bluuebunny/crossref_metadata_2025 huggingface dataset:
Tensor Graphical Lasso (TeraLasso)
Authors: Greenewald Kristjan , Zhou Shuheng , Hero Alfred
Published: October 2019

The paper introduces a multiway tensor generalization of the bigraphical lasso which uses a two-way sparse Kronecker sum multivariate normal model for the precision matrix to model parsimoniously conditional dependence relationships of matrix variate data based on the Cartesian product of graphs. We call this tensor graphical lasso generalization TeraLasso. We demonstrate by using theory and examples that the TeraLasso model can be accurately and scalably estimated from very limited data samples of high dimensional variables with multiway co-ordinates such as space, time and replicates. Statistical consistency and statistical rates of convergence are established for both the bigraphical lasso and TeraLasso estimators of the precision matrix and estimators of its support (non-sparsity) set respectively. We propose a scalable composite gradient descent algorithm and analyse the computational convergence rate, showing that the composite gradient descent algorithm is guaranteed to converge at a geometric rate to the global minimizer of the TeraLasso objective function. Finally, we illustrate TeraLasso by using both simulation and experimental data from a meteorological data set, showing that we can accurately estimate precision matrices and recover meaningful conditional dependence graphs from high dimensional complex data sets.
The blockade of PD‐1/PD‐L1 pathway promotes the apoptosis of CD19+CD25+ Bregs and suppresses the secretion of IL‐10 in patients with allergic rhinitis
Authors: Wang Zhao , Tan Fei
Published: October 2019

PD‐1/PD‐L1 pathway is crucial to immune regulation by controlling the balance between T cell tolerance and activation. However, the association between PD‐1/PD‐L1 pathway and regulatory B cells has not been fully investigated in allergic rhinitis. In this study, we detected the number of peripheral CD19+CD25+ Bregs and the expression of IL‐10 on this cell subset in healthy control and patients with allergic rhinitis using flow cytometry. Then, we evaluated the level of PD‐L1 in CD19+CD25+ Bregs and investigated the correlation between PD‐L1 and CD4+ follicular T helper cells. Finally, we studied the effects of anti–PD‐L1 on the apoptosis of Bregs and the production of IL‐10. Comparing with healthy controls, the percentage of CD19+CD25+ Bregs and the expression of IL‐10 were both significantly decreased in AR group. In addition, the expression of PD‐L1 on CD19+CD25+ Bregs was also lower in allergic rhinitis patients. Interestingly, a negative correlation was found between the expression of PD‐L1+ Bregs and CD4+CXCR5+ follicular T helper cells. In vitro assay revealed that anti–PD‐L1 promoted Bregs apoptosis and inhibited the expression of IL‐10 in CD19+CD25+ Bregs. Collectively, these results suggest that PD‐L1 expressed on CD19+CD25+ Bregs may be a potential regulator in the treatment of allergic rhinitis. Blockade of PD‐1/PD‐L1 pathway might be a valuable pathogenic target for allergic rhinitis through inhibiting the secretion of immunosuppressive cytokine and promoting CD19+CD25+ Bregs apoptosis.
Space, Place and Capitals in Rural Youth Mobility: Broadening the Focus of Rural Studies
Authors: Nugin Raili
Published: October 2019

Drawing on fieldwork in six Estonian rural areas from 2010–2019, the article calls for a nuanced understanding of the processes of mobility and migration in rural areas. Based on qualitative in‐depth and focus‐group interviews with rural youth and key stakeholders, several phenomena are identified as crucial to understanding the dynamics of mobility. Mobility is seen as a negotiated process, intertwined with the social structures of the location, and with the global, demographic and political processes around that location. As researchers, we should observe how the interrelatedness of the local context with mobility practices impacts mobilities in later life. Additionally, we must consider how these mobility practices relate to factors like social class and symbolic, social, and cultural capital.
RBC and platelet transfusion support in the first 30 and 100 days after haploidentical hematopoietic stem cell transplantation
Authors: Yuan Shan , Yang Dongyun , Nakamura Ryotaro , Zhuang Lefan , Al Malki Monzr M. , Wang Shirong
Published: October 2019

BACKGROUND

The volume of haploidentical hematopoietic stem cell transplant (haplo‐HSCT) has increased dramatically in recent years. However, the associated higher risk of delayed engraftment may increase patient transfusion requirements.

STUDY DESIGN AND METHODS

The post‐HSCT RBC and platelet transfusions of 195 haplo‐HSCT recipients were evaluated. Patient and transplant‐related factors potentially impacting the number of products transfused and time to transfusion independence were assessed.

RESULTS

Nearly all (98.4%) patients were transfused in the first 30 days, and 59.2% were transfused between days 31 and 100. Among the transfused patients, medians of 5 units (interquartile range [IQR] = 3‐8) of RBCs and 11 units (6‐20) platelets were given in the first 30 days, and medians of 3 units (IQR = 1‐7) of RBCs and 6 units (2‐18) of platelets were transfused between days 31 and 100. Median times for achieving RBC and platelet transfusion independence were 34 (95% CI: 28‐40) and 25 (95% CI: 23‐27) days, respectively.

Multivariable analyses showed that RBC transfusions in the 10 days before HSCT were associated with significantly increased and sustained RBC and platelet transfusion requirements. Major ABO incompatibility led to increased RBC transfusions. Advanced disease was associated with increased transfusions during the first 30 days, whereas GVHD increased platelet transfusions between days 31 and 100. Effects of age, sex, CD34+ cell dose, stem cell source, and conditioning regimen were limited or insignificant.

CONCLUSIONS

This study for the first time provided quantitative transfusion data on a large cohort of haplo‐HSCT recipients and identified factors predictive of increased transfusions.
Synthesis of GMA/EDMA Uniform Pores Monolith Using Melt blown Polypropylene Nanofibers Templates
Authors: Kamin Z. , Ramon N. , Misson M. , Ken C. C. , Sarbatly R. , Krishnaiah D. , Bono A.
Published: October 2019

Glycidyl methacrylate / ethyl dimethacrylate (GMA/ EDMA) monoliths consisting of pores induced by polypropylene nanofibers (PPNF) were developed. For creating these pores, templating technique was used where the PPNF act as a template. The PPNF were fabricated using a melt blowing technique at various process operations of polymer flowrate, air pressure and die-to-collector distance at ranges of 15 to 30 Hz, 0.15 to 0.3 MPa and 0.20 to 0.6 m respectively designed using a response surface methodology (RSM). Subsequently, a monolith solution was synthesis using the polymerization of GMA and EDMA, with azobisisobutyronitrile (AIBN) as initiator and cyclohexanol as porogen. The PPNF and GMA/ EDMA monoliths were characterized using SEM and melting point instrument. The findings show, PPNF fiber diameter and melting points were in the range of 5 to 14 x 103 nm and 120 to 130 °C respectively. RSM analysis suggests that air pressure and die-to-collector distance could be an important factor for  PPNF final diameter. Morphology studies demonstrate that GMA/ EDMA monolith have been successfully acquired mesoporous structure and creating uniform pores by PPNF template produce at 22.5 Hz, 0.22 MPa and 0.40 m. As a conclusion, the PPNF can be proposed as a template to prepare monolith having uniform pores.
A Heuristic Scaling Strategy for Multi-Robot Cooperative Three-Dimensional Printing
Authors: Poudel Laxmi , Blair Chandler , McPherson Jace , Sha Zhenghui , Zhou Wenchao
Published: October 2019

While three-dimensional (3D) printing has been making significant strides over the past decades, it still trails behind mainstream manufacturing due to its lack of scalability in both print size and print speed. Cooperative 3D printing (C3DP) is an emerging technology that holds the promise to mitigate both of these issues by having a swarm of printhead-carrying mobile robots working together to finish a single print job cooperatively. In our previous work, we have developed a chunk-based printing strategy to enable the cooperative 3D printing with two fused deposition modeling (FDM) mobile 3D printers, which allows each of them to print one chunk at a time without interfering with the other and the printed part. In this paper, we present a novel method in discretizing the continuous 3D printing process, where the desired part is discretized into chunks, resulting in multi-stage 3D printing process. In addition, the key contribution of this study is the first working scaling strategy for cooperative 3D printing based on simple heuristics, called scalable parallel arrays of robots for 3DP (SPAR3), which enables many mobile 3D printers to work together to reduce the total printing time for large prints. In order to evaluate the performance of the printing strategy, a framework is developed based on directed dependency tree (DDT), which provides a mathematical and graphical description of dependency relationships and sequence of printing tasks. The graph-based framework can be used to estimate the total print time for a given print strategy. Along with the time evaluation metric, the developed framework provides us with a mathematical representation of geometric constraints that are temporospatially dynamic and need to be satisfied in order to achieve collision-free printing for any C3DP strategy. The DDT-based evaluation framework is then used to evaluate the proposed SPAR3 strategy. The results validate the SPAR3 as a collision-free strategy that can significantly shorten the printing time (about 11 times faster with 16 robots for the demonstrated examples) in comparison with the traditional 3D printing with single printhead.
Scratch and Sliding Wear Testing of Electroless Ni–B–W Coating
Authors: Nemane Vaibhav , Chatterjee Satyajit
Published: October 2019

Electroless Ni–B–W coating is deposited on low carbon steel in an alkaline sodium borohydride-reduced electroless bath. The mechanical and tribological properties of such coatings are much necessary to be assessed to carry out application-based studies. The present work focuses mainly on the evaluation of hardness and fracture toughness of electroless Ni–B–W coatings using a scratch tester. Coating's response toward scratching is also studied thoroughly. The characteristic short-range order present in its lattice structure causes the generation of a specific behavioral pattern. Furthermore, a linear sliding wear test is carried out on coatings' surface to analyze the wear behavior at different loading conditions. The specific wear rate is observed to be minimum at a normal load of 22.5 N against Si3N4 counterbody. The patterns of tribological behavior of the coating at different load values are examined from the worn surface morphologies. But before embarking on the scratch and sliding wear tests, the synthesized coatings are characterized under field emission scanning electron microscope and X-ray diffraction in an exhaustive manner. The growth rates with respect to time and the changes in morphological aspects of the coating are also evaluated. The present study establishes electroless Ni–B–W deposits as a suitable option for protecting mechanical components against wear.
Elastosonographic evaluation after extracorporeal shockwave treatment in plantar fasciopathy
Authors: Alviti Federica , D'Ercole Chiara , Schillizzi Giuseppe , Mangone Massimiliano , Bernetti Andrea , Ioppolo Francesco , Di sante Luca , Minafra Paolo , Santilli Valter , Elia Daniela , Vallone Gianfranco , D'ambrosio Ferdinando , Cantisani Vito
Published: October 2019

Aim: To assess the ultrasound features in patients with plantar fasciopathy before and after extracorporeal shock waves therapy (ESWT), using conventional grey-scale imaging and both strain (SE) and shear wave (SWE) elastosonographic evaluation.Material and method: Consecutive patients of both sexes attending our outpatient’s clinic, with diagnosis of unilateral plantar fasciopathy, were enrolled. Patients were treated with 3 sessions of ESWT once a week, and underwent clinical and ultrasound evaluation at baseline and at one and three months after treatment. Roles and Maudsley score (RM), visual analog scale (VAS) and 17-Italian Foot Function Index (FFI), were used to assess pain and functional improvement.Results: Twenty patients (11 female and 9 male) were enrolled in the study. Contralateral asymptomatic healthy plantar fascia was used as a control. At baseline, SWE velocity (SWEv) showed statistically significant difference between affected 3.8 (1.5; 5.1) m/s and healthy side 4.7 (4.07; 7.04) m/s, (p=0.006); no significant difference was found for strain ratio values (p=0.656). SWEv post hoc test results showed a significant difference from baseline 3.8 (1.5-5.1) m/s and three month 5.23 (4.55-6.74) m/s follow up visit (p=0.003). Significant statistical negative correlation was found between the SWEv and VAS (p=0.001) and positive correlation between the SWEv and FFI (p=0.012).Conclusion: SWE was effective in assessing plantar fascia elasticity and its alteration in fasciopathy. Furthermore, on the basis of the correlation with pain and functional scales, this technique appears to be a useful additional technique to conventional ultrasound for monitoring the efficacy of treatment
Value of shear wave elastography for diagnosis of primary prostate cancer: a systematic review and meta-analysis
Authors: Yang Ye , Zhao Xinxin , Zhao Xinxin , Shi Jingwen , Huang Ying
Published: October 2019

Aim: To evaluate the difference in stiffness between prostate cancer (PCa) and benign tissue based on Young’s modulus determined by shear wave elastography (SWE). In addition, the diagnostic accuracy of SWE for the detection of PCa was evaluated comprehensively.Material and methods: We conducted our systematic review and meta-analysis based on databases of PubMed, Embase and Web of Science. Relevant studies regarding to the diagnostic accuracy of SWE for detecting PCa compared to a reference standard of histopathology were included. The pooled weighted mean difference (WMD) of Young’s modulus, sensitivity (SEN) and specificity (SPE), and area under the curve (AUC) were calculated using Stata software.Results: Based on our search strategy, 9 studies were ultimately included. The pooled results indicated that the mean Young’s modulus for detecting prostate cancer was significantly higher than that for prostate benign tissue (WMD = 38.01, 95%CI = 25.59–50.44, p<0.01). In addition, the pooled SEN was 0.86 (95%CI = 0.75–0.92), and the SPE was 0.89 (95%CI = 0.82–0.93). Moreover, an overall high degree of accuracy was indicated by the summary receiver operator characteristic curve with an AUC of 0.94 (95%CI = 0.91–0.95).Conclusion: Our study indicated that SWE is a useful technique for differentiating PCa and benign tissue with a high degree of diagnostic accuracy.
Optical properties of the crystalline silicon wafers described using the universal dispersion model
Authors: Franta Daniel , Vohánka Jiří , Bránecký Martin , Franta Pavel , Čermák Martin , Ohlídal Ivan , Čech Vladimír
Published: October 2019

The optical properties of a slightly boron doped float-zone crystalline silicon wafer are studied using ellipsometry and spectrophotometry in a wide spectral range from far IR to vacuum UV. One side of the wafer was cleaned in an argon plasma, which influenced the optical properties of silicon near the surface. The dielectric response of silicon was modeled using a simplified universal dispersion model which is constructed on the basis of parameterization of the joint density of states describing both the electronic and phonon excitations. Several variants of models describing phonon absorption and interband transitions are discussed. It was possible to accurately determine the optical constants of bulk silicon and the optical constants near the perturbed surface over a wide spectral range. These optical constants agree well with those found in other works. From the optical measurements, it was also possible to determine the thickness of the wafer and the static value of resistivity, and the determined values agreed with nominal values specified for the wafer.
On the externalization of sound sources with headphones without reference to a real source
Authors: Leclère Thibaud , Lavandier Mathieu , Perrin Fabien
Published: October 2019

Sounds presented over headphones are generally perceived as internalized, i.e., originating from a source inside the head. Prior filtering by binaural room impulse responses (BRIRs) can create externalized sources. Previous studies concluded that these BRIRs need to be listener-specific to produce good externalization; however, listeners were generally facing a loudspeaker and asked to rate externalization relative to that loudspeaker, meaning that the source had to be perceived outside the head and also at the right distance. The present study investigated externalization when there is no visual source to match. Overall, lateral sources were perceived as more externalized than frontal sources. Experiment 1 showed that the perceived externalization obtained with non-individualized BRIRs measured in three different rooms was similar to that obtained with a state-of-the-art simulation using individualized BRIRs. Experiment 2 indicated that when there is no real source spectrum to match, headphone equalization does not improve externalization. Experiment 3 further showed that reverberation improved externalization only when it introduced interaural differences. Correlation analyses finally showed a close correspondence between perceived externalization and binaural cues (especially interaural coherence).
Grand challenges in the science of wind energy
Authors: Veers Paul , Dykes Katherine , Lantz Eric , Barth Stephan , Bottasso Carlo L. , Carlson Ola , Clifton Andrew , Green Johney , Green Peter , Holttinen Hannele , Laird Daniel , Lehtomäki Ville , Lundquist Julie K. , Manwell James , Marquis Melinda , Meneveau Charles , Moriarty Patrick , Munduate Xabier , Muskulus Michael , Naughton Jonathan , Pao Lucy , Paquette Joshua , Peinke Joachim , Robertson Amy , Sanz Rodrigo Javier , Sempreviva Anna Maria , Smith J. Charles , Tuohy Aidan , Wiser Ryan
Published: October 2019

A multifaceted future for wind power

Modern wind turbines already represent a tightly optimized confluence of materials science and aerodynamic engineering. Veers
et al.
review the challenges and opportunities for further expanding this technology, with an emphasis on the need for interdisciplinary collaboration. They highlight the need to better understand atmospheric physics in the regions where taller turbines will operate as well as the materials constraints associated with the scale-up. The mutual interaction of turbine sites with one another and with the evolving features of the overall electricity grid will furthermore necessitate a systems approach to future development.

Science
, this issue p.
eaau2027
Quinazoline-Based Antivirulence Compounds Selectively Target
Salmonella
PhoP/PhoQ Signal Transduction System
Authors: Carabajal María Ayelén , Asquith Christopher R. M. , Laitinen Tuomo , Tizzard Graham J. , Yim Lucía , Rial Analía , Chabalgoity José A. , Zuercher William J. , García Véscovi Eleonora
Published: October 2019

The rapid emergence of multidrug resistance among bacterial pathogens has become a significant challenge to human health in our century. Therefore, development of next-generation antibacterial compounds is an urgent need. Two-component signal transduction systems (TCS) are stimulus-response coupling devices that allow bacteria to sense and elaborate adaptive responses to changing environmental conditions, including the challenges that pathogenic bacteria face inside the host.
A Rare Opportunist,
Morganella morganii
, Decreases Severity of Polymicrobial Catheter-Associated Urinary Tract Infection
Authors: Learman Brian S. , Brauer Aimee L. , Eaton Kathryn A. , Armbruster Chelsie E.
Published: October 2019

Catheter-associated urinary tract infections (CAUTIs) are common hospital-acquired infections and frequently polymicrobial, which complicates effective treatment. However, few studies experimentally address the consequences of polymicrobial interactions within the urinary tract, and the clinical significance of polymicrobial bacteriuria is not fully understood.
Salmonella enterica Requires Lipid Metabolism Genes To Replicate in Proinflammatory Macrophages and Mice
Authors: Reens Abigail L. , Nagy Toni A. , Detweiler Corrella S.
Published: October 2019

To survive and replicate during infection, pathogens utilize different carbon and energy sources depending on the nutritional landscape of their host microenvironment.
Salmonella enterica
serovar Typhimurium is an intracellular bacterial pathogen that occupies diverse cellular niches. While it is clear that
Salmonella
Typhimurium requires access to glucose during systemic infection, data on the need for lipid metabolism are mixed.
Line Immunoassay for Confirmation and Discrimination of Human T-Cell Lymphotropic Virus Infections in Inconclusive Western Blot Serum Samples from Brazil
Authors: Campos Karoline R. , Santos Fred L. N. , da Silva Brito Vanessa , Gonçalves Noilson L. S. , Araujo Thessika H. A. , Galvão-Castro Bernardo , Caterino-de-Araujo Adele
Published: October 2019

Difficulties in confirming and discriminating human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infections by serological Western blot (WB) assays (HTLV Blot 2.4; MP Biomedicals) have been reported in Brazil, mainly in HIV/AIDS patients, with a large number of WB-indeterminate and WB-positive but HTLV-untypeable results. Nonetheless, a line immunoassay (LIA) (INNO-LIA HTLV-I/II; Fujirebio) provided enhanced specificity and sensitivity for confirming HTLV-1/2 infections.
COPII Vesicle Transport Is Required for Rotavirus NSP4 Interaction with the Autophagy Protein LC3 II and Trafficking to Viroplasms
Authors: Crawford Sue E. , Criglar Jeanette M. , Liu Zheng , Broughman James R. , Estes Mary K.
Published: October 2019

In a morphogenic step that is exceedingly rare for nonenveloped viruses, immature rotavirus particles assemble in replication centers called viroplasms, and bud through cytoplasmic cellular membranes to acquire the outer capsid proteins for infectious particle assembly. Historically, the intracellular membranes used for particle budding were thought to be endoplasmic reticulum (ER) because the rotavirus nonstructural protein NSP4, which interacts with the immature particles to trigger budding, is synthesized as an ER transmembrane protein. This present study shows that NSP4 exits the ER in COPII vesicles and that the NSP4-containing COPII vesicles are hijacked by the cellular autophagy machinery, which mediates the trafficking of NSP4 to viroplasms. Changing the paradigm for rotavirus maturation, we propose that the cellular membranes required for immature rotavirus particle budding are not an extension of the ER but are COPII-derived autophagy isolation membranes.
Application of orphan drug designation to cancer treatments (2008–2017): a comprehensive and comparative analysis of the USA and EU
Authors: Vokinger Kerstin Noëlle , Kesselheim Aaron S
Published: October 2019

Objective

To determine differences in the characteristics of cancer drugs designated as orphan drugs by the Food and Drug Administration (FDA) and European Medicines Agency (EMA).

Design and setting

Identification of all cancer drugs (initial or supplementary indication) with orphan status approved by the FDA between 2008–2017 based on publicly accessible reports. The European public assessment reports (EPAR) was searched to determine whether these FDA-approved drugs were also approved by the EMA.

Main outcome measures

Extraction of active ingredient, trade name, approval date and approved indication from two FDA data sources (Orphan Drug Product Designation Database, Drugs@FDA) and comparison with the same data from EPAR.

Results

The FDA approved 135 cancer drugs with orphan indications that met our inclusion criteria, of which 101 (75%) were also approved by the EMA. 80/101 (79%) were first approved in the USA. Only 41/101 (41%) also received orphan designation by the EMA. 33/101 (33%) were approved for biomarker-based indications in the USA, however, only nine approved cancer drug indications by the EMA were biomarker-derived drugs. 78% (47/60) of approved cancer drugs that were only approved in the USA with orphan status were indicated for solid tumours, 22% (13/60) had indications for non-solid tumours. By contrast, out of those approved cancer drugs that received orphan designation by both agencies, 20% (8/41) were indicated for solid, and 80% (33/41) for non-solid tumours.

Conclusions

Orphan designation was intended to encourage drug development for rare conditions. This study shows that the FDA approves more cancer drugs with such designations compared with the EMA, especially for subgroups of more prevalent cancers. One reason for the difference could be that the European Union requires demonstration of significant benefit for drugs that target the same indication as a drug already on the market to earn the orphan designation.
Association of gout and colorectal cancer in Taiwan: a nationwide population-based cohort study
Authors: Chuang Jen-Pin , Lee Jenq-Chang , Leu Tzeng-Horng , Hidajah Atik Choirul , Chang Ya-Hui , Li Chung-Yi
Published: October 2019

Objectives

This study aimed to determine colorectal cancer (CRC) risks among patients with gout through a follow-up study on a nationwide population-based cohort that included patients with gout and the general population in Taiwan.

Participant

From the Taiwan National Health Insurance Research Database, we identified 28 061 patients who were newly diagnosed with gout between 2000 and 2010 as the study cohort. We randomly selected 84 248 subjects matching in gender, age and baseline year as comparison cohort. The cohorts were followed up until CRC occurrence, withdrawal from the system of National Health Insurance, or Dec. 31, 2013.

Primary and secondary outcome measures

Cumulative incidences and incidence rate ratios (IRRs) of CRC between two cohorts were examined. The Cox proportional hazards model was used to evaluate risk factors associated with CRC development.

Results

During the 13-year follow-up, the incidence rate of CRC development in the gout cohort reached 2.44 per 1000 person-years, which was higher than the 2.13 per 1000 person-years in the control cohort (IRR=1.15; 95% CI 1.04 to 1.26). After adjusting for age, gender, urbanisation status and comorbidities, including hypertension, diabetes and hyperlipidaemia, gout showed no significant association with increased risk of CRC occurrence (adjusted HR=1.03; 95% CI 0.93 to 1.14).

Conclusions

Similar risks of CRC incidence were observed in patients with and without gout in Taiwan. Allopurinol and colchicine are commonly used as urate-lowering drug and anti-inflammation medication in Taiwan and had been shown to reduce the risk of CRC incidence. Thus, further pharmaco-epidemiological studies should be carried out to specifically assess the role of allopurinol in the relationship between gout and CRC.
Process evaluation protocol for the I-WOTCH study: an opioid tapering support programme for people with chronic non-malignant pain
Authors: Nichols Vivien P , Abraham Charles , Eldabe Sam , Sandhu Harbinder K , Underwood Martin , Seers Kate
Published: October 2019

Introduction

The Improving the Wellbeing of people with Opioid Treated CHronic Pain (I-WOTCH) randomised controlled trial uses a multicomponent self-management intervention to help people taper their opioid use. This approach is not widely used and its efficacy is unknown. A process evaluation alongside the trial will help to assess how the intervention was delivered, looking at the dose of intervention received and the fidelity of the delivery. We will explore how the intervention may have brought about change through the experiences of the participants receiving and the staff delivering the intervention and whether there were contextual factors involved.

Methods and analysis

A mixed methods process evaluation will assess how the processes of the I-WOTCH intervention fared and whether these affected the outcomes. We will collect quantitative data, for example, group attendance analysed with statistical methods. Qualitative data, for example, from interviews and feedback forms will be analysed using framework analysis. We will use a ‘following a thread’ and a mixed methods matrix for the final integrated analysis.

Ethics and dissemination

The I-WOTCH trial and process evaluation were granted full ethics approval by Yorkshire and The Humber—South Yorkshire Research Ethics Committee on 13 September 2016 (16/YH/0325). All data were collected in accordance with data protection guidelines. Participants provided written informed consent for the main trial, and all interviewees provided additional written informed consent. The results of the process evaluation will be published and presented at conferences.

Trial registration number

ISRCTN49470934; Pre-results.
Emergency department visits for non-urgent conditions in Iran: a cross-sectional study
Authors: Bahadori Mohammadkarim , Mousavi Seyyed Meysam , Teymourzadeh Ehsan , Ravangard Ramin
Published: October 2019

Objectives

To determine the percentage of non-urgent (NU) visits in an Iranian emergency department (ED), to explore why patients with NU conditions refer to EDs and also to assess the association between patients’ characteristics and their visits.

Design

A cross sectional study based on face to face survey.

Setting

A territorial, teaching and military hospital in Tehran province, Iran.

Participants and data collection

All patients who visited the ED during the 2-week period were recruited. Data were collected using a validated questionnaire.

Results

Of 1884 patients who visited the ED, 1217 (64.6%) patients were triaged as NU while 667 (35.4%) were urgent and semiurgent visits cases. The most important reasons for NU visits were seeking prompt (36.6%) and less costly care (35.9%). We found that NU visits have increased with younger patients, during weekends and night shifts, and with patients suffering from recurrent symptoms lasting in 1 week or less.

Conclusions

EDs are a common source of care for NU problems in Iran. The most invaluable solution is building up special clinics for providing healthcare services to NU patients during the weekends and, in the busy and night shifts. Receiving higher fees from NU patients could also be adopted with caution. Promoting awareness and knowledge of both healthcare providers and patients about the main role of EDs will contribute in improving their performance. As a long-term solution, adopting the family physician programme and ameliorating the referral system are recommended.
Association of smoking with direct medical expenditures of chronic diseases in north of Jordan: a retrospective cohort study
Authors: Alefan Qais , Al-Issa Eman T , Alzoubi Karem H , Hammouri Hanan M
Published: October 2019

Objective

This study aimed to estimate the association of smoking with the direct medical expenditures for chronic disease management in north of Jordan.

Design, setting and participants

Retrospective cohort study using hospital database. Patients who were diagnosed with at least one chronic disease,were aged 18 years or older and had attended King Abdullah University Hospital for disease management and procedures from 1 July 2015 through 30 June 2016 were included in the study.

Main outcome measures

The outcome of interest was the direct medical expenditures for chronic disease management according to smoking status.

Results

Data were collected from 845 patients having at least one chronic disease (mean age of 61±10.7 years). Smokers formed 22% of total patients. The back transformed mean total expenditure per patient of smokers, former smokers and non-smokers was 875 JD, 928 JD and 774 JD, respectively. Drugs were the most expensive healthcare resource used, accounting for 43% of total expenditure, followed by inpatient-related and outpatient-related services (19%). Smokers and former smokers were associated with the highest inpatient expenditures and inpatient-related and outpatient-related services expenditures. However, smokers were associated with the lowest outpatient and medication expenditures.

Conclusions

Smokers and former smokers presented with higher statistically significant inpatient-related and outpatient-related services expenditures and higher transformed mean total expenditures compared to non-smokers; highlighting this economic burden is useful for promoting tobacco control policies.
What is multidisciplinary cancer care like in practice? a protocol for a mixed-method study to characterise ambulatory oncology services in the Australian public sector
Authors: Nic Giolla Easpaig Bróna , Arnolda Gaston , Tran Yvonne , Bierbaum Mia , Lamprell Klay , Delaney Geoffrey P , Liauw Winston , Chittajallu Renuka , Winata Teresa , Ward Robyn L , Currow David C , Olver Ian , Karnon Jonathan , Westbrook Johanna , Braithwaite Jeffrey
Published: October 2019

Introduction

An understanding of the real-world provision of oncology outpatient services can help maintain service quality in the face of escalating demand and tight budgets, by informing the design of interventions that improve the effectiveness or efficiency of provision. The aims of this study are threefold. First, to develop an understanding of cancer services in outpatient clinics by characterising the organisation and practice of multidisciplinary care (MDC). Second, to explore the key areas of: (a) clinical decision-making and (b) engagement with patients’ supportive needs. Third, to identify barriers to, and facilitators of, the delivery of quality care in these settings.

Methods and analysis

A suite of mixed-methods studies will be implemented at six hospitals providing cancer outpatient clinics, with a staged roll-out. In Stage One, we will examine policies, use unstructured observations and undertake interviews with key health professionals to characterise the organisation and delivery of MDC. In Stage Two, observations of practice will continue, to deepen our understanding, and to inform two focused studies. The first will explore decision-making practices and the second will examine how staff engage with patients’ needs; both studies involve interviews, to complement observation. As part of the study of supportive care, we will examine the implications of an introduction of patient-reported measures (PRMs) into care, adding surveys to interviews before and after PRMs roll-out. Data analysis will account for site-specific and cross-site issues using an adapted Qualitative Rapid Appraisal, Rigorous Analysis approach. Quantitative data from clinician surveys will be statistically analysed and triangulated with the related qualitative study findings.

Ethics and dissemination

Ethical approval was granted by South Eastern Sydney Local Health District Human Research Ethics Committee (no. 18/207). Findings will be shared with participating hospitals and widely disseminated through publications and presentations.
SCING—Spinal Cord Injury Neuroprotection with Glyburide: a pilot, open-label, multicentre, prospective evaluation of oral glyburide in patients with acute traumatic spinal cord injury in the USA
Authors: Minnema Amy Janelle , Mehta A , Boling Warren W , Schwab Jan , Simard J Marc , Farhadi H Francis
Published: October 2019

Introduction

Acute traumatic spinal cord injury (tSCI) is a devastating neurological disorder with no pharmacological neuroprotective strategy proven effective to date. Progressive haemorrhagic necrosis (PHN) represents an increasingly well-characterised mechanism of secondary injury after tSCI that negatively impacts neurological outcomes following acute tSCI. Preclinical studies evaluating the use of the Food and Drug Administration-approved sulfonylurea receptor 1-transient receptor potential melastatin 4 channel blocker glyburide in rodent models have shown reduced secondary microhaemorrhage formation and the absence of capillary fragmentation, the pathological hallmark of PHN.

Methods and analysis

In this initial phase multicentre open-label pilot study, we propose to enrol 10 patients with acute cervical tSCI to primarily assess the feasibility, and safety of receiving oral glyburide within 8 hours of injury. Secondary objectives include pharmacokinetics and preliminary evaluations on neurological recovery as well as blood and MRI-based injury biomarkers. Analysis will be performed using the descriptive and non-parametric statistics.

Ethics and dissemination

Glyburide has been shown as an effective neuroprotective agent in preclinical tSCI models and in the treatment of ischaemic stroke with the additional risk of a hypoglycaemic response. Given the ongoing secondary injury and the traumatic hyperglycaemic stress response seen in patients with tSCI, glyburide; thus, offers an appealing neuroprotective strategy to supplement standard of care treatment. The study protocol was approved by the Ohio State University Biomedical Institutional Review Board. The protocol was amended in February 2017 with changes related to study feasibility and patient recruitment. Specifically, the route of administration was changed to the oral form to allow for streamlined and rapid drug administration, and the injury-to-drug time window was extended to 8 hours in an effort to further enhance enrolment. Participants or legally authorised representatives are informed about the trial and its anticipated risks orally and in written form using an approved informed consent form prior to inclusion. The findings of this study will be disseminated to the participants and to academic peers through scientific conferences and peer-reviewed journal publications.

Trial registration numbers

NCT02524379and 2014H0335.
Comparing the predictive ability of a commercial artificial intelligence early warning system with physician judgement for clinical deterioration in hospitalised general internal medicine patients: a prospective observational study
Authors: Arnold Jonathan , Davis Alex , Fischhoff Baruch , Yecies Emmanuelle , Grace Jon , Klobuka Andrew , Mohan Deepika , Hanmer Janel
Published: October 2019

Objective

Our study compares physician judgement with an automated early warning system (EWS) for predicting clinical deterioration of hospitalised general internal medicine patients.

Design

Prospective observational study of clinical predictions made at the end of the daytime work-shift for an academic general internal medicine floor team compared with the risk assessment from an automated EWS collected at the same time.

Setting

Internal medicine teaching wards at a single tertiary care academic medical centre in the USA.

Participants

Intern physicians working on the internal medicine wards and an automated EWS (Rothman Index by PeraHealth).

Outcome

Clinical deterioration within 24 hours including cardiac or pulmonary arrest, rapid response team activation or unscheduled intensive care unit transfer.

Results

We collected predictions for 1874 patient days and saw 35 clinical deteriorations (1.9%). The area under the receiver operating curve (AUROC) for the EWS was 0.73 vs 0.70 for physicians (p=0.571). A linear regression model combining physician and EWS predictions had an AUROC of 0.75, outperforming physicians (p=0.016) and the EWS (p=0.05).

Conclusions

There is no significant difference in the performance of the EWS and physicians in predicting clinical deterioration at 24 hours on an inpatient general medicine ward. A combined model outperformed either alone. The EWS and physicians identify partially overlapping sets of at-risk patients suggesting they rely on different cues or decision rules for their predictions.

Trial registration number

NCT02648828.
Acute interventions for aggression and agitation in psychosis: study protocol for a systematic review and network meta-analysis
Authors: Ostinelli Edoardo G , D’Agostino Armando , Shokraneh Farhad , Salanti Georgia , Furukawa Toshi A
Published: October 2019

Introduction

Individuals with psychosis may access emergency services due to aggression and agitation. When the de-escalation technique fails to achieve tranquillisation, several pharmacological options are available. However, evidence on which intervention to prefer in terms of efficacy and tolerability to achieve resolution of the acute episode (ie, rapid tranquillisation) of aggression and agitation is currently fragmentary.

Methods and analysis

We will include all randomised controlled trials comparing drugs or drug combinations or placebo for aggression or agitation episodes in adult individuals with psychosis. We will include individuals with psychosis (eg, schizophrenia and related disorders, bipolar disorder with psychotic symptoms, psychotic depression) but not substance or medication-induced psychosis or psychosis due to another medical condition. Our primary outcomes are the change in aggression or agitation scores within few hours since the administration of the intervention (efficacy outcome) and the proportion of participants who dropped out due to adverse effects (tolerability outcome). We will retrieve relevant studies from the register of studies of the Cochrane Schizophrenia Group. Also, we will run additional searches on CENTRAL, Embase and PubMed to retrieve potentially eligible studies focusing on other psychiatric diagnoses than those in the schizophrenia spectrum. We will conduct a random-effects network meta-analysis (NMA) for primary and secondary outcomes. In case of rare events of dichotomous outcomes, a common-effect Mantel-Haenszel NMA will be used instead. We will use the surface under the cumulative ranking curve and the mean ranks to rank all available treatments. Local and global methods of evaluation of inconsistency will be employed. Quality of evidence contributing to network estimates of the main outcomes will also be assessed with Confidence in Network Meta-Analysis.

Ethics and dissemination

This study does not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal.

PROSPERO registration number

CRD42019137945.
Interventions for improving teamwork in intrapartum care: a systematic review of randomised controlled trials
Authors: Wu Michael , Tang Jennifer , Etherington Cole , Walker Mark , Boet Sylvain
Published: October 2019

Background

The labour and delivery environment relies heavily on interdisciplinary collaboration from anaesthesiologists, obstetricians and nurses or midwives to deliver optimal patient care. A large number of adverse events in obstetrics are associated with failure in communication and teamwork among team members, with substantive consequences. The objective of this study is to perform a systematic review of interventions aimed at improving teamwork in obstetrics.

Methods

This systematic review identified and assessed randomised controlled trials (RCTs) of interventions aimed at improving teamwork among interdisciplinary teams in obstetrical care. Medline, CENTRAL, CINAHL and Embase were searched for studies evaluating one of: patient outcomes, team performance or processes of clinical efficiency. Identified citations were reviewed in duplicate for eligibility.

Results

Nine RCTs met the inclusion criteria; five of these RCTs were conducted under simulated clinical environments. Simulation-based teamwork training interventions were the most represented (n=7 studies, 3047 healthcare providers (HCPs), 107 782 births), followed by checklists (n=1 study, 136 HCPs) and an electronic-based decision support tool (n=1 study, 296 HCPs). Simulation-based teamwork training was found to improve team performance in 100% of relevant studies (3 of 3 studies assessing team performance) and patient morbidity in 75% of relevant studies (3 of 4 studies assessing patient morbidity). However, no direct mortality benefit was identified among all the studies reviewed. Studies were assessed to be of low-moderate quality and had significant limitations in their study designs.

Conclusion

While the evidence is still limited and from low to moderate quality RCTs, simulation-based teamwork interventions appear to improve team performance and patient morbidity in labour and delivery care.

PROSPERO Trial registration number

CRD42018090452
Clinical effectiveness of cognitive behavioural therapy on alcohol-dependent patients: an observation with the WeChat platform
Authors: Chen Jing , Qian Mincai , Sun Conghao , Lin Min , Tang Weili
Published: October 2019

Background

With the continuous improvement of people’s material living standards, the consumption of alcoholic beverages is increasing. Alcohol dependence caused by alcohol addiction has become a widespread concern in society. As the brand-new medical and health model created by the modern biomedical technology revolution and the information technology revolution, mobile health has been used more and more widely in the field of medical health with the characteristics of convenience, rapidity and generalisability. With the general use of the social software WeChat, it is feasible to implement mobile health on the WeChat platform.

Aim

We aimed to explore the clinical effect of WeChat platform used in the cognitive behavioural therapy (CBT) on the maintenance period of alcohol dependence and addiction.

Methods

Seventy alcohol-dependent patients in the withdrawal maintenance stage admitted into our hospital were randomly divided into the CBT on WeChat platform group (the experiment group, n=35) and the general clinical treatment using sertraline group (the control group, n=35) with block randomisation grouping. They were evaluated with the Severity of Alcohol Dependence Questionnaire (SADQ-C) before the treatment, at the end of the fourth week, at the end of the eighth week and at the end of the twelfth week of treatment. In addition, Zung’s Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were employed to evaluate the degree of anxiety and depression of the two groups.

Results

The SADQ-C, SAS and SDS scores of the two groups after treatment decreased markedly compared with those before treatments, and the differences were statistically significant. Between-group comparison: the SADQ-C scores of the experiment group at the end of the fourth, eighth and twelfth weeks were lower than those of the control group, and the difference was statistically significant, which indicated that the score reduction in the experiment group was larger than that in the control group. The SAS and SDS scores of the experiment group at these time points were not significantly different from those of the control group, which indicated that these two treatment methods were comparable in treating patients’ anxiety and depression.

Conclusion

The CBT intervention using WeChat may improve the subjectively reported severity of alcohol dependence of patients who had completed detoxification. It is conducive to prevention of relapse, and is convenient for patients. It is worthy of clinical application and further study.