bluuebunny/crossref_metadata_2025 huggingface dataset:
UGT709G1: a novel uridine diphosphate glycosyltransferase involved in the biosynthesis of picrocrocin, the precursor of safranal in saffron (Crocus sativus)
Authors: Diretto Gianfranco , Ahrazem Oussama , Rubio‐Moraga Ángela , Fiore Alessia , Sevi Filippo , Argandoña Javier , Gómez‐Gómez Lourdes
Published: July 2019

Saffron, a spice derived from the dried red stigmas of Crocus sativus, is one of the oldest natural food additives. The flowers have long red stigmas, which store significant quantities of the glycosylated apocarotenoids crocins and picrocrocin. The apocarotenoid biosynthetic pathway in saffron starts with the oxidative cleavage of zeaxanthin, from which crocins and picrocrocin are derived. In the processed stigmas, picrocrocin is converted to safranal, giving saffron its typical aroma.

By a targeted search for differentially expressed uridine diphosphate glycosyltransferases (UGTs) in Crocus transcriptomes, a novel apocarotenoid glucosyltransferase (UGT709G1) from saffron was identified.

Biochemical analyses revealed that UGT709G1 showed a high catalytic efficiency toward 2,6,6‐trimethyl‐4‐hydroxy‐1‐carboxaldehyde‐1‐cyclohexene (HTCC), making it suited for the biosynthesis of picrocrocin, the precursor of safranal. The role of UGT709G1 in picrocrocin/safranal biosynthesis was supported by the absence or presence of gene expression in a screening for HTCC and picrocrocin production in different Crocus species and by a combined transient expression assay with CsCCD2L in Nicotiana benthamiana leaves.

The identification of UGT709G1 completes one of the most highly valued specialized metabolic biosynthetic pathways in plants and provides novel perspectives on the industrial production of picrocrocin to be used as a flavor additive or as a pharmacological constituent.
The effectiveness of app‐based mobile interventions on nutrition behaviours and nutrition‐related health outcomes: A systematic review and meta‐analysis
Authors: Villinger Karoline , Wahl Deborah R. , Boeing Heiner , Schupp Harald T. , Renner Britta
Published: July 2019

A systematic review and meta‐analysis were conducted to assess the effectiveness of app‐based mobile interventions for improving nutrition behaviours and nutrition‐related health outcomes, including obesity indices (eg, body mass index [BMI]) and clinical parameters (eg, blood lipids). Seven databases were searched for studies published between 2006 and 2017. Forty‐one of 10 132 identified records were included, comprising 6348 participants and 373 outcomes with sample sizes ranging from 10 to 833, including 27 randomized controlled trials (RCTs). A beneficial effect of app‐based mobile interventions was identified for improving nutrition behaviours (g = 0.19; CI, 0.06‐0.32, P = .004) and nutrition‐related health outcomes (g = 0.23; CI, 0.11‐0.36, P < .001), including positive effects on obesity indices (g = 0.30; CI, 0.15‐0.45, P < .001), blood pressure (g = 0.21; CI, 0.01‐0.42, P = .043), and blood lipids (g = 0.15; CI, 0.03‐0.28, P = .018). Most interventions were composed of four behaviour change technique (BCT) clusters, namely, “goals/planning,” “feedback/monitoring,” “shaping knowledge,” and “social support.” Moderating effects including study design, type of app (commercial/research app), sample characteristics (clinical/non‐clinical sample), and intervention characteristics were not statistically significant. The inclusion of additional treatment components besides the app or the number or type of BCTs implemented did not moderate the observed effectiveness, which underscores the potential of app‐based mobile interventions for implementing effective and feasible interventions operating at scale for fighting the obesity epidemic in a broad spectrum of the population.
How Do Different Types of Local Governments' Sustainability Programs Relate to Their Environmental Outcomes
Authors: Ji Hyunjung
Published: July 2019

Local governments worldwide have developed a suite of sustainability programs to improve environmental conditions within their jurisdictions. However, critics suggest that local governments' sustainability programs are more symbolic than substantial in that they are often developed to create the appearance of addressing environmental issues rather than actual environmental performance outcomes. Despite the skeptics, as yet, we have little empirical understanding of the environmental impact of local sustainability programs. This paper bridges the gap by considering how the design of 102 county governments' individual sustainability programs relates to improvement of their ozone quality between 2003 and 2013. After controlling for the spatial dependence of ozone quality among neighboring counties, this paper offers the evidence that local sustainability programs are related to improved environmental conditions. Moreover, the sustainability programs that are designed more comprehensively across environmental issues appear to have greater policy efficacy compared to those focusing on a few environmental issues. These findings provide optimistic views about the local, non‐regulatory policy effort for improving collective environmental quality. This implication is particularly salient given the lack of strong national and international environmental regulatory regimes.
HLA‐A, ‐B, ‐C, ‐DRB1, and ‐DQB1 allele and haplotype frequencies: An analysis of umbilical cord blood units at the Barcelona Cord Blood Bank
Authors: Enrich Emma , Campos Eva , Martorell Lluís , Herrero María José , Vidal Francisco , Querol Sergi , Rudilla Francesc
Published: July 2019

Allele‐level HLA compatibility in cord blood transplantation has been associated with better transplant outcomes and is recommended as a selection criterion. It is also a crucial aspect for other therapeutic applications involving cord blood‐derived cells. Determination of high‐resolution HLA frequencies is an important step towards improving the quality of cord blood banks. We analyzed HLA‐A, ‐B, ‐C, ‐DRB1, and ‐DQB1 allele frequencies in 5458 high‐quality cord blood units from the Barcelona Cord Blood Bank and identified 275 class I and 121 class II HLA alleles. A*02:01, B*44:03, C*07:01, DRB1*07:01 and DQB1*03:01 were the most frequent alleles at each locus. We detected 26 novel alleles and were able to determine the presence or absence of some null alleles, including C*04:09N, in a large number of units. We also analyzed maternal HLA typing information for 1877 units to determine real haplotype frequencies and linkage disequilibrium. A*29:02‐B*44:03‐C*16:01‐DRB1*07:01‐DQB1*02:02 was the most frequent HLA haplotype and the DRB1‐DQB1 gene pair contained the two‐locus haplotypes with the strongest linkage disequilibrium values. Four of the 11 unique haplotypes identified in the HLA‐homozygous cord blood units were the top‐ranking haplotypes identified and were present in 18% of the cohort. This is the first study to report on HLA allele and haplotype frequencies for umbilical cord blood units from the Barcelona Cord Blood Bank and the largest study to date involving two fields of HLA resolution typing of Spanish registry data.
Pre‐ and post‐transplant bacterial infections in liver transplant recipients
Authors: Heldman Madeleine R. , Ngo Stephen , Dorschner Peter B. , Helfrich Mia , Ison Michael G.
Published: July 2019

Background

Early (<1 month) bacterial infection after liver transplant is a major cause of morbidity and mortality among liver transplant recipients. We investigated the impact of pre‐transplant bacterial infection on early post‐transplant bacterial infection incidence and outcomes.

Methods

A retrospective cohort study identified all patients who underwent liver transplantation between January 1, 2011, and December 31, 2012, at a single tertiary center in the United States. Infections occurring within the 30 days prior to transplant and within the 30 following transplant were identified. Information regarding pre‐transplant morbidity and post‐transplant outcomes was collected.

Results

One‐hundred seventy‐four patients were included in the study. Forty patients (23%) experienced a total of 50 pre‐transplant infections. Fifty‐two (30%) developed a total of 62 post‐transplant infections. Patients with a pre‐transplant infection were more likely to develop a post‐transplant infection compared to patients without a pre‐transplant infection (48% [19 of 40] vs. 25% [33 of 134], respectively, P = .006). Patients with a pre‐transplant infection had a longer mean post‐transplant length of stay compared to those without a pre‐transplant infection (16.3 days vs. 10.4 days, respectively, P < .001), but survival at 30 days was similar in both groups (95% [38 of 40] vs. 97% [130 of 134, respectively, P = .56).

Conclusions

Among liver transplant recipients, pre‐transplant infection is an important risk factor for early post‐transplant bacterial infections. Pre‐transplant infection is associated with increased early morbidity but not mortality after transplant.
Angioinvasive, cutaneous infection due to Colletotrichum siamense in a stem cell transplant recipient: Report and review of prior cases
Authors: Werbel William A. , Baroncelli Riccardo , Shoham Shmuel , Zhang Sean X.
Published: July 2019

Colletotrichum is an important fungal plant pathogen, yet an uncommon cause of human disease. Herein we report a case of invasive, cutaneous infection in a stem cell transplant recipient due to Colletotrichum species, with accompanying review of the literature. The infection was successfully treated with a combination of liposomal amphotericin B and voriconazole. Multilocus phylogenetic analysis revealed that the distinct isolate belongs to Colletotrichum siamense, a member of the Colletotrichum gloeosporioides species complex not previously described as a human pathogen. Colletotrichum infection remains in the differential for skin lesions in the immune compromised host.
Population‐dependent reproducible deviation from natural bread wheat genome in synthetic hexaploid wheat
Authors: Jighly Abdulqader , Joukhadar Reem , Sehgal Deepmala , Singh Sukhwinder , Ogbonnaya Francis C. , Daetwyler Hans D.
Published: July 2019

Sequence elimination is one of the main mechanisms that increases the divergence among homoeologous chromosomes after allopolyploidization to enhance the stability of recently established lineages, but it can cause a loss of some economically important genes. Synthetic hexaploid wheat (SHW) is an important source of genetic variation to the natural hexaploid wheat (NHW) genepool that has low genetic diversity. Here, we investigated the change between SHW and NHW genomes by utilizing a large germplasm set of primary synthetics and synthetic derivatives. Reproducible segment elimination (RSE) was declared if a large chromosomal chunk (>5 cM) produced no aligned reads in more than five SHWs. RSE in five genomic regions was the major source of variation between SHW and NHW. One RSE eliminated almost the complete short arm of chromosome 1B, which contains major genes for flour quality, disease resistance and different enzymes. The occurrence of RSE was highly dependent on the choice of diploid and tetraploid parental lines, their ancestral subpopulation and admixture, e.g. SHWs derived from Triticum dicoccon or from one of two Aegilops tauschii subpopulations were almost free of RSE, while highly admixed parents had higher RSE rates. The rate of RSE in synthetic derivatives was almost double that in primary synthetics. Genome‐wide association analysis detected four loci with minor effects on the occurrence of RSE, indicating that both parental lines and genetic factors were affecting the occurrence of RSE. Therefore, pre‐pre‐breeding strategies should be applied before introducing SHW into pre‐breeding programs to ensure genomic stability and avoid undesirable gene loss.
GSK3‐like kinase BIN2 phosphorylates RD26 to potentiate drought signaling in Arabidopsis
Authors: Jiang Hao , Tang Buyun , Xie Zhouli , Nolan Trevor , Ye Huaxun , Song Gao‐Yuan , Walley Justin , Yin Yanhai
Published: July 2019

Plant steroid hormones brassinosteroids (BRs) regulate plant growth and development at many different levels. Recent research has revealed that stress‐responsive NAC (petunia NAM and Arabidopsis ATAF1, ATAF2, and CUC2) transcription factor RD26 is regulated by BR signaling and antagonizes BES1 in the interaction between growth and drought stress signaling. However, the upstream signaling transduction components that activate RD26 during drought are still unknown. Here, we demonstrate that the function of RD26 is modulated by GSK3‐like kinase BIN2 and protein phosphatase 2C ABI1. We show that ABI1, a negative regulator in abscisic acid (ABA) signaling, dephosphorylates and destabilizes BIN2 to inhibit BIN2 kinase activity. RD26 protein is stabilized by ABA and dehydration in a BIN2‐dependent manner. BIN2 directly interacts and phosphorylates RD26 in vitro and in vivo. BIN2 phosphorylation of RD26 is required for RD26 transcriptional activation on drought‐responsive genes. RD26 overexpression suppressed the brassinazole (BRZ)  insensitivity of BIN2 triple mutant bin2 bil1 bil2, and BIN2 function is required for the drought tolerance of RD26 overexpression plants. Taken together, our data suggest a drought signaling mechanism in which drought stress relieves ABI1 inhibition of BIN2, allowing BIN2 activation. Sequentially, BIN2 phosphorylates and stabilizes RD26 to promote drought stress response.
High‐intensity interval training changes the expression of muscle RING‐finger protein‐1 and muscle atrophy F‐box proteins and proteins involved in the mechanistic target of rapamycin pathway and autophagy in rat skeletal muscle
Authors: Cui Xinwen , Zhang Yimin , Wang Zan , Yu Jingjing , Kong Zhenxing , Ružić Lana
Published: July 2019

New Findings

What is the central question of this study?

What are the adaptations of protein synthesis and degradation that occur in skeletal muscle in response to high‐intensity interval training (HIIT), and what are the magnitudes of the changes in response to HIIT, compared to moderate‐intensity continuous training (MICT), and the mechanisms underlying these changes?

What is the main finding and its importance?

HIIT is more effective than MICT in altering the expression of muscle RING‐finger protein‐1 and muscle atrophy F‐box, and enhancing the autophagic flux in rat soleus muscle. In addition, HIIT could activate the mechanistic target of rapamycin pathway. These findings suggest that HIIT might be an effective exercise strategy for health promotion in skeletal muscle.

This study aimed to investigate the impact of high‐intensity interval training (HIIT) on the proteins involved in protein synthesis, the ubiquitin–proteasome system (UPS) and autophagy in skeletal muscle of middle‐aged rats. Nine‐month‐old male Wistar rats (n = 56) were randomly divided into three groups: a control (C) group, a moderate‐intensity continuous training (MICT) group and a HIIT group. Rats in the training groups ran on treadmills 5 days per week for 8 weeks. The MICT group ran for 50 min at 60% , while the HIIT group ran for 3 min at 80% of six times separated by 3‐min periods at 40% . Aerobic endurance, number of autophagosomes and expression of proteins involved in protein synthesis and degradation in the soleus muscle were measured at three time points: before training, after 4 weeks and after 8 weeks of training. Compared to the C group, HIIT and MICT increased the expression of phosphorylated mechanistic target of rapamycin (mTOR) after 8 weeks (P < 0.05 and P < 0.01, respectively). HIIT increased the expression of muscle RING‐finger protein‐1 (MuRF‐1) after 4 weeks (P < 0.01), and decreased its expression after 8 weeks (P < 0.01). Both HIIT and MICT decreased the expression of muscle atrophy F‐box (MAFbx) after 4 weeks (P < 0.05). HIIT improved the expression of microtubule‐associated protein 1A/1B‐light chain 3 (LC3)‐II (P < 0.05), and decreased the P62 content (P < 0.01) after 4 weeks. The LC3II/LC3I ratio was increased after 8 weeks (P < 0.01). This study demonstrated that HIIT could activate the mTOR pathway, alter the expression of MuRF‐1 and MAFbx proteins, and enhance autophagic flux in soleus muscle of middle‐aged rats.
Analysis of a Solar-Aided Natural Gas Cogeneration Plant Applied to the Textile Sector
Authors: Zuleta Marín Juan Sebastián , Konrad Burin Eduardo , Bazzo Edson
Published: July 2019

Two combined cooling heating power (CCHP) plant layouts are proposed to supply the electricity, heat, and cooling energy demands of textile industries. In the first scenario, natural gas fueled internal combustion engines are integrated with a heat recovery steam generator (HRSG) and a hot water absorption chiller to produce electricity, saturated steam, and chilled water for air conditioning purposes. In the second concept, a linear Fresnel solar field is integrated with the same CCHP to provide fuel economy during the sunny hours. The proposed plants were compared with a base case scenario in which electricity is imported from the grid, saturated steam is provided by a natural gas steam generator (NGSG), and chilled water is provided by electric chillers. Simulations were performed considering mass and energy conservation equations, information provided by equipment manufacturers and typical meteorological year (TMY) data sets for three different locations. The economic performance of plants was evaluated by calculating the net present value (NPV), the internal rate of return (IRR), and the discounted payback period (DPP) of investments. As an important result, a great potential for reducing the fuel consumption and CO2 emissions of hybrid concept was identified. However, the high investment of Fresnel collectors coupled with low natural gas prices showed the proposed hybrid concept as economically unfeasible. Nevertheless, it is expected that hybrid systems will have an important role once Fresnel technology costs are continuously declining and solar energy appears as a promising alternative for the sustainable transition to a low carbon future.
Observations of phase and intensity fluctuations for low-frequency, long-range transmissions in the Philippine Sea and comparisons to path-integral theory
Authors: Colosi John A. , Cornuelle Bruce D. , Dzieciuch Matthew A. , Worcester Peter F. , Chandrayadula Tarun K.
Published: July 2019

In the Philippine Sea, from April 2010 to March 2011, a 330-km radius pentagonal acoustic transceiver array with a sixth transceiver in the center transmitted broadband signals with center frequencies between 172 and 275 Hz and 100 Hz bandwidth eight times a day every other day. The signals were recorded on a large-aperture vertical-line array located near the center of the pentagon at ranges of 129, 210, 224, 379, 396, and 450 km. The acoustic arrival structures are interpretable in terms of ray paths. Depth and time variability of the acoustic observations are analyzed for six ray paths (one from each transceiver) with similar vertical sampling properties in the main thermocline. Acoustic-field statistics treated include: (1) variances of phase and intensity, (2) vertical coherence and intensity covariance, (3) glinting and fadeout rates, and (4) intensity probability density functions. Several observed statistics are compared to predictions using Feynman path-integral theory assuming the Garrett-Munk internal-wave spectrum. In situ oceanographic observations support this assumption and are used to estimate spectral parameters. Data and theory differ at most by a factor of two and reveal the wave propagation regimes of unsaturated, partially saturated, and fully saturated. Improvements to the evaluation of path-integral quantities are discussed.
Program Reach and Implementation Feasibility of a Physical Activity School Health Program: A Qualitative Study of Teachers’ Perception
Authors: Guldager Julie D. , Leppin Anja , von Seelen Jesper , Andersen Pernille T.
Published: July 2019

Background: The reasons for the mixed evidence of the effectiveness of school-based physical activity programs can be many, including implementation challenges. Studying program implementation can potentially contribute to enhancing effectiveness, the design of future interventions, improved implementation, and the interpretation of outcomes. Methods: For this process evaluation, individual interviews were conducted with 16 teachers who had implemented the program “Active All Year Round” in a fifth-grade school class (students aged 9–11 y) in 2017. Through systematic text condensation feasibility and barriers of program implementation, perceived program reach and the programs’ influence on social cohesion were identified and discussed. Results: Teachers described the program as very feasible to implement and identified very few implementation barriers, the most prominent being time constrains. Perceived program reach was very high, and teachers reported that those students who are less confident when it comes to physical activity did not have differential participation than those feeling more confident about physical activity. Finally, the program was perceived to positively affect social cohesion in class. Conclusions: Active All Year Round is a standardized, flexible, and easily implemented program in Danish schools. Future studies are needed to study implementation from a student’s perspective and/or students’ role in and experiences with competition-based health programs.
Mosquito-Borne Viruses and Insect-Specific Viruses Revealed in Field-Collected Mosquitoes by a Monitoring Tool Adapted from a Microbial Detection Array
Authors: Martin Estelle , Borucki Monica K. , Thissen James , Garcia-Luna Selene , Hwang Mona , Wise de Valdez Megan , Jaing Crystal J. , Hamer Gabriel L. , Frank Matthias
Published: July 2019

Viruses associated with mosquitoes have made a large impact on public and veterinary health. In the United States, several viruses, including WNV, DENV, and chikungunya virus (CHIKV), are responsible for human disease. From 2015 to 2018, imported Zika cases were reported in the United States, and in 2016 to 2017, local Zika transmission occurred in the states of Texas and Florida. With globalization and a changing climate, the frequency of outbreaks linked to arboviruses will increase, revealing a need to better detect viruses in vector populations. With the capacity of the LLMDA to detect viruses, bacteria, and fungi, this study highlights its ability to broadly screen field-collected mosquitoes and contribute to the surveillance and management of arboviral diseases.
Late Quaternary slip rates for faults of the central Walker Lane (Nevada, USA): Spatiotemporal strain release in a strike-slip fault system
Authors: Angster Stephen J. , Wesnousky Steven G. , Figueiredo Paula M. , Owen Lewis A. , Hammer Sarah J.
Published: July 2019

The Walker Lane is a broad shear zone that accommodates a significant portion of North American–Pacific plate relative transform motion through a complex of fault systems and block rotations. Analysis of digital elevation models, constructed from both lidar data and structure-from-motion modeling of unmanned aerial vehicle photography, in conjunction with 10Be and 36Cl cosmogenic and optically stimulated luminescence dating define new Late Pleistocene to Holocene minimum strike-slip rates for the Benton Springs (1.5 ± 0.2 mm/yr), Petrified Springs (0.7 ± 0.1 mm/yr), Gumdrop Hills (0.9 +0.3/−0.2 mm/yr), and Indian Head (0.8 ± 0.1 mm/yr) faults of the central Walker Lane (Nevada, USA). Regional mapping of the fault traces within Quaternary deposits further show that the Indian Head and southern Benton Springs faults have had multiple Holocene ruptures, with inferred coseismic displacements of ∼3 m, while absence of displaced Holocene deposits along the Agai Pah, Gumdrop Hills, northern Benton Springs, and Petrified Springs faults suggest they have not. Combining these observations and comparing them with geodetic estimates of deformation across the central Walker Lane, indicates that at least one-third of the ∼8 mm/yr geodetic deformation budget has been focused across strike-slip faults, accommodated by only two of the five faults discussed here, during the Holocene, and possibly half from all the strike-slip faults during the Late Pleistocene. These results indicate secular variations of slip distribution and irregular recurrence intervals amongst the system of strike-slip faults. This makes the geodetic assessment of fault slip rates and return times of earthquakes on closely spaced strike-slip fault systems challenging. Moreover, it highlights the importance of understanding temporal variations of slip distribution within fault systems when comparing geologic and geodetic rates. Finally, the study provides examples of the importance and value in using observations of soil development in assessing the veracity of surface exposure ages determined with terrestrial cosmogenic nuclide analysis.
Indocyanine green angiography for identifying telangiectatic capillaries in diabetic macular oedema
Authors: Castro Farías Daniela , Matsui Serrano Rodrigo , Bianchi Gancharov Juan , de Dios Cuadras Ulises , Sahel José , Graue Wiechers Federico , Dupas Benedicte , Paques Michel
Published: July 2019

Aims

During diabetic macular oedema (DME), a spectrum of capillary abnormalities is commonly observed, ranging from microaneurysms to large microvascular abnormalities. Clinical evidence suggests that targeted photocoagulation of large microvascular abnormalities may be beneficial, but their detection is not done in a routine fashion. It was reported that they are better identified by indocyanine green angiography (ICGA) than by fluorescein angiography. Here, we investigated the prevalence and ICGA and optical coherence tomography (OCT) features of retinal microvascular abnormalities in a group of patients with DME.

Methods

Observational study. The fundus photographs, ICGA and structural and angiographic OCT charts of 35 eyes from 25 consecutive patients with DME were reviewed.

Results

22 eyes (63%) had at least one focal area of microvascular abnormalities showing prolonged indocyanine green (ICG) staining (ie, beyond 10 mins after injection). In particular, all eyes (n=9) with circinate hard exudates showed foci of late ICG staining. These areas were either isolated globular capillary ecstasies or a cluster of ill-defined capillary abnormalities. They were located at a median distance of 2708 µm from the fovea (range: 1064–4583 µm). Their diameter ranged from 153 to 307 µm. During ICGA, 91% showed increased their contrast and apparent size in late frames, whereas 79% of microaneurysms showed reduced contrast on late frames. OCT angiography was not contributive for the detection of these lesions.

Conclusion

Late ICG staining revealing large microvascular abnormalities is commonly observed during DME. Because of their specific angiographic and OCT features relative to microaneurysms, we propose to name them telangiectatic capillaries (TelCaps).
Advancing research on the economic value of emergency care
Authors: Risko Nicholas , Chandra Amit , Burkholder Taylor W , Wallis Lee A , Reynolds Teri , Calvello Hynes Emilie J , Razzak Junaid
Published: July 2019

Emergency care and the emergency care system encompass an array of time-sensitive interventions to address acute illness and injury. Research has begun to clarify the enormous economic burden of acute disease, particularly in low-income and middle-income countries, but little is known about the cost-effectiveness of emergency care interventions and the performance of health financing mechanisms to protect populations against catastrophic health expenditures. We summarise existing knowledge on the economic value of emergency care in low resource settings, including interventions indicated to be highly cost-effective, linkages between emergency care financing and universal health coverage, and priority areas for future research.
How do stakeholders experience the adoption of electronic prescribing systems in hospitals? A systematic review and thematic synthesis of qualitative studies
Authors: Farre Albert , Heath Gemma , Shaw Karen , Bem Danai , Cummins Carole
Published: July 2019

Background

Electronic prescribing (ePrescribing) or computerised provider/physician order entry (CPOE) systems can improve the quality and safety of health services, but the translation of this into reduced harm for patients remains unclear. This review aimed to synthesise primary qualitative research relating to how stakeholders experience the adoption of ePrescribing/CPOE systems in hospitals, to help better understand why and how healthcare organisations have not yet realised the full potential of such systems and to inform future implementations and research.

Methods

We systematically searched 10 bibliographic databases and additional sources for citation searching and grey literature, with no restriction on date or publication language. Qualitative studies exploring the perspectives/experiences of stakeholders with the implementation, management, use and/or optimisation of ePrescribing/CPOE systems in hospitals were included. Quality assessment combined criteria from the Critical Appraisal Skills Programme Qualitative Checklist and the Standards for Reporting Qualitative Research guidelines. Data were synthesised thematically.

Results

79 articles were included. Stakeholders’ perspectives reflected a mixed set of positive and negative implications of engaging in ePrescribing/CPOE as part of their work. These were underpinned by further-reaching change processes. Impacts reported were largely practice related rather than at the organisational level. Factors affecting the implementation process and actions undertaken prior to implementation were perceived as important in understanding ePrescribing/CPOE adoption and impact.

Conclusions

Implementing organisations and teams should consider the breadth and depth of changes that ePrescribing/CPOE adoption can trigger rather than focus on discrete benefits/problems and favour implementation strategies that: consider the preimplementation context, are responsive to (and transparent about) organisational and stakeholder needs and agendas and which can be sustained effectively over time as implementations develop and gradually transition to routine use and system optimisation.
Exploring the sustainability of quality improvement interventions in healthcare organisations: a multiple methods study of the 10-year impact of the ‘Productive Ward: Releasing Time to Care’ programme in English acute hospitals
Authors: Robert Glenn , Sarre Sophie , Maben Jill , Griffiths Peter , Chable Rosemary
Published: July 2019

Background

The ‘Productive Ward: Releasing Time to Care’ programme is a quality improvement (QI) intervention introduced in English acute hospitals a decade ago to: (1) Increase time nurses spend in direct patient care. (2) Improve safety and reliability of care. (3) Improve experience for staff and patients. (4) Make changes to physical environments to improve efficiency.

Objective

To explore how timing of adoption, local implementation strategies and processes of assimilation into day-to-day practice relate to one another and shape any sustained impact and wider legacies of a large-scale QI intervention.

Design

Multiple methods within six hospitals including 88 interviews (with Productive Ward leads, ward staff, Patient and Public Involvement representatives and senior managers), 10 ward manager questionnaires and structured observations on 12 randomly selected wards.

Results

Resource constraints and a managerial desire for standardisation meant that, over time, there was a shift away from the original vision of empowering ward staff to take ownership of Productive Ward towards a range of implementation ‘short cuts’. Nonetheless, material legacies (eg, displaying metrics data; storage systems) have remained in place for up to a decade after initial implementation as have some specific practices (eg, protected mealtimes). Variations in timing of adoption, local implementation strategies and contextual changes influenced assimilation into routine practice and subsequent legacies. Productive Ward has informed wider organisational QI strategies that remain in place today and developed lasting QI capabilities among those meaningfully involved in its implementation.

Conclusions

As an ongoing QI approach Productive Ward has not been sustained but has informed contemporary organisational QI practices and strategies. Judgements about the long-term sustainability of QI interventions should consider the evolutionary and adaptive nature of change processes.
115 Is MBS restriction on EEGs truly beneficial? Retrospective observational analysis of EEG referral patterns
Authors: Ratnayake Chathri , Kokulan Ramja , Carney Patrick
Published: July 2019

Introduction

The November 2018 Medicare Benefits Schedule (MBS) Taskforce draft report recommends standardised national referral form for routine electroencephalogram (EEG) requests to prevent low value clinician referrals. MBS defines twelve clinical presentations where routine EEG is of relatively low diagnostic value. We aim to identify proportion of MBS defined low diagnostic value EEGs and likely referral patterns.

Methods

Retrospective single centre observational study was conducted from January to December 2018. All EEG referrals to a tertiary hospital neurodiagnostic unit were categorised as low or high yield based on MBS recommendation. Sub-group analysis of the low yield group was carried out.

Results

Total of 1210 EEG referrals were analysed and 5 were excluded from analysis due to insufficient clinical data. Of these referrals 1114 (92.4%) were for high yield indications, 77 (6.4%) for low yield and 14 (1.2%) were indeterminate as to low or high value. Of low yield referrals, 70% were referred for syncope or presyncope and 18.2% for psychogenic nonepileptic seizures. Low yield EEGs were referred by hospital doctors, neurologists and general partitioners by proportions of 37.7%, 33.7% and 28.6% respectively. Four (5.2%) low diagnostic value EEGs were abnormal.

Conclusion

Current clinical practice for EEG referrals is in line with MBS draft review recommendations. We believe addition of a standardised referral form and restricting referrals will have minimal impact on referral quality.
116 Altered peripheral axonal properties in fibromyalgia
Authors: Lin Cindy (Shin-YI) , Teng Hao-Wen , Tani Jowy , Chen Hung-Ju , Lin Yi-Chen , Chang Tsui-San , Sung Jia-Ying
Published: July 2019

Introduction

Fibromyalgia (FM), a common chronic widespread pain syndrome with neurological symptoms affecting ∼10% of the population worldwide. Whereas small fibre neuropathy is a recognized part of FM, surprisingly little is known about large fibre neuropathy. The present study investigates the sensory and motor axonal properties using novel nerve excitability testing (NET) to seek a better understanding of the pathogenesis of this painful disorder.

Methods

25 FM patients were recruited from the Wan Fang Hospital in Taiwan who fulfilled the American College of Rheumatology diagnostic criteria.1 NCS, pain scores, blood tests and NET were performed in all patients and patients with factors that may confound the results of NET were excluded. Control data were obtained from age and gender-matched healthy controls (HC) who had no neurological deficits or known pain disorders.

Results

The FM group showed an increase in superexcitability (p<0.05), subexcitability (p<0.05) and over-shoot during hyperpolarizing threshold electrotonus (p<0.05) in the sensory excitability profiles in contrast to HC. However, motor nerve excitability profiles showed no significant difference.

Conclusions

Alterations in the sensory axonal parameters can be detected while NCS is normal, these findings are compatible with the concept that the sensory system is mainly involved in the pathogenesis of FM. Results implied probable hypofunction of the paranodal fast K+ channel in the sensory axons, known to be associated with the generation of pain.2 Our study highlights the advantage of NET over NCS, in the early detection of axonal dysfunction and may provide further understandings of future therapeutic treatment.

References

Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Hauser W, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol 2011;38(6):1113–1122.

Kuwabara S, Misawa S. Pharmacologic intervention in axonal excitability: in vivo assessment of nodal persistent sodium currents in human neuropathies. Curr Mol Pharmacol 2008;1(1):61–67.
128 Late-onset pompe disease (LOPD) presenting with fulminant hypercapnic respiratory failure
Authors: Edwards Leon S , Tchan Michel , Crossley Kate M , Yee Brendon , Spies Judith M
Published: July 2019

Introduction

We report a case of LOPD with acute-on-chronic respiratory failure.

Case

A 57 year-old retired farmer presented with obtundation requiring intubation. He reported a 4 month history of hypophonia, intermittent diplopia, lethargy and orthopnea.

Initial arterial blood gas measurement displayed acute-on-chronic hypercapnic respiratory failure (pH 7.19, pO2 98 mmHg, pCO2 112 mmHg, HCO3 43 mmol/L). Muscle biopsy was suggestive of LOPD with myofibres demonstrating acid phosphatase and periodic acid-schiff positive vacuoles. Diagnosis was confirmed with low α-glucosidase activity on dried blood spot (0.4umol/h/L) and elevated urinary tetrasaccharide level (5 mmol/mol creatinine). Mutation analysis of the GAA gene demonstrated two known pathogenic mutations (c.-32–13T>G and c.1075+1G>T). With improved ventilation, he was able to be extubated. The only respiratory support on discharge was overnight bilevel positive airway pressure ventilation.

Conclusion

LOPD is a rare autosomal recessive metabolic disorder caused by a deficiency in acid α-glucosidase. This leads to intra-lysomal accumulation of glycogen in tissues. Particularly in the late form, there is significant phenotypic variability.1 Diagnosis remains challenging. Cases have been reported with a range of initial symptoms including stroke,2 syncope3 and chronic respiratory failure.4 Acute on chronic respiratory failure at presentation is rare.

Enzyme replacement therapy has been shown to improve both morbidity and mortality in LOPD.5 Earlier treatment is associated with better outcomes.6 Prompt recognition of cases is paramount. Unexplained acute-on-chronic respiratory failure should raise the possibility of this condition. In such cases, management of ventilation is vital.

References

Chan J, et al. The emerging phenotype of late-onset Pompe disease: A systematic literature review. Mol Genet Metab 2017;120(3):163–172.

Hossain MA, et al. A Case of Adult-onset Pompe Disease with Cerebral Stroke and Left Ventricular Hypertrophy. J Stroke Cerebrovasc Dis 2018;27(11):3046–3052.

Walczak-Galezewska M, et al, Late-onset Pompe disease in a 54 year-old sportsman with an episode of syncope: a case report. Eur Rev Med Pharmacol Sci 2017;21(16):3665–3667.

O’Callaghan C, et al, Adult-onset Pompe disease presenting with insidious hypercapnic respiratory failure. Respirol Case Rep 2016;4(5):e00178.

Schoser B, S A, Kanters S, Hamed A, Jansen J, Chan K, Karamouzian M, Toscano A. Survival and long-term outcomes in late-onset Pompe disease following alglucosidase alfa treatment: a systematic review and meta-analysis. J Neurol 2017;264(4):621–630.

Chien YH, HW, Lee NC. Pompe disease: early diagnosis and early treatment make a difference. Pediatr Neonatol 2013;54(4):219–227.
131 CLADIN: CLADribine and INnate immune responses
Authors: Monif Mastura , Abdollahi Shokoufeh , Stankovich Jim , Maltby Vicki , Lechner-Scott Jeannette , Kalincik Tomas , Hamilton John , O’Brien Terence , Butzkueven Helmut
Published: July 2019

Introduction

Cladribine Tablets (Mavenclad®) is nucleoside analogue of deoxyadenosine, and an oral treatment for relapsing remitting MS (RRMS). In RRMS clinical trials, Cladribine has been shown to reduce brain atrophy, relapse rates, and new lesions on brain MRI. P2X7R is a purinergic receptor expressed in innate immune cells, and is thought to play a critical role in neuroinflammation. The mechanism of action of Cladribine on peripheral innate immune cells (monocytes), and its effect on P2X7R, is unclear, and forms the basis of this study.

Methods

This will be a Phase IV, multi-centre, 3 year, translational trial. Patients who are starting Cladribine as part of their routine clinical care will consent to take part in the study. Monocyte numbers and activation states will be measured at various times prior and after commencement of therapy. In addition, and in an in vitro setting the effect of Cladribine on P2X7R expression and function will be assessed, as well as measuring various cytokines/chemokines in serum. The laboratory data will also be correlated with clinical data from another long-term Cladribine study, CLOBAS.

Results

This study has been approved by Alfred Health Human Research Ethics Committee. The study is to commence in April 2019.

Conclusion

This study will shed light on whether Cladribine is exerting its beneficial effects via action on peripheral monocytes and alterations of their P2X7Rs. The laboratory and clinical data will be analysed to understand the relationship between innate immune parameters and patient outcome.
015 Unravelling psychosis in motor neurone disease – a study of clinical features, cognition, and survival
Authors: Devenney Emma M , Ahmed Rebekah M , Caga Jashelle , Highton-Williamson Elizabeth , Ramsey Eleanor , Zoing Margaret , Hodges John , Kiernan Matthew
Published: July 2019

Introduction

Psychotic symptoms are now recognised to occur in patients with MND, often in association with FTD, and particularly in C9orf72 expansion carriers. As yet the impact of these symptoms on the clinical disease state is unknown and the relationship between severity and nature of these symptoms is not well understood. This study aimed to comprehensively explore the relationship between psychotic symptoms, clinical features, cognitive status and survival.

Methods

In total 148 participants; MND (n=100) and MND-FTD (n=48), were enrolled in the study. A detailed clinical interview in addition to a neurological, neuropsychological and behavioural assessment, genetic testing and brain MRI was undertaken in each participant

Results

Psychotic symptoms were present in 25% of the cohort. The majority of participants in the psychosis cohort were male (83%) and were negative for the C9orf72 expansion (70%). Psychotic symptoms in younger patients were more likely to be florid, require medication and delay diagnosis. Within the MND subgroup, patients with psychotic symptoms were more impaired in the cognitive subdomains of attention, memory and executive functioning and exhibited more disinhibition, apathy and stereotypy, than patients without psychotic symptoms (all p<0.01), but no differences were identified for the MND-FTD subgroup (all p>0.2). Symptoms of depression were more common in those without psychotic symptoms (p>0.1). Survival was prolonged for patients with psychotic symptoms (HR=4.7, 95% CI: 2.1–10, p<0.001)

Conclusion

MND with psychosis represents a distinct clinical, cognitive and behavioural phenotype that has a positive impact on survival and may represent an overlap with psychiatric disorders.
020 Increased risk of an abnormal cervical screening test in women with MS exposed to high-efficacy disease-modifying treatments
Authors: Walt Anneke Van der , Yuvaraj Jeremy , Stankovich Jim , McGuinn Nicola , Rath Louise , Skibina Olga , Nesbitt Cassie , Wesselingh Robb , Monif Mastura , Richards Janene , Kalincik Tomas , Taylor Lisa , Baker Josephine , Nguyen Ai-Lan , Wrede David C , Butzkueven Helmut , Brotherton Julia , Jokubaitis Vilija
Published: July 2019

Introduction

Long-term exposure of women with Multiple sclerosis (MS, wwMS) to immunomodulatory or immunosuppressive treatments may increase the risk of cervical dysplasia. However, little is known about cervical dysplasia risk and Human Papillomavirus (HPV)-vaccine coverage in wwMS.

Methods

Adult wwMS were recruited from two tertiary MS clinics. To explore the association between MS treatments (DMTs) and abnormal cervical screening tests (CSTs), we linked individual data from MSBase, the Victorian Cervical Screening Registry, and National HPV vaccination program registry (NHPVPR).

Results

To date, we have recruited 208 wwMS of whom 102 had complete data (vaccination status, cervical screening tests, MSBase data) and no previous history of abnormal CST at MS onset for this interim analysis. The average age was 33.8 (18 to 59 yrs) and most (n=58, 88%) were unvaccinated. 19 wwMS (19%) had an abnormal CST after MS onset (incidence rate 20.6 cases/1000 person-years, 95% confidence interval 12.4–32.1) over average 9.0 years of follow-up. 57 wwMS were treated with lower-efficacy therapies (56%), 73 with a high-efficacy therapy (72%), and 44 were exposed to both. Eight abnormal CSTs were detected before starting high-efficacy therapy (rate 12.6, 95% CI (5.4–24.8)) and 11 were detected after starting high-efficacy therapy (rate 38.6, 95% CI (19.3–69.0), p=0.022.

Conclusion

We provide preliminary data that high efficacy DMTs may increase the risk of abnormal CSTs over time. A larger cohort and inclusion of additional cervical dysplasia risk factors are required to fully elucidate risk in wwMS.
021 Profiles of benign positional vertigo tested on the epley omniax chair
Authors: Argaet Emma C , Lechner Corinna , Bradshaw Andrew P , Michael Halmagyi G , Welgampola Miriam S
Published: July 2019

Introduction

Benign positional vertigo (BPV) has a characteristic pattern of nystagmus specific to the affected semicircular canal and the underlying mechanism of canalithiasis (where otoconia float freely) or cupulolithiasis (where otoconia are adherent to the cupula).

Methods

We analysed the nystagmus slow-phase velocity (SPV) profiles of 100 subjects with posterior-canalithiasis, 30 with lateral-canalithiasis, 10 with lateral-cupulolithiasis and 3 with anterior-canalithiasis. Subjects were examined on the Epley Omniax Rotator, a mechanical chair with real-time video-oculography. Video data was analysed using custom-made LabVIEW software. Nystagmus onset, duration, peak-velocity, peak-latency and time taken for the peak-velocity to halve (t50), were measured.

Results

In posterior-canalithiasis, nystagmus occurred within 14.2 seconds of positioning and lasted 2.5–34.5 seconds. The median vertical peak-SPV was 37.3°/s. The median peak-latency was 2.9 seconds and the median t50 was 3.4 seconds. In lateral-canalithiasis, nystagmus onset was mostly immediate. With the affected ear down, the median peak-SPV was 52.2°/s and the median peak-latency was 3.6 seconds; the t50 was 7 seconds (median) and the paroxysms lasted 9.9–48.5 seconds. In lateral-cupulolithiasis, nystagmus onset was instantaneous. With the unaffected ear down, the median peak-SPV was 69.6°/s. The peak-latency (median 18.6 s) and t50 (median 34.5 s) were significantly prolonged compared to canalithiasis. For anterior-canalithiasis, the onset was 0–2.9 seconds, the peak-latency was 3–5.4 seconds, the t50 was 6.4–10.5 seconds and the duration was 13.4–23.1 seconds.

Conclusions

Canalithiasis and cupulolithiasis produce distinct SPV profiles, which enable their identification and the separation of BPV from other causes of positional nystagmus.