bluuebunny/crossref_metadata_2025 huggingface dataset:
Geotechnical Characterization of Gulf of Mexico Clay
Authors: Murali Madhuri , Biscontin Giovanna
Published: July 2018

With increasing development in the oil and gas industry, exploration and production are continuously moving deeper off the continental shelf and onto the continental slopes. The hazard of submarine slope failures increases in these locations, potentially leading to damage to offshore structures. Thus there is a need to study and understand properties of offshore marine clays with particular attention to slopes. Submarine failures can be much larger than subaerial ones and typically occur on very gentle slopes that do not fail on land. It is particularly important, therefore, to focus on marine clays because of the possible differences in the response of these soils compared to other clays. This study was undertaken in order to better understand the geotechnical characteristics of a submarine clay deposits from the Gulf of Mexico. The paper presents the results of triaxial testing performed on undisturbed samples of Gulf of Mexico clay. Background information is given about the clay, the sampling program and the laboratory testing program. A SHANSEP approach was used for Ko consolidated-undrained (CKoU) triaxial compression and extension tests. The consolidation tests provided most of the pre-consolidation pressure values used to establish the stress history at the test site and the variation of Ko with OCR. The undrained shear phase provides detailed information on the undrained shear strength, effective stress failure envelopes and stress path characteristics.
Analysis of Subsea Foundations Subjected to Significant Torsion
Authors: McDonald Sean , Suroor Hadi , Malachowski Jim , Wang Qi , Qi Xinhai
Published: July 2018

The interest in the adequacy of shallow foundations to withstand the forces in the subsea realm is growing. Subsea structures such as PLETs and PLEMs often experience significant torsion loads in addition to vertical, horizontal and moment loads which are typically supported by shallow foundations. In this paper, the interactions between torsional and sliding loads for shallow foundations on sand were evaluated using available analytical methods as well as by a comprehensive 3-dimensional finite element analysis (FEA). The calculated pure sliding and pure torsional resistances of un-skirted mudmat calculated by simple analytical method compared well with FEA results. There appears to be a lack of analytical methods to include torsional resistance generated by skirts. It was evident from FEA that even shallow mudmat skirts can contribute significant torsional resistances. The FEA results indicate that torsional load on foundation can significantly reduce pure sliding resistance, and the foundation design should consider sliding (H) – torsion (T) interaction, particularly when significant torsion load is present. Finally, a case history is presented involving existing shallow foundations that were deemed inadequate to support the new torsional and sliding forces. Additional clump weights required to improve overall foundation stability were determined considering H-T interactions. A comprehensive ABAQUS model of an existing PLEM foundation under combined uplift, compression, sliding forces, torsion and bending moments was analyzed to confirm the improvement in foundation stability.
Functional response of the predaceous mites Amblyseius largoensis and Euseius concordis when feeding on eggs of the cashew tree giant whitefly Aleurodicus cocois
Authors: De Alfaia Josiane P , Melo Luana L , Monteiro Neville V , Lima Debora B , Melo Jose Wagner S
Published: July 2018

The giant whitefly, Aleurodicus cocois, is one of the main pests of cashew trees around the world. In the present study we evaluated the biological potential of the predaceous mites Amblyseius largoensis and Euseius concordis against A. cocois. The consumption and functional responses to prey egg densities of A. largoensis and E. concordis were investigated in laboratory experiments. Logistic regression indicated that both predators exhibited a type II response to prey eggs, and the eggs consumption increased with egg density up to a maximum, after which it slowly decreased. The value of the attack rate (a') was higher for A. largoensis than that for E. concordis, but the handling time (Th) did not differ between the two predators. The predicted maximum daily consumption was 35 eggs for A. largoensis and 32 eggs for E. concordis. Our results indicate that A. largoensis and E. concordis could be effective biocontrol agents of the cashew tree giant whitefly, especially in conditions of low pest population density.
From acoustic radiation pressure to three-dimensional acoustic radiation forces
Authors: Zhang Likun
Published: July 2018

This paper presents three-dimensional acoustic radiation forces exerted by an arbitrary field on an obstacle as a sum of two parts due to momentum transfers by ingoing and outgoing spherical waves, respectively. This view of momentum conservation establishes a connection of the force with asymmetry of far fields and acoustic radiation pressure exerted by a plane wave on a planar reflector. These geometrical interpretations and physical aspects are useful for finding and interpreting special force conditions by examining far-field patterns and scattering functions of sound fields. Multipole expansion of the force as a function of beam shape coefficients and scattering functions is simplified for connection with complex phase shifts of scattering functions. A relation of the scattering function dependence in the small-particle limit is identified.
Time-domain analysis of power law attenuation in space-fractional wave equations
Authors: Zhao Xiaofeng , McGough Robert J.
Published: July 2018

Ultrasound attenuation in soft tissue follows a power law as a function of the ultrasound frequency, and in medical ultrasound, power law attenuation is often described by fractional calculus models that contain one or more time- or space-fractional derivatives. For certain time-fractional models, exact and approximate time-domain Green's functions are known, but similar expressions are not available for the space-fractional models that describe power law attenuation. To address this deficiency, a numerical approach for calculating time-domain Green's functions for the Chen–Holm space-fractional wave equation and Treeby–Cox space-fractional wave equation is introduced, where challenges associated with the numerical evaluation of a highly oscillatory improper integral are addressed with the Filon integration formula combined with the Pantis method. Numerical results are computed for both of these space-fractional wave equations at different distances in breast and liver with power law exponents of 1.5 and 1.139, respectively. The results show that these two space-fractional wave equations are causal and that away from the origin, the time-domain Green's function for the Treeby–Cox space-fractional wave equation is very similar to the time-domain Green's function for the time-fractional power law wave equation.
Using Video Direct Observation to Assess Children’s Physical Activity During Recess
Authors: Howe Cheryl A. , Clevenger Kimberly A. , Plow Brian , Porter Steve , Sinha Gaurav
Published: July 2018

Purpose: Traditional direct observation cannot provide continuous, individual-level physical activity (PA) data throughout recess. This study piloted video direct observation to characterize children’s recess PA overall and by sex and weight status. Methods: Children (N = 23; 11 boys; 6 overweight; third to fifth grade) were recorded during 2 recess periods, coding for PA duration, intensity, location, and type. Duration of PA type and intensity across sex and weight status overall and between/within locations were assessed using 1- and 2-way analysis of variances. Results: The field elicited more sedentary behavior (39% of time) and light PA (17%) and less moderate to vigorous PA (41%) compared with the fixed equipment (13%, 7%, and 71%, respectively) or the court (21%, 7%, and 68%, respectively). Boys engaged in significantly more vigorous-intensity activity on the court (35%) than girls (14%), whereas girls engaged in more moderate to vigorous PA on the fixed equipment (77% vs 61%) and field (46% vs 35%) than boys (all Ps > .05). PA type also differed by sex and weight status. Conclusion: Video direct observation was capable of detecting and characterizing children’s entire recess PA while providing valuable context to the behavior. The authors confirmed previous findings that PA intensity was not uniform by schoolyard location and further differences exist by sex and weight status.
PCR-Based Approach Targeting Mucorales-Specific Gene Family for Diagnosis of Mucormycosis
Authors: Baldin Clara , Soliman Sameh S. M. , Jeon Heewon H. , Alkhazraji Sondus , Gebremariam Teclegiorgis , Gu Yiyou , Bruno Vincent M. , Cornely Oliver A. , Leather Helen L. , Sugrue Michele W. , Wingard John R. , Stevens David A. , Edwards John E. , Ibrahim Ashraf S.
Published: July 2018

Mucormycosis is an aggressive, life-threatening infection caused by fungi in the order Mucorales. The current diagnosis of mucormycosis relies on mycological cultures, radiology and histopathology.
Tracing the
De Novo
Origin of Protein-Coding Genes in Yeast
Authors: Wu Baojun , Knudson Alicia
Published: July 2018

De novo
genes are very important for evolutionary innovation. However, how these genes originate and spread remains largely unknown. To better understand this, we rigorously searched for
de novo
genes in
Saccharomyces cerevisiae
S288C and examined their spread and fixation in the population. Here, we identified 84
de novo
genes in
S. cerevisiae
S288C since the divergence with their sister groups. Transcriptome and ribosome profiling data revealed at least 8 (10%) and 28 (33%)
de novo
genes being expressed and translated only under specific conditions, respectively. DNA microarray data, based on 2-fold change, showed that 87% of the
de novo
genes are regulated during various biological processes, such as nutrient utilization and sporulation. Our comparative and evolutionary analyses further revealed that some factors, including single nucleotide polymorphism (SNP)/indel mutation, high GC content, and DNA shuffling, contribute to the birth of
de novo
genes, while domestication and natural selection drive the spread and fixation of these genes. Finally, we also provide evidence suggesting the possible parallel origin of a
de novo
gene between
S. cerevisiae
and
Saccharomyces paradoxus
. Together, our study provides several new insights into the origin and spread of
de novo
genes.

IMPORTANCE
Emergence of
de novo
genes has occurred in many lineages during evolution, but the birth, spread, and function of these genes remain unresolved. Here we have searched for
de novo
genes from
Saccharomyces cerevisiae
S288C using rigorous methods, which reduced the effects of bad annotation and genomic gaps on the identification of
de novo
genes. Through this analysis, we have found 84 new genes originating
de novo
from previously noncoding regions, 87% of which are very likely involved in various biological processes. We noticed that 10% and 33% of
de novo
genes were only expressed and translated under specific conditions, therefore, verification of
de novo
genes through transcriptome and ribosome profiling, especially from limited expression data, may underestimate the number of bona fide new genes. We further show that SNP/indel mutation, high GC content, and DNA shuffling could be involved in the birth of
de novo
genes, while domestication and natural selection drive the spread and fixation of these genes. Finally, we provide evidence suggesting the possible parallel origin of a new gene.
Effects of physical activity interventions on cognitive and academic performance in children and adolescents: a novel combination of a systematic review and recommendations from an expert panel
Authors: Singh Amika S , Saliasi Emi , van den Berg Vera , Uijtdewilligen Léonie , de Groot Renate H M , Jolles Jelle , Andersen Lars B , Bailey Richard , Chang Yu-Kai , Diamond Adele , Ericsson Ingegerd , Etnier Jennifer L , Fedewa Alicia L , Hillman Charles H , McMorris Terry , Pesce Caterina , Pühse Uwe , Tomporowski Phillip D , Chinapaw Mai J M
Published: July 2018

Objective

To summarise the current evidence on the effects of physical activity (PA) interventions on cognitive and academic performance in children, and formulate research priorities and recommendations.

Design

Systematic review (following PRISMA guidelines) with a methodological quality assessment and an international expert panel. We based the evaluation of the consistency of the scientific evidence on the findings reported in studies rated as of high methodological quality.

Data sources

PubMed, PsycINFO, Cochrane Central, Web of Science, ERIC, and SPORTDiscus.

Eligibility criteria for selecting studies

PA-intervention studies in children with at least one cognitive or academic performance assessment.

Results

Eleven (19%) of 58 included intervention studies received a high-quality rating for methodological quality: four assessed effects of PA interventions on cognitive performance, six assessed effects on academic performance, and one on both. All high-quality studies contrasted the effects of additional/adapted PA activities with regular curriculum activities. For cognitive performance 10 of 21 (48%) constructs analysed showed statistically significant beneficial intervention effects of PA, while for academic performance, 15 of 25 (60%) analyses found a significant beneficial effect of PA. Across all five studies assessing PA effects on mathematics, beneficial effects were reported in six out of seven (86%) outcomes. Experts put forward 46 research questions. The most pressing research priority cluster concerned the causality of the relationship between PA and cognitive/academic performance. The remaining clusters pertained to PA characteristics, moderators and mechanisms governing the ‘PA–performance’ relationship and miscellaneous topics.

Conclusion

There is currently inconclusive evidence for the beneficial effects of PA interventions on cognitive and overall academic performance in children. We conclude that there is strong evidence for beneficial effects of PA on maths performance.

The expert panel confirmed that more ‘high-quality’ research is warranted. By prioritising the most important research questions and formulating recommendations we aim to guide researchers in generating high-quality evidence. Our recommendations focus on adequate control groups and sample size, the use of valid and reliable measurement instruments for physical activity and cognitive performance, measurement of compliance and data analysis.

PROSPERO registration number

CRD42017082505.
Reviewing progress in public involvement in NIHR research: developing and implementing a new vision for the future
Authors: Staniszewska Sophie , Denegri Simon , Matthews Rachel , Minogue Virginia
Published: July 2018

Objectives

To review the progress of public involvement (PPI) in NIHR (National Institute for Health Research) research, identify barriers and enablers, reflect on the influence of PPI on the wider health research system in the UK and internationally and develop a vision for public involvement in research for 2025. The developing evidence base, growing institutional commitment and public involvement activity highlight its growth as a significant international social movement.

Design

The ‘Breaking Boundaries Review’ was commissioned by the Department of Health. An expert advisory panel was convened. Data sources included: an online survey, international evidence sessions, workshop events, open submission of documents and supporting materials and existing systematic reviews. Thematic analysis identified key themes. NVivo was used for data management. The themes informed the report’s vision, mission and recommendations, published as ‘Going the Extra Mile—Improving the health and the wealth of the nation through public involvement in research’. The Review is now being implemented across the NIHR.

Results

This paper reports the Review findings, the first of its type internationally. A range of barriers and enablers to progress were identified, including attitudes, resources, infrastructure, training and support and leadership. The importance of evidence to underpin practice and continuous improvement emerged. Co-production was identified as a concept central to strengthening public involvement in the future. The Vision and Mission are supported by four suggested measures of success, reach, refinement, relevance and relationships.

Conclusions

The NIHR is the first funder of its size and importance globally to review its approach to public involvement. While significant progress has been made, there is a need to consolidate progress and accelerate the spread of effective practice, drawing on evidence. The outcomes of the Review are being implemented across the NIHR. The findings and recommendations have transferability for other organisations, countries and individuals.
Global implementation survey of Integrated Management of Childhood Illness (IMCI): 20 years on
Authors: Boschi-Pinto Cynthia , Labadie Guilhem , Dilip Thandassery Ramachandran , Oliphant Nicholas , Dalglish Sarah L , Aboubaker Samira , Agbodjan-Prince Olga Adjoa , Desta Teshome , Habimana Phanuel , Butron-Riveros Betzabe , Al-Raiby Jamela , Siddeeg Khalid , Kuttumuratova Aigul , Weber Martin , Mehta Rajesh , Raina Neena , Daelmans Bernadette , Diaz Theresa
Published: July 2018

Objective

To assess the extent to which Integrated Management of Childhood Illness (IMCI) has been adopted and scaled up in countries.

Setting

The 95 countries that participated in the survey are home to 82% of the global under-five population and account for 95% of the 5.9 million deaths that occurred among children less than 5 years of age in 2015; 93 of them are low-income and middle-income countries (LMICs).

Methods

We conducted a cross-sectional self-administered survey. Questionnaires and data analysis focused on (1) giving a general overview of current organisation and financing of IMCI at country level, (2) describing implementation of IMCI’s three original components and (3) reporting on innovations, barriers and opportunities for expanding access to care for children. A single data file was created using all information collected. Analysis was performed using STATA V.11.

Participants

In-country teams consisting of representatives of the ministry of health and country offices of WHO and Unicef.

Results

Eighty-one per cent of countries reported that IMCI implementation encompassed all three components. Almost half (46%; 44 countries) reported implementation in 90% or more districts as well as all three components in place (full implementation). These full-implementer countries were 3.6 (95% CI 1.5 to 8.9) times more likely to achieve Millennium Development Goal 4 than other (not full implementer) countries. Despite these high reported implementation rates, the strategy is not reaching the children who need it most, as implementation is lowest in high mortality countries (39%; 7/18).

Conclusion

This survey provides a unique opportunity to better understand how implementation of IMCI has evolved in the 20 years since its inception. Results can be used to assist in formulating strategies, policies and activities to support improvements in the health and survival of children and to help achieve the health-related, post-2015 Sustainable Development Goals.
Scoping review assessing the evidence used to support the adoption of mobile health (mHealth) technologies for the education and training of community health workers (CHWs) in low-income and middle-income countries
Authors: Winters Niall , Langer Laurenz , Geniets Anne
Published: July 2018

Objectives

Undertake a systematic scoping review to determine how a research evidence base, in the form of existing systematic reviews in the field of mobile health (mHealth), constitutes education and training for community health workers (CHWs) who use mobile technologies in everyday work. The review was informed by the following research questions: does educational theory inform the design of the education and training component of mHealth interventions? How is education and training with mobile technology by CHWs in low-income and middle-income countries categorised by existing systematic reviews? What is the basis for this categorisation?

Setting

The review explored the literature from 2000 to 2017 to investigate how mHealth interventions have been positioned within the available evidence base in relation to their use of formal theories of learning.

Results

The scoping review found 24 primary studies that were categorised by 16 systematic reviews as supporting CHWs’ education and training using mobile technologies. However, when formal theories of learning from educational research were used to recategorise these 24 primary studies, only four could be coded as such. This identifies a problem with how CHWs’ education and training using mobile technologies is understood and categorised within the existing evidence base. This is because there is no agreed on, theoretically informed understanding of what counts as learning.

Conclusion

The claims made by mHealth researchers and practitioners regarding the learning benefits of mobile technology are not based on research results that are underpinned by formal theories of learning. mHealth suffers from a reductionist view of learning that underestimates the complexities of the relationship between pedagogy and technology. This has resulted in miscategorisations of what constitutes CHWs’ education and training within the existing evidence base. This can be overcome by informed collaboration between the health and education communities.
Effect of multiple risk behaviours in adolescence on educational attainment at age 16 years: a UK birth cohort study
Authors: Wright Caroline , Kipping Ruth , Hickman Matthew , Campbell Rona , Heron Jon
Published: July 2018

Objectives

To explore the association between adolescent multiple risk behaviours (MRBs) and educational attainment.

Design

Prospective population-based UK birth cohort study.

Setting

Avon Longitudinal Study of Parents and Children (ALSPAC), a UK birth cohort of children born in 1991–1992.

Participants

Data on some or all MRB measures were available for 5401 ALSPAC participants who attended a clinic at age 15 years and/or completed a detailed questionnaire at age 16 years. Multiple imputation was used to account for missing data.

Primary outcome measures

Capped General Certificate of Secondary Education (GCSE) score and odds of attaining five or more GCSE examinations at grades A*–C. Both outcome measures come from the National Pupil Database and were linked to the ALSPAC data.

Results

Engagement in MRB was strongly associated with poorer educational attainment. Each additional risk equated to −6.31 (95% CI −7.03 to −5.58, p<0.001) in capped GCSE score, equivalent to a one grade reduction or reduced odds of attaining five or more A*–C grades of 23% (OR 0.77, 95% CI 0.74 to 0.81, p<0.001). The average cohort member engaged in 3.24 MRB and therefore have an associated reduction in GCSE score equivalent to three and a half grades in one examination, or reduced odds of attaining five or more A*–C grades of 75%.

Conclusion

Engagement in adolescent MRB is strongly associated with poorer educational attainment at 16 years. Preventing MRB could improve educational attainment and thereby directly and indirectly improve longer-term health.
Investigating the discriminative value of Early Warning Scores in patients with respiratory disease using a retrospective cohort analysis of admissions to Nottingham University Hospitals Trust over a 2-year period
Authors: Forster Sarah , Housley Gemma , McKeever Tricia M , Shaw Dominick E
Published: July 2018

Objective

Early Warning Scores (EWSs) are used to monitor patients for signs of imminent deterioration. Although used in respiratory disease, EWSs have not been well studied in this population, despite the underlying cardiopulmonary pathophysiology often present. We examined the performance of two scoring systems in patients with respiratory disease.

Design

Retrospective cohort analysis of vital signs observations of all patients admitted to a respiratory unit over a 2-year period. Scores were linked to outcome data to establish the performance of the National EWS (NEWS) compared results to a locally adapted EWS.

Setting

Nottingham University Hospitals National Health Service Trust respiratory wards. Data were collected from an integrated electronic observation and task allocation system employing a local EWS, also generating mandatory referrals to clinical staff at set scoring thresholds.

Outcome measures

Projected workload, and sensitivity and specificity of the scores in predicting mortality based on outcome within 24 hours of a score being recorded.

Results

8812 individual patient episodes occurred during the study period. Overall, mortality was 5.9%. Applying NEWS retrospectively (vs local EWS) generated an eightfold increase in mandatory escalations, but had higher sensitivity in predicting mortality at the protocol cut points.

Conclusions

This study highlights issues surrounding use of scoring systems in patients with respiratory disease. NEWS demonstrated higher sensitivity for predicting death within 24 hours, offset by reduced specificity. The consequent workload generated may compromise the ability of the clinical team to respond to patients needing immediate input. The locally adapted EWS has higher specificity but lower sensitivity. Statistical evaluation suggests this may lead to missed opportunities for intervention, however, this does not account for clinical concern independent of the scores, nor ability to respond to alerts based on workload. Further research into the role of warning scores and the impact of chronic pathophysiology is urgently needed.
Epidemiology and aetiologies of cryptococcal meningitis in Africa, 1950–2017: protocol for a systematic review
Authors: Nyazika Tinashe K , Tatuene Joseph Kamtchum , Kenfak-Foguena Alain , Verweij Paul E , Meis Jacques F , Robertson Valerie J , Hagen Ferry
Published: July 2018

Introduction

Cryptococcal meningitis is a neglected disease and an AIDS-defining illness, responsible for 15% of all AIDS-related deaths globally. In 2014, the estimated number of incident cryptococcal meningitis cases was 223 100, with 73% of them occurring in Africa. Currently available data on the prevalence, incidence, aetiologies and mortality of cryptococcal meningitis across Africa are sparse and of limited quality. We propose to conduct the first systematic review to summarise the epidemiological data available on cryptococcal meningitis and its aetiological causes in Africa.

Methods and analysis

We will search PubMed, MEDLINE, Excerpta Medica Database, ISI Web of Science, Africa Index Medicus, Cumulative Index to Nursing and Allied Health for studies on cryptococcal meningitis published between 1st January 1950 and 31st December 2017, involving adults and/or children residing in Africa. After study selection, full text paper acquisition and data extraction, we will use validated tools and checklists to assess the quality of reporting and risk of bias for each study. Heterogeneity across studies will be assessed using the χ2test on Cochrane’s Q statistic and a random effect meta-analysis will be used to estimate the overall prevalence, incidence density and mortality of cryptococcal meningitis across studies with similar characteristics. This protocol is prepared and presented in accordance with the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Reporting of the results will be compliant with the Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) guidelines.

Ethics and dissemination

There is no requirement for ethical approval since we will be using data from published studies. The final report will be published in a peer-reviewed journal and further presented at conferences. This study is expected to provide useful contextual estimates needed to inform treatment policies on the African continent and assess the impact of diagnostic and prevention strategies on the burden of cryptococcal meningitis in the post antiretroviral therapy era.

PROSPERO registration number

CRD42017081312.
Exploring the role of regulation and the care of older people with depression living in long-term care? A systematic scoping review protocol
Authors: Crick Michelle , Angus Douglas E , Backman Chantal
Published: July 2018

Introduction

This systematic scoping review will explore the role of regulation on the care of older people living with depression in long-term care. Depression presents a significant burden to older people living in long-term care. Regulation in the long-term care sector has increased, but there are still concerns about quality of care in the sector.

Methods and analysis

Using Arksey and O’Malley’s scoping review methodology as a guide, our scoping review will search several databases: Embase; MEDLINE (using the OVID platform); Psych info; Ageline; and CINAHL, alongside the grey literature. An expert librarian has assisted the research team, using the Peer Review of Electronic Search Strategies, to assess the search strategy. The research team has formulated search strategies and two reviewers will independently screen studies for final study selection. We will summarise extracted data in tabular format; use a narrative format to describe their relevance; and finally, identify knowledge gaps and topics for future research.

Ethics and dissemination

This scoping review will outline the scope of the existing literature related to the influence of regulation on the care of older people living with depression in long-term care. The scoping review findings will be disseminated through publication in a peer-reviewed journal. The findings will be useful to policy-makers, managers and clinicians working in the long-term care sector.
Costs and effects of on-demand treatment of hereditary angioedema in Italy: a prospective cohort study of 167 patients
Authors: Federici Carlo , Perego Francesca , Borsoi Ludovica , Crosta Valentina , Zanichelli Andrea , Gidaro Antonio , Tarricone Rosanna , Cicardi Marco
Published: July 2018

Objectives

To explore treatment behaviours in a cohort of Italian patients with hereditary angioedema due to complement C1-inhibitor deficiency (C1-INH-HAE), and to estimate how effects and costs of treating attacks in routine practice differed across available on-demand treatments.

Design

Cost analyses and survival analyses using attack-level data collected prospectively for 1 year.

Setting

National reference centre for C1-INH-HAE.

Participants

167 patients with proved diagnosis of C1-INH-HAE, who reported data on angioedema attacks, including severity, localisation and duration, treatment received, and use of other healthcare services.

Interventions

Attacks were treated with either icatibant, plasma-derived C1-INH (pdC1-INH) or just supportive care.

Main outcome measures

Treatment efficacy in reducing attack duration and the direct costs of acute attacks.

Results

Overall, 133 of 167 patients (79.6%) reported 1508 attacks during the study period, with mean incidence of 11 attacks per patient per year. Only 78.9% of attacks were treated in contrast to current guidelines. Both icatibant and pdC1-INH significantly reduced attack duration compared with no treatment (median times from onset 7, 10 and 47 hours, respectively), but remission rates with icatibant were 31% faster compared with pdC1-INH (HR 1.31, 95% CI 1.14 to 1.51). However, observed treatment behaviours suggest patterns of suboptimal dosing for pdC1-INH. The average cost per attack was €1183 (SD €789) resulting in €1.58 million healthcare costs during the observation period (€11 912 per patient per year). Icatibant was 54% more expensive than pdC1-INH, whereas age, sex and prophylactic treatment were not associated to higher or lower costs.

Conclusions

Both icatibant and pdC1-INH significantly reduced attack duration compared with no treatment, however, icatibant was more effective but also more expensive. Treatment behaviours and suboptimal dosing of pdC1-INH may account for the differences, but further research is needed to define their role.
Patient safety issues and concerns in Bhutan’s healthcare system: a qualitative exploratory descriptive study
Authors: Pelzang Rinchen , Hutchinson Alison M
Published: July 2018

Objectives

To investigate what healthcare professionals perceived and experienced as key patient safety concerns in Bhutan’s healthcare system.

Design

Qualitative exploratory descriptive inquiry.

Settings

Three different levels of hospitals, a training institute and the Ministry of Health, Bhutan.

Participants

In total, 140 healthcare professionals and managers.

Methods

Narrative data were collected via conversational in-depth interviews and Nominal Group Meetings. All data were subsequently analysed using thematic analysis strategies.

Results

The data revealed that medication errors, healthcare-associated infections, diagnostic errors, surgical errors and postoperative complications, laboratory/blood testing errors, falls, patient identification and communication errors were perceived as common patient safety concerns. Human and system factors were identified as contributing to these concerns. Instituting clinical governance, developing and improving the physical infrastructure of hospitals, providing necessary human resources, ensuring staff receive patient safety education and promoting ‘good’ communication and information systems were, in turn, all identified as processes and strategies critical to improving patient safety in the Bhutanese healthcare system.

Conclusion

Patient safety concerns described by participants in this study were commensurate with those identified in other low and middle-income countries. In order to redress these concerns, the findings of this study suggest that in the Bhutanese context patient safety needs to be conceptualised and prioritised.
Responsive and Equitable Health Systems—Partnership on Non-Communicable Diseases (RESPOND) study: a mixed-methods, longitudinal, observational study on treatment seeking for hypertension in Malaysia and the Philippines
Authors: Palafox Benjamin , Seguin Maureen L , McKee Martin , Dans Antonio L , Yusoff Khalid , Candari Christine J , Idris Khairuddin , Ismail Johan Rizwal , Krauss Steven Eric , Lasco Gideon , Majid Fadhlina A , Palileo-Villanueva Lia M , Razak Azlina A , Renedo Alicia , Balabanova Dina
Published: July 2018

Introduction

Hypertension is a leading contributor to the global burden of disease. While safe and effective treatment exists, blood pressure control is poor in many countries, often reflecting barriers at the levels of health systems and services as well as at the broader level of patients’ sociocultural contexts. This study examines how these interact to facilitate or hinder hypertension control, taking into account characteristics of service provision components and social contexts.

Methods and analysis

The study, set in Malaysia and the Philippines, builds on two systematic reviews of barriers to effective hypertension management. People with hypertension (pre-existing and newly diagnosed) will be identified in poor households in 24–30 communities per country. Quantitative and qualitative methods will be used to examine their experiences of and pathways into seeking and obtaining care. These include two waves of household surveys of 20–25 participants per community 12–18 months apart, microcosting exercises to assess the cost of illness (including costs due to health seeking activities and inability to work (5 per community)), preliminary and follow-up in-depth interviews and digital diaries with hypertensive adults over the course of a year (40 per country, employing an innovative mobile phone technology), focus group discussions with study participants and structured assessments of health facilities (including formal and informal providers).

Ethics and dissemination

Ethical approval has been granted by the Observational Research Ethics Committee at the London School of Hygiene and Tropical Medicine and the Research Ethics Boards at the Universiti Putra Malaysia and the University of the Philippines Manila. The project team will disseminate findings and engage with a wide range of stakeholders to promote uptake and impact. Alongside publications in high-impact journals, dissemination activities include a comprehensive stakeholder analysis, engagement with traditional and social media and ‘digital stories’ coproduced with research participants.
Novel aspiration catheter design for acute stroke thrombectomy
Authors: Long Troy D , Kallmes David F , Hanel Ricardo , Shigematsu Tomoyoshi , Halaszyn Alexander Michael , Wolter Julia , Berenstein Alejandro
Published: July 2018

Background

Navigable, large diameter aspiration catheters demonstrate markedly improved recanalization rates over smaller lumen devices in suction embolectomy. We evaluated the performance of a novel aspiration catheter system designed to maximize lumen size, and compare it to other commercially available aspiration catheters.

Methods

The 6F R4Q aspiration catheter system comprises a proximal pusher wire of 117 cm length connected to a distal catheter of 25 cm length. When placed through standard guide catheters and into the cerebral circulation, the proximal catheter makes a tight seal between its outer surface and the guide catheter’s inner surface. During aspiration, in vitro flow rates and tip suction force under gentle retraction were compared among 10 commercially available aspiration catheters and the R4Q system.

Results

The R4Q 6F, 5F, 4F, and 3F catheters achieved flow rates at least 21.9%, 24.7%, 61.9%, and 244.7% greater than the other catheters tested respectively and the R4Q 6F produced a 140.2% higher tip force than a catheter of similar size. Fluid flow rate in the R4Q 6F increased on retraction into the guide catheter, delivering a 58.2% increase from fully extended to fully retracted.

Conclusion

The R4Q design demonstrates a substantial increase in aspirated flow rate and suction force due to an increased effective diameter than standard tubular catheter designs tested. The prominent increase in the aspiration parameters measured in vitro supports the potential for improved clinical results during stroke thrombectomy procedures.
ADAPT technique with ACE68 and ACE64 reperfusion catheters in ischemic stroke treatment: results from the PROMISE study
Authors: Schramm Peter , Navia Pedro , Papa Rosario , Zamarro Joaquin , Tomasello Alejandro , Weber Werner , Fiehler Jens , Michel Patrik , Pereira Vitor M , Krings Timo , Gralla Jan , Santalucia Paola , Pierot Laurent , Lo T H
Published: July 2018

Background and purpose

The recent randomized trials demonstrated the benefit of mechanical thrombectomy in stroke therapy. However, treatment using different strategies is an ongoing area of investigation. The PROMISE study analyzed the safety and effectiveness of the Penumbra System with the ACE68 and ACE64 reperfusion catheters in aspiration thrombectomy of stroke, using A Direct Aspiration First Pass Technique (ADAPT).

Methods

PROMISE was a prospective study which enrolled 204 patients with intracranial anterior circulation large vessel occlusion (LVO) ischemic stroke in 20 centers from February 2016 to May 2017. Initial treatment was with the ACE68/ACE64 catheters within 6 hours of symptom onset. Imaging and safety review was performed by an independent Core Laboratory and a Clinical Events Committee. The primary angiographic outcome was revascularization to mTICI 2b-3 at immediate post-procedure and the primary clinical outcome was 90-day modified Rankin Scale (mRS) score ≤2. Safety assessment included device- and procedure-related serious adverse events (SAEs), symptomatic intracranial hemorrhage (sICH), mortality, and embolization of new territory (ENT).

Results

Enrolled patients had a median age of 74 (IQR 65–80) years and a median admission NIHSS of 16 (IQR 11–20). The post-procedure mTICI 2b-3 revascularization rate was 93.1% and the 90-day mRS 0–2 rate was 61%. Device- and procedure-related SAEs at 24 hours occurred in 1.5% and 3.4%, respectively, 90-day mortality was 7.5%, sICH occurred in 2.9% while ENT occurred in 1.5%.

Conclusions

For frontline therapy of LVO stroke, the ACE68/ACE64 catheters for aspiration thrombectomy were found to be safe and showed similar efficacy to randomized trials using other revascularization techniques.

Clinical Trial Registration

NCT02678169; Pre-results.
Diagnostic performance of PCR assays for the diagnosis of neurosyphilis: a systematic review
Authors: Marks Michael , Lawrence David , Kositz Christian , Mabey David
Published: July 2018

Introduction

Syphilis continues to be a major public health problem and the recent resurgence in syphilis in high-income settings has seen an accompanying increase in cases of neurosyphilis. While the introduction of PCR has had a significant impact on the diagnosis of early syphilis, cerebrospinal fluid (CSF) serological assays remain the most commonly used tests to diagnosis neurosyphilis. We reviewed data on the performance of CSF-PCR for the diagnosis of neurosyphilis.

Methods

We searched Pubmed, Medline, EMBASE and the grey literature for references on PCR in neurosyphilis. We calculated the sensitivity and specificity of PCR compared with reference testing for the diagnosis of neurosyphilis.

Results

We identified 66 articles of which seven met the study inclusion criteria. The sensitivity of PCR for definite neurosyphilis varied between 40% and 70% and specificity between 60% and 100% across the studies. The most commonly used PCR assay targeted Tp47 which had an overall sensitivity of 68% and a specificity of 91.9%.

Discussion

The sensitivity of PCR was low compared with CSF-serological assays but the challenges of evaluating a diagnostic test in the absence of a clear gold standard make definitive interpretation challenging. Most studies were small and not adequately powered highlighting the need for multicentre, multicountry trials to provide adequate statistical power in evaluations of new tests the diagnosis of neurosyphilis.
Phenotypic ASCOD characterisations of ischaemic stroke in the young at an urban tertiary care centre
Authors: Liu Angela , Pirastehfar Mohsen , Yu Daohai , Linares Guillermo
Published: July 2018

Background and purpose

Stroke in young individuals is a serious public health burden. This study aimed to characterise the various phenotypes of ischaemic stroke in a young urban population (≤50 years old) using the ASCOD classification system, which assigns a score to five stroke categories: atherosclerosis, small vessel disease (SVD), cardioembolism, other and dissection. Within each category, a numerical score represents the degree of causality attributed to the stroke.

Methods

This retrospective study cohort was composed of patients from an urban tertiary care academic centre. Cases were selected by searching Get With the Guidelines database for adults ≤50 years old with ischaemic stroke. The study sample included 175 ischaemic strokes in 157 patients, with 16 subjects re-infarcting. Using retrospective chart review, each stroke was scored according to the ASCOD classification system. Multivariable logistic regression analyses were performed to explore each ASCOD category’s association with causal risk factors.

Results

Of possible causal mechanisms, defined as receiving a grade 1 or 2, a cardiovascular aetiology was most prevalent (25.7%), followed by SVD (22.3%), and closely by atherosclerosis (21.1%). Of general phenotypes, defined as receiving a grade 1 or 2 or 3, atherosclerosis was the most prevalent (51.4%), followed by SVD (47.4%), cardioembolism (42.3%) and other (35.4%). 31.6% of all strokes were of unclear aetiology. Subjects between 45 and 50 years old were more likely to develop a cardioembolic or SVD stroke when compared with subjects <45 years old.

Conclusion

This study took a novel approach to ASCOD phenotyping, allowing several observations: (1) In patients with advanced atherosclerosis receiving the score A1, the vast majority had systemic atherosclerosis in multiple vascular territories; (2) the cardiac score C2(6), defined as a radiographic pattern highly suggestive of a central embolic source, may overestimate the prevalence of true cardiac disease; (3) incidental laboratory findings may detect some underlying pathology, but causality to the stroke is unlikely.
Environmental exposures and systemic hypertension are risk factors for decline in lung function
Authors: Miele Catherine H , Grigsby Matthew R , Siddharthan Trishul , Gilman Robert H , Miranda J Jaime , Bernabe-Ortiz Antonio , Wise Robert A , Checkley William
Published: July 2018

Background

Chronic lung disease is a leading contributor to the global disease burden; however, beyond tobacco smoke, we do not fully understand what risk factors contribute to lung function decline in low-income and middle-income countries.

Methods

We collected sociodemographic and clinical data in a randomly selected, age-stratified, sex-stratified and site-stratified population-based sample of 3048 adults aged ≥35 years from four resource-poor settings in Peru. We assessed baseline and annual pre-bronchodilator and post-bronchodilator lung function over 3 years. We used linear mixed-effects models to assess biological, socioeconomic and environmental risk factors associated with accelerated lung function decline.

Results

Mean±SD enrolment age was 55.4±12.5 years, 49.2% were male and mean follow-up time was 2.36 (SD 0.61) years. Mean annual pre-bronchodilator FEV1 decline was 30.3 mL/year (95% CI 28.6 to 32.0) and pre-bronchodilator FVC decline was 32.2 mL/year (30.0 to 34.4). Using multivariable linear mixed-effects regression, we found that urban living, high-altitude dwelling and having hypertension accounted for 25.9% (95% CI 15.7% to 36.1%), 21.3% (11.1% to 31.5%) and 15.7% (3.7% to 26.9%) of the overall mean annual decline in pre-bronchodilator FEV1/height2, respectively. Corresponding estimates for pre-bronchodilator FVC/height2 were 42.1% (95% CI% 29.8% to 54.4%), 36.0% (23.7% to 48.2%) and 15.8% (2.6% to 28.9%) of the overall mean annual decline, respectively.

Conclusion

Urbanisation, living at high altitude and hypertension were associated with accelerated lung function decline in a population with low daily smoking prevalence.
The human cortical autonomic network and volitional exercise in health and disease
Authors: Al-Khazraji Baraa K. , Shoemaker J. Kevin
Published: July 2018

The autonomic nervous system elicits continuous beat-by-beat homeostatic adjustments to cardiovascular control. These modifications are mediated by sensory inputs (e.g., baroreceptors, metaboreceptors, pulmonary, thermoreceptors, and chemoreceptors afferents), integration at the brainstem control centres (i.e., medulla), and efferent autonomic neural outputs (e.g., spinal, preganglionic, and postganglionic pathways). However, extensive electrical stimulation and functional imaging research show that the brain’s higher cortical regions (e.g., insular cortex, medial prefrontal cortex, anterior cingulate cortex) partake in homeostatic regulation of the cardiovascular system at rest and during exercise. We now appreciate that these cortical areas form a network, namely the “cortical autonomic network” (CAN), which operate as part of a larger central autonomic network comprising 2-way communication of cortical and subcortical areas to exert autonomic influence. Interestingly, differential patterns of CAN activity and ensuing cardiovascular control are present in disease states, thereby highlighting the importance of considering the role of CAN as an integral aspect of cardiovascular regulation in health and disease. This review discusses current knowledge on human cortical autonomic activation during volitional exercise, and the role of exercise training on this activation in both health and disease.