bluuebunny/crossref_metadata_2025 huggingface dataset:
The Australian burden of invasive group A streptococcal disease: a narrative review
Authors: Wright Cameron M. , Langworthy Kristyn , Manning Laurens
Published: May 2020

The Australian and New Zealand governments have allocated significant funding to advance efforts towards a group A Streptococcus (Strep A) vaccine. The argument for Strep A vaccine development has to date focussed on prevention of non‐invasive disease (e.g. pharyngitis) and immune‐mediated complications (especially rheumatic heart disease). Because of the poorer prognosis and theoretically more precisely known burden of invasive, compared to non‐invasive disease, exploration of the burden of invasive Strep A disease could lend further support to the vaccine business case. This narrative review critically assesses the Australian incidence of invasive Strep A disease. Case notification data were first assessed through government sources, expressing annual incidence as cases per 100 000 population. Published literature accessed through PubMed and MEDLINE was assessed to March 2020. Where estimates could be updated by replicating reported methods with publicly available data, this was performed. Invasive Strep A disease is currently notifiable in Queensland and the Northern Territory only. The magnitude, degree of certainty and recency of estimates vary by state/territory and between sub‐populations, including higher incidence among Indigenous Australians compared to non‐Indigenous Australians. According to inpatient records from 2017 to 2018, the Australian incidence of invasive Strep A disease was 8.3 per 100 000. However, this is likely to be an underestimate. Preventing invasive Strep A disease is an important use for a Strep A vaccine. This narrative review highlights deficiencies in our current understanding of the Australian disease burden. These difficulties would be overcome by nationally consistent mandatory case reporting.
Role of energy transfer, defect, and lattice dimension in photophysical characteristics of AWO4:Nd3+ (A=Ca, Sr and Ba)
Authors: Datrik Chandra S. , Sudarshan Kathi , Gupta Santosh K. , Nandi Purnananda
Published: May 2020

The fact that the scheelite based compounds are of high technological importance in the area of scintillator and optoelectronics, makes their detailed photophysical study relevant not only for fundamental material science but also in tailoring their optical properties for advanced applications. With this view, we have carried out a very systematic study on near infra‐red (NIR) emitting Nd3+ doped CaWO4, SrWO4, and BaWO4 compounds. Light emitting efficiency in AWO4:Nd3+ is governed strongly by radiative/nonradiative properties, host‐dopant energy transfer (HDET) efficiency and defect density. We have used photoluminescence, positron annihilation, and photoacoustic (PA) spectroscopy to study the factors effecting light emission. These scheelites are known to exhibit self activated luminescence in visible region due to charge transfer within the tungstate group and wavelength maxima exhibited red shift as we move from Ca→Sr→Ba. This can provide a new strategy to achieve spectral tunability in AWO4 scheelite by changing A2+ ionic radius. The fractional intensity in the green region is least in the case of SrWO4 samples suggesting that the oxygen vacancy density is minimal in case of SrWO4 which is well‐supported by the positron annihilation lifetime spectroscopy (PALS). Based on our studies, we found that the HDET was highly efficient in CaWO4:Nd3+ and minimal in BaWO4:Nd3+ which get's reflected in photoluminescence intensity. Emission lifetimes are shorter in CaWO4 and highest in SrWO4 host which are in sync with positron annihilation lifetime values. Based on our results of PALS, it was found that CaWO4:Nd3+ has the highest concentration of defects i.e. cation vacancies; so larger is the probability of nonradiative signals and hence higher PA intensity from it.
Predictions of structural, electronic, mechanical, and thermodynamic properties of TMBCs (TM = Ti, Zr, and Hf) ceramics
Authors: Bao Longke , Qu Deyi , Kong Zhuangzhuang , Duan Yonghua
Published: May 2020

In the present work, we have investigated the structural, electronic, elastic, and thermodynamic properties of transition‐metal boron‐carbon compounds (TMBCs) (TM = Ti, Zr, Hf) using the first‐principles calculations. The results showed that TMBCs are energetically and thermodynamically stable, and the sequence of phase stability is HfBC > ZrBC > TiBC. B‐C bonds can be formed in TMBCs ceramics due to the strong hybridization between B‐2p and C‐2p states. The elastic anisotropies of TMBCs were illustrated by elastic anisotropy indexes, 3D surface constructions, and 2D projections, and the results indicated that the sequence of elastic anisotropy is ZrBC > TiBC > HfBC. Finally, the calculated minimum thermal conductivities, based on the Clarke's and Cahill's models, of all TMBCs are anisotropic with the sequence of ZrBC > TiBC > HfBC.
Recovery and chemical disinfection of foot-and-mouth disease and African swine fever viruses from porous concrete surfaces
Authors: Gabbert L.R. , Neilan J.G. , Rasmussen M.
Published: May 2020

Aims

Develop an effective laboratory method to consistently recover viral loads from porous concrete coupons sufficient for disinfectant efficacy testing. Investigate the role of concrete matrix pH on the recovery of foot-and-mouth disease virus (FMDV) and African Swine Fever virus (ASFV) from porous concrete. Compare parameters off FMDV and ASFV inactivation on porous and nonporous surfaces in quantitative carrier tests of a liquid chemical disinfectant.

Methods and results

Concrete test coupons were fabricated from commercial and industrial sources and carbonated by exposure to 5% CO2 in a humidified incubator, lowering the matrix pH. Neither dried FMDV nor ASFV were recovered from high-pH concrete control coupons. Recovery of infectious virus from lower pH carbonated concrete was similar to stainless steel coupon controls. Exposure to the liquid disinfectant Virkon™ S inactivated FMDV and ASFV on porous concrete.

Conclusions

Concrete matrix pH had a greater impact than surface porosity on the ability to recover viable virus from unsealed concrete.

Significance and Impact of the Study

Concrete is commonly found in environments where virus decontamination is required. This study demonstrates a reproducible method to recover sufficient viral loads from porous concrete coupons to facilitate quantitative carrier testing. This method provides a basis for evidence-based validation testing of chemical disinfectants to inactivate pH-sensitive viruses on unsealed concrete.
Comparison of high‐power and conventional‐power radiofrequency energy deliveries in pulmonary vein isolation using unipolar signal modification as a local endpoint
Authors: Ejima Koichiro , Higuchi Satoshi , Yazaki Kyoichiro , Kataoka Shohei , Yagishita Daigo , Kanai Miwa , Shoda Morio , Hagiwara Nobuhisa
Published: May 2020

Introduction

Negative component abolition of the unipolar signal (unipolar signal modification [USM]) reflects the lesion transmurality. The purpose of this study was to compare the procedural safety and outcome between high‐power and conventional‐power atrial radiofrequency applications during a pulmonary vein isolation (PVI) using USM as a local endpoint.

Methods and Results

High‐power (50 W) and conventional‐power (25‐40 W) applications were compared among 120 consecutive patients with paroxysmal atrial fibrillation who underwent a USM‐guided PVI. The first 60 patients were treated with conventional‐power (CP) group and last 60 with high‐power (HP) group. The atrial radiofrequency applications lasted for 5 to 10 seconds (CP group) or 3 to 5 seconds (HP group) after the USM. All procedures were performed using 3D mapping systems with image integration and esophageal temperature monitoring. The baseline characteristics were similar between the two groups. The HP group had fewer acute PV reconnections (62% vs 78%; P = .046) and a reduced procedure time (119.3 ± 28.1 vs 140.1 ± 51.2 minutes; P = .04). Freedom from recurrence after a single ablation procedure without any antiarrhythmic drugs was higher in the HP group than CP group (88.3% vs 73.3% at 12‐months after the procedure, log‐rank; P = .0423). There were no major complications that required any intervention.

Conclusions

The high‐power PVI guided by USM decreased the procedural time and may improve the procedural outcomes without compromising the safety.
Inhibition of TGFβ‐activated protein kinase 1 ameliorates myocardial ischaemia/reperfusion injury via endoplasmic reticulum stress suppression
Authors: Zeng Jingjing , Jin Qike , Ruan Yongxue , Sun Changzheng , Xu Guangyu , Chu Maoping , Ji Kangting , Wu Lianpin , Li Lei
Published: May 2020

Transforming growth factor β‐activated protein kinase 1 (TAK1) involves in various biological responses and is a key regulator of cell death. However, the role of TAK1 on acute myocardial ischaemia/reperfusion (MI/R) injury is unknown. We observed that TAK1 activation increased significantly after MI/R and hypoxia/reoxygenation (H/R), and we hypothesized that TAK1 has an important role in MI/R injury. Mice (TAK1 inhibiting by 5Z‐7‐oxozeaenol or silencing by AAV9 vector) were exposed to MI/R injury. Primary cardiomyocytes (TAK1 silencing by siRNA; and overexpressing TAK1 by adenovirus vector) were used to induce H/R injury model in vitro. Inhibition of TAK1 significantly decreased MI/R‐induced myocardial infarction area, reduced cell death and improved cardiac function. Mechanistically, TAK1 silencing suppressed MI/R‐induced myocardial oxidative stress and attenuated endoplasmic reticulum (ER) stress both in vitro and in vivo. In addition, the inhibition of ROS by NAC partially reversed the damage of TAK1 in vitro. Our study presents the first direct evidence that inhibition of TAK1 mitigated MI/R injury, and TAK1 mediated ROS/ER stress/apoptosis signal pathway is important for the pathogenesis of MI/R injury.
Evidence and Power in EU Governance of Health Promotion: Discursive Obstacles to a “Health in All Policies” Approach
Authors: Godziewski Charlotte
Published: May 2020

This article explores the relation between the meaning of what constitutes ‘evidence’ in the European Commission (EC) and the Health in All Policies (HiAP) concept. Since the 2006 Finnish EU presidency, HiAP is regularly referred to by the Commission, but has not yet been implemented as an overarching political vision. While there is a growing literature on technical implementation of HiAP, little work has delved into the political obstacles to HiAP. This article explores three ways in which the dominant meaning of ‘evidence’ in the EC reinforces neoliberal institutional characteristics in a way that undermines HiAP: The problematization of health reinforces constitutional asymmetry; the definition of ‘EU added value’ hampers positive integration; and the politicization of evidence strengthens the Better Regulation meta‐regulatory agenda. The article suggests that the meaning of evidence in the EC reinforces neoliberal rationality present at institutional level, and calls for more dialogue across public health ontologies.
Roles of Adenylate Cyclases in Ciliary Responses of Paramecium to Mechanical Stimulation
Authors: Kawano Mutsumi , Tominaga Takashi , Ishida Masaki , Hori Manabu
Published: May 2020

Paramecium shows rapid forward swimming due to increased beat frequency of cilia in normal (forward swimming) direction in response to various kinds of stimuli applied to the cell surface that cause K+‐outflow accompanied by a membrane hyperpolarization. Some adenylate cyclases are known to be functional K+ channels in the membrane. Using gene‐specific knockdown methods, we examined nine paralogues of adenylate cyclases in P. tetraurelia to ascertain whether and how they are involved in the mechanical stimulus‐induced hyperpolarization‐coupled acceleration of forward swimming. Results demonstrated that knockdown of the adenylate cyclase 1 (ac1)‐gene and 2 (ac2)‐gene inhibited the acceleration of forward swimming in response to mechanical stimulation of the cell, whereas that spared the acceleration response to external application of 8‐Br‐cAMP and dilution of extracellular [K+] induced hyperpolarization. Electrophysiological examination of the knockdown cells revealed that the hyperpolarization‐activated inward K+ current is smaller than that of a normal cell. Our results suggest that AC1 and AC2 are involved in the mechanical stimulus‐induced acceleration of ciliary beat in Paramecium.
The use of Carboxytherapy alone or in combination with fractional CO2 laser for facial rejuvenation: A split‐face comparative study
Authors: El‐Domyati Moetaz , Hosam El‐Din Wael , Medhat Walid , Ibrahim Michel R. , Khaled Yasmin
Published: May 2020

Background

A wide variety of minimally invasive treatments are available for skin aging. Recently, carbon dioxide therapy (CDT) or carboxytherapy was used in many cosmetic indications including facial rejuvenation.

Objective

To compare the efficacy of CDT alone versus combined CDT and fractional CO2 laser in management of facial aging.

Methods

Twenty‐Five female patients with bilateral and symmetrical facial aging were included in the study. The right (Rt) hemiface received 8 sessions of CDT whereas the left (Lt) side was treated with combined technique (6 sessions of CDT and 2 sessions of fractional CO2 in between. Clinical and objective evaluation using 3D skin analysis, histological, and morphometric analysis were performed.

Results

Clinical evaluation demonstrated that all patients (100%) were satisfied with no significant difference between both sides of the face (P > .05). Regarding texture and pigmentation improvement, the Lt side (combined) showed significant improvement compared to the Rt side (P < .05). Using Antera 3D camera, there was a significant difference (P < .05) in 3D improvement percent in textural changes while there was no significant difference (P > .05) in the 3D percent of wrinkles improvement between both sides. The Lt side showed more significant increase in epidermal thickness after treatment when compared to the Rt side (P < .05) with evident neocollagen formation.

Conclusion

Carboxytherapy is an easy, safe, simple, and a relatively effective method for facial rejuvenation with minimal downtime. Better results were achieved when used in combination with fractional CO2 laser.
Effect of long‐term overfeeding of a high‐energy diet on glucose tolerance in Shetland pony mares
Authors: d' Fonseca Nicky M. M. , Gibson Charlotte M. E. , van Doorn David A. , de Ruijter‐Villani Marta , Stout Tom A. E. , Roelfsema Ellen
Published: May 2020

Background

Overfeeding is associated with obesity and insulin dysregulation (ID), which are both risk factors for equine metabolic syndrome. How chronic overfeeding affects development of these factors is poorly understood.

Objectives

To examine the influence of long‐term high‐energy diet provision on body condition and ID.

Animals

Eleven Shetland pony mares.

Methods

In a 3‐phase study, the high‐energy group (n = 7) was fed 200% of net energy (NE) requirements (hay; concentrate: 36% sugar and starch, 13% fat) for 24 weeks, followed by 17 weeks hay‐only feeding before resuming the high‐energy diet (n = 4) for an additional 29 weeks. Mares were weighed weekly. Oral glucose tolerance tests were performed 3 to 4 times per dietary period. Results were compared with those of a control group (phase 1, n = 4; phases 2 and 3, n = 6) that received 100% NE requirements, using a general linear mixed model with post hoc Bonferroni testing.

Results

The mean body weight of the high‐energy group increased by 27% per high‐energy feeding period. During both feeding periods, area under the curve (AUC) for plasma glucose concentration decreased (P < .01), whereas AUC for plasma insulin concentration increased. Mean basal plasma glucose concentration and peak plasma insulin concentrations were higher (P < .05) in the high‐energy group than in the control group.

Conclusion and Clinical Importance

Feeding a high‐energy diet to healthy nonobese Shetland pony mares led to more efficient glucose metabolism within 5 weeks, followed by significant hyperinsulinemia and obesity. Hyperinsulinemic status was reversed during 17 weeks of hay‐only feeding, regardless of body condition, but returned rapidly after restarting the high‐energy diet.
Student nurses exposed to sustainability education can challenge practice: A cohort study
Authors: Aronsson Jennie , Clarke Daniel , Grose Jane , Richardson Janet
Published: May 2020

Climate change will adversely affect the health of populations and the ability of healthcare systems to deliver appropriate and timely care. Furthermore, resource scarcity requires nurses to practice in more sustainable ways. This study investigated the extent to which student nurses reported that they were able to apply their knowledge of sustainability in clinical practice following educational sessions on relevant topics. Students were exposed to scenario‐based sustainability education in years 1, 2, and 3 of their 3‐year program. Data were collected using a questionnaire that asked participants if they were able to implement sustainable practice. In year 2,121 students, and in year 3, 68 stated they made a change or challenged practice as a consequence of learning about sustainability. Barriers preventing them from challenging unsustainable practice were lack of confidence and resistance to change. Year‐3 students were more able to influence unsustainable practice than were those in year 2. This study indicates that sustainability sessions, focused on aspects of clinical relevance, can support nurses to implement change; barriers remain that require confidence building for the students.
Diet differentially regulates enterochromaffin cell serotonin content, density and nutrient sensitivity in the mouse small and large intestine
Authors: Martin Alyce M. , Jones Lauren A. , Jessup Claire F. , Sun Emily W. , Keating Damien J.
Published: May 2020

Background

Enterochromaffin (EC) cells are specialized enteroendocrine cells lining the gastrointestinal (GI) tract and the source of almost all serotonin (5‐hydroxytryptamine; 5‐HT) in the body. Gut‐derived 5‐HT has a plethora of physiological roles, including regulation of gastrointestinal motility, and has been implicated as a driver of obesity and metabolic disease. This is due to 5‐HT influencing key metabolic processes, such as hepatic gluconeogenesis, adipose tissue lipolysis and hindering thermogenic capacity. Increased circulating 5‐HT occurs in humans with obesity and type 2 diabetes. However, despite the known metabolic roles of gut‐derived 5‐HT, the mechanisms underlying the cellular‐level change in EC cells under obesogenic conditions remains unknown.

Methods

We use a mouse model of diet‐induced obesity (DIO) to identify the regional changes that occur in primary EC cells from the duodenum and colon. Transcriptional changes in the nutrient sensing profile of primary EC cells were assessed, and responses to nutrient stimuli in culture were determined by 5‐HT ELISA.

Key Results

We find that obesogenic conditions affect EC cells in a region‐dependent manner. Duodenal EC cells from DIO mice have impaired sugar sensing even in the presence of increased 5‐HT content per cell, while colonic EC cell numbers are significantly increased, but have unaltered nutrient sensing capacity.

Conclusions & Inferences

Our findings from this study add novel insights into the mechanisms by which functional changes to EC cells occur at a cellular level, which may contribute to the altered circulating 5‐HT seen with obesity and metabolic disease, and associated gastrointestinal disorders.
Relationship between problematic gaming and age at the onset of habitual gaming
Authors: Nakayama Hideki , Matsuzaki Takanobu , Mihara Satoko , Kitayuguchi Takashi , Higuchi Susumu
Published: May 2020

Background

Some studies have revealed that a substantial proportion of the younger population has engaged in problematic gaming with even infants recently being able to enjoy video games. However, the relationship between the risk for problematic gaming and age at which habitual gaming starts remains unknown. This study therefore investigated this relationship among adolescents.

Methods

A survey was conducted at eight public junior high schools across Japan. The questionnaire included items regarding the background, night‐time sleep, age at which weekly gaming began, time spent on the Internet and gaming, the Japanese version of Young’s Diagnostic Questionnaire, the Ten‐Item Internet Gaming Disorder Test (IGDT‐10), and others. We analyzed 549 participants who engaged in weekly gaming and have played games during the past year.

Results

Among the participants, 1.8% were suspected to have Internet gaming disorder (IGDT‐10 ≥ 5). Bedtime and wake‐up time on weekdays and holidays were significantly later among problematic gamers (IGDT‐10 ≥ 3) than among normal gamers (IGDT‐10 ≤ 2). Onset of weekly gaming before the age of 5 was associated with a significantly higher risk of problematic gaming than onset of weekly gaming after the age of 10.

Conclusions

Our results revealed that the risk for problematic gaming was positively associated with a younger age at which weekly gaming begins. Longitudinal problematic gaming prevention, starting from an early stage, is thus necessary.
Investigation of vaginal mucus parameters: Development of models for staging the oestrous cycle of the Bunaji cow
Authors: Agbugba Linda Chinyere , Oyewunmi Adetomi Oyelola , Ogundumade Tayo Peter , Leigh Olufisayo Oluwadamilare
Published: May 2020

Changes in some vaginal mucus parameters were studied in order to generate predictive models capable of enhancing oestrous cycle staging, using equal groups (unsynchronized‐USC [no treatment] and synchronized‐SC [Synchromate® i/m on d0, d11]) of Bunaji cows (n = 48) aged 3–4 years. Vaginal mucus was collected (starting d11 in SC) daily over 26 days using standard procedures. Physical (viscosity, elasticity, density, resistivity) and biochemical (pH, glucose, cholesterol, total protein, calcium, magnesium, sodium, potassium) parameters were evaluated using standard procedures. Data were analysed using chi‐square and multinomial logit regression modelling. Models generated using oestrus as reference categories were ascertained for accuracies. Chi‐square values for viscosity, elasticity and density were significant (p < .01) in USC and SC across stages of the cycle. Results for USC showed that pH and cholesterol were predictive (p < .01) for pro‐oestrus, metoestrus and dioestrus, while total protein was predictive (p < .01) for dioestrus only. Similarly, magnesium was predictive (p < .05) for pro‐oestrus. For SC, pH, magnesium and cholesterol were predictive (p < .01) for pro‐oestrus, metoestrus and dioestrus, while total protein was predictive (p < .01) for pro‐oestrus and dioestrus. Potassium and total protein were also predictive for metoestrus at 10% and 5% significance levels, respectively. Though findings suggest the usefulness of magnesium in staging the oestrous cycle only in synchronized cows, pH, total protein and cholesterol appeared to be the more important vaginal mucus parameters in Bunaji cows, regardless synchronization. Furthermore, the models developed showed high accuracy levels for staging the oestrous cycle in USC (100%) and SC (89%).
Governing complex societal problems: The impact of private on public regulation through technological change
Authors: Schmid Nicolas , Haelg Leonore , Sewerin Sebastian , Schmidt Tobias S. , Simmen Irina
Published: May 2020

When addressing complex societal problems, public regulation is increasingly complemented by private regulation. Extant literature has provided valuable insights into the effectiveness of such complex governance structures, with most empirical studies focusing on how public regulation influences private regulation. Conversely, the impact of private on public regulation is less well studied. Here, we investigate this impact with a focus on technological change as possible mechanism. Based on a case study of energy efficiency in buildings in Switzerland, we find evidence of a symbiotic interaction between public and private regulation that leads to ratcheting‐up of regulatory stringency. We identify technological change as the mechanism linking private and public regulation. We discuss the relevance of our findings for governance literature and regulators.
The politics of safety net reform in Southern Europe during the Great Recession: Introduction to the regional issue
Authors: Aguilar‐Hendrickson Manuel , Arriba González de Durana Ana
Published: May 2020

This is an introduction to the regional issue on the politics of safety net reform in Southern Europe during the Great Recession.
The Effectiveness of Implicit and Explicit Instruction on German L2 Learners’ Pronunciation
Authors: Peltekov Peter
Published: May 2020

Previous research has investigated the effectiveness of implicit and explicit instructional methods on second language (L2) learners’ grammatical accuracy. However, there is a scarcity of studies focused on the effects of the two teaching methods on L2 learners’ pronunciation. To fill this gap, the present study examined the effects of implicit and explicit instruction on the pronunciation of beginning learners of German. Over the course of one semester, one group of learners (n=5) was taught pronunciation explicitly (i.e., using phonetic rules), another group (n=5) implicitly (i.e., without phonetic rules), and a third group (n=5) received no pronunciation instruction. A pretest‐posttest design was used to measure learners’ improve ment in accent and comprehensibility. A slight improvement in both variables was observed under all conditions, but no significant difference in progress was found across the three groups. The findings suggest that some learner variables (e.g., age) might be better predictors of improvement than the type of instruction. Moreover, not all pronunciation features were equally relevant for L2 learners’ comprehensibility and accent. The results have implications for L2 pronunciation teaching.
Perinephric abscess in a renal transplant recipient due to Mycoplasma hominis: Case report and review of the literature
Authors: Adams Matthew , Bouzigard Rory , Al‐Obaidi Mohanad , Zangeneh Tirdad T.
Published: May 2020

A 42‐year‐old man presented with nausea, malaise, and pain at his renal graft site 4 months following deceased donor renal transplant. His transplantation had been complicated by urinary leak with delayed wound closure requiring ureteral revision with biologic mesh placement. The initial evaluation in the hospital revealed urinalysis with significant pyuria as well as abdominal CT imaging concerning for abscess formation anterior to the grafted kidney. Interventional radiology (IR) guided drainage of this abscess yielded growth of Enterococcus faecalis treated with intravenous ampicillin/sulbactam. He continued to have pain at his graft site and repeat imaging revealed a persistent abscess despite prolonged antimicrobial therapy. Urine cultures isolated Mycoplasma species. A repeat aspirate of abscess fluid collected and Mycoplasma hominis was identified by molecular test. Patient's symptoms abated and his abscess completely resolved on repeat imaging after completing a course of oral moxifloxacin and doxycycline. His immunosuppression did not require adjustment and the renal graft continued to function well following this therapy. Mycoplasma and Ureaplasma should be considered as a potential etiology for perinephric abscess in renal transplant recipients.
Revisiting study design and methodology for pathogen reduced platelet transfusions: a round table discussion
Authors: Heddle Nancy M. , Cardoso Marcia , van der Meer Pieter F.
Published: May 2020

Pathogen inactivation/reduction technologies for platelet components have been developed to enhance microbial safety, and many studies have been carried out to determine whether this technique adversely affects the platelet's ability to stop or prevent bleeding. These clinical trials require inclusion of several hundred patients, are costly, and take many years to complete. To address these challenges, a meeting was organized consisting of two expert presentations followed by a roundtable discussion focused on possible new approaches to evaluate the clinical efficacy of pathogen‐reduced platelets. The value of laboratory measures to provide information on platelet count after transfusion or to serve as a surrogate for bleeding risk was discussed. Also, other types of trial designs (cluster trials, stepped wedge designs, and Phase 4 postmarketing surveillance studies) as well as a clinically meaningful standardized safety endpoint to evaluate pathogen‐ reduced platelets were also discussed.
Colloid osmotic pressure of contemporary and novel transfusion products
Authors: Klanderman Robert B. , Bosboom Joachim J. , Korsten Herbert , Zeiler Thomas , Musson Ruben E. A. , Veelo Denise P. , Geerts Bart. F. , van Bruggen Robin , de Korte Dirk , Vlaar Alexander P. J.
Published: May 2020

Background and Objectives

Colloid osmotic pressure (COP) is a principal determinant of intravascular fluid homeostasis and a pillar of fluid therapy and transfusion. Transfusion‐associated circulatory overload (TACO) is a leading complication of transfusion, and COP could be responsible for recruiting additional fluid. Study objective was to measure COP of blood products as well as investigate the effects of product concentration and storage lesion on COP.

Materials and Methods

Three units of each product were sampled longitudinally. COP was measured directly as well as the determinants thereof albumin and total protein. Conventional blood products, that is red blood cell (RBC), fresh‐frozen plasma (FFP) and platelet concentrates (PLTs), were compared with their concentrated counterparts: volume‐reduced RBCs, hyperconcentrated PLTs, and fully and partially reconstituted lyophilized plasma (prLP). Fresh and maximally stored products were measured to determine changes in protein and COP. We calculated potential volume load (PVL) to estimate volume recruited using albumin's water binding per product.

Results

Colloid osmotic pressure varies widely between conventional products (RBCs, 1·9; PLTs, 7·5; and FFP, 20·1 mmHg); however, all are hypooncotic compared with human plasma COP (25·4 mmHg). Storage lesion did not increase COP. Concentrating RBCs and PLTs did not increase COP; only prLP showed a supraphysiological COP of 47·3 mm Hg. The PVL of concentrated products was lower than conventional products.

Conclusion

Colloid osmotic pressure of conventional products was low. Therefore, third‐space fluid recruitment is an unlikely mechanism in TACO. Concentrated products had a lower calculated fluid load and may prevent TACO. Finally, storage did not significantly increase oncotic pressure of blood products.
Feasibility of ventricular volumetry by cardiovascular MRI to assess cardiac function in the fetal sheep
Authors: Cho Steven K. S. , Darby Jack R. T. , Saini Brahmdeep S. , Lock Mitchell C. , Holman Stacey L. , Lim Jessie Mei , Perumal Sunthara Rajan , Macgowan Christopher K. , Morrison Janna L. , Seed Mike
Published: May 2020

Key points

The application of fetal cardiovascular magnetic resonance imaging (CMR) to assess fetal cardiovascular physiology and cardiac function through the quantification of ventricular volumes has previously been investigated, but the approach has not yet been fully validated.

Ventricular output measurements calculated from heart rate and stroke volumes (SV) of the right and left ventricles measured by ventricular volumetry (VV) exhibited a high level of agreement with phase‐contrast (PC) blood flow measurements in the main pulmonary artery and ascending aorta, respectively.

Ejection fraction of the right ventricle, which is lower than that of the left ventricle in postnatal subjects, was similar to the left ventricular ejection fraction in the fetus; probably due to the different loading conditions present in the fetal circulation.

This study provides evidence to support the reliability of VV in the sheep fetus, providing evidence for its use in animal models of human diseases affecting the fetal circulation.

The application of ventricular volumetry (VV) by cardiovascular magnetic resonance imaging (CMR) in the fetus remains challenging due to the small size of the fetal heart and high heart rate. The reliability of this technique in utero has not yet been established. The aim of this study was to assess the feasibility and reliability of VV in a fetal sheep model of human pregnancy. Right and left ventricular outputs by stroke volume (SV) measured using VV were compared with 2D phase‐contrast (PC) CMR measurements of blood flow in the main pulmonary artery (MPA) and ascending aorta (AAo). At 124–140 days (d) gestation, singleton bearing Merino ewes underwent CMR under general anaesthesia using fetal femoral artery catheters, implanted at 109–117d, to trigger cine steady state free precession acquisitions of ventricular short‐axis stacks. The short‐axis cine stacks were segmented at end‐systole and end‐diastole, yielding right and left ventricular SV, ejection fraction, and cardiac outputs (SV × heart rate). PC cine acquisitions of MPA and AAo were analysed to measure blood flow, which served as comparators for the right and left cardiac outputs by VV. There was good correlation and agreement between VV and PC measures of ventricular outputs with no significant bias (r2 = 0.926; P < 0.0001; Bias = −4.7 ± 10.5 ml min−1 kg−1; 95% limits of agreement: −15.9 to 25.2 ml min−1 kg−1). This study validates fetal VV by CMR in a large animal model of human pregnancy and provides preliminary reference values of fetal sheep right and left ventricles in late gestation.
Some Remarks on the Equilibrium of Granular Materials Described by Constitutive Relations That Depend on the Gradients of the Density or Volume Fraction
Authors: Atul Narayan S. P. , Rajagopal K. R.
Published: May 2020

One of the ways of determining the properties of granular materials is to subject the material to a tri-axial state of stress with three distinct eigenvalues, in a cubical tri-axial testing equipment, the material tested being in a static state. A constitutive relation for granular materials that does not allow the body to be in tri-axial static equilibrium would not be a reasonable model as experiments clearly show that granular materials can exist in such tri-axial states. In this short note, we observe that a large class of models that have been developed and used to describe the response of granular materials will not allow them to be in a static tri-axial state of stress with three different principal stresses.
Quantifying the Effect of Kinetic Uncertainties on NO Predictions at Engine-Relevant Pressures in Premixed Methane–Air Flames
Authors: Durocher Antoine , Bourque Gilles , Bergthorson Jeffrey M.
Published: May 2020

Accurate and robust thermochemical models are required to identify future low-NOx technologies that can meet the increasingly stringent emissions regulations in the gas turbine industry. These mechanisms are generally optimized and validated for specific ranges of operating conditions, which result in an abundance of models offering accurate nominal solutions over different parameter ranges. Under atmospheric conditions, and for methane combustion, relatively good agreement between models and experiments is currently observed. At engine-relevant pressures, however, a large variability in predictions is obtained as the models are often used outside their validation region. The high levels of uncertainty found in chemical kinetic rates enable such discrepancies between models, even if the reactions are within recommended rate values. This work investigates the effect of such kinetic uncertainties in NO predictions by propagating the uncertainties of 30 reactions that are both uncertain and important to NO formation, through the combustion model at engine-relevant pressures. Understanding the uncertainty sources in model predictions and their effect on emissions at these pressures is key in developing accurate thermochemical models to design future combustion chambers with any confidence. Lean adiabatic, freely propagating, laminar flames are therefore chosen to study the effect of parametric kinetic uncertainties. A nonintrusive, level 2, nested sparse-grid approach is used to obtain accurate surrogate models to quantify NO prediction intervals at various pressures. The forward analysis is carried up to 32 atm to quantify the uncertainty in emissions predictions to pressures relevant to the gas turbine community, which reveals that the NO prediction uncertainty decreases with pressure. After performing a reaction pathway analysis (RPA), this reduction is attributed to the decreasing contribution of the prompt-NO pathway to total emissions, as the peak CH concentration and the CH layer thickness decrease with pressure. In the studied lean condition, the contribution of the pressure-dependent N2O production route increases rapidly up to 10 atm before stabilizing toward engine-relevant pressures. The uncertain prediction ranges provide insight into the accuracy and precision of simulations at high pressures and warrant further research to constrain the uncertainty limits of kinetic rates to capture NO concentrations with confidence in early design phases.
Experimental Research of Diffusion Combustion and Emissions Characteristics Under Oxy-Fuel Combustion Mode
Authors: Kang Zhe , Wu Zhijun , Deng Jun , Hu Zongjie , Li Liguang
Published: May 2020

Internal combustion Rankine cycle (ICRC) concept implements oxy-fuel combustion, direct water injection (DWI), and waster heat recovery (WHR) into traditional Otto or diesel cycle to realize high thermal efficiency and low emission powertrain. In order to support ICRC realization, this paper is dedicated to investigate the feasibility of implementing oxy-fuel combustion into diffusion combustion which provides fundamental information for future compression ignition (CI)-ICRC engine. The prototype oxy-fuel diffusion combustion engine test bench is established based on a retrofitted diesel engine, and the O2/CO2 mixture intake system, high-pressure common rail fuel injection system, and high-performance electronic controller are designed and installed within engine test bench to investigate the combustion and emission characteristics under different intake oxygen fractions (OF), fuel injection durations, and fuel injection timing. The optimum intake OF and fuel injection strategies are acquired within the selected experimental conditions, a 41.1% brake thermal efficiency (BTE), and 1.2% coefficient of variation (CoV) is achieved utilizing 55% intake OF, 0.7 ms fuel injection duration and 352 °CA (after exchange top dead center (TDC)) fuel injection timing. The oxy-fuel diffusion combustion proved to be a feasible solution for simultaneously reduction in NOX and particulate emissions, and NOX emissions lower than 90 × 10−6 with particulate matters (PM) around 0.1 filter smoke number (FSN) is observed during engine bench testing. The result of this study provides fundamental information for future CI-ICRC prototype engine establishment and optimization, which also could be utilized as reference guidance for potential industrialization of internal combustion engine (ICE) with oxy-fuel combustion mode.
The effect of simulated room acoustic parameters on the intelligibility and perceived reverberation of monosyllabic words and sentences
Authors: Fogerty Daniel , Alghamdi Ahmed , Chan Wai-Yip
Published: May 2020

Individual acoustic parameters of reverberation have the potential to affect both the intelligibility of speech and the degree of perceived reverberation. The current experiments used monaural acoustic simulations to investigate the effect of reverberation time (RT) and direct-to-reverberant ratio (DRR) on word and sentence intelligibility at different levels of analysis (phonemes, words, and sentences). Perceived reverberation and recall of sentences were also assessed. Intelligibility and perceived reverberation decreased with increasing RT and decreasing DRR (particularly between 0 and −10 dB). Results indicate consistent effects of both RT and DRR on the intelligibility and perceived reverberation of words and sentences.
The Comprehensive School Physical Activity Program Model: A Proposed Illustrative Supplement to Help Move the Needle on Youth Physical Activity
Authors: Webster Collin A. , Rink Judith E. , Carson Russell L. , Moon Jongho , Gaudreault Karen Lux
Published: May 2020

Birthed over a decade ago and built on a solid foundation of conceptual and empirical work in public health, the comprehensive school physical activity program (CSPAP) model set the stage for a new and exciting chapter of physical activity promotion through schools. On the academic front, there has been much enthusiasm around the potential of CSPAPs to positively affect youth physical activity behaviors and trajectories. However, program uptake in schools has yet to take hold. This article examines the CSPAP model and proposes an illustrative supplement to enhance communication about its application. The authors begin by charting the model’s challenging contextual landscape and then highlight the model’s early successes in spite of such challenges. Subsequently, they turn their attention to limitations in the way the model is presented, which appear to undermine CSPAP advocacy, and focus on improving the messaging about CSPAPs as an immediate step toward increased implementation.
Controlling interdependent meso-nanosecond dynamics and defect generation in metal 3D printing
Authors: Khairallah Saad A. , Martin Aiden A. , Lee Jonathan R. I. , Guss Gabe , Calta Nicholas P. , Hammons Joshua A. , Nielsen Michael H. , Chaput Kevin , Schwalbach Edwin , Shah Megna N. , Chapman Michael G. , Willey Trevor M. , Rubenchik Alexander M. , Anderson Andrew T. , Wang Y. Morris , Matthews Manyalibo J. , King Wayne E.
Published: May 2020

Circumventing spatter

Laser powder bed fusion is an additive manufacturing technique that laser-melts powder layer by layer to build a three-dimensional (3D) part. Khairallah
et al.
used experiments and a multiphysics model to determine the origin of the melt spatter and defect formation that degrade the properties of built parts (see the Perspective by Polonsky and Pollock). Informed modulation of laser power is important to avoid disturbing the powder bed and creating laser shadowing. This reduces pore formations and leads to more uniform properties of 3D-printed parts.

Science
, this issue p.
660
; see also p.
583
The challenge of early detection in cancer
Authors: Pashayan Nora , Pharoah Paul D. P.
Published: May 2020

Tumor growth dynamics and the timing of metastasis impose limits on cancer screening
Light-powered CO
2
fixation in a chloroplast mimic with natural and synthetic parts
Authors: Miller Tarryn E. , Beneyton Thomas , Schwander Thomas , Diehl Christoph , Girault Mathias , McLean Richard , Chotel Tanguy , Claus Peter , Cortina Niña Socorro , Baret Jean-Christophe , Erb Tobias J.
Published: May 2020

Hybrid approach catches light

Plant chloroplasts enclose two major photosynthetic processes: light reactions, which generate the energy carriers adenosine triphosphate and reduced nicotinamide dinucleotide phosphate (NADPH), and dark reactions, which use these molecules to fix carbon dioxide and build biomass. Miller
et al.
appropriated natural components, thylakoid membranes from spinach, for the light reactions and showed that these could be coupled to a synthetic enzymatic cycle that fixes carbon dioxide within water-in-oil droplets. The composition of the droplets could be tuned and optimized and the metabolic activity monitored in real time by NADPH fluorescence (see the Perspective by Gaut and Adamala). These chloroplast-mimicking droplets bring together natural and synthetic components in a small space and are amenable to further functionalization to perform complex biosynthetic tasks.

Science
, this issue p.
649
; see also p.
587
Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice
Authors: Guthrie Liam M. , Soma Shivatheja , Yuan Sai , Silva Andres , Zulkifli Mohammad , Snavely Thomas C. , Greene Hannah Faith , Nunez Elyssa , Lynch Brogan , De Ville Courtney , Shanbhag Vinit , Lopez Franklin R. , Acharya Arjun , Petris Michael J. , Kim Byung-Eun , Gohil Vishal M. , Sacchettini James C.
Published: May 2020

Elesclomol rescues Menkes disease mice

Menkes disease results from loss-of-function mutations in the P-type copper-transporting adenosine triphosphatase ATP7A. Children diagnosed with Menkes present with connective tissue abnormalities and neurodegenerative changes that result in death caused by severe copper deficiency, typically before 3 years of age. In the brain, lack of copper impairs cytochrome c oxidase (complex IV) in the electron transport chain, which leads to progressive neurological injury in Menkes patients. No treatment exists for Menkes disease because of the difficulty in supplying the brain with copper using traditional hydrophilic copper complexes such as copper histidine. Guthrie
et al.
developed a treatment involving the drug elesclomol that successfully alleviated disease symptoms in a mouse model of Menkes disease (see the Perspective by Lutsenko).

Science
, this issue p.
620
; see also p.
584
Vaccination strategies to enhance immunity in neonates
Authors: Kollmann Tobias R. , Marchant Arnaud , Way Sing Sing
Published: May 2020

Neonates are particularly susceptible to infection. This vulnerability occurs despite their responsiveness to most vaccines. However, current vaccines do not target the pathogens responsible for most of the severe neonatal infections, and the time it takes to induce protective pathogen-specific immunity after vaccination limits protection in the first days to weeks of life. Alternative strategies include using vaccines to broadly stimulate neonatal immunity in a pathogen-agnostic fashion or vaccinating women during pregnancy to induce protective antibodies that are vertically transferred to offspring within their window of vulnerability. Protection may be further improved by integrating these approaches, namely vaccinating the neonate under the cover of vertically transferred maternal immunity. The rationale for and knowledge gaps related to each of these alternatives are discussed.
Comment on “A noninteracting low-mass black hole–giant star binary system”
Authors: van den Heuvel Ed P. J. , Tauris Thomas M.
Published: May 2020

Thompson
et al
. (Reports, 1 November 2019, p. 637) interpreted the unseen companion of the red giant star 2MASS J05215658+4359220 as most likely a black hole. We argue that if the red giant’s mass is ~1 solar mass, its companion can be a close binary consisting of two main-sequence stars. This would explain why no x-ray emission is detected from the system.
Response to Comment on “A noninteracting low-mass black hole–giant star binary system”
Authors: Thompson Todd A. , Kochanek Christopher S. , Stanek Krzysztof Z. , Badenes Carles , Jayasinghe Tharindu , Tayar Jamie , Johnson Jennifer A. , Holoien Thomas W.-S. , Auchettl Katie , Covey Kevin
Published: May 2020

Van den Heuvel and Tauris argue that if the red giant star in the system 2MASS J05215658+4359220 has a mass of 1 solar mass (
M
☉
), then its unseen companion could be a binary composed of two 0.9
M
☉
stars, making a triple system. We contend that the existing data are most consistent with a giant of mass

3.2

−
1.0

+
1.0

M
☉
, implying a black hole companion of

3.3

−
0.7

+
2.8

M
☉
.
Making ultrastrong steel tough by grain-boundary delamination
Authors: Liu L. , Yu Qin , Wang Z. , Ell Jon , Huang M. X. , Ritchie Robert O.
Published: May 2020

Strong and tough steel

Ultrahard materials often do not have similarly impressive fracture toughness. Liu
et al.
discovered a processing route for medium manganese steel alloy in which ultrahigh strength accompanies high fracture toughness. The steel relies on both transformation-induced plasticity and delamination toughening to boost the fracture properties. The steel is composed of less expensive elements, making it a potentially inexpensive material attractive for structural applications.

Science
, this issue p.
1347