bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization and Scaling of Forced Convective Swirl in Sinusoidal Wavy-Plate-Fin Cores of Compact Heat Exchangers
Authors: Shi Dantong , Lin Kuan-Ting , Jog Milind A. , Manglik Raj M.
Published: October 2020

The characterization and scaling of the thermal-hydraulic performance in wavy plate-fin compact heat exchanger cores, based on the understanding of the physical phenomena and heat transfer enhancement mechanism is delineated. Experimental data are presented for forced convection in air (Pr = 0.71) with flow rates in the range 50 ≤ Re ≤ 4000. A variety of wavy-fin cores that span viable applications, with geometrical attributes described by the cross section aspect ratio α (ratio of fin spacing to height), fin corrugation aspect ratio γ (ratio of 2× corrugation amplitude to wave pitch), and fin spacing ratio ζ (ratio of fin spacing to wave pitch), are considered. To characterize and correlate the vortex-flow mixing in interfin spaces, a Swirl number Sw is introduced from the balance of viscous, inertial and centrifugal forces. It is shown that the laminar, transitional and turbulent flow regimes can be explicitly identified by this Swirl number. Based on the experimental results and extended analysis, new correlations for Fanning friction factor f and Colburn factor j are developed with Sw, α, γ, and ζ as scaling parameters. Requisite expressions are devised by a superposition of both enhancement components due to the corrugated surface area enlargement and induced swirl flow field, and they are combined to cover the laminar, transitional and turbulent regimes by the method of asymptotic matching. The resulting generalized correlations are further shown to predict all available experimental data for f and j factors to within ±20% and ±15%, respectively.
No need to shout? Harbor porpoises (Phocoena phocoena) echolocate quietly in confined murky waters of the Wadden Sea
Authors: Dähne Michael , Bär Tom , Gallus Anja , Benke Harald , Herold Elisabeth , Stilz Peter
Published: October 2020

Porpoise echolocation parameters may vary depending on their acoustic habitat and predominant behavior. Research was conducted in the Wadden Sea, an acoustically complex, tidally driven habitat with high particle resuspension. Source levels and echolocation parameters of wild harbor porpoises were estimated from time-of-arrival-differences of a six-element hydrophone array. The back-calculated peak-to-peak apparent source level of 169 ± 5 dB re 1 μPa was significantly lower than reported from Inner Danish Waters (−20 dB) and British Columbia (−9 dB) with narrower bandwidth. Porpoises therefore reduce their source level in the Wadden Sea under acoustically complex conditions suggesting an avoidance of cluttering.
What’s Holding Them Back? Informing Retention and Success of Kinesiology Undergraduates
Authors: Kutz Jessica L. , Bopp Melissa , Gravish Hurtack Lori A.
Published: October 2020

As the need for qualified medical and allied health professions has grown, so too have the natural feeder undergraduate programs of kinesiology across the country. With an impending “enrollment cliff,” it is necessary to assess the needs of our students and be proactive in addressing curricular issues, initiatives, internship opportunities, and academic advising support. The purpose of this article is to highlight formal and informal data collection strategies and suggest solutions to undergraduate issues that pertain to retention and success. Data from current students and alumni shed light on issues that plague kinesiology programs and present unique challenges to students as they attempt to pursue careers in the medical and allied health fields. Two R1 kinesiology programs identified similarly themed issues using informal and formal data collection approaches. Those themes were undergraduate major identification, career options, curricular issues, financial concern, and emotional fortitude. Suggested solutions and current best practices are provided to address the common themes that hold our undergraduates back from achieving their career goals.
Spatial heterogeneities shape the collective behavior of signaling amoeboid cells
Authors: Eckstein Torsten F. , Vidal-Henriquez Estefania , Bae Albert J. , Gholami Azam
Published: October 2020

Imaging and mathematical analyses reveal how
Dictyostelium discoideum
cells navigate around obstacles in their environment.
Emerging roles for angiomotin in the nervous system
Authors: Wigerius Michael , Quinn Dylan , Fawcett James P.
Published: October 2020

The scaffolding protein AMOT-p130 promotes the development of the central nervous system.
A Real-Time PCR Assay for Simultaneous Detection and Differentiation of Four Common
Entamoeba
Species That Infect Humans
Authors: Ali Ibne Karim M. , Roy Shantanu
Published: October 2020

There are over 40 species within the genus
Entamoeba
, eight of which infect humans. Of these, four species (
Entamoeba histolytica
,
E. dispar
,
E. moshkovskii
, and
E. bangladeshi
) are morphologically indistinguishable from each other, and yet differentiation is important for appropriate treatment decisions. Here, we developed a hydrolysis probe-based tetraplex real-time PCR assay that can simultaneously detect and differentiate these four species in clinical samples.
Bacterial Vivisection: How Fluorescence-Based Imaging Techniques Shed a Light on the Inner Workings of Bacteria
Authors: Cambré Alexander , Aertsen Abram
Published: October 2020

The rise in fluorescence-based imaging techniques over the past 3 decades has improved the ability of researchers to scrutinize live cell biology at increased spatial and temporal resolution. In microbiology, these real-time vivisections structurally changed the view on the bacterial cell away from the “watery bag of enzymes” paradigm toward the perspective that these organisms are as complex as their eukaryotic counterparts. Capitalizing on the enormous potential of (time-lapse) fluorescence microscopy and the ever-extending pallet of corresponding probes, initial breakthroughs were made in unraveling the localization of proteins and monitoring real-time gene expression.
Staphylococcal Protein A (
spa
) Locus Is a Hot Spot for Recombination and Horizontal Gene Transfer in Staphylococcus pseudintermedius
Authors: Zukancic Alem , Khan Mubin A. , Gurmen Sumayya J. , Gliniecki Quinn M. , Moritz-Kinkade Dayna L. , Maddox Carol W. , Alam Md Tauqeer
Published: October 2020

Staphylococcus pseudintermedius
is a major canine pathogen but can also occasionally infect humans. Identification of genetic factors contributing to the virulence and clonal success of multidrug-resistant
S. pseudintermedius
clones is critical for the development of therapeutics against this pathogen. Here, we characterized the genome sequences of a global collection of 622
S. pseudintermedius
isolates. We show that all major clones, besides carrying core virulence genes, which are present in all strains, carry one or more lineage-specific genes. Many of these genes have been acquired from other bacterial species through a horizontal gene transfer mechanism. Importantly, we have discovered that the staphylococcal protein A gene (
spa
), a widely used marker for molecular typing of
S. pseudintermedius
strains and a potential vaccine candidate antigen, is deleted in 62% of strains. Furthermore, the
spa
locus in
S. pseudintermedius
acts as a reservoir to accumulate lineage-associated genes with adaptive functions.
Structured RNA Contaminants in Bacterial Ribo-Seq
Authors: Fremin Brayon J. , Bhatt Ami S.
Published: October 2020

Structured ncRNAs are pivotal mediators of bioregulation in bacteria, and their functions are often reliant on their specific structures. Here, we first inspect Ribo-Seq reads across noncoding regions, identifying contaminant reads in these libraries. We observe that contaminant reads in bacterial Ribo-Seq experiments that are often disregarded, in fact, strongly overlap with structured regions of ncRNAs. We then perform several bioinformatic analyses to determine why these contaminant reads may persist in Ribo-Seq libraries. Finally, we highlight some structured RNA contaminants in Ribo-Seq and support the hypothesis that structures in the RNA protect them from MNase digestion. We conclude that researchers should be cautious when interpreting Ribo-Seq signal as coding without considering signal distribution. These findings also may enable us to partially resolve RNA structures, identify novel structured RNAs, and elucidate RNA structure-function relationships in bacteria at a large scale and
in vivo
through the reanalysis of existing Ribo-Seq data sets.
Genetic Determinants of Resistance to Extended-Spectrum Cephalosporin and Fluoroquinolone in Escherichia coli Isolated from Diseased Pigs in the United States
Authors: Hayer Shivdeep Singh , Lim Seunghyun , Hong Samuel , Elnekave Ehud , Johnson Timothy , Rovira Albert , Vannucci Fabio , Clayton Jonathan B. , Perez Andres , Alvarez Julio
Published: October 2020

Understanding the genetic mechanisms conferring resistance is critical to design informed control and preventive measures, particularly when involving critically important antimicrobial classes such as extended-spectrum cephalosporins and fluoroquinolones. The genetic determinants of extended-spectrum cephalosporin and fluoroquinolone resistance were highly diverse, with multiple plasmids, insertion sequences, and genes playing key roles in mediating resistance in swine
Escherichia coli
. Plasmids assembled in this study are known to be disseminated globally in both human and animal populations and environmental samples, and
E. coli
in pigs might be part of a global reservoir of key antimicrobial resistance (AMR) elements. Virulent plasmids found in this study have been shown to confer fitness advantages to pathogenic
E. coli
strains. The presence of international, high-risk zoonotic clones provides worrisome evidence that resistance in swine isolates may have indirect public health implications, and the swine population as a reservoir for these high-risk clones should be continuously monitored.
The Guerrero terrane, a para-autochthonous block on the paleo-Pacific continental margin of North America: Evidence from zircon U-Pb dating and Hf isotopes
Authors: Ortega-Flores* Berlaine , Solari Luigi A. , Martini Michelangelo , Ortega-Obregón Carlos
Published: October 2020

Two main tectonic scenarios have been proposed for the area corresponding to the Guerrero terrane in western Mexico. The first model suggests that the Guerrero terrane was an allochthonous volcanic arc developed over oceanic substrate, which was accreted to nuclear Mexico. The second tectonic model proposes that the Guerrero terrane was a para-autochthonous volcanic arc developed over continental crust, which was rifted during the extensional phase of the Arperos back-arc basin and then tectonically attached to nuclear Mexico. Based on U-Pb geochronology and Hf isotope analyses of detrital zircon grains extracted from Mesozoic sedimentary successions of the Guerrero terrane and western nuclear Mexico, this study provides new evidence to support the interpretation that the Late Jurassic–Early Cretaceous Guerrero terrane was built above a pre–Late Jurassic continentally sourced basement. Hf isotopic signatures of detrital zircon from Late Jurassic–Early Cretaceous sedimentary rocks of the Guerrero terrane range from –14 to +13 and display depleted mantle model ages (TDMc, using a mean crustal value of 176Lu/177Hf = 0.015) between ca. 2.0 and 0.3 Ga, indicating provenance from both pre–Late Jurassic basement and juvenile crustal components. The most juvenile magmas were formed during the earliest Cretaceous extensional phase, which resulted in the formation of the Arperos basin. Additionally, the negative εHf(t) values are consistent with recycling of Proterozoic and Paleozoic continental materials in Mesozoic magmas.
Supplemental Material: Latitudinal variability in the Quaternary development of the Eurasian ice sheets—Evidence from the marine domain
Authors: Hjelstuen Berit , Sejrup Hans
Published: October 2020

Overview of published studies included in the present compilation, methods used, calculated sedimentation rates and sediment volumes, uncertainties, and figures of the configuration of the EurIS marine margin and IRD records.
Supplemental Material: Development of surface ruptures by hanging-wall extension over a thrust ramp along the Ragged Mountain fault, Katalla, Alaska, USA: Applications of high-resolution three-dimensional terrain models
Authors: Heinlein S.N. , al. et
Published: October 2020

Video S1: Grayscale digital elevation model generated from high-resolution lidar data illustrating surface expressions at the 1 m to tens of meters scale. Video S2: False-color digital elevation model generated from high-resolution lidar data illustrating surface expressions at the 1 m to tens of meters scale.
Deep decoupling in subduction zones: Observations and temperature limits
Authors: Abers Geoffrey A. , van Keken Peter E. , Wilson Cian R.
Published: October 2020

The plate interface undergoes two transitions between seismogenic depths and subarc depths. A brittle-ductile transition at 20–50 km depth is followed by a transition to full viscous coupling to the overlying mantle wedge at ∼80 km depth. We review evidence for both transitions, focusing on heat-flow and seismic-attenuation constraints on the deeper transition. The intervening ductile shear zone likely weakens considerably as temperature increases, such that its rheology exerts a stronger control on subduction-zone thermal structure than does frictional shear heating. We evaluate its role through analytic approximations and two-dimensional finite-element models for both idealized subduction geometries and those resembling real subduction zones. We show that a temperature-buffering process exists in the shear zone that results in temperatures being tightly controlled by the rheological strength of that shear zone’s material for a wide range of shear-heating behaviors of the shallower brittle region. Higher temperatures result in weaker shear zones and hence less heat generation, so temperatures stop increasing and shear zones stop weakening. The net result for many rheologies are temperatures limited to ≤350–420 °C along the plate interface below the cold forearc of most subduction zones until the hot coupled mantle is approached. Very young incoming plates are the exception. This rheological buffering desensitizes subduction-zone thermal structure to many parameters and may help explain the global constancy of the 80 km coupling limit. We recalculate water fluxes to the forearc wedge and deep mantle and find that shear heating has little effect on global water circulation.
Senior-Løken syndrome misdiagnosed as nephrosclerosis related to hypertensive disorders of pregnancy
Authors: Hirai Yuri , Mizumoto Aya , Mitsumoto Kensuke , Uzu Takashi
Published: October 2020

A 31-year-old woman with retinitis pigmentosa who had been diagnosed with renal failure due to nephrosclerosis related to hypertensive disorders of pregnancy was referred to our hospital to prepare for renal replacement therapy. Ultrasonography and MRI of the kidneys revealed multiple corticomedullary cysts. A renal biopsy showed that the tubules were tortuous and atrophic with segmented tubular basement membrane thickening. These findings indicated that she had Senior-Løken syndrome. A molecular genetic analysis was performed, and homozygous deletion of the gene encoding nephronophthisis-1 was found. Thus, the clinical diagnosis of Senior-Løken syndrome was genetically confirmed. Because her renal function was gradually worsening, she was scheduled to undergo living donor kidney transplantation. Senior-Løken syndrome, which is recognised as a very rare paediatric inherited disease characterised by nephronophthisis and eye problems, can cause adult-onset end-stage renal failure.
A systematic review of psychological training or interventions given to UK military personnel prior to deployment
Authors: Harden Larissa , Jones N , Whelan C , Phillips A , Simms A , Greenberg N
Published: October 2020

Introduction

Predeployment stress management/mental health training is routinely delivered in an effort to mitigate potential adverse psychological effects. Little is known about the effectiveness of such interventions.

Methods

A systematic literature review explored research outcomes related to this subject, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. An electronic database search using key terms identified studies published between January 2007 and March 2019. Comprehensive inclusion/exclusion criteria were applied and study quality was appraised by two reviewers using 12 criteria adapted from the Critical Appraisal Skills Programme (CASP) checklist. Papers were excluded if they were allocated CASP scores ≤10 out of 24.

Results

2003 references were identified; 15 papers fulfilled inclusion criteria and quality threshold requirements. Included studies were randomised controlled trial design (n=8), quasi-experimental (n=5), case report (n=1) and cross-sectional (n=1). Duration of follow-up assessment varied from immediately postintervention to 24 months. The included studies were heterogeneous so clear recommendations relating to predeployment training for military personnel could not be made. Although somewhat disparate, predeployment interventions shared the aim of promoting prior to, during and after deployment health and well-being. Social benefits such as improved cohesion and improved stress management skills were identified in some studies, although substantial mental health and well-being benefits were not found.

Conclusions

Evidence for the effectiveness of predeployment psychological interventions is scant. Every attempt should be made to use methods and measures to facilitate comparisons across studies, to attempt a longer follow-up timescale and to clarify key trainer characteristics.
Exploring the association between adverse maternal circumstances and low birth weight in neonates: a nationwide population-based study in Bangladesh
Authors: Khan Md Mostaured Ali , Mustagir Md Golam , Islam Md Rafiqul , Kaikobad Md Sharif , Khan Hafiz TA
Published: October 2020

Objective

This study is concerned with helping to improve the health and care of newborn babies in Bangladesh by exploring adverse maternal circumstances and assessing whether these are contributing towards low birth weight (LBW) in neonates.

Study designs and settings

Data were drawn and analysed from the Bangladesh Demographic and Health Survey, 2014. Any association between LBW and adverse maternal circumstances were assessed using a Chi-square test with determinants of LBW identified by multivariate logistic regression analysis.

Participants

The study is based on 4728 children aged below 5 years and born to women from selected households.

Results

The rate of LBW was around 19.9% (199 per 1000 live births) with the highest level found in the Sylhet region (26.2%). The rate was even higher in rural areas (20.8%) and among illiterate mothers (26.6%). Several adverse maternal circumstances of the women included in the survey were found to be significant for increasing the likelihood of giving birth to LBW babies. These circumstances included the women being underweight (adjusted odds ratio (AOR) 1.26, 95% CI 1.06 to 1.49); having unwanted births (AOR 1.22, 95% CI 1.03 to 1.44); had previous pregnancies terminated (AOR 1.28, 95% CI 1.05 to 1.57); were victims of intimate partner violence (AOR 1.23, 95% CI 1.05 to 1.45) and taking antenatal care <4 times (AOR 1.23, 95% CI 1.03 to 1.48). Other important risk factors that were revealed included age at birth <18 years (AOR 1.42, 95% CI 1.11 to 1.83) and intervals between the number of births <24 months (AOR 1.25, 95% CI 1.01 to 1.55). When taking multiple fertility behaviours together such as, the ages of the women at birth (<18 years with interval <24 months (AOR 1.26, 95% CI 1.02 to 1.57) and birth order (>3 with interval <24 months (AOR 1.68, 95% CI 1.18 to 2.37), then the risk of having LBW babies significantly increased.

Conclusion

This study finds that adverse maternal circumstances combined with high-risk fertility behaviours are significantly associated with LBW in neonates. This situation could severely impede progress in Bangladesh towards achieving the sustainable development goal concerned with the healthcare of newborns.
Cost-effectiveness analysis of a community paramedicine programme for low-income seniors living in subsidised housing: the community paramedicine at clinic programme (CP@clinic)
Authors: Agarwal Gina , Pirrie Melissa , Angeles Ricardo , Marzanek Francine , Thabane Lehana , O'Reilly Daria
Published: October 2020

Objectives

To evaluate the cost-effectiveness of the Community Paramedicine at Clinic (CP@clinic) programme compared with usual care in seniors residing in subsidised housing.

Design

A cost–utility analysis was conducted within a large pragmatic cluster randomised controlled trial (RCT). Subsidised housing buildings were matched by sociodemographics and location (rural/urban), and allocated to intervention (CP@clinic for 1 year) or control (usual care) via computer-assisted paired randomisation.

Setting

Thirty-two subsidised seniors’ housing buildings in Ontario.

Participants

Building residents 55 years and older.

Intervention

CP@clinic is a weekly community paramedic-led, chronic disease prevention and health promotion programme in the building common areas. CP@clinic is free to residents and includes risk assessments, referrals to resources, and reports back to family physicians.

Outcome measures

Quality-adjusted life years (QALYs) gained, measured with EQ-5D-3L. QALYs were estimated using area-under-the curve over the 1-year intervention, controlling for preintervention utility scores and building pairings. Programme cost data were collected before and during implementation. Costs associated with emergency medical services (EMS) use were estimated. An incremental cost effectiveness ratio (ICER) based on incremental costs and health outcomes between groups was calculated. Probabilistic sensitivity analysis using bootstrapping was performed.

Results

The RCT included 1461 residents; 146 and 125 seniors completed the EQ-5D-3L in intervention and control buildings, respectively. There was a significant adjusted mean QALY gain of 0.03 (95% CI 0.01 to 0.05) for the intervention group. Total programme cost for implementing in five communities was $C128 462 and the reduction in EMS calls avoided an estimated $C256 583. The ICER was $C2933/QALY (bootstrapped mean ICER with Fieller’s 95% CI was $4850 ($2246 to $12 396)) but could be even more cost effective after accounting for the EMS call reduction.

Conclusion

The CP@clinic ICER was well below the commonly used Canadian cost–utility threshold of $C50 000. CP@clinic scale-up across subsidised housing is feasible and could result in better health-related quality-of-life and reduced EMS use in low-income seniors.

Trial registration number

Clinicaltrials.gov, NCT02152891.
Personalising Outcomes after Child Cardiac Arrest (POCCA): design and recruitment challenges of a multicentre, observational study
Authors: Fink Ericka L , Clark Robert S B , Panigrahy Ashok , Berger Rachel , Wisnowski Jessica , Bluml Stefan , Maloney David , Rubin Pamela , Haller Tamara , Bayir Hulya , Beers Sue R , Kochanek Patrick M , Fabio Anthony
Published: October 2020

Introduction

Blood and imaging biomarkers show promise in prognosticating outcomes after paediatric cardiac arrest in pilot studies. We describe the methods and early recruitment challenges and solutions for an ongoing multicentre (n=14) observational trial, Personalising Outcomes following Child Cardiac Arrest to validate clinical, blood and imaging biomarkers individually and together in a clinically relevant panel.

Methods and analysis

Children (n=164) between 48 hours and 17 years of age who receive chest compressions irrespective of provider, duration, or event location and are admitted to an intensive care unit are eligible. Blood samples will be taken on days 1–3 for the measurement of brain-focused biomarkers analysed to predict the outcome. Clinically indicated and timed brain MRI and spectroscopy biomarkers will be analysed to predict the outcome. The primary outcome for the trial is survival with favourable (Vineland Adaptive Behavioural Scale score >70) outcome at 1 year. Secondary outcomes include mortality and pre-event and postdischarge measures of emotional, cognitive, physical and family functioning and health-related quality of life. Early enrollment targets were not met due to prolonged regulatory and subcontract processes. Multiple, simultaneous interventions including modification to inclusion criteria, additional sites and site visits were implemented with successful improvement in recruitment. Study procedures including outcomes and biomarker analysis are ongoing.

Ethics and dissemination

Twelve of 14 sites will use the centralised Institutional Review Board (IRB) at the University of Pittsburgh (PRO14030712). Two sites will use individual IRBs: Children’s Healthcare of Atlanta Institutional Review Board and Children’s Hospital of Wisconsin IRB. Parents and/or guardians are consented and children assented (when possible) by the site Primary investigator (PI) or research coordinator for enrollment. Study findings will be disseminated through scientific conferences, peer-reviewed journal publications, public study website materials and invited lectures.

Trial registration number

NCT02769026.
Mediating effect of health consciousness in the relationship of lifestyle and suboptimal health status: a cross-sectional study involving Chinese urban residents
Authors: Xue Yunlian , Liu Guihao , Feng Yefang , Xu Mengyao , Jiang Lijie , Lin Yuanqi , Xu Jun
Published: October 2020

Objective

Suboptimal health status (SHS), a third state between good health and disease, can easily develop into chronic diseases, and can be influenced by lifestyle and health consciousness. No study has surveyed the intermediation of health consciousness on the relationship between lifestyle and SHS. This study aimed to analyse the association of lifestyle and SHS, and intermediation of health consciousness in Chinese urban residents.

Design

A cross-sectional face-to-face survey using a four-stage stratified sampling method.

Participants

We investigated 5803 Chinese urban residents aged 18 years and over. We measured SHS using the Sub-Health Measurement Scale V1.0. We adopted a structural equation model to analyse relationships among lifestyle, health consciousness and SHS. We applied a bootstrapping method to estimate the mediation effect of health consciousness.

Results

Lifestyle had stronger indirect associations with physical (β −0.185, 95% CI −0.228 to −0.149), mental (β −0.224, 95% CI −0.265 to −0.186) and social SHS (β −0.216, 95% CI −0.257 to −0.179) via health consciousness than direct associations of physical (β −0.144, 95% CI −0.209 to −0.081), mental (β −0.146, 95% CI −0.201 to −0.094) and social SHS (β −0.130, 95% CI −0.181 to −0.077). Health consciousness has a strong direct association with physical (β 0.360, 95% CI 0.295 to 0.427), mental (β 0.452, 95% CI 0.392 to 0.510) and social SHS (β 0.434, 95% CI 0.376 to 0.490). Ratio of mediating effect of health consciousness to direct effect of lifestyle with physical, mental and social SHS was 1.28, 1.53 and 1.66, respectively.

Conclusions

Health consciousness was more important in preventing physical, mental and social SHS than lifestyle. Therefore, it might be useful in changing unhealthy lifestyle and reducing the influence of poor lifestyle on physical, mental and social SHS.
Efficacy and safety of oral hydroxyurea in transfusion-dependent β-thalassaemia: a protocol for randomised double-blind controlled clinical trial
Authors: Yasara Nirmani , Wickramarathne Nethmi , Mettananda Chamila , Manamperi Aresha , Premawardhena Anuja , Mettananda Sachith
Published: October 2020

Introduction

Despite being one of the first diseases to be genetically characterised, β-thalassaemia remains a disorder without a cure in a majority of patients. Most patients with β-thalassaemia receive only supportive treatment and therefore have a poor quality of life and shorter life spans. Hydroxyurea, which has shown to induce fetal haemoglobin synthesis in human erythroid cells, is currently recommended for the treatment of sickle cell disease. However, its clinical usefulness in transfusion-dependent β-thalassaemia is unclear. Here, we present a protocol for a randomised double-blind controlled clinical trial to evaluate the efficacy and safety of oral hydroxyurea in transfusion-dependent β-thalassaemia.

Methods and analysis

This single-centre randomised double-blind placebo-controlled clinical trial is conducted at the Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Adult and adolescent patients with haematologically and genetically confirmed transfusion-dependent β-thalassaemia are enrolled and randomised into the intervention or control group. The intervention group receives oral hydroxyurea 10–20 mg/kg daily for 6 months, while the control group receives a placebo which is identical in size, shape and colour to hydroxyurea without its active ingredient. Transfused blood volume, pretransfusion haemoglobin level, fetal haemoglobin percentage and adverse effects of treatment are monitored during treatment and 6 months post-treatment. Cessation or reduction of blood transfusions during the treatment period will be the primary outcome measure. The statistical analysis will be based on intention to treat.

Ethics and dissemination

Ethical approval has been obtained from the Ethics Committee of Faculty of Medicine, University of Kelaniya (P/116/05/2018) and the trial is approved by the National Medicinal Regulatory Authority of Sri Lanka. Results of the trial will be disseminated in scientific publications in reputed journals.

Trial registration number

SLCTR/2018/024; Pre-results.
Age-stratified outcomes of bioprosthetic and mechanical aortic valve replacements in an Australian cohort of 13 377 patients
Authors: Sotade Oluwadamisola Temilade , Falster Michael , Girardi Leonard N , Pearson Sallie-Anne , Jorm Louisa R
Published: October 2020

Objectives

To quantify age-stratified outcomes of bioprosthetic valve (BV) and mechanical valve (MV) surgical aortic valve replacement (AVR) in Australian patients.

Design

Retrospective cohort study using population-based linked hospital morbidity and mortality data.

Setting

Public and private hospitals.

Participants

Patients aged 18 years and over undergoing AVR from 2001 to 2013, stratified by age (18–64 years; 65+ years).

Main outcome measures

Age-standardized index AVR rates; rates and multivariable-adjusted (age, sex, Charlson Comorbidity Index) incidence rate ratios (IRRs) for reoperation, incident cardiovascular events (hospitalization or death for acute myocardial infarction (AMI), stroke, major hemorrhage or thromboembolism) and mortality (cardiovascular and all-cause).

Results

Our cohort comprised 13 377 patients, of whom 3464 (26%) were aged 18–64 years. Annual age-standardized AVR rates increased by 2.7% with BV implants increasing in both age groups. After 5 years of follow-up, patients implanted with BV had lower rates of stroke (IRR: 0.40, 95% CI 0.27 to 0.60) and hemorrhage (IRR: 0.36, 95% CI 0.26 to 0.50). Among patients 65+ years, those implanted with BV had lower rates of AMI, hemorrhage, and cardiovascular and all-cause mortality than those implanted with MV (IRR: 0.71, 95% CI 0.53 to 0.96; IRR: 0.77, 95% CI 0.62 to 0.95; IRR: 0.80, 95% CI 0.69 to 0.92 and IRR: 0.85, 95% CI 0.74 to 0.97, respectively). After 6–10 years of follow-up, reoperation rates among patients 18–64 years were markedly higher in those implanted with BV compared with MV (IRR: 5.48, 95% CI 2.38 to 12.62) and rates of AMI were lower among patients implanted with BV compared with MV (IRR: 0.49, 95% CI 0.26 to 0.94). Among patients 65+ years rates of cardiovascular and all-cause mortality remained significantly lower for patients implanted with BV compared with MV.

Conclusions

This study provides real-world evidence of AVR use and outcomes. Use of BV implants is increasing irrespective of age. Valve choice in younger patients requires thorough evaluation of patient factors influencing both short-term outcomes and longer-term risks of reoperation, stroke and hemorrhage.
Considering complexity in the genetic evaluation of dilated cardiomyopathy
Authors: Jordan Elizabeth , Hershberger Ray E
Published: October 2020

Dilated cardiomyopathy (DCM) is a cardiovascular disease of genetic aetiology that causes substantial morbidity and mortality, and presents considerable opportunity for disease mitigation and prevention in those at risk. Foundational to the process of caring for patients diagnosed with DCM is a clinical genetic evaluation, which always begins with a comprehensive family history and clinical evaluation. Genetic testing of the proband, the first patient identified in a family with DCM, within the context of genetic counselling is always indicated, regardless of whether the DCM is familial or non-familial. Clinical screening of at-risk family members is also indicated, as is cascade genetic testing for actionable variants found at genetic testing in the proband. Clinicians now have expansive panels with many genes available for DCM genetic testing, and the approaches used to evaluate rare variants to decide which are disease-causing continues to rapidly evolve. Despite these recent advances, only a minority of cases yield actionable variants, even in familial DCM where a genetic aetiology is highly likely. This underscores that our knowledge of DCM clinical genetics remains incomplete, including variant interpretation and DCM genetic architecture. Emerging data suggest that the single-variant Mendelian disease model is insufficient to explain some DCM cases, and rather that multiple variants, both common and rare, and at times key environmental factors, interact to cause DCM. A simple model illustrating the intersection of DCM genetic architecture with environmental impact is provided.
Checkpoint therapeutic target database (CKTTD): the first comprehensive database for checkpoint targets and their modulators in cancer immunotherapy
Authors: Zhang Yixiao , Yao Yuan , Chen Peng , Liu Yu , Zhang Hao , Liu He , Liu­ Yu , Xu Hong , Tian Xibao , Wang Zichu , Chu Peng , Zhao Dongyu , Liu Hongxu , Zhang Chenlei , Chen Shuyuan , Zhao Yuhong , Liu Caigang , Yang Yongliang
Published: October 2020

Background

Checkpoint targets play a key role in tumor-mediated immune escape and therefore are critical for cancer immunotherapy. Unfortunately, there is a lack of bioinformatics resource that compile all the checkpoint targets for translational research and drug discovery in immuno-oncology.

Methods

To this end, we developed checkpoint therapeutic target database (CKTTD), the first comprehensive database for immune checkpoint targets (proteins, miRNAs and LncRNAs) and their modulators. A scoring system was adopted to filter more relevant targets with high confidence. In addition, a few biological databases such as Oncomine, Drugbank, miRBase and Lnc2Cancer database were integrated into CKTTD to provide an in-depth information. Moreover, we computed and provided ligand-binding site information for all the targets which may support bench scientists for drug discovery efforts.

Results

In total, CKTTD compiles 105 checkpoint protein targets, 53 modulators (small-molecules and antibody), 30 miRNAs and 18 LncRNAs in cancer immunotherapy with validated experimental evidences curated from 10 649 literatures via an enhanced text-mining system.

Conclusions

In conclusion, the CKTTD may serve as a useful platform for the research of cancer immunotherapy and drug discovery. The CKTTD database is freely available to public at http://www.ckttdb.org/.
Hospital leadership perspectives on the value of the 3 Wishes Project: a qualitative study
Authors: Swinton Marilyn , Vanstone Meredith , Phung Peter , Neville Thanh H , Takaoka Alyson , Smith Orla M , Baker Andrew , LeBlanc Allana , Foster Denise , Dhingra Vinay , Clarke France J , Hoad Neala , Woods Anne , Boyle Anne , Toledo Feli , Cook Deborah J
Published: October 2020

Background

Healthcare organisations are increasingly interested in improving the work life of their employees. By encouraging individualised acts of compassion for dying patients and their families, the 3 Wishes Project (3WP) has been shown to ease grief for both families and clinicians.

Purpose

The objective of this study was to explore the perspectives of hospital leaders on the value of the 3WP to the hospital and how decisions are made about which programmes to support.

Methods

We conducted semistructured interviews with 20 hospital leaders in four North American institutions. Transcripts were analysed using qualitative content analysis.

Results

Interviews with 12 clinical managers and 8 senior administrators identified the institutional value of the 3WP as improving patient and family experiences, enhancing staff morale, translating institutional mission and values into front-line practice, and creating positive public relations. Hospital leaders acknowledged potential resource challenges, including staff time, space to store supplies and funds to purchase items for some wishes. However, citing stories they had heard from families and staff, hospital leaders shared their view of how their decisions about the value of clinical programmes extend beyond quantifiable outcomes.

Conclusions

When reflecting on this personalised palliative care programme, hospital leaders described how inspiring narratives promoted institutional values in ways that are difficult to measure quantitatively. Leaders underscored the need to balance the value that a programme brings with the resources it requires, stating how different types of evidence influence their support of new programmes.

Trial registration number

NCT04147169.
Myocardial fibrosis, diastolic dysfunction and elevated liver stiffness in the Fontan circulation
Authors: Alsaied Tarek , Moore Ryan A , Lang Sean M , Truong Vien , Lubert Adam M , Veldtman Gruschen R , Averin Konstantin , Dillman Jonathan R , Trout Andrew T , Mazur Wojciech , Taylor Michael D , He Quan , Morales David LS , Redington Andrew N , Goldstein Bryan H
Published: October 2020

Introduction

Single ventricle diastolic dysfunction and hepatic fibrosis are frequently observed in patients with a Fontan circulation. The relationship between adverse haemodynamics and end-organ fibrosis has not been investigated in adolescents and young adults with Fontan circulation.

Methods

Prospective observational study of Fontan patients who had a cardiac catheterisation. Cardiac MRI with T1 mapping was obtained to measure extracellular volume (ECV), a marker of myocardial fibrosis. Hepatic magnetic resonance elastography was performed to assess liver shear stiffness. Serum biomarkers of fibrosis including matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) were measured. Very high ECV was defined as >30% and elevated serum biomarkers as >75th percentile for each biomarker.

Results

25 Fontan patients (52% female) with mean age of 16.3±6.8 years were included. Mean ECV was 28%±5%. There was a significant correlation between ECV and systemic ventricular end-diastolic pressure (r=0.42, p=0.03) and between ECV and liver stiffness (r=0.45, p=0.05). Patients with elevated ECV demonstrated elevations in MMPs and TIMPs. Similarly, patients with elevated MMPs and TIMPs had greater liver stiffness compared with patients with normal levels of these biomarkers.

Conclusions

In Fontan patients, cardiac magnetic resonance evidence of myocardial fibrosis is associated with diastolic dysfunction, increased liver stiffness and elevated circulating biomarkers of fibrosis. These findings suggest the presence of a profibrotic milieu, with end-organ implications, in some patients with Fontan circulation.
Has primary production declined in the Salish Sea?
Authors: Johannessen Sophia C. , Macdonald Robie W. , Strivens Jonathan E.
Published: October 2020

Declining primary production has been proposed as an explanation for the declines in coho (Oncorhynchus kisutch) and Chinook (Oncorhynchus tshawytscha) salmon in the Salish Sea since the 1970s. Marine sediments maintain a continuous record of conditions in the overlying water. We used stable isotopes of organic carbon and nitrogen measured in 21 sediment cores to determine the contributions and fluxes of marine-derived and terrigenous organic matter over time. The flux of marine-derived organic matter shows no trend for at least the last 100 years. An apparent increase in the marine flux in recent years is due to remineralization of organic matter as it passes through surface sediments. In contrast, the flux of terrigenous organic matter has increased over the last century in the Strait of Georgia, while in Puget Sound, terrigenous flux peaked in the mid-20th century. Total primary production has neither increased nor decreased in the Salish Sea over the last century. Consequently, a decline in primary production cannot explain recent declines in fish populations.
Pyrosilviculture: Combining prescribed fire with gap-based silviculture in mixed-conifer forests of the Sierra Nevada
Authors: York Robert A. , Noble Hunter , Quinn-Davidson Lenya N. , Battles John J.
Published: October 2020

We used a prescribed fire study to demonstrate the concept of pyrosilviculture, defined here as (i) using prescribed fire to meet management objectives or (ii) altering nonfire silvicultural treatments explicitly in order to optimize the incorporation of prescribed fire in the future. The study included implementation of relatively hot prescribed burns in mixed-conifer forests that have been managed with gap-based silviculture. The fires burned through 12-, 22-, 32-, and 100-year-old cohorts, thus enabling an analysis of stand age influences on fire effects. Mastication and precommercial thinning were assessed as prefire treatments in the 12-year-old stands. Postburn mortality and crown scorch declined with stand age. There was a clear tradeoff between fuel consumption and high rates of tree damage and mortality in the 12-year-old stands. Masticated stands had higher levels of mean crown scorch (78%) compared with precommercially thinned stands (52%). Mortality for all 12-year-old stands was high, as nearly half of the trees were dead 1 year after the fires. Giant sequoia and ponderosa pine had relatively high resistance to fire-related mortality. When applying the concept of pyrosilviculture, there may be opportunities to combine prescribed fire with regeneration harvests that create a variety of gap sizes to sustain both low fire hazard and promote structural heterogeneity and sustainable age structures that may not be achieved with prescribed fire alone.
Probabilistic definition of the perturbative theoretical uncertainty from missing higher orders
Authors: Bonvini Marco
Published: October 2020

We consider the problem of quantifying the uncertainty on theoretical predictions based on perturbation theory due to missing higher orders. The most widely used approach, scale variation, is largely arbitrary and it has no probabilistic foundation, making it not suitable for robust data analysis. In 2011, Cacciari and Houdeau proposed a model based on a Bayesian approach to provide a probabilistic definition of the theory uncertainty from missing higher orders. In this work, we propose an improved version of the Cacciari–Houdeau model, that overcomes some limitations. In particular, it performs much better in case of perturbative expansions with large high-order contributions (as it often happens in QCD). In addition, we propose an alternative model based on the same idea of scale variation, which overcomes some of the shortcomings of the canonical approach, on top of providing a probabilistically-sound result. Moreover, we address the problem of the dependence of theoretical predictions on unphysical scales (such as the renormalization scale), and propose a solution to obtain a scale-independent result within the probabilistic framework. We validate these methods on expansions with known sums, and apply them to a number of physical observables in particle physics. We also investigate some variations, improvements and combinations of the models. We believe that these methods provide a powerful tool to reliably estimate theory uncertainty from missing higher orders that can be used in any physics analysis. The results of this work are easily accessible through a public code named .
The dependence of the critical temperature on pressure
Authors: Chanpoom Thaipanya
Published: October 2020

The aim of this research is to study the critical temperature depending on the pressure of one-band superconductor. We derive the exact equation of the critical temperature [Formula: see text] by using the BCS-like model. The effect of pressure and pseudogap on critical temperature has been investigated. The analytic form and the approximation of the critical temperature are shown. First, we consider the effect of pressure on the critical temperature and find that the critical temperature increased as pressure is increased which fits well with the experimental data of Tl-based and Bi-based superconductors. Second, the effect of the pseudogap on the critical temperature is considered. We found that the critical temperature is decreased as pressure increased which agrees to the data of [Formula: see text], the iron chalcogenides [Formula: see text], intermetallic compounds [Formula: see text] and [Formula: see text] superconductors.
The Implication of the Oscillations in Exchange Rate for the Commodity-wise Trade Flows between Pakistan and China: An Evidence from ARDL Approach
Authors: Chishti Muhammad Zubair , Iqbal Javed , Mahmood Farrukh , Azeem Hafiz Syed Muhammad
Published: October 2020

This study intends to explore the impact of oscillations in the exchange rate on commodity-wise trade flows between Pakistan and its major trading partner China, while employing the annual data for 1982–2017. Applying the ARDL bounds testing approach, this study confirms that 94% of the selected exporting and 86% of the chosen importing industries possess “cointegration”. Further, the findings reveal that 81%, in the short run, and 52%, in the long run, of exporting industries respond to the volatile exchange rate. Moreover, the volatility affects 77%, in the short run, while 65%, in the long term, of the importing industries. Fascinatingly, the findings also indicate that a major shareholder exporting industry coded as 651 (“Textile yarn and thread” with 57% share) gets benefitted from the volatile exchange rate.
Nonfinancial Stakeholder Orientation and Conditional Accounting Conservatism
Authors: Burke Qing Liao , Wang Mengying , Zhao Yijia Eddie
Published: October 2020

This study examines the relation between conditional accounting conservatism and nonfinancial stakeholder orientation. Using the staggered passage of constituency statutes to identify increases in nonfinancial stakeholder orientation, we document that firms report more conservatively after statute adoption. Cross-sectional analyses indicate the increase in conditional conservatism after statute enactment is more pronounced for firms with higher agency costs between shareholders and managers, and less pronounced for firms with customers that have greater bargaining strength. Collectively, our study sheds light on how the increasing trend of nonfinancial stakeholder orientation plays a role in shaping financial reporting practices.