bluuebunny/crossref_metadata_2025 huggingface dataset:
Interplay of cardiac remodelling and myocardial stiffness in hypertensive heart disease: a shear wave imaging study using high-frame rate echocardiography
Authors: Cvijic Marta , Bézy Stéphanie , Petrescu Aniela , Santos Pedro , Orlowska Marta , Chakraborty Bidisha , Duchenne Jürgen , Pedrosa João , Vanassche Thomas , D’hooge Jan , Voigt Jens-Uwe
Published: July 2019

Aims

To determine myocardial stiffness by means of measuring the velocity of naturally occurring myocardial shear waves (SWs) at mitral valve closure (MVC) and investigate their changes with myocardial remodelling in patients with hypertensive heart disease.

Methods and results

Thirty-three treated arterial hypertension (HT) patients with hypertrophic left ventricular (LV) remodelling (59 ± 14 years, 55% male) and 26 aged matched healthy controls (55±15 years, 77% male) were included. HT patients were further divided into a concentric remodelling (HT1) group (13 patients) and a concentric hypertrophy (HT2) group (20 patients). LV parasternal long-axis views were acquired with an experimental ultrasound scanner at 1266 ± 317 frames per seconds. The SW velocity induced by MVC was measured from myocardial acceleration maps. SW velocities differed significantly between HT patients and controls (5.83 ± 1.20 m/s vs. 4.04 ± 0.96 m/s; P < 0.001). In addition, the HT2 group had the highest SW velocities (P < 0.001), whereas values between controls and the HT1 group were comparable (P = 0.075). Significant positive correlations were found between SW velocity and LV remodelling (interventricular septum thickness: r = 0.786, P < 0.001; LV mass index: r = 0.761, P < 0.001). SW velocity normalized for wall stress indicated that myocardial stiffness in the HT2 group was twice as high as in controls (P < 0.001), whereas values of the HT1 group overlapped with the controls (P = 1.00).

Conclusions

SW velocity as measure of myocardial stiffness is higher in HT patients compared with healthy controls, particularly in advanced hypertensive heart disease. Patients with concentric remodelling have still normal myocardial properties whereas patients with concentric hypertrophy show significant stiffening.
Space closure versus space opening for bilateral absent upper lateral incisors: what is the duration of orthodontic treatment?
Authors: Seehra Jadbinder , Al-Ali Anwar , Pandis Nikolaos , Cobourne Martyn T
Published: July 2019

Background

Assessment of orthodontic treatment outcomes such as treatment duration in patients with hypodontia are lacking.

Objectives

To assess the overall treatment duration of cases of bilateral absent upper lateral incisors treated with either orthodontic space closure (SC) or space opening (SO). The secondary aim was to determine factors which influence overall treatment duration.

Subjects and methods

A retrospective cohort study was undertaken within the Orthodontic department at Kings College Hospital NHS Foundation Trust. Consecutively treated patients between 2008 and 2018 with bilateral absent upper lateral incisors were identified from clinic lists, clinical logbooks, and multidisciplinary clinics. All study data variables were collected by a single investigator using a pre-specified data collection sheet.

Results

In total, 52 cases were included, 29 in the SC group and 23 in the SO group. Overall non-extraction treatment was favoured (P = 0.001) with differences in restorations provided post-treatment evident (P = 0.01). Although not statistically significant, the mean overall orthodontic treatment duration was less in the SC group 25.7 months (SD 7.6) compared to the SO group 27.4 (SD 6.1). Overall treatment duration was reduced if treatment was carried out on an extraction basis (−7.02, 95% CI: −11.93, 2.11, P = 0.01) but increased as the amount of crowding in the lower arch increased (0.89, 95% CI: 0.08, 1.71, P = 0.03).

Conclusions

Within the study limitations, there is no difference in the overall treatment duration between both treatment approaches. Treatment duration is reduced in both SO or SC treatment plans if extractions are undertaken. The presence of lower arch crowding increases the duration of treatment.
Out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation in patients with normal electrocardiograms: results from a multicentre long-term registry
Authors: Conte Giulio , Belhassen Bernard , Lambiase Pier , Ciconte Giuseppe , de Asmundis Carlo , Arbelo Elena , Schaer Beat , Frontera Antonio , Burri Haran , Calo’ Leonardo , Letsas Kostantinos P , Leyva Francisco , Porter Bradley , Saenen Johan , Zacà Valerio , Berne Paola , Ammann Peter , Zardini Marco , Luani Blerim , Rordorf Roberto , Sarquella Brugada Georgia , Medeiros-Domingo Argelia , Geller Johann-Christoph , de Potter Tom , Stokke Mathis K , Márquez Manlio F , Michowitz Yoav , Honarbakhsh Shohreh , Conti Manuel , Sticherling Christian , Martino Annamaria , Zegard Abbasin , Özkartal Tardu , Caputo Maria Luce , Regoli François , Braun-Dullaeus Rüdiger C , Notarangelo Francesca , Moccetti Tiziano , Casu Gavino , Rinaldi Christopher A , Levinstein Moises , Haugaa Kristina H , Derval Nicolas , Klersy Catherine , Curti Moreno , Pappone Carlo , Heidbuchel Hein , Brugada Josép , Haïssaguerre Michel , Brugada Pedro , Auricchio Angelo
Published: July 2019

Aims 

To define the clinical characteristics and long-term clinical outcomes of a large cohort of patients with idiopathic ventricular fibrillation (IVF) and normal 12-lead electrocardiograms (ECGs).

Methods and results

Patients with ventricular fibrillation as the presenting rhythm, normal baseline, and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular conduction abnormalities, and without structural heart disease were included in a registry. A total of 245 patients (median age: 38 years; males 59%) were recruited from 25 centres. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25–110 months), 12 patients died (5%); in four of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, P = 0.001). Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.18–0.92; P = 0.03].

Conclusion 

Patients with IVF and persistently normal ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences.
Arrhythmia development during inhibition of small-conductance calcium-activated potassium channels in acute myocardial infarction in a porcine model
Authors: Lubberding Anniek F , Sattler Stefan M , Grunnet Morten , Sørensen Ulrik S , Tfelt-Hansen Jacob , Jespersen Thomas
Published: July 2019

Aims 

Acute myocardial infarction (AMI) is associated with intracellular Ca2+ build-up. In healthy ventricles, small conductance Ca2+-activated K+ (SK) channels are present but do not participate in repolarization. However, SK current is increased in chronic myocardial infarction and heart failure, and recently, SK channel inhibition was demonstrated to reduce arrhythmias in AMI rats. Hence, we hypothesized that SK channel inhibitors (NS8593 and AP14145) could reduce arrhythmia development during AMI in a porcine model.

Methods and results 

Twenty-seven pigs were randomized 1:1:1 to control, NS8593, or AP14145. Haemodynamic and electrophysiological parameters [electrocardiogram (ECG) and monophasic action potentials (MAP)] were continuously recorded. A balloon was placed in the mid-left anterior descending artery, blinded to treatment. Infusion lasted from 10 min before occlusion until 30 min after. Occlusion was maintained for 1 h, followed by 2 h of reperfusion. Upon occlusion, cardiac output dropped similarly in all groups, while blood pressure remained stable. Heart rate decreased in the NS8593 and AP14145 groups. QRS duration increased upon occlusion in all groups but more prominently in AP14145-treated pigs. Inhibition of SK channels did not affect QT interval. Infarct MAP duration shortened comparably in all groups. Ventricular fibrillation developed in 4/9 control-, 4/9 AP14145-, and 2/9 NS8593-treated pigs. Ventricular tachycardia was rarely observed in either group, whereas ventricular extrasystoles occurred comparably in all groups.

Conclusion 

Inhibition of SK channels was neither beneficial nor detrimental to ventricular arrhythmia development in the setting of AMI in this porcine model.
Explanations for medically unexplained symptoms: a qualitative study on GPs in daily practice consultations
Authors: Terpstra Tom , Gol Janna M , Lucassen Peter L B J , Houwen Juul , van Dulmen Sandra , Berger Marjolein Y , Rosmalen Judith G M , olde Hartman Tim C
Published: July 2019

Background

General practice is the centre of care for patients with medically unexplained symptoms (MUS). Providing explanations for MUS, i.e. making sense of symptoms, is considered to be an important part of care for MUS patients. However, little is known how general practitioners (GPs) do this in daily practice.

Objective

This study aimed to explore how GPs explain MUS to their patients during daily general practice consultations.

Methods

A thematic content analysis was performed of how GPs explained MUS to their patients based on 39 general practice consultations involving patients with MUS.

Results

GP provided explanations in nearly all consultations with MUS patients. Seven categories of explanation components emerged from the data: defining symptoms, stating causality, mentioning contributing factors, describing mechanisms, excluding explanations, discussing the severity of symptoms and normalizing symptoms. No pattern of how GPs constructed explanations with the various categories was observed. In general, explanations were communicated as a possibility and in a patient-specific way; however, they were not very detailed.

Conclusion

Although explanations for MUS are provided in most MUS consultations, there seems room for improving the explanations given in these consultations. Further studies on the effectiveness of explanations and on the interaction between patients and GP in constructing these explanations are required in order to make MUS explanations more suitable in daily primary care practice.
Barriers and facilitators to the timely diagnosis of endometriosis in primary care in the Netherlands
Authors: van der Zanden Moniek , Teunissen Doreth A M , van der Woord Inger W , Braat Didi D M , Nelen Willianne L D M , Nap Annemiek W
Published: July 2019

Background

Endometriosis is an invalidating gynaecological condition in women of reproductive age, and a frequent cause of infertility. Unfortunately, the condition is characterized by a long interval between onset of symptoms and diagnosis. GPs in the Netherlands are educated to provide basic gynaecological care and serve as gatekeepers for specialist medical care. Therefore, it is of great importance that they recognize signs and symptoms possibly caused by endometriosis to initiate adequate actions.

Objective

The main objective of this study was to identify barriers and facilitators to the timely diagnosis of endometriosis from the GPs’ perspective.

Methods

Semi-structured focus group discussions with GPs were organized throughout the Netherlands. The participants were encouraged to brainstorm about their perspective on daily practice regarding endometriosis and suggestions for interventions to enable early diagnosis and treatment. Analysis was based on grounded theory methodology.

Results

Forty-three GPs participated in six focus groups. Analysis of the transcripts revealed relevant determinants of practice in four main themes: professionals’ experience and competence, patient characteristics, guideline factors and professional collaboration. A lack of knowledge and awareness appeared to result in a low priority for establishing the diagnosis of endometriosis, especially in young women. Infertility, patient engagement and a recent serious case or training facilitated referral.

Conclusion

Several factors in daily primary health care contribute to the diagnostic delay in endometriosis. Future interventions to reduce this delay may be aimed at increasing awareness by means of education, incorporating the subject into national clinical guidelines and improvements in interdisciplinary collaboration.
Defending sovereignty without collaboration: Vichy and the Italian Fascist threats of 1940–1942
Authors: Varley Karine
Published: July 2019

This article asks how Vichy sought to defend French sovereignty against Italian threats across those unoccupied areas of France and its colonial empire which were covered by the Italian armistice between June 1940 and November 1942. It suggests that, while Vichy’s response to German violations of French sovereignty was limited by its policy of collaboration, no such constraints were in place when it came to Italian interventions. Despite this, however, the defence of French sovereignty against Italian threats was not a straightforward story of defiance. Opposing Italian actions in one policy domain in one territory had to be weighed against the potential repercussions in another policy domain in another territory. It also had to be calibrated with the implications for French relations with Berlin. The Italian dimension to Vichy’s actions therefore suggests that the biggest challenge in negotiations was not Vichy’s desire to defend its sovereign status so much as the lure of collaboration.
Challenges, tactics and integrated management of emerald ash borer in North America
Authors: McCullough Deborah G
Published: July 2019

Emerald ash borer (EAB) (Agrilus planipennis Fairmaire), discovered in southeastern Michigan, USA in 2002, has become the most destructive and costly invasive forest insect in North America. This phloem-boring beetle has also invaded Moscow, Russia and continued spread of EAB potentially threatens European ash (Fraxinus spp.) species. This review summarizes EAB life history, including interspecific variation in host preference, invasion impacts and challenges of detecting new infestations and provides an overview of available management tactics. Advances in systemic insecticides, particularly emamectin benzoate products applied via trunk injection, have yielded effective and practical options both to protect individual trees and to slow EAB population growth and ash decline on an area-wide basis without disrupting natural enemies. Economic costs of treating ash are substantially lower than removal costs, retain ecosystem services provided by the trees, reduce sociocultural impacts and conserve genetic diversity in areas invaded by EAB. Girdled ash trees are highly attractive to EAB adults in low-density populations and debarking small girdled trees to locate larval galleries is the most effective EAB detection method. An array of woodpeckers, native larval parasitoids and introduced parasitoids attack EAB life stages but mortality is highly variable. Area-wide management strategies that integrate insecticide-treated trees, girdled ash trap trees and biological control can be adapted for local conditions to slow and reduce EAB impacts.
Genes Related to Education Predict Frailty Among Older Adults in the United States
Authors: Huibregtse Brooke M , Newell-Stamper Breanne L , Domingue Benjamin W , Boardman Jason D
Published: July 2019

Objective

This article expands on research that links education and frailty among older adults by considering the role of genes associated with education.

Method

Data come from a sample of 7,064 non-Hispanic, white adults participating in the 2004–2012 waves of the Health and Retirement Study. Frailty was measured with two indices: (a) The Frailty Index which corresponds to a deficit accumulation model; and (b) The Paulson–Lichtenberg Frailty Index which corresponds to the biological syndrome/phenotype model. Genes associated with education were quantified using an additive polygenic score. Associations between the polygenic score and frailty indices were tested using a series of multilevel models, controlling for multiple observations for participants across waves.

Results

Results showed a strong and negative association between genes for education and frailty symptoms in later life. This association exists above and beyond years of completed education and we demonstrate that this association becomes weaker as older adults approach their 80s.

Discussion

The results contribute to the education–health literature by highlighting new and important pathways through which education might be linked to successful aging.
Lithospheric structure beneath the central and western North China Craton and adjacent regions from S-receiver function imaging
Authors: Zhang Yaoyang , Chen Ling , Ai Yinshuang , Jiang Mingming
Published: July 2019

To elucidate the nature and extent of the lithospheric modification in the central and western North China Craton (NCC) and adjacent regions, we used the wave equation–based migration technique of S-receiver function on teleseismic data collected from 314 broadband stations in this region to image the lithospheric structure. Incorporating data from previous lithospheric structure studies, we obtained unprecedented high-resolution depth maps of the lithosphere–asthenosphere boundary (LAB) and mid-lithospheric discontinuity (MLD) in the NCC. Our results show more detailed variations of the lithospheric thickness in the central and western NCC and adjacent regions, which ranges from 100 to >170 km, in marked contrast to the thinned lithosphere (60–100 km) in the eastern NCC. Despite its generally thick lithosphere (>130 km), the Ordos Block shows a concordant N–S difference from the surface to deep lithosphere with a boundary at the latitude of 37–38°N. The central NCC is laterally heterogeneous in the lithospheric structure, and the thick lithosphere (∼160 km) in the south is interpreted as a remnant cratonic mantle root. The central Qinling Orogenic Belt preserves a thick lithosphere (∼150 km), which may block the asthenospheric flow driven by extrusion of the Tibetan Plateau to the west of the NCC. Moreover, a negative MLD is widely identified at the depth of 80–110 km within the thick lithosphere, which corroborates the global existence of the MLD in continental regions. The consistence in the depth of the MLD and the shallow LAB in the eastern NCC supports the conjecture that the MLD may have played an important role in the lithospheric modification of the eastern NCC.
Anthropogenic seismicity as aftershocks for geo-resource production? Implications for Mmax estimates (reservoir impoundment cases)
Authors: Grasso J-R , Amorese D , Karimov A
Published: July 2019

Developing a model for anthropogenic seismic hazard remains an open challenge whatever the geo-resource production. We analyse the (Mmax) largest reported magnitude on each site where (RTS) Reservoir Triggered Seismicity in documented (37 events, 1933–2008), for aftershocks of reservoir impoundment loading. We relate each reservoir impoundment to its magnitude-equivalent M*reservoir = M*(Lr). We use (Lr) the reservoir length as a proxy for a rupture length of the reservoir main shock-equivallent. This latter is derived from the empirical relationship that exists for tectonic earthquake among magnitude and rupture length. We resolve (i) Mmax for RTS are bounded by M*reservoir at a 95 per cent confidence level; (ii) in average Mmax are smaller than M*reservoir by 2.2 units (iii) 50 per cent of the Mmax occurrence is within 2 ± 1 yr from the reservoir impoundment. These triggering patterns support the signature of fluid driven seismicity during the slow reservoir impoundment emerges as a weaker efficiency (larger ΔM = M*reservoir – Mmax) to trigger Mmax events than from earthquake interactions.
A generalized Rytov approximation for accurate calculation of phase variation in strong perturbation media
Authors: Feng Bo , Wu Ru-Shan , Wang Huazhong
Published: July 2019

In the case of long-range propagation of forward scattering, due to the accumulation of phase changes caused by the velocity perturbations, the validity of the Born approximation will be violated. In contrast, the phase-change accumulation can be handled by the Rytov approximation, which has been widely used for long-distance propagation with only forward scattering or small-angle scattering involved. However, the weak scattering assumption (i.e. small velocity perturbation) in the Rytov approximation limits its scope of application. To address this problem, we analyse the integral kernel of the Rytov transform using the Wentzel-Kramers-Brillouin-Jeffreys (WKBJ) approximation and we demonstrate that the integral kernel is a function of velocity perturbation and scattering angle. By applying a small scattering angle approximation, we show that the phase variation has a linear relationship with the slowness perturbation, no matter how strong the magnitude of perturbation is. Therefore, the new integral equation is then referred to as the generalized Rytov approximation (GRA) because it overcomes the weak scattering assumption of the Rytov approximation. To show the limitations of the Rytov approximation and the advantages of the proposed GRA method, first we design a two-layer model and we analytically calculate the errors introduced by the small scattering angle assumption using plane wave incidence. We show that the phase (traveltime) variations predicted by the GRA are always more accurate than the Rytov approximation. Particularly, the GRA produces accurate phase variations for the normal incident plane wave regardless of the magnitude of velocity perturbation. Numerical examples using Gaussian anomaly models demonstrate that the scattering angle has a crucial impact on the accuracy of the GRA. If the small scattering angle assumption holds, the GRA can produce an accurate phase approximation even if the velocity perturbation is very strong. On the contrary, both the first-order Rytov approximation and the GRA fail to get satisfying results when the scattering angle is large enough. The proposed GRA method has the potential to be used for traveltime modelling and inversion for large-scale strong perturbation media.
Insights into local health and wellbeing policy process in Australia
Authors: Lilly Kara , Hallett Jonathan , Robinson Suzanne , Selvey Linda A
Published: July 2019

To investigate factors that enable or challenge the initiation and actioning of health and wellbeing policy in Australian local governments using political science frameworks. An online survey was distributed to staff and elected members of Australian local governments. The survey sought responses to a range of variables as informed by political science frameworks. Data were analysed using descriptive statistics and results were compared between local governments of different geographical sizes and locations using Kruskal–Wallis non-parametric testing. There were 1825 survey responses, including 243 CEOs, representing 45% of Australian local governments. Enablers for local government policy initiation and action included the high priority given to health and wellbeing (44%), local leadership (56%) and an organizational (70%) and personal obligation (68%) to the community to act. Less true is a favourable legislative environment (33%), leadership from higher levels of government (29%) and sufficient financial capacity (22%). Cities are better positioned to initiate and action health policy, regardless of the broader legislative environment. Health and wellbeing is a high priority for Australian local governments, despite lack of funding and limited lobbying and support from other sectors and higher levels of government. The insights from political science frameworks assist to understand the policy process, including the interrelatedness of enablers and challenges to initiating and actioning health and wellbeing policy. Further understanding the policy drivers would support practitioners and researchers advocating to influence local health and wellbeing policy.
Space-time analysis of unhealthy food advertising: New Zealand children’s exposure and health policy options
Authors: Liu Wei , Barr Michelle , Pearson Amber L , Chambers Tim , Pfeiffer Karin A , Smith Moira , Signal Louise
Published: July 2019

Reducing children’s exposure to unhealthy food advertising is an accepted strategy to end childhood obesity. This study aimed to (i) measure children’s space-time exposures to unhealthy food advertising in public outdoor spaces, using GPS and wearable cameras; and (ii) test effectiveness of banning options. We compiled data (collected July 2014—June 2015) on 138 12-year-old children in Wellington, New Zealand, using wearable cameras and GPS devices worn over 4 days. In 2017–18, we linked 59 150 images taken in public outdoor spaces to GPS data. Of these, 1631 contained unhealthy food advertising exposures, defined as ≥50% of an advertisement observed in each image. We examined spatial patterns using kernel density mapping and graphed space-time trends. We interpolated a kriged exposure rate across Wellington to estimate exposure reductions for potential bans. Children were exposed to 7.4 (95% CI 7.0–7.8) unhealthy food advertisements/hour spent in outdoor public spaces. Exposures occurred in shopping centres, residential areas and sports facilities, commonly involving fast food, sugary drinks and ice cream. Peak exposure times were weekend afternoons/evenings and weekdays before/after school. In Wellington, we estimated that banning such advertising within 400 m of playgrounds would yield a 33% reduction in exposure, followed by in residential areas (27%), within 400 m of schools (25%), and 50% for a ban combining all above. This work documents the extent of children’s exposure to unhealthy food advertising and the potential impact of bans. Given the ubiquity of advertising in public spaces, this New Zealand research offers innovative methods and findings likely relevant in other jurisdictions.
Progress in the genetic analysis of Parkinson’s disease
Authors: Singleton Andrew , Hardy John
Published: July 2019

The pace of genetic discovery in complex disease has accelerated exponentially over the last decade. Our fund of knowledge of the foundational genetics in disease has never been as great. There is a clear path forward to the resolution of the genetic architecture toward a point at which we will saturate the biological understanding of disease through genetics. This understanding continues to provide fundamental insights into disease biology and, with the advent of new data and methodologies, the path from gene to function is becoming clearer and cleaner. In this opinion piece, we discuss progress in the genetics of Parkinson disease. We explore what genetics has revealed thus far in the context of disease biology. We highlight mitophagy/autophagy, dopamine metabolism and the adaptive immune system. We try and link these findings together to give a holistic view of pathogenesis with the underlying theme that disease pathogenesis relates to a failure of damage response pathways. In the 1990s, Parkinson’s disease wa disorders and diseases. This review highlights recent advances in our understanding of the methylome's functionality and covers potential new roles for DNA methylation, their readers, writers, and erasers. Additionally, we examine novel insights into the relationship between the methylome, DNA–protein interactions, and their contribution to neurodegenerative diseases. Lastly, we outline the gaps in our knowledge that will likely be filled through the widespread use of newer technologies that provide greater resolution into how individual cell types are affected by disease and the contribution of each individual modification site to disease pathogenicity.
The technical risks of human gene editing
Authors: Davies Benjamin
Published: July 2019

A recent report from Dr He Jiankui concerning the birth of twin girls harbouring mutations engineered by CRISPR/Cas nucleases has been met with international condemnation. Beside the serious ethical concerns, there are known technical risks associated with CRISPR/Cas gene editing which further raise questions about how these events could have been allowed to occur. Numerous studies have reported unexpected genomic mutation and mosaicism following the use of CRISPR/Cas nucleases, and it is currently unclear how prevalent these disadvantageous events are and how robust and sensitive the strategies to detect these unwanted events may be. Although Dr Jiankui’s study appears to have involved certain checks to ascertain these risks, the decision to implant the manipulated embryos, given these unknowns, must nonetheless be considered reckless. Here I review the technical concerns surrounding genome editing and consider the available data from Dr Jiankui in this context. Although the data remains unpublished, preventing a thorough assessment of what was performed, it seems clear that the rationale behind the undertaking was seriously flawed; the procedures involved substantial technical risks which, when added to the serious ethical concerns, fully justify the widespread criticism that the events have received.
A Population-Based Study of Combination vs Monotherapy of Anti-TNF in Persons With IBD
Authors: Elias Evan D , Targownik Laura E , Singh Harminder , Bernstein Charles N
Published: July 2019

Background

Few data exist about the utilization of combination therapy (anti–tumor necrosis factor [anti-TNF] plus immunosuppressives) in clinical practice. We assessed the prevalence and predictors of combination therapy use vs anti-TNF monotherapy in inflammatory bowel disease (IBD) in the Canadian province of Manitoba.

Methods

All 23 prescribers of anti-TNF medications for IBD in Manitoba facilitated chart review of their comprehensive lists of adult anti-TNF patients from 2005 to 2015. Subjects were stratified by year of first anti-TNF exposure. Patient, disease, and prescriber factors influencing combination therapy use were explored.

Results

A total of 774 patients met inclusion criteria. Seventy-one point one percent had Crohn’s disease (CD), 28.3% had ulcerative colitis (UC), and 0.6% had IBD unclassified; 45.3% received combination therapy, with no difference between CD and UC. Crohn’s disease subjects receiving combination therapy were more likely to have penetrating or perianal disease (56.9% vs 42.8%; P = 0.001) and less likely to have had previous IBD-related surgeries (36.2% vs 46.2%; P = 0.02). The median age at diagnosis and at anti-TNF initiation was lower among combination therapy users. Adalimumab users were as likely as infliximab users to receive combination therapy but persisted with treatment for a shorter time. The proportion of new anti-TNF users receiving combination therapy did not change over time (P = 0.43). There was substantial variation in combination therapy use between prescribers (P = 0.002). The most frequently encountered reasons for avoiding combination therapy were previous intolerance or ineffectiveness of immunosuppressive monotherapy.

Conclusion

Use of combination therapy has remained unchanged over time despite the publication of high-quality data supporting its efficacy over anti-TNF monotherapy.
Beyond the Powerhouse: Integrating Mitonuclear Evolution, Physiology, and Theory in Comparative Biology
Authors: Havird Justin C , Weaver Ryan J , Milani Liliana , Ghiselli Fabrizio , Greenway Ryan , Ramsey Adam J , Jimenez Ana G , Dowling Damian K , Hood Wendy R , Montooth Kristi L , Estes Suzanne , Schulte Patricia M , Sokolova Inna M , Hill Geoffrey E
Published: July 2019

Eukaryotes are the outcome of an ancient symbiosis and as such, eukaryotic cells fundamentally possess two genomes. As a consequence, gene products encoded by both nuclear and mitochondrial genomes must interact in an intimate and precise fashion to enable aerobic respiration in eukaryotes. This genomic architecture of eukaryotes is proposed to necessitate perpetual coevolution between the nuclear and mitochondrial genomes to maintain coadaptation, but the presence of two genomes also creates the opportunity for intracellular conflict. In the collection of papers that constitute this symposium volume, scientists working in diverse organismal systems spanning vast biological scales address emerging topics in integrative, comparative biology in light of mitonuclear interactions.
Individual Cryptic Scaling Relationships and the Evolution of Animal Form
Authors: Frankino W Anthony , Bakota Eric , Dworkin Ian , Wilkinson Gerald S , Wolf Jason B , Shingleton Alexander W
Published: July 2019

Artificial selection offers a powerful tool for the exploration of how selection and development shape the evolution of morphological scaling relationships. An emerging approach models the expression and evolution of morphological scaling relationships as a function of variation among individuals in the developmental mechanisms that regulate trait growth. These models posit the existence of genotype-specific morphological scaling relationships that are unseen or “cryptic.” Within-population allelic variation at growth-regulating loci determines how these individual cryptic scaling relationships are distributed, and exposure to environmental factors that affect growth determines the size phenotype expressed by each individual on their cryptic, genotype-specific scaling relationship. These models reveal that evolution of the intercept and slope of the population-level static allometry is determined, often in counterintuitive ways, largely by the shape of the distribution of these underlying individual-level scaling relationships. Here we review this modeling framework and present the wing-body size individual cryptic scaling relationships from a population of Drosophila melanogaster. To determine how these models might inform interpretation of published work on scaling relationship evolution, we review studies where artificial selection was applied to alter the parameters of population-level static allometries. Finally, motivated by our review, we outline areas in need of empirical work and describe a research program to address these topics; the approach includes describing the distribution of individual cryptic scaling relationships across populations and environments, empirical testing of the model’s predictions, and determining the effects of environmental heterogeneity on realized trait distributions and how this affects allometry evolution.
Multi-Scale Drivers of Immunological Variation and Consequences for Infectious Disease Dynamics
Authors: Becker Daniel J , Downs Cynthia J , Martin Lynn B
Published: July 2019

The immune system is the primary barrier to parasite infection, replication, and transmission following exposure, and variation in immunity can accordingly manifest in heterogeneity in traits that govern population-level infectious disease dynamics. While much work in ecoimmunology has focused on individual-level determinants of host immune defense (e.g., reproductive status and body condition), an ongoing challenge remains to understand the broader evolutionary and ecological contexts of this variation (e.g., phylogenetic relatedness and landscape heterogeneity) and to connect these differences into epidemiological frameworks. Ultimately, such efforts could illuminate general principles about the drivers of host defense and improve predictions and control of infectious disease. Here, we highlight recent work that synthesizes the complex drivers of immunological variation across biological scales of organization and scales these within-host differences to population-level infection outcomes. Such studies note the limitations involved in making species-level comparisons of immune phenotypes, stress the importance of spatial scale for immunology research, showcase several statistical tools for translating within-host data into epidemiological parameters, and provide theoretical frameworks for linking within- and between-host scales of infection processes. Building from these studies, we highlight several promising avenues for continued work, including the application of machine learning tools and phylogenetically controlled meta-analyses to immunology data and quantifying the joint spatial and temporal dependencies in immune defense using range expansions as model systems. We also emphasize the use of organismal traits (e.g., host tolerance, competence, and resistance) as a way to interlink various scales of analysis. Such continued collaboration and disciplinary cross-talk among ecoimmunology, disease ecology, and mathematical modeling will facilitate an improved understanding of the multi-scale drivers and consequences of variation in host defense.
Innovations in emerging markets: the case of mobile money
Authors: Pelletier Adeline , Khavul Susanna , Estrin Saul
Published: July 2019

Mobile money is a financial innovation that provides transfers, payments, and other financial services at a low or zero cost to individuals in developing countries where banking and capital markets are deficient and financial inclusion is low. We use transaction costs and institutional theories to explain the growth and impact of mobile money. Having developed a new archival dataset that tracks mobile money deployment across 90 emerging economies during 16 years between 2000 and 2015, we address the question of relative economic impact of the banking and telecoms sectors in the provision of mobile money. We show that telecom groups and not banks are more likely to launch mobile money in countries where legal rights are weaker and credit information less prevalent. However, it is when mobile money is offered via a banking channel that the spillover effects on the economy are greater. Findings have significant implications for policy and strategy.
The association of melanoma-associated antigen-A gene expression with clinicopathological characteristics and prognosis in resected non-small-cell lung cancer: a meta-analysis
Authors: Wang Yan , Lu Yuqing , Li Jialong , Wu Yanming , Che Guowei
Published: July 2019

Our goal was to explore the association of melanoma-associated antigen-A (MAGE-A) gene expression with clinicopathological parameters and survival rates in patients with non-small-cell lung cancer (NSCLC) who had surgery. A systematic search of EMBASE, PubMed, Web of Science and The Cochrane Library databases was performed through 20 April 2019. The combined risk ratios (RRs) and hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were calculated to assess the association of MAGE-A gene expression with clinicopathological characteristics and prognosis of patients with resected NSCLC, respectively. All statistical analyses were performed with Stata software, version 12.0. A total of 9 articles involving 1538 patients were included in our meta-analysis; most of the studies were from Asian countries. The results indicated that the expression of the MAGE-A gene was significantly correlated with lymph node metastases (RR 1.21, 95% CI 1.09–1.34; P = 0.001), high tumour-node-metastasis stage (RR 1.24, 95% CI 1.12–1.38; P < 0.001), histological type (squamous cell carcinoma) (RR 1.82, 95% CI 1.15–2.87; P = 0.01), poor overall survival (HR 2.11, 95% CI 1.73–2.57; P < 0.001) and cancer-specific survival (HR 1.76, 95% CI 1.12–2.78; P = 0.015). MAGE-A gene expression is related to tumour development and metastasis and is more prevalent in squamous cell carcinomas of the lung; besides, it is an independent prognostic factor for patients with resected NSCLC.
Theoretical and experimental investigations of different area ratios of a supersonic ejector driven by compressed air
Authors: AL-nuaimi Ahmed , Worall Mark , Riffat Saffa
Published: July 2019

Ejectors have some advantages such as being simple, reliable and no moving parts. They can be used in air-conditioning and refrigeration applications. This paper presents a comparison of ejector performance, primary pressure (Pp), back pressure (Pb) and area ratios of ejectors (A2/At) predictions by an analytical model and a computational fluid dynamics model for different operating conditions. Six different area ratios of ejector using air as working fluid in this study were proposed and tested experimentally. The variable area ratios of ejectors (A2/At) were used with a range from 10.68 to 30.62. Two sets of ejectors (A and C) are studied and examined depend on the kind of nozzle. The aim of this study was to investigate these ejectors under variation of primary pressure (Pp) (1.5–6.0 bar) and adjustable spindle position (0 to −25 mm). Two groups of ejectors (A and C) were categorized based on the type of nozzle. The experimental results validate the solutions of the main parameters of ejectors using air as working fluid. The results show that group A is more appropriate for higher values of back pressure, while group C is more suitable for high performance of the ejector. Finally, the main parameters were carried out on six different ejectors to find the best combination based on various nozzles and constant area sections.
Centre modes in pipe flow
Authors: Ozcakir Ozge , Hall Philip , Tanveer Saleh
Published: July 2019

In two previous papers, Ozcakir, Tanveer, Hall, & Overman (2016, Travelling waves in pipe flow, J. Fluid Mech., 791, 284–328) and Ozcakir, Hall & Tanveer (2019, Nonlinear exact coherent structures in pipe flow and their instabilities, J. Fluid Mech., 868, 341–368) investigated numerically and asymptotically high Reynolds number exact coherent structures in pipe flow. It was found that, in addition to the structures described by the vortex–wave interaction theory by Hall & Smith (1991, On strongly nonlinear vortex/wave interactions in boundary layer transition. J. Fluid Mech., 227, 641–666), there exists vortical structures localized near the centre of the pipe with a core of size $O(Re^{-1/4})$ convected downstream at a speed that deviates from the pipe centreline speed by $O(Re^{-1/2})$, where $Re$ is the Reynolds number. In the finite Reynolds number calculations by Ozcakir, Tanveer, Hall & Overman (2016, Travelling waves in pipe flow, J. Fluid Mech., 791, 284–328), asymptotic state was referred to as a nonlinear viscous core state (NVC). However the reduced asymptotic equations were not solved and only limited confirmation of the theory was found numerically. Here, in order to conclusively confirm the existence of the NVC state we first describe direct numerical calculations on the asymptotically reduced $Re>>1$ equations for such state states. The results are then compared in detail to the finite $Re$ calculations up-to $Re=10^6$; the latter regime is at much higher values of the Reynolds number than those reported in Ozcakir, Tanveer, Hall & Overman (2016, Travelling waves in pipe flow, J. Fluid Mech., 791, 284–328). The results are found to be in excellent agreement with the finite $Re$ calculations in a region between $Re=10^5$ and $10^6$, thereby confirming that the structure observed by Ozcakir, Tanveer, Hall & Overman (2016, Travelling waves in pipe flow, J. Fluid Mech., 791, 284–328) is indeed a finite Reynolds number realization of an asymptotic NVC state.
Evaluation of the Impact of Meningococcal Serogroup A Conjugate Vaccine Introduction on Second-Year-of-Life Vaccination Coverage in Burkina Faso
Authors: Zoma Robert L , Walldorf Jenny A , Tarbangdo Felix , Patel Jaymin C , Diallo Alpha Oumar , Nkwenkeu Sylvain F , Kambou Ludovic , Nikiema Moumouni , Ouedraogo Arnaud , Bationo Ange B , Ouili Romeo , Badolo Hermann , Sawadogo Guetawende , Krishnaswamy Akshaya , Hatcher Cynthia , Hyde Terri B , Aké Flavien , Novak Ryan T , Wannemuehler Kathleen , Mirza Imran , Medah Isaïe , Soeters Heidi M
Published: July 2019

Background

After successful meningococcal serogroup A conjugate vaccine (MACV) campaigns since 2010, Burkina Faso introduced MACV in March 2017 into the routine Expanded Programme for Immunization schedule at age 15–18 months, concomitantly with second-dose measles-containing vaccine (MCV2). We examined MCV2 coverage in pre- and post-MACV introduction cohorts to describe observed changes regionally and nationally.

Methods

A nationwide household cluster survey of children 18–41 months of age was conducted 1 year after MACV introduction. Coverage was assessed by verification of vaccination cards or recall. Two age groups were included to compare MCV2 coverage pre-MACV introduction (30–41 months) versus post-MACV introduction (18–26 months).

Results

In total, 15 925 households were surveyed; 7796 children were enrolled, including 3684 30–41 months of age and 3091 18–26 months of age. Vaccination documentation was observed for 86% of children. The MACV routine coverage was 58% (95% confidence interval [CI], 56%–61%) with variation by region (41%–76%). The MCV2 coverage was 62% (95% CI, 59%–65%) pre-MACV introduction and 67% (95% CI, 64%–69%) post-MACV introduction, an increase of 4.5% (95% CI, 1.3%–7.7%). Among children who received routine MACV and MCV2, 93% (95% CI, 91%–94%) received both at the same visit. Lack of caregiver awareness about the 15- to 18-month visit and vaccine unavailability were common reported barriers to vaccination.

Conclusions

A small yet significant increase in national MCV2 coverage was observed 1 year post-MACV introduction. The MACV/MCV2 coadministration was common. Findings will help inform strategies to strengthen second-year-of-life immunization coverage, including to address the communication and vaccine availability barriers identified.
Neisseria meningitidis Serogroup W Meningitis Epidemic in Togo, 2016
Authors: Mounkoro Didier , Nikiema Christelle S , Maman Issaka , Sakandé Souleymane , Bozio Catherine H , Tall Haoua , Sadji Adodo Yao , Njanpop-Lafourcade Berthe-Marie , Sibabe Agoro , Landoh Dadja E , Abodji Essofa O , Kodjo Agbenoko , Tamekloe Tsidi A , Essoh Téné Alima , Maba Détèma W , Gessner Bradford D , Moïsi Jennifer C
Published: July 2019

Background

During 2014, 4 regions in Togo within the African meningitis belt implemented vaccination campaigns with meningococcal serogroup A conjugate vaccine (MACV). From January to July 2016, Togo experienced its first major Neisseria meningitidis serogroup W (NmW) outbreak. We describe the epidemiology, response, and management of the outbreak.

Methods

Suspected, probable, and confirmed cases were identified using World Health Organization case definitions. Through case-based surveillance, epidemiologic and laboratory data were collected for each case. Cerebrospinal fluid specimens were analyzed by polymerase chain reaction, culture, or latex agglutination. Vaccination campaigns were conducted in affected districts.

Results

From January 11 to July 5, 2016, 1995 suspected meningitis cases were reported, with 128 deaths. Among them, 479 (24.0%) were confirmed by laboratory testing, and 94 (4.7%) and 1422 (71.3%) remained as probable and suspected cases, respectively. Seven epidemic districts had cumulative attack rates greater than 100 per 100 000 population. Of the confirmed cases, 91.5% were NmW; 39 of 40 available NmW isolates were sequence type-11/clonal complex-11.

Conclusions

This outbreak demonstrates that, although high coverage with MACV has reduced serogroup A outbreaks, large meningococcal meningitis outbreaks due to other serogroups may continue to occur; effective multivalent meningococcal conjugate vaccines could improve meningococcal disease prevention within meningitis belt populations.