bluuebunny/crossref_metadata_2025 huggingface dataset:
Gentamicin plasma concentrations in hospitalized horses and retrospective minimal inhibitory concentrations of gram‐negative equine pathogens
Authors: Schoster Angelika , Amsler Morena , Kirchgaessner Constanze , Saleh Lanja , Schwarzwald Colin , Schmitt Sarah
Published: December 2020

Objectives

The optimal dosage regimen of gentamicin in horses is still under investigation. The objectives of this study were to determine gentamicin plasma concentrations in hospitalized horses treated with 10 mg/kg gentamicin (IV, q 24 h) and to determine whether a plasma concentration to minimum inhibitory concentration (MIC) ratio of 10:1 is reached for equine pathogens using this dose.

Design

Prospective clinical observational study; retrospective study on MICs of 131 gram‐negative bacteria isolated from horses (2012–2015).

Setting

University teaching hospital.

Animals

Ninety‐eight horses >6 months old, treated with gentamicin for their primary disease, consecutive samples.

Measurements and main results

Plasma concentrations were measured 1 hour (C1h) and 20 hours (C20h) after gentamicin administration using fluorescence polarization. Presence of systemic inflammatory response syndrome (SIRS) and azotemia was recorded, as well as the reason for antimicrobial administration (primary disease) and whether administration was prophylactic or therapeutic. The target C1hof ≥20 µg/mL gentamicin was reached in 90% of horses and was sufficient to reach a plasma concentration:MIC of 10:1 in 32 of 131 (24%) of gram‐negative aerobic bacteria. A C20h≤ 2 µg/mL was reached in 97% horses. Therapeutic versus prophylactic administration, primary disease, azotemia, and systemic inflammatory response syndrome were not associated with a failure to reach a desired peak or trough.

Conclusions

The gentamicin dose of 10 mg/kg every 24 hours should be further investigated and safety assessed because a target gentamicin plasma concentration of ≥20 µg/mL was achieved in the majority of cases. Nephrotoxic side effects were not assessed. Individual drug monitoring should be performed because clinical factors are unreliable predictors of plasma concentrations. A gentamicin target concentration of ≥40 µg/mL does not offer additional benefits compared to ≥20 µg/mL, due to the bimodal distribution of resistance in bacterial isolates.
Insight into the removal and reapplication of small inhibitor molecules during area-selective atomic layer deposition of SiO2
Authors: Merkx Marc J. M. , Jongen Rick G. J. , Mameli Alfredo , Lemaire Paul C. , Sharma Kashish , Hausmann Dennis M. , Kessels Wilhelmus M. M. , Mackus Adriaan J. M.
Published: December 2020

As the semiconductor industry progresses toward more complex multilayered devices with ever smaller features, accurately aligning these layers with respect to each other has become a bottleneck in the advancement to smaller transistor nodes. To avoid alignment issues, area-selective atomic layer deposition (ALD) can be employed to deposit material in a self-aligned fashion. Previously, we demonstrated area-selective ALD of SiO2 using three-step (i.e., ABC-type) ALD cycles comprising an acetylacetone (Hacac) dose (step A), a bis(diethylamino)silane precursor dose (step B), and an O2 plasma exposure (step C). In this work, the mechanisms of the removal and reapplication of the inhibitor molecules during area-selective ALD were studied, with the aim of enhancing the selectivity of the process. In situ infrared spectroscopy shows that the O2 plasma exposure does not completely remove the adsorbed Hacac species (i.e., acac adsorbates) at the end of the cycle. The persisting species were found to contain fragments of Hacac molecules, which hinder subsequent inhibitor adsorption in the next ALD cycle, and thereby contribute to a loss in selectivity. Alternatively, it was found that an H2 plasma is able to completely remove all acac species from the surface. An improvement in selectivity was achieved by using a four-step ALD cycle that includes an H2 plasma step, allowing the nucleation delay to be prolonged from 18 ± 2 to 30 ± 3 ALD cycles. As a result, 2.7 ± 0.3 nm SiO2 can be deposited with a selectivity of 0.9, whereas only 1.6 ± 0.2 nm can be achieved without the H2 plasma step. This work shows that the addition of a dedicated inhibitor removal step before the reapplication of the inhibitors can significantly improve the selectivity.
Bilateral Dorsolateral Prefrontal Cortex High-Definition Transcranial Direct-Current Stimulation Improves Time-Trial Performance in Elite Cyclists
Authors: Pollastri Luca , Gallo Gabriele , Zucca Milena , Filipas Luca , La Torre Antonio , Riba Ugo , Molino Luigi , Geda Elisabetta
Published: December 2020

Background: The effects of anodal transcranial direct-current stimulation (tDCS) on endurance exercise performance are not yet fully understood. Different stimulated areas and low focality of classical tDCS technique may have led to discordant results. Purpose: This study investigated the effect of a bilateral anodal high-definition tDCS (HD-tDCS) of the dorsolateral prefrontal cortex on the cycling time-trial (TT) performance and physiological and perceptual response at moderate intensity in elite cyclists. Methods: A total of 8 elite cyclists (maximal oxygen consumption: 72.2 [4.3] mL·min−1·kg−1) underwent in a double-blind, counterbalanced, and randomized order the experimental treatment (HD-tDCS) or control treatment (SHAM). After 20 minutes of receiving either HD-tDCS on the dorsolateral prefrontal cortex (F3 and F4) or SHAM stimulation, the participants completed a constant-load trial (CLT) at 75% of the second ventilatory threshold. Thereafter, they performed a simulated 15-km TT. The ratings of perceived exertion, heart rate, cadence,  oxygen consumption, and respiratory exchange ratio were recorded during the CLT; the ratings of perceived exertion and heart rate were recorded during the TT. Results: The total time to complete the TT was 1.3% faster (HD-tDCS: 1212 [52] s vs SHAM: 1228 [56] s; P = .04) and associated with a higher heart rate (P < .001) and a tendency toward higher mean power output (P = .05). None of the physiological and perceptual variables measured during the CLT highlighted differences between the HD-tDCS and SHAM condition. Conclusions: The findings suggest that bilateral HD-tDCS on the dorsolateral prefrontal cortex improves cycling TT performance without altering the physiological and perceptual response at moderate intensity, indicating that an upregulation of the prefrontal cortex could enhance endurance exercise performance.
“It’s Better Together”: A Nested Longitudinal Study Examining the Benefits of Walking Regularly With Peers Versus Primarily Alone in Older Adults
Authors: Kritz Marlene , Thøgersen-Ntoumani Cecilie , Mullan Barbara , Stathi Afroditi , Ntoumanis Nikos
Published: December 2020

The authors examined whether purposeful walking with peers at least once a week contributes to better behavioral and health outcomes in older adults than primarily walking alone. The authors used a longitudinal cohort design and recruited participants aged 60 years and older (N = 136) at the start of a 16-week walking intervention. Participants who walked on average at least once a week in the final 8 weeks of the intervention were included in the analysis (N = 79; 66 females, Mage [SD] = 77.73 [6.91]). The authors found that autonomous motivation, walking self-efficacy, functional capacity, body fat, and physical activity improved more in the walking with peers group compared with the walking alone group, after controlling for whether participants lived alone/with others and their health status. The results extend current literature by providing longitudinal evidence for the added benefits of regular peer-accompanied walking in older adults and highlight the importance of investing in peer-supported interventions.
Debate of Ideas and Understanding With Regard to Tactical Learning in Team Sports
Authors: Gréhaigne Jean-Francis , Godbout Paul
Published: December 2020

Purpose: The researchers discuss the debate of ideas (DoI) and student understanding conducted on questioning and student answers or discussions in game-based approaches and on DoI as used in the tactical-decision learning model.Literature Review: Literature regarding types of questions and expected student answers and questioning for learning in game-based approaches is reviewed. In addition, a brief overview of the context in which DoI was originally developed is presented.Findings and Discussion: Studies that used DoI are discussed with regard to the management of game play and observation, DoI content and the dynamics of student discussions, and impact on game play statistics and on students’ tactical knowledge. Challenges for teachers and students are discussed, as a student-centered approach encourages changes in traditional teacher and student roles. Finally, the importance of understanding the internal logic of team sports for solving tactical problems and learning is discussed.
Three-Year Trajectory of Interest in Learning Physical Activity Knowledge: Influences of Gender and Prior Knowledge
Authors: Wang Yubing , Zhang Tan , Chen Ang
Published: December 2020

Purpose: The purpose of this study was to determine the 3-year trajectory of students’ interest in learning physical activity (PA) knowledge during middle school and the effects of gender and prior knowledge on the trajectory. Methods: Using a repeated-measures design, a cohort of 447 sixth-grade students’ interest in learning PA knowledge was measured eight times from the beginning of sixth grade to the end of eighth grade. Students’ prior PA knowledge was measured at the beginning of sixth grade. Results: Hierarchical linear modeling analyses showed that students’ interest in PA knowledge in general declined over time. Girls’ interest declined faster than that of the boys before eighth grade, but their decline slowed during the eighth-grade year. Prior knowledge did not influence the trajectories. Discussion: These findings provide insights regarding students’ interest in learning PA knowledge and indicate that prior knowledge may not be a central component that contributes to interest development.
‘The game has changed.’ AI triumphs at protein folding
Authors: Service Robert F.
Published: December 2020

In milestone, software predictions finally match structures calculated from experimental data.
Amid the cheering, some vaccines face questions
Authors: Cohen Jon
Published: December 2020

A candidate from AstraZeneca and the University of Oxford has puzzling efficacy data.
The role of the microbiota in human genetic adaptation
Authors: Suzuki Taichi A. , Ley Ruth E.
Published: December 2020

Getting to the guts of local evolution

The microbiota of mammals is a product of coevolution. However, humans exhibit a range of adaptive peculiarities that can be quite geographically specific. The human microbiota also displays a variety of community compositions and a range of overlapping and redundant metabolic characteristics that can alter host physiology. For example, lactase persistence is a genetic characteristic of European populations, but in populations lacking the lactase gene, milk sugar digestion is endowed by the microbiota instead. Suzuki and Ley review the evidence for the role that the microbiota plays in local adaptation to new and changing human circumstances.

Science
, this issue p.
eaaz6827
Directly visualizing the momentum-forbidden dark excitons and their dynamics in atomically thin semiconductors
Authors: Madéo Julien , Man Michael K. L. , Sahoo Chakradhar , Campbell Marshall , Pareek Vivek , Wong E. Laine , Al-Mahboob Abdullah , Chan Nicholas S. , Karmakar Arka , Mariserla Bala Murali Krishna , Li Xiaoqin , Heinz Tony F. , Cao Ting , Dani Keshav M.
Published: December 2020

Probing the dark state

Excitons, electron-hole pairs held together by Coulomb attraction, can be generated in semiconductors under excitation and greatly influence the material's optoelectronic properties. Although bright excitons are optically active, their dark-state cousins have been more difficult to detect. They do, however, affect the optoelectronic properties through their interaction with light and bright excitons. Madéo
et al.
developed a pump-probe photoemission technique that is used reveal the spatial, temporal, and spectral dynamics of excitons (see the Perspective by Na and Ye). Demonstrated in two-dimensional monolayer films of tungsten diselenide, the technique could also be applicable to other semiconductor systems hosting excitonic excitations.

Science
, this issue p.
1199
; see also p.
1166
Selection enhances protein evolvability by increasing mutational robustness and foldability
Authors: Zheng Jia , Guo Ning , Wagner Andreas
Published: December 2020

Selection enhances mutation toleration

Mutations generate variability that is either neutral or subject to natural selection. Robustness is a measure of the ability to withstand deleterious mutational effects. Zheng
et al.
exposed
Escherichia coli
populations expressing a yellow fluorescent protein to strong, weak, or no selection for yellow fluorescence for four generations. They then selected these populations to a related function, green fluorescence, for four more generations. The strong selection first for yellow and then green fluorescence resulted in the most green fluorescence and the accumulation of the most mutations. This outcome likely was due to the increased foldability of the protein. Selection thus provides a threshold for mutation accumulation, but robustness maintains a buffer necessary for protein evolution.

Science
, this issue p.
eabb5962
Temperature limits to deep subseafloor life in the Nankai Trough subduction zone
Authors: Heuer Verena B. , Inagaki Fumio , Morono Yuki , Kubo Yusuke , Spivack Arthur J. , Viehweger Bernhard , Treude Tina , Beulig Felix , Schubotz Florence , Tonai Satoshi , Bowden Stephen A. , Cramm Margaret , Henkel Susann , Hirose Takehiro , Homola Kira , Hoshino Tatsuhiko , Ijiri Akira , Imachi Hiroyuki , Kamiya Nana , Kaneko Masanori , Lagostina Lorenzo , Manners Hayley , McClelland Harry-Luke , Metcalfe Kyle , Okutsu Natsumi , Pan Donald , Raudsepp Maija J. , Sauvage Justine , Tsang Man-Yin , Wang David T. , Whitaker Emily , Yamamoto Yuzuru , Yang Kiho , Maeda Lena , Adhikari Rishi R. , Glombitza Clemens , Hamada Yohei , Kallmeyer Jens , Wendt Jenny , Wörmer Lars , Yamada Yasuhiro , Kinoshita Masataka , Hinrichs Kai-Uwe
Published: December 2020

Deep, hot, and more alive than we thought

Marine sediments represent a massive microbial ecosystem, but we still do not fully understand what factors shape and limit life underneath the seafloor. Analyzing samples from a subduction zone off the coast of Japan, Heuer
et al.
found that microbial life, in particular bacterial vegetative cells, decreases as depth and temperature increases down to ∼600 meters below the seafloor, corresponding to temperatures of ∼70°C. Below this limit, endospores are common—a remnant, and a potential reservoir, of bacterial life. Deeper still is a sterile zone, and below 1000 meters is a scalding realm populated by vegetative cells. At such great depths, high concentrations of acetate and sulfate coexist, and there are also signs of hyperthermophilic methanogenesis. These data provide a fascinating window into an extreme and inhospitable environment that nonetheless supports microbial life.

Science
, this issue p.
1230
Structure of the activated ROQ1 resistosome directly recognizing the pathogen effector XopQ
Authors: Martin Raoul , Qi Tiancong , Zhang Haibo , Liu Furong , King Miles , Toth Claire , Nogales Eva , Staskawicz Brian J.
Published: December 2020

Tetrameric immune receptors

Nucleotide-binding/leucine-rich repeat (NLR) immune receptors detect pathogen effectors and trigger a plant's immune response. Two groups have now defined the structures of two NLRs that carry Toll-like interleukin-1 receptor (TIR) domains (TIR-NLRs) (see the Perspective by Tian and Li). Ma
et al.
studied the
Arabidopsis thaliana
TIR-NLR RPP1 (recognition of
Peronospora parasitica
1) and its response to effectors from an oomycete pathogen. Martin
et al.
studied the
Nicotiana benthamiana
TIR-NLR ROQ1 (recognition of XopQ 1) and its response to the
Xanthomonas
effector. Both groups found that these TIR-NLRs formed tetramers that, when activated by binding to the pathogen effector, exposed the active site of a nicotinamide adenine dinucleoside (NAD) hydrolase. Thus, recognition of the pathogen effector initiates NAD hydrolysis and begins the immune response.

Science
, this issue p.
eabe3069
, p.
eabd9993
; see also p.
1163
Super-resolution lightwave tomography of electronic bands in quantum materials
Authors: Borsch M. , Schmid C. P. , Weigl L. , Schlauderer S. , Hofmann N. , Lange C. , Steiner J. T. , Koch S. W. , Huber R. , Kira M.
Published: December 2020

Probing quantum materials

Unraveling the functionalities of quantum materials such as spin-valley-electronic, topological, and many-body effects provides a route to exploiting these materials for applications. Borsch
et al.
introduce a spectroscopic technique based on the concept of crystal-momentum combs. By extending the ideas of frequency combs of metrology and superresolution imaging, they demonstrate the ability to directly map out the properties of quantum electronic structures under ambient conditions. Using this technique combined with accurate many-body computations, they were able to reveal tomographic images of two-dimensional quantum materials.

Science
, this issue p.
1204
Miniaturization of robots that fly on beetles' wings
Authors: Sun Jiyu
Published: December 2020

The shock-absorbing wings of the rhinoceros beetle battle in-flight collisions
COVID-19 vaccine trial ethics once we have efficacious vaccines
Authors: Wendler David , Ochoa Jorge , Millum Joseph , Grady Christine , Taylor Holly A.
Published: December 2020

Some placebo-controlled trials can continue ethically after a candidate vaccine is found to be safe and efficacious
Prospective cohort study of water immersion for labour and birth compared with standard care in an Irish maternity setting
Authors: Barry Paula L , McMahon Lean E , Banks Ruth AM , Fergus Ann M , Murphy Deirdre J
Published: December 2020

Objective

To examine the birth outcomes for women and babies following water immersion for labour only, or for labour and birth.

Design

Prospective cohort study.

Setting

Maternity hospital, Ireland, 2016–2019.

Participants

A cohort of 190 low-risk women who used water immersion; 100 gave birth in water and 90 laboured only in water. A control group of 190 low-risk women who received standard care.

Methods

Logistic regression analyses examined associations between water immersion and birth outcomes adjusting for confounders. A validated Childbirth Experience Questionnaire was completed.

Main outcome measures

Perineal tears, obstetric anal sphincter injuries (OASI), postpartum haemorrhage (PPH), neonatal unit admissions (NNU), breastfeeding and birth experiences.

Results

Compared with standard care, women who chose water immersion had no significant difference in perineal tears (71.4% vs 71.4%, adj OR 0.83; 95% CI 0.49 to 1.39) or in OASI (3.3% vs 3.8%, adj OR 0.91; 0.26–2.97). Women who chose water immersion were more likely to have a PPH ≥500 mL (10.5% vs 3.7%, adj OR 2.60; 95% CI 1.03 to 6.57), and to exclusively breastfeed at discharge (71.1% vs 45.8%, adj OR 2.59; 95% CI 1.66 to 4.05). There was no significant difference in NNU admissions (3.7% vs 3.2%, adj OR 1.06; 95% CI 0.33 to 3.42). Women who gave birth in water were no more likely than women who used water for labour only to require perineal suturing (64% vs 80.5%, adj OR 0.63; 95% CI 0.30 to 1.33), to experience OASI (3.0% vs 3.7%, adj OR 1.41; 95% CI 0.23 to 8.79) or PPH (8.0% vs 13.3%, adj OR 0.73; 95% CI 0.26 to 2.09). Women using water immersion reported more positive memories than women receiving standard care (p<0.01).

Conclusions

Women choosing water immersion for labour or birth were no more likely to experience adverse birth outcomes than women receiving standard care and rated their birth experiences more highly.
Effect of Housing First on violence-related traumatic brain injury in adults with experiences of homelessness and mental illness: findings from the At Home/Chez Soi randomised trial, Toronto site
Authors: Mejia-Lancheros Cilia , Lachaud James , Stergiopoulos Vicky , Matheson Flora I. , Nisenbaum Rosane , O’Campo Patricia , Hwang Stephen W.
Published: December 2020

Objectives

People experiencing homelessness have a high prevalence and incidence of traumatic brain injury (TBI) due to violence. Little is known about the effectiveness of interventions to reduce TBI in this population. This study assessed the effect of Housing First (HF) on violence-related TBI in adults with experiences of homelessness and mental illness.

Design

Pragmatic randomised trial.

Participants

381 participants in the Toronto site of the At Home/Chez randomised trial.

Intervention

HF participants were provided with scattered-site housing using rent supplements and supports from assertive community treatment or intensive case management teams (n=218, 57.2%). Control participants had access to treatment as usual (TAU) in the community (n=163, 42.8%).

Main outcome measures

Primary outcomes were an incident physical violence-related TBI event and the number of physical violence-related TBI events during the follow-up period (January 2014 to March 2017). Interval-censored survival time regression and zero-inflated negative binomial regression were used to assess the effect of HF on primary outcomes.

Results

Among study participants, 9.2% (n=35) had an incident physical violence-related TBI event, and the mean physical violence-related TBI events was 0.16 (SD ±0.6). Compared with TAU participants, HF participants did not have a significantly lower risk of an incident violence-related TBI event (adjusted HR : 0.58 (95% CI, 0.29 to 1.14)), but they had a significantly lower number of physical violence-related TBI events (unadjusted incidence rate ratio (IRR): 0.22 (95% CI, 0.06 to 0.78); adjusted IRR: 0.15 (95% CI, 0.05 to 0.48)).

Conclusion

HF may be a useful intervention to reduce the burden of TBI due to physical violence among homeless individuals with mental illness.

Trial registration number

ISRCTN42520374.
Adiposity change and mortality in middle-aged to older Chinese: an 8-year follow-up of the Guangzhou Biobank Cohort Study
Authors: Huang Ying Yue , Jiang Chao Qiang , Xu Lin , Zhang Wei Sen , Zhu Feng , Jin Ya Li , Thomas G Neil , Cheng Kar Keung , Lam Tai Hing
Published: December 2020

Objective

To examine the associations of change in body mass index (BMI) and waist circumference (WC) over an average of 4 years with subsequent mortality risk in middle-aged to older Chinese.

Design

Prospective cohort study based on the Guangzhou Biobank Cohort Study.

Setting

Community-based sample.

Participants

17 773 participants (12 956 women and 4817 men) aged 50+ years.

Primary and secondary outcome measures

Primary outcome measure was all-cause mortality. Secondary outcome measures were cardiovascular disease (CVD) and cancer mortality. Causes of death were obtained via record linkage, and coded according to the International Classification of Diseases (tenth revision).

Results

1424 deaths (53.4% women) occurred in the 17 773 participants (mean age 61.2, SD 6.8 years) during an average follow-up of 7.8 (SD=1.5) years, and 97.7% of participants did not have an intention of weight loss . Compared with participants with stable BMI, participants with BMI loss (>5%), but not gain, had a higher risk of all-cause mortality (HR=1.49, 95% CI 1.31 to 1.71), which was greatest in those who were underweight (HR=2.45, 95% CI 1.31 to 4.59). Similar patterns were found for WC. In contrast, for participants with a BMI of ≥27.5 kg/m2, BMI gain, versus stable BMI, was associated with 89% higher risk of all-cause mortality (HR=1.89, 95% CI 1.25 to 2.88), 72% higher risk of CVD mortality (HR=1.72, 95% CI 0.80 to 3.72) and 2.27-fold risk of cancer mortality (HR=2.27, 95% CI 1.26 to 4.10).

Conclusion

In older people, unintentional BMI/WC loss, especially in those who were underweight was associated with higher mortality risk. However, BMI gain in those with obesity showed excess risks of all-cause and cancer mortality, but not CVD mortality. Frequent monitoring of changes in body size can be used as an early warning for timely clinical investigations and interventions and is important to inform appropriate health management in older Chinese.
US veterans administration diabetes risk (VADR) national cohort: cohort profile
Authors: Avramovic Sanja , Alemi Farrokh , Kanchi Rania , Lopez Priscilla M , Hayes Richard B , Thorpe Lorna E , Schwartz Mark D
Published: December 2020

Purpose

The veterans administration diabetes risk (VADR) cohort facilitates studies on temporal and geographic patterns of pre-diabetes and diabetes, as well as targeted studies of their predictors. The cohort provides an infrastructure for examination of novel individual and community-level risk factors for diabetes and their consequences among veterans. This cohort also establishes a baseline against which to assess the impact of national or regional strategies to prevent diabetes in veterans.

Participants

The VADR cohort includes all 6 082 018 veterans in the USA enrolled in the veteran administration (VA) for primary care who were diabetes-free as of 1 January 2008 and who had at least two diabetes-free visits to a VA primary care service at least 30 days apart within any 5-year period since 1 January 2003, or veterans subsequently enrolled and were diabetes-free at cohort entry through 31 December 2016. Cohort subjects were followed from the date of cohort entry until censure defined as date of incident diabetes, loss to follow-up of 2 years, death or until 31 December 2018.

Findings to date

The incidence rate of type 2 diabetes in this cohort of over 6 million veterans followed for a median of 5.5 years (over 35 million person-years (PY)) was 26 per 1000 PY. During the study period, 8.5% of the cohort were lost to follow-up and 17.7% died. Many demographic, comorbidity and other clinical variables were more prevalent among patients with incident diabetes.

Future plans

This cohort will be used to study community-level risk factors for diabetes, such as attributes of the food environment and neighbourhood socioeconomic status via geospatial linkage to residence address information.
Study protocol: treatment with caffeine of the very preterm infant in the delivery room: a feasibility study
Authors: Dani Carlo , Cecchi Alessandra , Remaschi Giulia , Mercadante Domenica , la Marca Giancarlo , Boni Luca , Mosca Fabio
Published: December 2020

Introduction

Early treatment with caffeine in the delivery room has been proposed to decrease the need for mechanical ventilation (MV) by limiting episodes of apnoea and improving respiratory mechanics in preterm infants. Thus, the purpose of this feasibility study is to verify the hypothesis that intravenous or enteral administration of caffeine can be performed in the preterm infant in the delivery room.

Methods and analysis

In this multicentre prospective study, infants with 25+0–29+6 weeks of gestational age will be enrolled and randomised to receive 20 mg/kg of caffeine citrate intravenously, via the umbilical vein, or enterally, through an orogastric tube, within 10 min of birth. Caffeine plasma level will be measured at 60±15 min after administration and 60±15 min before the next dose (5 mg/kg). The primary endpoint will be evaluation of the success rate of intravenous and enteral administration of caffeine in the delivery room. Secondary endpoints will be the comparison of success rate of intravenous versus oral administration and the evaluation of the need for MV in treated infants. In the absence of previous references, we arbitrarily decided to study 20 infants treated with intravenous caffeine and 20 infants treated with enteral caffeine. Primary endpoint will be evaluated measuring the success rate of intravenous and enteral caffeine administration which will be considered a success when it is followed by the achievement of the caffeine therapeutic level (8–25 µg/mL) 60±15 min before administration of the second dose.

Ethics and dissemination

The study has been approved by the Italian Medicines Agency (AIFA: AIFA/RSC/P/32755) and by Comitato Etico Pediatrico Regione Toscana. The results will be published in peer-reviewed academic journals.

Trial registration number

ClinicalTrials.gov identifier NCT04044976; EudraCT number 2018-003626-91.
Impact of a compression garment, on top of the usual care, in patients with breast cancer with early disturbance of the lymphatic transport: protocol of a randomised controlled trial
Authors: Thomis Sarah , Devoogdt Nele , Bechter-Hugl Beate , Nevelsteen Ines , Neven Patrick , Fourneau Inge
Published: December 2020

Introduction

Breast cancer-related lymphoedema (BCRL) is a common phenomenon. When lymphoedema is diagnosed late, options for treatment are diminished. Therefore, early diagnosis and treatment are very important to alter the potential deleterious evolution. Lymphofluoroscopy visualises the superficial lymphatic architecture in detail, giving the opportunity to detect a disturbance in the lymphatic transport (ie, dermal backflow) before the lymphoedema is clinically visible.

The main objective is to investigate if there is an additional effect of a compression garment on top of the usual care (ie, information and exercises) in patients with early disturbance of the lymphatic transport after breast cancer treatment. Development of clinical lymphoedema and/or deterioration of the dermal backflow visualised by lymphofluoroscopy is investigated.

Methodology

All patients scheduled for breast cancer surgery with unilateral axillary lymph node dissection or sentinel node biopsy in the Multidisciplinary Breast Clinic of the University Hospitals Leuven are being considered. Patients are assessed before surgery and at 1, 3, 6, 9, 12, 18, 24 and 36 months postoperatively. At each visit, a clinical assessment is performed determining the volume difference between both arms and hands (through circumference measurements and water displacement), the water content, the extracellular fluid, the pitting status and the skinfold thickness. Quality of life questionnaires are filled in. At each visit, a lymphofluoroscopy is performed as well. When a disturbance of the lymphatic transport is seen on lymphofluoroscopy, without the presence of clinical lymphoedema, the patient is randomised in either a control group receiving usual care or a preventive treatment group receiving usual care and a compression garment (whether or not combined with a glove).

Ethics and dissemination

The trial is conducted in compliance with the principles of the Declaration of Helsinki (2008), the principles of Good Clinical Practice and in accordance with all applicable regulatory requirements. This protocol has been approved by the Ethical Committee of the University Hospitals Leuven. Results will be disseminated by peer-reviewed scientific journals and presentation at international congresses.

Trial registration number

NCT03210311

Conclusion

The investigators hypothesise that development of clinical BCRL can be prevented and/or the dermal backflow can be stabilised or improved, if a preventive treatment with compression garment is started in the early phase of disturbance.
Mechanics, energetics and implementation of grounded running technique: a narrative review
Authors: Davis Sheeba , Fox Aaron , Bonacci Jason , Davis Fiddy
Published: December 2020

Grounded running predominantly differs from traditional aerial running by having alternating single and double stance with no flight phase. Approximately, 16% of runners in an open marathon and 33% of recreational runners in a 5 km running event adopted a grounded running technique. Grounded running typically occurs at a speed range of 2–3 m·s−1, is characterised by a larger duty factor, reduced vertical leg stiffness, lower vertical oscillation of the centre of mass (COM) and greater impact attenuation than aerial running. Grounded running typically induces an acute increase in metabolic cost, likely due to the larger duty factor. The increased duty factor may translate to a more stable locomotion. The reduced vertical oscillation of COM, attenuated impact shock, and potential for improved postural stability may make grounded running a preferred form of physical exercise in people new to running or with low loading capacities (eg, novice overweight/obese, elderly runners, rehabilitating athletes). Grounded running as a less impactful, but metabolically more challenging form, could benefit these runners to optimise their cardio-metabolic health, while at the same time minimise running-related injury risk. This review discusses the mechanical demands and energetics of grounded running along with recommendations and suggestions to implement this technique in practice.
Risk of serious spinal adverse events associated with epidural corticosteroid injections in the Medicare population
Authors: Eworuke Efe , Crisafi Leah , Liao Jiemin , Akhtar Sandia , Van Clief Martha , Racoosin Judith A , Wernecke Michael , MaCurdy Thomas E , Kelman Jeffrey A , Graham David J
Published: December 2020

Background

Epidural corticosteroid injections (ESIs) are widely performed and have an unquantified risk of serious spinal adverse events (SSAEs). We sought to determine the rate of SSAEs following ESI and to compare the rates by spinal level, injection approach and corticosteroid formulation.

Methods

We included patients enrolled in Medicare parts A and B who had an ESI between 1 January 2009 and 30 September 2015. We identified potential cases as patients with spine-related diagnoses within 3 days after the first eligible ESI. Event categorization as probable, possible or non-case was based on review of medical records. The rates of probable and possible cases were expressed per 1 000 000 patients overall, and by spinal level, injection approach and corticosteroid formulation. A score test was used to compare these rates.

Results

We identified 1 355 957 eligible ESIs during the study period. Of the 110 potential cases, 43 were selected for medical record review and 11 were categorized as probable, yielding a rate of 8.1 per 1 000 000 patients (95% CI 4.5 to 14.5). Risk of SSAEs was statistically higher with cervical/thoracic injections (29.4, 95% CI 12.5 to 68.8) compared with lumbar/sacral injections (5.1, 95% CI 2.3 to 11.0) (p value 0.001). Event rates for lumbar/sacral non-transforaminal injections was 8.8 (95% CI 4.0 to 19.1). Event rates for particulate (7.5, 95% CI 3.9 to 14.2) and non-particulate formulations (13.1, 95% CI 3.6 to 47.9) appeared similar (p value 0.47).

Conclusion

Between 2009 and 2015, rates of SSAEs following ESI in the Medicare population were low. Patients receiving cervical/thoracic ESIs were at higher risk of SSAE than those receiving lumbar/sacral ESIs. Event rates were similar for each corticosteroid formulation.
Antioxidant and anti-inflammatory properties of alpha-lipoic acid protect against valproic acid–induced liver injury
Authors: Mohammed Marwa Abdeltawab , Gharib Doaa Mostafa , Reyad Hoda Ramadan , Mohamed Alaa Aboud , Elroby Fadwa A. , Mahmoud Hoda Sayed
Published: December 2020

Valproic acid (VPA) is one of the most used antiepileptic drugs despite of its many adverse effects such as anemia, leucopenia, thrombocytopenia, and liver toxicity. The hepatoprotective effect of alpha-lipoic acid (ALA) was confirmed. The aim of this study was to detect the protective effect of ALA against the adverse effects of VPA. To study this, 30 white albino Wistar male rats were divided into four groups. Group I was the control group; Group II included rats that received ALA (100 mg·kg−1·day−1) orally for 14 days; Group III and Group IV included rats that received VPA (500 mg·kg−1·day−1) for 15 days intraperitoneally, but Group IV rats received ALA (100 mg·kg−1·day−1) orally for 14 days prior to VPA. Blood samples were collected and livers were excised from rats for colorimetric analysis and quantitative real-time PCR. The rats that received VPA showed leucopenia, thrombocytopenia, a significant decrease of superoxide dismutase, glutathione, nuclear factor erythroid 2-related factor 2, and sirtuin 1, besides a significant increase of malondialdehyde and tumor necrosis factor α. Prior treatment with ALA prevented all these results; ALA protected against VPA-induced liver damage and hematological disturbance via antioxidant and anti-inflammatory properties.
Effects of urbanization and nest-box design on reproduction vary by species in three cavity-nesting passerines in the Okanagan Valley, British Columbia, Canada
Authors: Dale C.A. , Reudink M.W. , Ratcliffe L.M. , McKellar A.E.
Published: December 2020

Artificial nest boxes provide an important resource for secondary cavity-nesting passerines, whose populations may be limited by the availability of nesting sites. However, previous studies have demonstrated that the design and placement of boxes may affect the reproductive success of the birds that use them. In this study, we asked whether the habitat surrounding a nest box or the type of box influenced reproduction in three cavity-nesting passerines. We studied Western Bluebirds (Sialia mexicana Swainson, 1832), Mountain Bluebirds (Sialia currucoides (Bechstein, 1798)), and Tree Swallows (Tachycineta bicolor (Vieillot, 1808)) breeding in artificial nest boxes at sites across 70 km of the Okanagan Valley of British Columbia, Canada. Sites varied in their degree of urbanization, from relatively undisturbed ranchland, to cultivated vineyards, to frequently disturbed “suburban” habitat, and boxes varied in type of entrance (slot or hole). Western Bluebirds nested earlier in vineyards, and Tree Swallows produced significantly fewer fledglings in suburban habitat. In addition, Tree Swallows nested earlier and produced more fledglings in slot boxes. Our results suggest that conservation actions for cavity-nesting passerines may depend on the target species, which in turn should dictate the appropriate box type and habitat when erecting or replacing nest boxes.
Confronting Einstein Yang Mills Higgs dark energy in light of observations
Authors: Adak Debabrata
Published: December 2020

We study the observational aspects of Einstein Yang Mills Higgs dark energy model and constrain the parameters space from the latest observational data from type Ia supernovae, observational Hubble data, baryon acoustic oscillation data and cosmic microwave background radiation shift parameter data. It is found from the analysis of data that the Higgs field in presence of gauge fields can successfully describe the present accelerated expansion of the universe consistent with the astrophysical observations.
Flow optimization process in a transportation network
Authors: Forgerini F. L. , de Sousa O. F.
Published: December 2020

Numerous networks, such as transportation, distribution, and delivery networks optimize their designs in order to increase efficiency and lower costs, improving the stability of its intended functions, etc. Networks that distribute goods, such as electricity, water, gas, telephone, and data (Internet), or services as mail, railways, and roads are examples of transportation networks. The optimal design fixes network architecture, including clustering, degree distribution, hierarchy, community structures, and other structural metrics. These networks are specifically designed for efficient transportation, minimizing transit times and costs. All sorts of transportation networks face the same problem: traffic congestion among their channels. In this work, we considered a transportation network model in which we optimize/minimize a cost function for the flow/current at each channel/link of the network. We performed simulations and an analytical study of this problem, focusing on the fraction of used channels and the flow distribution through these channels. In this work we show that, after the initial time, the number of used channels are constant and, remarkably, do not depends on the lattice structure. One can see in our results two different regimes, for high and for small current flows. In the first regime, all channels in the network are used, whereas for the small current flow, surprisingly, the fraction of used channels depends on the square root of the flow.
Availability of Systems Subject to Multiple Failure Modes Under Calendar-based Inspection
Authors: Pant Himani , Singh S. B. , Chantola Neelam
Published: December 2020

The availability of a maintained system subject to multiple failure modes undergoing periodic inspection is studied in this paper. Calendar-based inspection policy is being incorporated. Explicitly, a system with a functional state and [Formula: see text] failure modes is taken into account. Failure time of each failure mode is random. As the [Formula: see text]th ([Formula: see text]) failure occurs, the respective corrective repair taking a random time [Formula: see text] [Formula: see text] is carried out. Some theorems on the point availability and limiting average availability are obtained in this study. The application of the derived result is explained through an example of wind turbine system.
Reconstructing the Mass Distribution Function of a Two-Span Beam With an Overhang via the Fundamental Mode
Authors: Zhang Li-Hua , He Min , Wang Qi-Shen , Elishakoff I.
Published: December 2020

In this paper, we discuss the following inverse problem: how to reconstruct the mass distribution function of a two-span beam with an overhang via its polynomial fundamental mode and polynomial stiffness function. This leads to a basic equations group constituted by the coefficients of the mass distribution and the stiffness distribution function. To make the basic equations group match, one way is to divide it into two sub- equations, and solve them. We specify the method for solving this inverse problem, and research the existence and rationality of the positive solutions.
"Our perspective matters."
Authors: Kirabo Lynn
Published: December 2020

Traditional approaches to accessible human-computer interaction focus on the needs and requirements of users in the Global North. While there has been some work on interaction accessibility for people in the Global South, these efforts usually focus on assistive technology rather than universal design. The work described here uses the goals of universal design, like cultural appropriateness, to understand the needs of diverse users in Kampala, Uganda, and Kigali, Rwanda. Preliminary results have revealed prominent absences of features related to physical mobility and hearing impairments. The subsequent phase of this work is to partner with local organizations to implement the resulting recommendations. Our goal is for these recommendations to inform new information technology and interactions designs that can support local stakeholders in their efforts to provide transportation services to people of all abilities.
Mechanical Properties of Carbon/Basalt Fabric Hybrid Composites Doped with Hexagonal Boron Nitride Nanopowders
Authors: Bakal Gumus Fatma , Yapici Ahmet
Published: December 2020

The effect of various amounts (1, 2, and 4 wt%) of hexagonal nano boron nitride on the mechanical properties of carbon/basalt fabric reinforced epoxy hybrid composite laminates has been investigated through experimental methods. The hybrid composites were fabricated using hand lay-up and vacuum infusion techniques. The produced hybrid nanocomposites were characterized by SEM-EDS Mapping, XRD, and FT-IR analyses. In order to find the strength of the composites under the influence of uniaxial tensile, tensile experiments were conducted in ASTM D3039 standard, bending experiments in ASTM 7264, and impact experiments in ASTM D256 standard. The fracture morphologies were investigated after the tensile test using a stereomicroscope. The results of this study showed that the mechanical properties of hybrid composites were substantially improved by the addition of h-nBNs fillers at 1 wt% because of the high adhesion strength in the interphase between h-nBNs epoxy-fiber interactions.
Long Noncoding RNA MALAT1 Promotes Colorectal Cancer Progression by Acting as a ceRNA of miR‐508‐5p to Regulate RAB14 Expression
Authors: Zhang Chen , Yao Kunhou , Zhang Junjie , Wang Chenyu , Wang Chaoyang , Qin Changjiang
Published: December 2020

Accumulating evidence suggested that lncRNA MALAT1 plays critical roles in the commencement and progression of malignant cancers. Nevertheless, the function of MALAT1 in colorectal cancer (CRC) remains largely unknown. In the present study, we reported that MALAT1 expression is significantly upregulated in CRC and correlated with advanced TNM stage, lymph node metastasis, and worse prognosis in patients. Functional assays revealed that MALAT1 knockdown reduced CRC cell growth and invasion abilities in vitro. Mechanistically, we discovered that MALAT1 may serve as a competing endogenous RNA (ceRNA) to miR‐508‐5p in CRC progression. Bioinformatics analysis and luciferase assays confirmed that RAB14 acts as a target of miR‐508‐5p. In addition, downregulation of RAB14 reduced the progression of CRC. Collectively, our findings indicated that MALAT1 could promote CRC progress by sponging miR‐508‐5p and enhancing RAB14 expression, which provides a therapeutic target in CRC treatment.
Anemoside B4 Protects against Acute Lung Injury by Attenuating Inflammation through Blocking NLRP3 Inflammasome Activation and TLR4 Dimerization
Authors: Yuan Renyikun , He Jia , Huang Liting , Du Li-Jun , Gao Hongwei , Xu Qiongming , Yang Shilin
Published: December 2020

Acute lung injury (ALI) is an acute inflammatory process in the lung parenchyma. Anemoside B4 (B4) was isolated from Pulsatilla, a plant-based drug against inflammation and commonly applied in traditional Chinese medicine. However, the anti-inflammatory effect and the mechanisms of B4 are not clear. In this study, we explored the potential mechanisms and anti-inflammatory activity of B4 both in vitro and in vivo. The results indicated that B4 suppressed the expression of iNOS, COX-2, NLRP3, caspase-1, and IL-1β. The ELISA assay results showed that B4 significantly restrained the release of inflammatory cytokines like TNF-α, IL-6, and IL-1β in macrophage cells. In addition, B4 rescued mitochondrial membrane potential (MMP) loss in (lipopolysaccharide) LPS plus ATP stimulated macrophage cells. Co-IP and molecular docking results illustrated that B4 disrupted the dimerization of TLR4. For in vivo results, B4 exhibited a protective effect on LPS and bleomycin- (BLM-) induced ALI in mice through suppressing the lesions of lung tissues, the release of inflammatory cytokines, and the levels of white blood cells, neutrophils, and lymphoid cells in the blood. Collectively, B4 has a protective effect on ALI via blocking TLR4 dimerization and NLRP3 inflammasome activation, suggesting that B4 is a potential agent for the treatment of ALI.