bluuebunny/crossref_metadata_2025 huggingface dataset:
Hospital Community Benefit in Rural Appalachia: One More Gap*
Authors: Cronin Cory E. , Franz Berkeley , Gran Brian K.
Published: April 2020

Non‐profit hospitals are important anchors in Appalachian communities, in part because of the concentration of health care dollars within these institutions. Community benefit efforts of these hospitals, therefore, have the potential to fill gaps in public health and social service provision in underserved areas with documented health disparities and access barriers. To date, however, we do not fully understand how community benefit practices vary by hospital setting. Employing hierarchical linear modeling using a multilevel mixed‐effects approach, this study analyzes data from the years 2010 to 2016 to assess community benefit practices and spending between hospitals in Appalachia and non‐Appalachian counties. Findings indicate that hospitals within Appalachian counties, and rural hospitals in this region, in particular, spent less on community benefit than hospitals, not in this region. Given the potential for community benefit to impact health outcomes and access to care, this disparity is important to state and local public health efforts and suggests the need for additional support for hospitals to engage their communities around critical health needs.
Bioinformatics analysis of gene expression profiles of Inclusion body myositis
Authors: Zhang Jiuchang , Khasanova Elona , Zhang Liming
Published: April 2020

Inclusion body myositis (IBM) is a disease with a poor prognosis and limited treatment options. This study aimed at exploring gene expression profile alterations, investigating the underlying mechanisms and identifying novel targets for IBM. We analysed two microarray datasets (GSE39454 and GSE128470) derived from the Gene Expression Omnibus (GEO) database. The GEO2R tool was used to screen out differentially expressed genes (DEGs) between IBM and normal samples. Gene Ontology（GO）function and Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery to identify the pathways and functional annotation of DEGs. Finally, protein‐protein interaction (PPI) networks were constructed using STRING and Cytoscape, in order to identify hub genes. A total of 144 upregulated DEGs and one downregulated DEG were identified. The GO enrichment analysis revealed that the immune response was the most significantly enriched term within the DEGs. The KEGG pathway analysis identified 22 significant pathways, the majority of which could be divided into the immune and infectious diseases. Following the construction of PPI networks, ten hub genes with high degrees of connectivity were picked out, namely PTPRC, IRF8, CCR5, VCAM1, HLA‐DRA, TYROBP, C1QB, HLA‐DRB1, CD74 and CXCL9. Our research hypothesizes that autoimmunity plays an irreplaceable role in the pathogenesis of IBM. The novel DEGs and pathways identified in this study may provide new insight into the underlying mechanisms of IBM at the molecular level.
Redox regulation of PGRL1 at the onset of low light intensity
Authors: Wolf Bat‐Chen , Isaacson Tal , Tiwari Vivekanand , Dangoor Inbal , Mufkadi Sapir , Danon Avihai
Published: April 2020

PGR5‐LIKE PHOTOSYNTHETIC PHENOTYPE1 (PGRL1) regulates photosystem I cyclic electron flow which transiently activates non‐photochemical quenching at the onset of light. Here, we show that a disulfide‐based mechanism of PGRL1 regulated this process in vivo at the onset of low light levels. We found that PGRL1 regulation depended on active formation of key regulatory disulfides in the dark, and that PGR5 was required for this activity. The disulfide state of PGRL1 was modulated in plants by counteracting reductive and oxidative components and reached a balanced state that depended on the light level. We propose that the redox regulation of PGRL1 fine‐tunes a timely activation of photosynthesis at the onset of low light.
Influence of a customized three‐dimensionally printed drill guide on the accuracy of pedicle screw placement in lumbosacral vertebrae: An ex vivo study
Authors: Beer Patricia , Park Brian H. , Steffen Frank , Smolders DECVN Lucas A. , Pozzi Antonio , Knell Sebastian C.
Published: April 2020

Objective

To compare the accuracy of pedicle screw insertion (PSI) into canine lumbosacral vertebrae with custom‐made three‐dimensionally (3D)‐printed drill guides or freehand insertion.

Study design

Ex vivo study.

Sample population

Nineteen canine lumbosacral specimens.

Methods

Drill guides for PSI were designed on the basis of safe screw insertion trajectories by using preoperative computed tomography (CT) and produced by 3D printing of templates. Right and left sides of the specimens were randomly allocated to two groups; 4‐mm pedicle screws were inserted in L5‐L6 and L7‐S1 spinal segments either freehand (control group) or with custom‐made drill guides (guide group). Sixty‐six screws were inserted with each method. Insertion angles (α, β), bone stock, and vertebral canal breach were assessed according to postoperative CT. χ2 Tests were used to compare vertebral canal breach between groups and vertebrae.

Results

Breaches in the vertebral canal were less common (P < .001) when screws were placed with a guide in the guide group (9/66, 14%) than without a guide (30/66, 45%). The rate of vertebral canal breach differed at L5 (P = .021) but not at L6 (P = .05), L7 (P = .075) or S1 (P = .658). The angle of insertion (α) did not differ between specimens with and without breaches (guide, P = .068; control, P = .394).

Conclusion

The use of a customized 3D‐printed guide generally improved the accuracy of PSI in canine lumbosacral vertebrae, although statistical significance was reached only at L5.

Clinical significance

The use of customized drill guides may be considered as an alternative to freehand PSI in the lumbosacral area, especially for L5‐L6 vertebrae.
Electromigration Damage of Flexible Electronic Lines Printed With Ag Nanoparticle Ink
Authors: Saito Daiki , Sasagawa Kazuhiko , Moriwaki Takeshi , Fujisaki Kazuhiro
Published: April 2020

Flexible printed circuits (FPCs) are widely used in electronic equipment such as mobile devices and wearable sensors. The conductive electric lines in these circuits are printed using nanoparticle metal ink and ink-jet direct write methods. Physical characteristics such as flexibility and mechanical durability of metal nanoparticle ink lines have been evaluated by bending or tensile tests. In contrast, the electrical characteristics of these lines have not been sufficiently evaluated, and the failure mechanism under high-density current has not been clarified. When electric devices are scaled down, current density and Joule heating increase in conductive lines and electromigration (EM) damage becomes a severe problem. Therefore, reducing the EM damage is extremely important to enhance the device reliability. In this study, a failure analysis of Ag nanoparticle ink lines were assessed using current loading tests and microscopic observations to discuss the damage mechanism and evaluate electrical reliability under high-density current. Atomic transport due to EM was observed at 60 kA/cm2 current loading, and relatively large aggregates and grain growth were observed at 120 kA/cm2 current loading. The time to open circuit was longer at 120 kA/cm2 than at 60 kA/cm2. The formation of large aggregates and unstable changes in the potential drop were observed at the two values of current density. It is considered that aggregate formation and grain growth affected the atomic transport by EM.
Nonlinear Elastic and Inelastic Properties of Cells
Authors: Jung Wonyeong , Li Jing , Chaudhuri Ovijit , Kim Taeyoon
Published: April 2020

Mechanical forces play an important role in various physiological processes, such as morphogenesis, cytokinesis, and migration. Thus, in order to illuminate mechanisms underlying these physiological processes, it is crucial to understand how cells deform and respond to external mechanical stimuli. During recent decades, the mechanical properties of cells have been studied extensively using diverse measurement techniques. A number of experimental studies have shown that cells are far from linear elastic materials. Cells exhibit a wide variety of nonlinear elastic and inelastic properties. Such complicated properties of cells are known to emerge from unique mechanical characteristics of cellular components. In this review, we introduce major cellular components that largely govern cell mechanical properties and provide brief explanations of several experimental techniques used for rheological measurements of cell mechanics. Then, we discuss the representative nonlinear elastic and inelastic properties of cells. Finally, continuum and discrete computational models of cell mechanics, which model both nonlinear elastic and inelastic properties of cells, will be described.
Sparsity-driven adaptive enhancement of underwater acoustic tonals for passive sonars
Authors: Hao Yu , Chi Cheng , Liang Guolong
Published: April 2020

Acoustic tonals, radiated by underwater and surface vehicles, are an important feature for passive sonar detection. An adaptive line enhancer (ALE) is usually employed in passive sonar systems as a preprocessing step to enhance the acoustic tonals from these vehicles. Unfortunately, the performance of the conventional ALE is limited by the high steady-state misadjustment, which is caused by the weight noise in the adaptation process. This paper makes use of the frequency-domain sparsity of these tonals to develop better ALEs for passive sonars. The adaptation of the proposed ALE is performed in the frequency domain. Three typical sparse penalties, l1-norm, log-sum, and l0-pseudo-norm, are incorporated into the cost function of the frequency-domain adaptation, which yield three sparsity-driven ALEs: zero-attracting (ZA), reweighted zero-attracting (RZA), and l0. The simulation shows that the signal-to-noise ratio gains of the ZA-ALE, RZA-ALE, and l0-ALE are 5.9, 8.7, and 9.7 dB, higher than that of the conventional ALE, respectively. The results of processing the real data also validate that all the sparsity-driven ALEs outperform the conventional ALE, and the l0-ALE performs the best. The proposed sparsity-driven l0-ALE is thus a promising candidate for passive sonars to enhance the tonals.
Can IGF-1 Serum Levels Really be Changed by Acute Physical Exercise? A Systematic Review and Meta-Analysis
Authors: de Alcantara Borba Diego , da Silva Alves Eduardo , Rosa João Paulo Pereira , Facundo Lucas Alves , Costa Carlos Magno Amaral , Silva Aldo Coelho , Narciso Fernanda Veruska , Silva Andressa , de Mello Marco Túlio
Published: April 2020

Background: Physical exercise plays an important role in metabolic health, especially in the insulin-like growth factor-1 (IGF-1) system. The objective of this study was to perform a systematic review and meta-analysis to evaluate the effects of a single endurance and resistance exercise session on IGF-1 serum. Methods: The systematic review was performed in SPORTDiscus, MEDLINE, PubMed, and Google Scholar databases. All analyses are based on random-effect models. The study identified 249 records of which 21 were included. Results: There was an effect of endurance exercise on total IGF-1 (P = .01), but not for free IGF-1 (P = .36). Resistance exercise similarly only affected total IGF-1 (P = .003) and not free IGF-1 (P = .37). The effect size indicated that total IGF-1 is more affected (ES = 0.81) by endurance than by resistance exercise (ES = 0.46). The present study showed that IGF-1 serum concentrations are altered by exercise type, but in conditions which are not well-defined. Conclusions: The systematic review and meta-analysis suggest that there is no determinant in serum IGF-1 changes for the exercise load characteristic. Therefore, physical exercise may be an alternative treatment to control changes in IGF-1 metabolism and blood concentration.
Endothelium-targeted deletion of the miR-15a/16-1 cluster ameliorates blood-brain barrier dysfunction in ischemic stroke
Authors: Ma Feifei , Sun Ping , Zhang Xuejing , Hamblin Milton H. , Yin Ke-Jie
Published: April 2020

Targeting of
Claudin-5
by a microRNA cluster may contribute to blood-brain barrier leakage after stroke.
Imipenem Population Pharmacokinetics: Therapeutic Drug Monitoring Data Collected in Critically Ill Patients with or without Extracorporeal Membrane Oxygenation
Authors: Chen Wenqian , Zhang Dan , Lian Wenwen , Wang Xiaoxue , Du Wenwen , Zhang Zhu , Guo Dongjie , Zhang Xianglin , Zhan Qingyuan , Li Pengmei
Published: April 2020

Carbapenem pharmacokinetic (PK) profiles are significantly different in critically ill patients because of the drastic variability of the patients’ physiological parameters. Published population PK studies have mainly focused on specific diseases, and the majority of these studies had small sample sizes. The aim of this study was to develop a population PK model of imipenem in critically ill patients that estimated the influence of various clinical and biological covariates and the use of extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT).
How Microbes Use Force To Control Adhesion
Authors: Viljoen Albertus , Mignolet Johann , Viela Felipe , Mathelié-Guinlet Marion , Dufrêne Yves F.
Published: April 2020

Microbial adhesion and biofilm formation are usually studied using molecular and cellular biology assays, optical and electron microscopy, or laminar flow chamber experiments. Today, atomic force microscopy (AFM) represents a valuable addition to these approaches, enabling the measurement of forces involved in microbial adhesion at the single-molecule level. In this minireview, we discuss recent discoveries made applying state-of-the-art AFM techniques to microbial specimens in order to understand the strength and dynamics of adhesive interactions.
Development of a Multiplex PCR-Based Assay for Rapid Serotyping of
Erysipelothrix
Species
Authors: Shimoji Yoshihiro , Shiraiwa Kazumasa , Tominaga Haruka , Nishikawa Sayaka , Eguchi Masahiro , Hikono Hirokazu , Ogawa Yohsuke
Published: April 2020

The Gram-positive bacterium
Erysipelothrix rhusiopathiae
is a zoonotic pathogen that causes erysipelas in a wide range of mammalian and avian species. Historically,
E. rhusiopathiae
has been differentiated from other
Erysipelothrix
species by serotyping. Among 28 serovars of
Erysipelothrix
species, specific serovars, namely, 1a, 1b, and 2 of
E. rhusiopathiae
, are associated mainly with the disease in pigs, poultry, and humans; however, other serovar strains are often simultaneously isolated from diseased and healthy animals, indicating the importance of isolate serotyping for epidemiology.
Early OXA-48-Producing
Enterobacterales
Isolates Recovered in a Spanish Hospital Reveal a Complex Introduction Dominated by Sequence Type 11 (ST11) and ST405 Klebsiella pneumoniae Clones
Authors: Gijón Desirèe , Tedim Ana P. , Valverde Aránzazu , Rodríguez Irene , Morosini María-Isabel , Coque Teresa M. , Manrique Marina , Pareja Eduardo , Tobes Raquel , Ruiz-Garbajosa Patricia , Cantón Rafael
Published: April 2020

We present results of microbiological analysis of the first
Enterobacterales
isolates that were isolated in 2012 in our institution expressing OXA-48 carbapenemase. This enzyme confers resistance to carbapenems, an important group of antibiotics widely used in the hospitals. OXA-48 carbapenemase is currently present in many parts of the world, but it is found particularly frequently in the Mediterranean area. It was disseminated at the Ramón y Cajal Hospital and found to be associated with a particular
Klebsiella pneumoniae
strain, so-called high-risk clone ST11, which was previously found in our institution in association with other enzymes such as CTX-M-15, VIM-1, and KPC-3. This clone might have acquired a plasmid harboring the
bla
OXA-48
gene. Our results point out the importance of local epidemiology in the dissemination and maintenance of multidrug-resistant bacteria.
Regulation of Antimycin Biosynthesis Is Controlled by the ClpXP Protease
Authors: Bilyk Bohdan , Kim Sora , Fazal Asif , Baker Tania A. , Seipke Ryan F.
Published: April 2020

Natural products produced by
Streptomyces
species underpin many industrially and medically important compounds. However, the majority of the ∼30 biosynthetic pathways harbored by an average species are not expressed in the laboratory. This unrevealed biochemical diversity is believed to comprise an untapped resource for natural product drug discovery. Major roadblocks preventing the exploitation of unexpressed biosynthetic pathways are a lack of insight into their regulation and limited technology for activating their expression. Our findings reveal that the abundance of σ
AntA
, which is the cluster-situated regulator of antimycin biosynthesis, is controlled by the ClpXP protease. These data link proteolysis to the regulation of natural product biosynthesis for the first time to our knowledge, and we anticipate that this will emerge as a major strategy by which actinobacteria regulate production of their natural products. Further study of this process will advance understanding of how expression of secondary metabolism is controlled and will aid pursuit of activating unexpressed biosynthetic pathways.
HIV Env-Specific IgG Antibodies Induced by Vaccination of Neonatal Rhesus Macaques Persist and Can Be Augmented by a Late Booster Immunization in Infancy
Authors: Curtis Alan D. , Dennis Maria , Eudailey Joshua , Walter Korey L. , Cronin Kenneth , Alam S. Munir , Choudhary Neelima , Tuck Ryan H. , Hudgens Michael , Kozlowski Pamela A. , Pollara Justin , Ferrari Guido , Van Rompay Koen K. A. , Permar Sallie , De Paris Kristina
Published: April 2020

The majority of new HIV-1 infections occur in young adults, with adolescent women being 3 times more likely to acquire HIV than young men. Implementation of HIV prevention strategies has been less successful in this age group; thus, a vaccine given prior to adolescence remains a high priority. We propose that instead of starting HIV vaccination during adolescence, an HIV vaccine regimen initiated in early infancy, aligned with the well-accepted pediatric vaccine schedule and followed with booster immunizations, will provide an alternative means to reduce HIV acquisition in adolescence. Importantly, the long window of time between the first infant vaccine dose and the adolescence vaccine dose will allow for the maturation of highly functional HIV Env-specific antibody responses. Our study provides evidence that early life vaccination induces durable Env-specific plasma IgG responses that can be boosted to further improve the quality of the antibody response.
mSphere of Influence: Going Native, or the Risk of Overreliance on Recombinant Antigens
Authors: Lopez-Perez Mary
Published: April 2020

Mary Lopez-Perez works on immunology and pathogenesis of malaria. In this mSphere of Influence article, she reflects on how the paper “Functional antibodies against VAR2CSA in nonpregnant populations from Colombia exposed to
Plasmodium falciparum
and
Plasmodium vivax
”
by S. Gnidehou, J. Doritchamou, E. M. Arango, A. Cabrera, et al. (Infect Immun 82:2565−2573, 2014,
https://doi.org/10.1128/IAI.01594-14
) made her cautious of relying exclusively on recombinant proteins when evaluating antibody responses.
Isolated cardiovascular involvement in light chain amyloidosis
Authors: Ahmed Ahamed Shaheer , Kumar Sampath , Sharma Gautam , Arava Sudheer
Published: April 2020

A 50-year-old woman presented with complaints of palpitations and breathlessness of 6 months’ duration. She was being treated elsewhere as a case of dilated cardiomyopathy. On evaluation she had racoon eyes, poor progression of R wave on ECG and low-voltage complexes in the limb leads. Echocardiography revealed biventricular hypertrophy, diastolic dysfunction and moderate systolic dysfunction. Cardiac MRI showed features suggestive of amyloidosis. Bone marrow biopsy revealed raised plasma cell count, and endomyocardial biopsy showed amyloid deposits in the myocardium. Free lambda light chain levels were elevated, even though serum and urine electrophoresis did not show any monoclonal band. In this ‘text book case of cardiac amyloidosis’, apart from cardiovascular system no other organ system was affected, which is uncommon in primary light chain amyloidosis. The patient was started on CyBorD (cyclophosphamide, bortezomib and dexamethasone) regimen.
Ocular manifestations of a hospitalised patient with confirmed 2019 novel coronavirus disease
Authors: Chen Lu , Liu Meizhou , Zhang Zheng , Qiao Kun , Huang Ting , Chen Miaohong , Xin Na , Huang Zuliang , Liu Lei , Zhang Guoming , Wang Jiantao
Published: April 2020

Purpose

To report the ocular characteristics and the presence of viral RNA of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in conjunctival swab specimens in a patient with confirmed 2019 novel coronavirus disease (COVID-19).

Participant and methods

A 30-year-old man with confirmed COVID-19 and bilateral acute conjunctivitis which occurred 13 days after illness onset. Based on detailed ophthalmic examination, reverse transcription PCR (RT-PCR) was performed to detect SARS-CoV-2 virus in conjunctival swabs. The ocular characteristics, presence of viral RNA and viral dynamics of SARS-CoV-2 in the conjunctival specimens were evaluated.

Results

Slit lamp examination showed bilateral acute follicular conjunctivitis. RT-PCR assay demonstrated the presence of viral RNA in conjunctival specimen 13 days after onset (cycle threshold value: 31). The conjunctival swab specimens remained positive for SARS-CoV-2 on 14 and 17 days after onset. On day 19, RT-PCR result was negative for SARS-CoV-2.

Conclusion

SARS-CoV-2 is capable of causing ocular complications such as viral conjunctivitis in the middle phase of illness. Precautionary measures are recommended when examining infected patients throughout the clinical course of the infection. However, conjunctival sampling might not be useful for early diagnosis because the virus may not appear initially in the conjunctiva.
Biomarker-guided implementation of the KDIGO guidelines to reduce the occurrence of acute kidney injury in patients after cardiac surgery (PrevAKI-multicentre): protocol for a multicentre, observational study followed by randomised controlled feasibility trial
Authors: Küllmar Mira , Massoth Christina , Ostermann Marlies , Campos Sara , Grau Novellas Neus , Thomson Gary , Haffner Michael , Arndt Christian , Wulf Hinnerk , Irqsusi Marc , Monaco Fabrizio , Di Prima Ambra , Garcia Alvarez Mercedes , Italiano Stefano , Cegarra SanMartin Virginia , Kunst Gudrun , Nair Shrijit , L'Acqua Camilla , Hoste Eric A J , Vandenberghe Wim , Honore Patrick , Kellum John , Forni Lui , Grieshaber Philippe , Weiss Raphael , Gerss Joachim , Wempe Carola , Meersch Melanie , Zarbock Alexander
Published: April 2020

Introduction

Acute kidney injury (AKI) is a frequent complication after cardiac surgery with adverse short-term and long-term outcomes. Although prevention of AKI (PrevAKI) is strongly recommended, the optimal strategy is uncertain. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommended a bundle of supportive measures in high-risk patients. In a single-centre trial, we recently demonstrated that the strict implementation of the KDIGO bundle significantly reduced the occurrence of AKI after cardiac surgery. In this feasibility study, we aim to evaluate whether the study protocol can be implemented in a multicentre setting in preparation for a large multicentre trial.

Methods and analysis

We plan to conduct a prospective, observational survey followed by a randomised controlled, multicentre, multinational clinical trial including 280 patients undergoing cardiac surgery with cardiopulmonary bypass. The purpose of the observational survey is to explore the adherence to the KDIGO recommendations in routine clinical practice. The second phase is a randomised controlled trial. The objective is to investigate whether the trial protocol is implementable in a large multicentre, multinational setting. The primary endpoint of the interventional part is the compliance rate with the protocol. Secondary endpoints include the occurrence of any AKI and moderate/severe AKI as defined by the KDIGO criteria within 72 hours after surgery, renal recovery at day 90, use of renal replacement therapy (RRT) and mortality at days 30, 60 and 90, the combined endpoint major adverse kidney events consisting of persistent renal dysfunction, RRT and mortality at day 90 and safety outcomes.

Ethics and dissemination

The PrevAKI multicentre study has been approved by the leading Research Ethics Committee of the University of Münster and the respective Research Ethics Committee at each participating site. The results will be used to design a large, definitive trial.

Trial registration number

NCT03244514.
Core outcome set in paediatric sepsis in low- and middle-income countries: a study protocol
Authors: Wooldridge Gavin , Murthy Srinivas , Kissoon Niranjan
Published: April 2020

Introduction

Sepsis is the leading cause of death in children worldwide and has recently been declared a major global health issue. New interventions and a concerted effort to enhance our understanding of sepsis are required to address the huge burden of disease, especially in low- and middle-income countries (LMIC) where it is highest. An opportunity therefore exists to ensure that ongoing research in this area is relevant to all stakeholders and is of consistently high quality. One method to address these issues is through the development of a core outcome set (COS).

Methods and analysis

This study protocol outlines the phases in the development of a core outcome set for paediatric sepsis in LMIC. The first step involves performing a systematic review of all outcomes reported in the research of paediatric sepsis in low middle-income countries. A three-stage international Delphi process will then invite a broad range of participants to score each generated outcome for inclusion into the COS. This will include an initial two-step online survey and finally, a face-to-face consensus meeting where each outcome will be reviewed, voted on and ratified for inclusion into the COS.

Ethics and dissemination

No core outcome sets exist for clinical trials in paediatric sepsis. This COS will serve to not only highlight the heavy burden of paediatric sepsis in this setting and aid collaboration and participation between all stakeholders, but to promote ongoing essential high quality and relevant research into the topic. A COS in paediatric sepsis in LMIC will advocate for a common language and facilitate interpretation of findings from a variety of settings. A waiver for ethics approval has been granted by University of British Columbia Children’s and Women’s Research Ethics Board.
Investigating the critical elements and psychosocial outcomes of Youth Flexible Assertive Community Treatment: a study protocol for an observational prospective cohort study
Authors: Broersen Marieke , Creemers Daan H M , Frieswijk Nynke , Vermulst Ad A , Kroon Hans
Published: April 2020

Introduction

When adolescents experience complex psychiatric and social problems, numerous healthcare services usually become involved. In these cases, fragmentation of care services is a risk that often results in both ineffective care and in patients disengaging from care services. To address these issues, Youth Flexible Assertive Community Treatment (Youth Flexible ACT) was developed in the Netherlands. This client-centred service delivery model aims to tackle the fragmented care system by providing psychiatric treatment and support in a flexible and integrated manner. While Youth Flexible ACT is gaining in popularity, the effectiveness of the care model remains largely unexamined.

Methods and analysis

Here, we present an observational prospective cohort (2017–2021) in which a broad range of treatment outcomes will be monitored. The primary aim of the study is to examine change in treatment outcomes over the course of the Flexible ACT care. The secondary aim is to examine the association between (elements of) Youth Flexible ACT model fidelity and treatment outcomes. An estimated total number of 200 adolescents who receive care from one of the 16 participating Youth Flexible ACT teams will be included in the study. Participants will be asked to complete assessments at four time points in 6-month intervals, resulting in a study duration of 18 months. Latent growth curve analysis will be conducted to examine change in psychosocial functioning over time and its relation to model fidelity.

Ethics and dissemination

This study received ethical approval from Trimbos Ethics Committee (201607_75-FACT2). This approval applies for all participating institutions. The results of the study will be reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology statement. Results will be disseminated via peer-reviewed academic journals and presentations at conferences. In addition, results will be made available for participating sites, funders and researchers.
Persistence of patient and family experiences of critical illness
Authors: Hirshberg Eliotte L , Butler Jorie , Francis Morgan , Davis Francis A , Lee Doriena , Tavake-Pasi Fahina , Napia Edwin , Villalta Jeanette , Mukundente Valentine , Coulter Heather , Stark Louisa , Beesley Sarah J , Orme James F , Brown Samuel M , Hopkins Ramona O
Published: April 2020

Objective

To investigate: (1) patient and family experiences with healthcare and the intensive care unit (ICU); (2) experiences during their critical illness; (3) communication and decision making during critical illness; (4) feelings about the ICU experience; (5) impact of the critical illness on their lives; and (6) concerns about their future after the ICU.

Design

Four semistructured focus group interviews with former ICU patients and family members.

Settings

Multicultural community group and local hospitals containing medical/surgical ICUs.

Participants

Patients and family who experienced a critical illness within the previous 10 years.

Interventions

None.

Measurements and main results

Four separate focus groups each lasting a maximum of 150 min and consisting of a total of 21 participants were held. Focus groups were conducted using a semistructured script including six topics relating to the experience of critical illness that facilitated deduction and the sorting of data by thematic analysis into five predominant themes. The five main themes that emerged from the data were: (1) personalised stories of the critical illness; (2) communication and shared decision making, (3) adjustment to life after critical illness, (4) trust towards clinical team and relevance of cultural beliefs and (5) end-of-life decision making. Across themes, we observed a misalignment between the medical system and patient and family values and priorities.

Conclusions

The experience of critical illness of a diverse group of patients and families can remain vivid for years after ICU discharge. The identified themes reflect the strength of memory of such pivotal experiences and the importance of a narrative around those experiences. Clinicians need to be aware of the lasting effects of critical illness has on patients and families.
Comparative study on prevalence of metabolic syndrome based on three criteria among adults in Zhejiang province, China: an observational study
Authors: Wang Xiyi , Howell Doris , Tang Leiwen , Shao Jing , Ye Zhihong
Published: April 2020

Objectives

In this study, we aimed to estimate the prevalence of metabolic syndrome (MetS) among Chinese adults, describe the disease components and compare utility of the existing international criteria and Chinese diagnostic criteria.

Design, setting and participants

A retrospective database analysis was conducted for one hospital in Zhejiang province, China. We analysed data (collected in 2017) from a total of 64 902 participants (37 500 males and 27 402 females), aged between 18 and 97 years, and who met the eligibility criteria.

Main outcome measures

We employed three criteria for MetS proposed by the International Diabetes Federation (IDF) in 2005, the 2009 Joint Scientific Statement (harmonising criteria) and the China Diabetes Society (CDS) in 2013 to detect prevalence of MetS. Specifically, we analysed waist circumference, blood pressure, fasting plasma glucose, plasma triglycerides and plasma high-density lipoprotein cholesterol.

Results

We found an estimated age-adjusted MetS prevalence of 20.4% using IDF 2005, 30.0% based on harmonising criteria 2009 and 16.3% under the CDS 2013. This prevalence was higher in males, older adults and increased body mass index. Analysis of agreements among the criteria were 87.2% (IDF and CDS), 87.1% (IDF and harmonising criteria) and 81.6% (CDS and harmonising criteria), while their kappa coefficients were 0.641, 0.708 and 0.572 for IDF versus CDS, IDF versus harmonising criteria and CDS versus harmonising criteria, respectively. The most prevalent MetS component was abdominal obesity (50.1%), followed by dyslipidaemia (49.5%) and hypertension (46.8%) using harmonising criteria.

Conclusion

These findings revealed moderate agreement among the three criteria with utility in Chinese clinical settings. The harmonising criteria 2009 performed better in early identification of MetS in the Chinese population.
Leadership development in complex health systems: a qualitative study
Authors: Curry Leslie A , Ayedun Adeola A , Cherlin Emily J , Allen Nikole H , Linnander Erika L
Published: April 2020

Objective

Leadership is associated with organisational performance in healthcare, including quality, safety and clinical outcomes for patients. Leadership development programmes have proliferated in recent years. Nevertheless, very few have examined participant experiences in depth in order to understand which programmatic aspects they regard as most valuable relative to leadership in increasingly complex systems, or whether and how learnings may sustain over time. Accordingly, we explored experiences of participants in an interdisciplinary leadership development programme using qualitative methods over an extended look-back period.

Setting

Health and social care sectors in the UK.

Participants

Key informants from three cohorts of individuals working in leadership roles in health and social care in the UK: 2013/2014, 2015/2016 and 2017/2018. We contacted 32 participants, and 26 completed interviews (81% response rate).

Primary and secondary outcomes

We explored (1) whether and how specific skills and competencies developed during the programme were applied and/or sustained over time, and (2) whether and how the impact of the programme changed as alumni progressed through their career.

Results

Three major recurrent themes emerged from participants’ experiences: (1) specific features of the programme meaningfully impact professional development at multiple levels; (2) the coupling of a professional network and practical tools allowed participants to address system-wide problems in new ways and (3) participants describe a level of learning that sustained and amplified over time with increased complexity in their work.

Conclusion

This work highlights specific design characteristics of leadership development programmes that may help promote relevance and impact. Programme learnings can be translated into practice in substantive ways, with potential for the benefits of successful leadership development efforts to amplify, not fade, over time.
Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study
Authors: Holliday Elizabeth , Lillicrap Thomas , Kleinig Timothy , Choi Philip M C , Maguire Jane , Bivard Andrew , Lincz Lisa F , Hamilton-Bruce Monica Anne , Rao Sushma R , Snel Marten F , Trim Paul J , Lin Longting , Parsons Mark W , Worrall Bradford B , Koblar Simon , Attia John , Levi Chris
Published: April 2020

Introduction

Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is the only approved pharmacological reperfusion therapy for acute ischaemic stroke. Despite population benefit, IVT is not equally effective in all patients, nor is it without significant risk. Uncertain treatment outcome prediction complicates patient treatment selection. This study will develop and validate predictive algorithms for IVT response, using clinical, radiological and blood-based biomarker measures. A secondary objective is to develop predictive algorithms for endovascular thrombectomy (EVT), which has been proven as an effective reperfusion therapy since study inception.

Methods and analysis

The Targeting Optimal Thrombolysis Outcomes Study is a multicenter prospective cohort study of ischaemic stroke patients treated at participating Australian Stroke Centres with IVT and/or EVT. Patients undergo neuroimaging using multimodal CT or MRI at baseline with repeat neuroimaging 24 hours post-treatment. Baseline and follow-up blood samples are provided for research use. The primary outcome is good functional outcome at 90 days poststroke, defined as a modified Rankin Scale (mRS) Score of 0–2. Secondary outcomes are reperfusion, recanalisation, infarct core growth, change in stroke severity, poor functional outcome, excellent functional outcome and ordinal mRS at 90 days. Primary predictive models will be developed and validated in patients treated only with rt-PA. Models will be built using regression methods and include clinical variables, radiological measures from multimodal neuroimaging and blood-based biomarkers measured by mass spectrometry. Predictive accuracy will be quantified using c-statistics and R2. In secondary analyses, models will be developed in patients treated using EVT, with or without prior IVT, reflecting practice changes since original study design.

Ethics and dissemination

Patients, or relatives when patients could not consent, provide written informed consent to participate. This study received approval from the Hunter New England Local Health District Human Research Ethics Committee (reference 14/10/15/4.02). Findings will be disseminated via peer-reviewed publications and conference presentations.
Factors influencing the decision-making of carers of children with bilateral cataract in Nepal
Authors: Bell Suzannah J , Singh Tirtha , Bunce Catey , Singh Sanjay Kumar , Bascaran Cova , Gilbert Clare , Foster Allen
Published: April 2020

Objectives

Two hundred thousand children worldwide are blind from cataract. Late presentation for surgery resulting in poor visual outcomes is a problem globally. We aimed to explore the reasons why children are not brought earlier for surgery in Nepal.

Methods and analysis

Mixed-method study of carers of children with bilateral cataract attending a large non-government eye hospital were administered a proforma. A random sample took part in semistructured interviews and focus group discussions.

Results

Carers of 102 children completed proformas; 10 interviews and 2 focus group discussions were held. 80.4% were Indian, 35.3% of children were female, and their mean age was 58 months (range 4 months to 10 years). Median delay in time between the carer first noticing a problem to presentation was 182 days IQR (60.8–364.8). This was significantly longer for girls (median 304 IQR (91.2–1094.4)) than boys (median 121.6 IQR (30.4–364.8); p=0.02). Cost to access care was a problem for 42 (41.2%) carers. 13 (12.8%) participants were not aware of treatment and 12 (11.8%) were aware but did not seek treatment. The community influenced carer’s health-seeking behaviour. Cataract was sometimes described as ‘phula’, meaning something white seen on the eye.

Conclusion

Fewer girls presented for surgery, and they also had a significantly longer delay to presentation than boys. Carers are influenced by factors at family, community and socio-organisational levels. Approaches to increase timely access, particularly by girls, are required, such as health education using the term phula, which is widely understood.
Use of menstruation and fertility app trackers: a scoping review of the evidence
Authors: Earle Sarah , Marston Hannah R , Hadley Robin , Banks Duncan
Published: April 2020

Introduction

There has been a phenomenal worldwide increase in the development and use of mobile health applications (mHealth apps) that monitor menstruation and fertility. Critics argue that many of the apps are inaccurate and lack evidence from either clinical trials or user experience. The aim of this scoping review is to provide an overview of the research literature on mHealth apps that track menstruation and fertility.

Methods

This project followed the PRISMA Extension for Scoping Reviews. The ACM, CINAHL, Google Scholar, PubMed and Scopus databases were searched for material published between 1 January 2010 and 30 April 2019. Data summary and synthesis were used to chart and analyse the data.

Results

In total 654 records were reviewed. Subsequently, 135 duplicate records and 501 records that did not meet the inclusion criteria were removed. Eighteen records from 13 countries form the basis of this review. The papers reviewed cover a variety of disciplinary and methodological frameworks. Three main themes were identified: fertility and reproductive health tracking, pregnancy planning, and pregnancy prevention.

Conclusions

Motivations for fertility app use are varied, overlap and change over time, although women want apps that are accurate and evidence-based regardless of whether they are tracking their fertility, planning a pregnancy or using the app as a form of contraception. There is a lack of critical debate and engagement in the development, evaluation, usage and regulation of fertility and menstruation apps. The paucity of evidence-based research and absence of fertility, health professionals and users in studies is raised.
Evaluation of a primary to secondary care referral pathway and novel nurse-led one-stop clinic for patients with suspected non-alcoholic fatty liver disease
Authors: Fowell Andrew J , Fancey Kirsty , Gamble Karen , Bicknell Kelly , Dowman Joanna K , Howden Paul , Aspinall Richard J
Published: April 2020

Objective

Non-alcoholic fatty liver disease (NAFLD) affects approximately one in four adults of the general population, with an important minority of cases at high risk of developing cirrhosis. We evaluated the utility of a primary care NAFLD pathway incorporating a specialist nurse-led NAFLD clinic and a two-step testing approach for advanced liver fibrosis.

Design/Method

We performed a retrospective evaluation of prospectively collected demographic and clinical data on all patients diagnosed with NAFLD and intermediate NAFLD fibrosis score seen in our nurse-led NAFLD clinic between 1 May 2014 and 30 April 2017. Patients were assessed using a specific clerking pro forma and transient elastography (TE). Discharge to primary care with lifestyle advice was considered where TE<7.9 kPa.

Results

904 patients were identified, 114 (12.6%) of whom did not meet NAFLD criteria. Among the NAFLD population (n=790 (87.4%)), TE<7.9 kPa was present in 558 patients (70.6%), 519 of whom were discharged to primary care. Selected patients were followed up in secondary care despite TE<7.9 kPa or discharged with TE≥7.9 kPa. TE was unreliable in 22 patients (2.7%). Overall, 559 (70.8%) of patients with confirmed NAFLD were discharged from the nurse-led clinic. Introduction of the new pathway was associated with increased screening for hepatitis B and C viruses in primary care, and 17 new cases of alpha-1-antitrypsin deficiency were identified.

Conclusion

An integrated primary/secondary care NAFLD pathway, including a specialist nurse-led clinic may be a useful way of managing increasing demand on secondary care hepatology services.
Prognostic significance of patent foramen ovale in anticoagulated patients with atrial fibrillation
Authors: Melduni Rowlens M , Wysokinski Waldemar E , Wang Zhenzhen , Gersh Bernard J , Asirvatham Samuel J , Patlolla Sri Harsha , Greene Eddie L , Oh Jae K , Lee Hon-Chi
Published: April 2020

Objective

Previous studies have postulated a causal role of patent foramen ovale (PFO) in the aetiology of embolic stroke in the general population. We hypothesised that the presence of concomitant PFO and atrial fibrillation (AF) will add incremental risk of ischaemic stroke to that linked to AF alone.

Methods

We analysed data on 3069 consecutive patients (mean age 69.4±12.2 years; 67.1% men) undergoing transoesophageal echocardiography-guided electrical cardioversion (ECV) for AF between May 2000 and March 2012. PFO was identified by colour Doppler and agitated saline contrast study. All patients were followed up after ECV for first documentation of ischaemic stroke. Outcomes were compared using Cox regression models.

Results

The prevalence of PFO was 20.0% and the shunt direction was left-to-right in the majority of patients (71.4%). Patients with PFO had a higher frequency of obstructive sleep apnoea (21.7% vs 17.1%, p=0.01) and higher mean peak left atrial appendage emptying velocity (38.3±21.8 vs 36.1±20.4 cm/s; p=0.04) compared with those without PFO. Otherwise, baseline characteristics were similar between groups. During a mean follow-up period of 7.3±4.6 years, 214 patients (7.0%) had ischaemic stroke. Multivariable analysis showed no significant association between PFO and ischaemic stroke (HR, 0.82 (95% CI 0.57 to 1.18)). PFO shunt direction was strongly associated with stroke: HR, 1.91 (95% CI 1.16 to 3.16) for right-to-left shunt and HR, 0.58 (95% CI 0.36 to 0.93) for left-to-right shunt.

Conclusions

The presence of concurrent PFO in this largely anticoagulated group of patients with AF was not associated with increased risk of ischaemic stroke.
Investigations on 54–60Fe + 238–244Pu → 296–302120 fusion reactions
Authors: Manjunatha H.C. , Seenappa L. , Sowmya N. , Sridhar K.N.
Published: April 2020

We have studied the 54–60Fe-induced fusion reactions to synthesize the superheavy nuclei296–302120 by studying the compound nucleus formation probability, survival probability, and evaporation residue cross-sections. The comparison of the evaporation residue cross-section for different targets reveals that the evaporation residue cross-section is larger for projectile target combination 58Fe+243Pu→301120. We have identified the most probable 58Fe-induced fusion reactions to synthesize superheavy nuclei 296–302120. The suggested reactions may be useful to synthesize the superheavy element Z = 120.
The effect of an anomalous Higgs trilinear self-coupling on the $$h \rightarrow \gamma \, Z$$ decay
Authors: Degrassi G. , Vitti M.
Published: April 2020

We compute the two-loop effects induced by an anomalous Higgs trilinear self-coupling in the partial decay width $$\Gamma (h \rightarrow \gamma Z)$$Γ(h→γZ). The computation is performed using the anomalous coupling approach, working in the unitary gauge, and in a theory in which the anomalous coupling is generated via the addition to the scalar potential part of the Standard Model Lagrangian of an (in)finite tower of $$(\Phi ^\dagger \Phi )^n$$(Φ†Φ)n terms. The former computation is automatically finite while the latter requires the renormalization of the lowest order contribution. We discuss the renormalization conditions that should be employed in order to obtain the same result in the two approaches. We find that the $$h \rightarrow \gamma Z$$h→γZ process is one of the most sensitive mode to an anomalous trilinear Higgs self-coupling. As a by-product of this work we confirm one of two different results present in the literature concerning the contribution of an anomalous Higgs trilinear coupling in the $$h \rightarrow \gamma \gamma $$h→γγ decay.