital in 2015 was associated with increases in mortality, accounting for up to a fifth of mortality increases. Our study provides evidence that a lower quality of performance of the NHS and adult social care as a result of austerity may be having an adverse impact on population health.
Underemployment and its impacts on mental health among those with disabilities: evidence from the HILDA cohort
Authors: Milner Allison , King Tania Louise , LaMontagne Anthony D , Aitken Zoe , Petrie Dennis , Kavanagh Anne M
Published: October 2017

Background

Underemployment (defined as when a person in paid employment works for fewer hours than their desired full working capacity) is increasingly recognised as a component of employment precarity. This paper sought to investigate the effects of underemployment on the mental health of people with disabilities.

Methods

Using 14 waves of the Household, Income and Labour Dynamics in Australia survey, we used fixed-effects models to assess whether the presence of a disability modified the association between underemployment and mental health. Both disability and underemployment were assessed as time-varying factors. Measures of effect measure modification were presented on the additive scale.

Results

The experience of underemployment was associated with a significantly greater decline in mental health when a person reported a disability (mean difference −1.38, 95% CI −2.20 to −0.57) compared with when they did not report a disability (mean difference −0.49, 95% CI −0.84 to −0.14). The combined effect of being underemployed and having a disability was nearly one point greater than the summed independent risks of having a disability and being underemployed (−0.89, 95% CI −1.75 to –0.03).

Conclusion

People with disabilities are more likely to experience underemployment and more likely to have their mental health adversely affected by it. There is a need for more research and policy attention on how to ameliorate the effects of underemployment on the mental health of persons with disabilities.