bluuebunny/crossref_metadata_2025 huggingface dataset:
Is bilateral corticospinal connectivity impaired in patients with chronic obstructive pulmonary disease?
Authors: Cabibel Vincent , Héraud Nelly , Perrey Stéphane , Oliver Nicolas , Alexandre François , Varray Alain
Published: July 2020

Key points

During moderate and high levels of quadriceps force production, the ipsilateral motor cortex is concomitantly activated with the contralateral motor cortex throughout the corpus callosum to generate the motor command.

Chronic obstructive pulmonary disease (COPD) patients display a structurally impaired corpus callosum that may explain the reduced motor command in this population, which in turn contributes to COPD‐related muscle weakness of the knee extensors.

The study aimed to determine whether bilateral connectivity was impaired and ipsilateral activation was lowered during unilateral strength production of the knee extensors.

Our results indicate impaired bilateral connectivity but preserved ipsilateral activation in patients during unilateral isometric contractions of 50% of maximum voluntary strength.

The preservation of ipsilateral activation during force production despite impaired bilateral connectivity is consistent with a reorganization of bilateral motor network function that drives unilateral strength production.

The contralateral primary motor cortex (M1) is not the only brain area implicated in motor command generation. During moderate and high levels of quadriceps force production, the ipsilateral M1 is concomitantly activated. Such activation is mediated by the corpus callosum, the main component of bilateral connectivity. Structural damage to the corpus callosum has been observed in chronic obstructive pulmonary disease (COPD) patients, which might reduce ipsilateral activation and contribute to the lower motor command associated with COPD muscle weakness. We thus aimed to determine whether bilateral connectivity and ipsilateral activation were impaired in COPD. Twenty‐two COPD patients and 21 healthy age‐matched controls were evaluated by transcranial magnetic stimulation, at rest and during 50% of maximal voluntary isometric contraction (MVIC) of the dominant vastus lateralis muscle. Bilateral connectivity was determined by the ipsilateral silent period (iSP) during 50% MVIC. Ipsilateral activation was determined as the increase in ipsilateral excitability from rest to 50% MVIC. As expected, COPD patients had significantly lower MVIC (−25%, p = 0.03). These patients also showed a significantly lower iSP (−53%, p < 0.001) compared to controls. The ipsilateral excitability was increased in patients and controls (×2.5 and ×3.5, respectively, p < 0.001) but not differently between groups (p = 0.84). Despite impaired bilateral connectivity in COPD, ipsilateral activation was not increased. Reorganization in the patients’ interhemispheric pathways could explain the preserved ipsilateral activation.
Adaptation to a low carbohydrate high fat diet is rapid but impairs endurance exercise metabolism and performance despite enhanced glycogen availability
Authors: Burke Louise M. , Whitfield Jamie , Heikura Ida A. , Ross Megan L. R. , Tee Nicolin , Forbes Sara F. , Hall Rebecca , McKay Alannah K. A. , Wallett Alice M. , Sharma Avish P.
Published: July 2020

Key points

Brief (5–6 days) adaptation to a low carbohydrate high fat diet in elite athletes increased exercise fat oxidation to rates previously observed with medium (3–4 weeks) or chronic (>12 months) adherence to this diet, with metabolic changes being washed out in a similar time frame.

Increased fat utilisation during exercise was associated with a 5–8% increase in oxygen cost at speeds related to Olympic Programme races.

Acute restoration of endogenous carbohydrate (CHO) availability (24 h high CHO diet, pre‐race CHO) only partially restored substrate utilisation during a race warm‐up. Fat oxidation continued to be elevated above baseline values although it was lower than achieved by 5–6 days’ keto adaptation; CHO oxidation only reached 61% and 78% of values previously seen at exercise intensities related to race events.

Acute restoration of CHO availability failed to overturn the impairment of high‐intensity endurance performance previously associated with low carbohydrate high fat adaptation, potentially due to the blunted capacity for CHO oxidation.

We investigated substrate utilisation during exercise after brief (5–6 days) adaptation to a ketogenic low‐carbohydrate (CHO), high‐fat (LCHF) diet and similar washout period. Thirteen world‐class male race walkers completed economy testing, 25 km training and a 10,000 m race (Baseline), with high CHO availability (HCHO), repeating this (Adaptation) after 5–6 days’ LCHF (n = 7; CHO: <50 g day−1, protein: 2.2 g kg−1 day−1; 80% fat) or HCHO (n = 6; CHO: 9.7 g kg−1 day−1; protein: 2.2 g kg−1 day−1) diet. An Adaptation race was undertaken after 24 h HCHO and pre‐race CHO (2 g kg−1) diet, identical to the Baseline race. Substantial (>200%) increases in exercise fat oxidation occurred in the LCHF Adaptation economy and 25 km tests, reaching mean rates of ∼1.43 g min−1. However, relative (ml min−1 kg−1) was higher (P < 0.0001), by ∼8% and 5% at speeds related to 50 km and 20 km events. During Adaptation race warm‐up in the LCHF group, rates of fat and CHO oxidation at these speeds were decreased and increased, respectively (P < 0.001), compared with the previous day, but were not restored to Baseline values. Performance changes differed between groups (P = 0.009), with all HCHO athletes improving in the Adaptation race (5.7 (5.6)%), while 6/7 LCHF athletes were slower (2.2 (3.4)%). Substrate utilisation returned to Baseline values after 5–6 days of HCHO diet. In summary, robust changes in exercise substrate use occurred in 5–6 days of extreme changes in CHO intake. However, adaptation to a LCHF diet plus acute restoration of endogenous CHO availability failed to restore high‐intensity endurance performance, with CHO oxidation rates remaining blunted.
Multilevel Validation of a Male Neck Finite Element Model With Active Musculature
Authors: Barker Jeffrey B. , Cronin Duane S.
Published: July 2020

Computational models of the human neck have been developed to assess human response in impact scenarios; however, the assessment and validation of such models is often limited to a small number of experimental data sets despite being used to evaluate the efficacy of safety systems and potential for injury risk in motor vehicle collisions. In this study, a full neck model (NM) with active musculature was developed from previously validated motion segment models of the cervical spine. Tissue mechanical properties were implemented from experimental studies, and were not calibrated. The neck model was assessed with experimental studies at three levels of increasing complexity: ligamentous cervical spine in axial rotation, axial tension, frontal impact, and rear impact; postmortem human subject (PMHS) rear sled impact; and human volunteer frontal and lateral sled tests using an open-loop muscle control strategy. The neck model demonstrated good correlation with the experiments ranging from quasi-static to dynamic, assessed using kinematics, kinetics, and tissue-level response. The contributions of soft tissues, neck curvature, and muscle activation were associated with higher stiffness neck response, particularly for low severity frontal impact. Experiments presenting single-value data limited assessment of the model, while complete load history data and cross-correlation enabled improved evaluation of the model over the full loading history. Tissue-level metrics demonstrated higher variability and therefore lower correlation relative to gross kinematics, and also demonstrated a dependence on the local tissue geometry. Thus, it is critical to assess models at the gross kinematic and the tissue levels.
Model-Order Reduction of Flexible Multibody Dynamics Via Free-Interface Component Mode Synthesis Method
Authors: Tian Qinglong , Lan Peng , Yu Zuqing
Published: July 2020

A new method of model-order reduction for the flexible multibody system which undergoes large deformation and rotation is proposed. At first, the flexible multibody system is modeled by absolute nodal coordinate formulation (ANCF), and then, the whole motion process of the system is divided into a series of quasi-static equilibrium configurations according to a given criterion. Afterward, motion equation is locally linearized based on the Taylor expansion. Therefore, the constant tangent stiffness matrix is obtained and does not need to be updated until the next configuration. Based on the locally linearized motion equation, the free-interface component mode synthesis (CMS) method is adopted to reduce the degrees-of-freedom (DOF) of the flexible multibody system molded by ANCF. The generalized-α integrator is used to solve the reduced motion equation. To verify the accuracy and efficiency of the proposed method, three examples including a free-falling pendulum, a flexible spinning beam and a deployable sail arrays are presented. Results show that the proposed method is able to reduce the computing time and maintain high accuracy.
Technical Basis Part 2 for Code Case N-889: Reference Stress Corrosion Crack Growth Rate Curves for Irradiated Austenitic Stainless Steels in Light Water Reactor Environments
Authors: Eason Ernest D. , Pathania Raj , Jenssen Anders , Weakland Dennis P.
Published: July 2020

A multiyear international data collection, data review, modeling, and implementation project was recently completed, producing stress corrosion crack growth rate (CGR) reference curves for irradiated austenitic stainless steels in light water reactor (LWR) environments that were adopted as ASME B&PV Section XI Code Case N-889. As described in a technical basis Part 1 paper, over 800 CGR data points were collected from six laboratories worldwide, an international expert panel reviewed and ranked the data, and the better-ranked data were used to calibrate empirical models for irradiation-assisted stress corrosion cracking (IASCC) CGR in boiling water reactor (BWR) normal water chemistry (NWC), BWR hydrogen water chemistry (HWC) and pressurized water reactor (PWR) primary water environments. Part 1 also describes the custom fitting process, quality of fit, and comparisons with related literature and data not used for fitting. This technical basis Part 2 paper describes shifting the mean models to the 75th percentile of the calibration data, simplifying to produce the N-889 curves, and comparing with previous reference curves and over 500 data points not used for developing the N-889 curves, including weld, cast, and heat-affected-zone (HAZ) materials, additional wrought laboratory data, and field data from repeated inspection of BWR core shrouds. Part 2 also describes the irradiated yield stress model in Case N-889, compares that model with its calibration data and other data not used for calibration, and presents example calculations using both yield stress and CGR equations.
Technical Basis Part 1 for Code Case N-889: Data Selection and Modeling of Stress Corrosion Crack Growth Rates for Irradiated Austenitic Stainless Steels in Light Water Reactor Environments
Authors: Eason Ernest D. , Pathania Raj , Jenssen Anders
Published: July 2020

A multiyear international data collection, data review, modeling, and implementation project was recently completed, producing stress corrosion crack growth rate (CGR) models and reference curves for irradiated austenitic stainless steels in light water reactor (LWR) environments. The curves have been approved as ASME B&PV Section XI Code Case N-889, and this paper is the technical basis Part 1 for Case N-889, summarizing collection, review, and selection of calibration data, modeling, and analysis of fit. Over 800 CGR data points were collected from six laboratories worldwide, an international expert panel reviewed and ranked the data, and the better-ranked data were used to calibrate empirical models for irradiation-assisted stress corrosion cracking (IASCC) CGR in boiling water reactor (BWR) normal water chemistry (NWC), BWR hydrogen water chemistry (HWC), and pressurized water reactor (PWR) primary water environments. This Part 1 paper also discusses related literature and compares with other data not used for mean model calibration. A technical basis Part 2 paper describes shifting the mean models to the 75th percentile, simplifying to produce Case N-889 reference curves, and comparing with previous reference curves and over 500 data points not used for reference curve development, including weld, cast, and heat affected zone (HAZ) materials, additional wrought laboratory data, and field data from repeated inspection of BWR core shrouds. Part 2 also describes the irradiated yield stress model in Case N-889, compares that model with its calibration data and other data not used for calibration, and presents example calculations.
Fault-Tolerance Techniques and Global Positioning Systems Based on Artificial Intelligence for the Analysis of Corrosion Impact on the Pipelines of Oil and Gas Industry
Authors: Cid-Galiot Jonathan J. , Aguilar-Lasserre Alberto A. , Rodriguez-Jarquín José P. , Villanueva-Vasquez Daniel , Posada-Gómez Rubén , Juárez-Martínez Ulises
Published: July 2020

The pipeline transport system (PTS) is a means of land and marine transport, reliable in the oil sector as well as in various industries, considering its economy and speed to transport a product. The instability of this system, though, currently takes several variables, which directly affect the mechanical integrity (MI) of the same, due to the imminent internal and external formation of the phenomenon classified as corrosion (C). To address this problem, fault tolerance control techniques (FTCS), global positioning systems (GPS), and artificial intelligence (AI), are useful tools to deal with uncertainty and minimize subjectivity, through system modeling. That will allow the identification, control, and timely monitoring of risk factors. During the last 30 years, important contributions on corrosion to pipelines in the oil and gas industry have been published. This document aims to build a systematic literary review (SLR), from an integrative perspective, recognizing various studies in the periods 1987–2018, analyzing 245 documents, from three posts previously not addressed together within the context of corrosion to PTS, offering an apology if any document relevant to the subject was excluded from the work. Findings about the topics of analysis, discussions, and future lines of research are described.
General and adaptive synthesis protocol for high-quality organosilane self-assembled monolayers as tunable surface chemistry platforms for biochemical applications
Authors: Artusio Fiora , Fumagalli Francesco , Bañuls-Ciscar Jorge , Ceccone Giacomo , Pisano Roberto
Published: July 2020

The controlled modification of surface properties represents a pervasive requirement to be fulfilled when developing new technologies. In this paper, we propose an easy-to-implement protocol for the functionalization of glass with self-assembled monolayers (SAMs). The adaptivity of the synthesis route was demonstrated by the controlled anchoring of thiol, amino, glycidyloxy, and methacrylate groups onto the glass surface. The optimization of the synthetic pathway was mirrored by extremely smooth SAMs (approximately 150 pm roughness), layer thickness comparable to the theoretical molecule length, absence of silane islands along the surface, quasi-unitary degree of packing, and tailored wettability and charge. The functionalization kinetics of two model silanes, 3-mercapto- and 3-amino-propyltrimethoxysilane, was determined by cross-comparing x-ray photoelectron spectroscopy and time of flight secondary ion mass spectrometry data. Our SAMs with tailored physicochemical attributes will be implemented as supports for the crystallization of pharmaceuticals and biomolecules in upcoming studies. Here, the application to a small molecule drug model, namely aspirin, was discussed as a proof of concept.
Mapping of host-parasite-microbiome interactions reveals metabolic determinants of tropism and tolerance in Chagas disease
Authors: Hossain E. , Khanam S. , Dean D. A. , Wu C. , Lostracco-Johnson S. , Thomas D. , Kane S. S. , Parab A. R. , Flores K. , Katemauswa M. , Gosmanov C. , Hayes S. E. , Zhang Y. , Li D. , Woelfel-Monsivais C. , Sankaranarayanan K. , McCall L.-I.
Published: July 2020

Chemical cartography of experimental gastrointestinal Chagas disease identifies previously-unknown mechanisms of disease tolerance.
Role of Ca
2+
transients at the node of the mouse embryo in breaking of left-right symmetry
Authors: Mizuno Katsutoshi , Shiozawa Kei , Katoh Takanobu A. , Minegishi Katsura , Ide Takahiro , Ikawa Yayoi , Nishimura Hiromi , Takaoka Katsuyoshi , Itabashi Takeshi , Iwane Atsuko H. , Nakai Junichi , Shiratori Hidetaka , Hamada Hiroshi
Published: July 2020

Left-right (L-R) asymmetric intraciliary calcium transient at the node is the determinant of L-R axis in mice.
The elusive cyclotriphosphazene molecule and its Dewar benzene–type valence isomer (P
3
N
3
)
Authors: Zhu Cheng , Eckhardt André K. , Bergantini Alexandre , Singh Santosh K. , Schreiner Peter R. , Kaiser Ralf I.
Published: July 2020

Cyclotriphosphazene (P
3
N
3
) and its Dewar benzene–type isomer were identified on the basis of their photochemical properties.
Speech perception at birth: The brain encodes fast and slow temporal information
Authors: Cabrera Laurianne , Gervain Judit
Published: July 2020

At birth, the auditory system is able to encode speech in fine acoustic details on the basis of its slowest amplitude modulations.
Illuminating dark fishing fleets in North Korea
Authors: Park Jaeyoon , Lee Jungsam , Seto Katherine , Hochberg Timothy , Wong Brian A. , Miller Nathan A. , Takasaki Kenji , Kubota Hiroshi , Oozeki Yoshioki , Doshi Sejal , Midzik Maya , Hanich Quentin , Sullivan Brian , Woods Paul , Kroodsma David A.
Published: July 2020

Multisensor satellite technologies reveal large-scale illegal fishing in some of the world’s least monitored waters.
Enabling the assessment of trauma-induced hemorrhage via smart wearable systems
Authors: Zia Jonathan , Kimball Jacob , Rolfes Christopher , Hahn Jin-Oh , Inan Omer T.
Published: July 2020

Assessing the mechanical function of the heart using wearable sensors may soon enable robust, data-driven treatment of hemorrhage.
Peptidoglycan editing provides immunity to
Acinetobacter baumannii
during bacterial warfare
Authors: Le Nguyen-Hung , Peters Katharina , Espaillat Akbar , Sheldon Jessica R. , Gray Joe , Di Venanzio Gisela , Lopez Juvenal , Djahanschiri Bardya , Mueller Elizabeth A. , Hennon Seth W. , Levin Petra Anne , Ebersberger Ingo , Skaar Eric P. , Cava Felipe , Vollmer Waldemar , Feldman Mario F.
Published: July 2020

A peptidoglycan editing mechanism confers protection against T6SS assaults without relying on immunity proteins.
Content-based features predict social media influence operations
Authors: Alizadeh Meysam , Shapiro Jacob N. , Buntain Cody , Tucker Joshua A.
Published: July 2020

Coordinated political influence operations leave a distinct signature in content that machine learning can detect.
Treatment of psoriasis with NFKBIZ siRNA using topical ionic liquid formulations
Authors: Mandal Abhirup , Kumbhojkar Ninad , Reilly Charles , Dharamdasani Vimisha , Ukidve Anvay , Ingber Donald E. , Mitragotri Samir
Published: July 2020

A method is reported using ionic liquids for topical delivery of siRNA into skin for the treatment of psoriasis.
Geometrically reconfigurable 3D mesostructures and electromagnetic devices through a rational bottom-up design strategy
Authors: Bai Ke , Cheng Xu , Xue Zhaoguo , Song Honglie , Sang Lei , Zhang Fan , Liu Fei , Luo Xiang , Huang Wen , Huang Yonggang , Zhang Yihui
Published: July 2020

A rational bottom-up design strategy was developed to build microelectronic devices capable of 3D geometrical reconfiguration.
Oysters Booming on New Reefs, But Can They Survive Disease?
Authors: Stokstad Erik
Published: July 2020

Thanks to a large network of reefs created in 2004, a booming population of native oysters has taken hold in the Great Wicomico River, a small tributary of the Chesapeake Bay, researchers report in a paper published online by
Science
this week.
Apoptosis of hematopoietic progenitor-derived adipose tissue–resident macrophages contributes to insulin resistance after myocardial infarction
Authors: Vasamsetti Sathish Babu , Coppin Emilie , Zhang Xinyi , Florentin Jonathan , Koul Sasha , Götberg Matthias , Clugston Andrew S. , Thoma Floyd , Sembrat John , Bullock Grant C. , Kostka Dennis , St. Croix Claudette M. , Chattopadhyay Ansuman , Rojas Mauricio , Mulukutla Suresh R. , Dutta Partha
Published: July 2020

Myocardial infarction promotes insulin resistance via apoptosis of macrophages in visceral adipose tissue.
Multichannel optogenetic stimulation of the auditory pathway using microfabricated LED cochlear implants in rodents
Authors: Keppeler Daniel , Schwaerzle Michael , Harczos Tamas , Jablonski Lukasz , Dieter Alexander , Wolf Bettina , Ayub Suleman , Vogl Christian , Wrobel Christian , Hoch Gerhard , Abdellatif Khaled , Jeschke Marcus , Rankovic Vladan , Paul Oliver , Ruther Patrick , Moser Tobias
Published: July 2020

Optogenetic hearing restoration in rodents by LED-based multichannel optical cochlear implants provides improved spectral selectivity.
Draft Genome Sequences of Three Fusarium circinatum Isolates Used To Inoculate a Pedigreed Population of
Pinus elliottii
Seedlings
Authors: Fulton James C. , Huguet-Tapia Jose C. , Adams Stephanie M. , Dufault Nicholas S. , Quesada Tania , Brawner Jeremy T.
Published: July 2020

Here, we announce the draft genome sequences of three
Fusarium circinatum
isolates that were used to inoculate slash pines (
Pinus elliottii
) at the U.S. Forest Service Resistance Screening Center in Asheville, North Carolina. The genomes of these isolates were similar to other publicly available genomes, with average nucleotide identity values of >0.98.
Middle Mississippian (late Osagean; early Viséan) Floyds Knob glauconite interval, Borden and Fort Payne Formations, Appalachian and Illinois Basins, Kentucky, USA: Synergistic influence of tectonics, paleoclimate, and paleogeography
Authors: Udgata* Devi B.P. , Ettensohn Frank R.
Published: July 2020

During latest Devonian to Middle Mississippian parts of the Neoacadian and Ouachita orogenies, the Appalachian Basin and parts of the Illinois Basin were filled with clastic debris derived from the westward-prograding Borden-Grainger-Price-Pocono clastic wedge. This delta complex is overlain by the widespread shallow-water Newman–Greenbrier–Slade–St. Louis–Warsaw–Salem–Harrodsburg carbonate interval across sediment-starved surfaces, comprising the Floyds Knob bed or interval. The Middle Mississippian (late Osagean; early Viséan) Floyds Knob interval is less than a meter to several meters thick and is composed of multiple zones of pelletal glauconite, finely divided glauconitic shales, glauconitic carbonates, and locally derived carbonate mud mounds. The interval occurs across most of the Borden-Grainger delta platform, delta front, prodelta, and within the starved-basin area seaward of the delta complex, which was then filled with the Fort Payne Formation. This study reports herein the first occurrence of the Floyds Knob interval within the Fort Payne Formation. Glauconite deposition in this interval apparently occurred in mildly oxic to dysoxic, sediment-starved, shallow-marine settings and is believed to represent termination of major clastic influx in more proximal parts of the Neoacadian foreland basin during lowstand conditions. Moreover, these starved-basin conditions can be correlated with delta diversion following bulge migration during flexural loading–type relaxation. During these sediment-starved, lowstand conditions, glauconite was deposited across deltaic and basinal settings in central and distal parts of the Neoacadian foreland basin, as well as in eastern parts of the present-day Illinois intracratonic basin. The cessation of deltaic clastic sedimentation permitted development of carbonate mud mounds and associated glauconitic shales on and near reactivated structures in central parts of the Fort Payne starved basin and set the stage for the widespread deposition of thick, Meramecian–Chesterian carbonates throughout the basins during succeeding subtropical and lowstand conditions. Whether less-than-a-meter or tens-of-meters thick, the Floyds Knob interval is a widespread Middle Mississippian chronostratigraphic interval in the east-central United States that reflects a change in tectonic regime, which is recorded in the shift from predominantly clastic to carbonate sedimentation across a broad region. Aside from its correlative value, the unit demonstrates consequent sedimentary responses to the interplay among tectonism, paleoclimate, and paleogeography.
Association of anterior segment parameters and 5-year incident narrow angles: findings from an older Chinese population
Authors: Jiang Yu , Wang Wei , Wang Lanhua , He Mingguang
Published: July 2020

Purpose

To assess the association of anterior segment optical coherence tomography (AS-OCT) parameters and 5-year incident narrow angle in China.

Methods

This was a prospective cohort study of people aged 50 and older residing in Liwan District, Guangzhou, China. Random clustering sampling was used to identify adults aged 50 years and older in Liwan District, Guangzhou. In 2008 and 2013, this study was repeated and added AS-OCT imaging under dark and light conditions. Customised software (ZAAP) was used to analyse horizontal AS-OCT scans. Angle opening distance (AOD), trabecular iris space area (TISA), anterior chamber volume (ACV) and maximal iris thickness (ITM) were measured. Multiple logistic regression analysis models were used to investigate the associations of the final angle status with baseline AS-OCT parameters. ORs and 95% CIs were calculated.

Results

Of the 220 subjects with eligible AS-OCT images and gonioscopic results in 2008, the response rate was 77.3%. A total of 27 (15.9%) subjects developed narrow angles and 143 (84.1%) had open angles on gonioscopy in 2013. Subjects developed narrow angles had greater spherical equivalent and shallower anterior chamber depth, smaller angle parameters, thicker IT750 and ITM, smaller anterior chamber parameters, greater lens vault, and smaller dynamic parameters (ΔITM, ΔACA, ΔACV) at baseline. After adjusting confounders, the predictors of incident narrow angles included smaller AOD750, TISA750, ΔACA and greater ITM, ΔIarea.

Conclusions

Incident narrow angles were associated with smaller anterior ocular dimensions, thicker iris and smaller light-to-dark changes at baseline. These findings can help in early diagnosis in this population.
Subclinical dysthyroid optic neuropathy: tritan deficiency as an early sign of dysthyroid optic neuropathy
Authors: Garip-Kuebler Aylin , Halfter Kathrin , Reznicek Lukas , Klingenstein Annemarie , Priglinger Siegfried , Hintschich Christoph R
Published: July 2020

Purpose

The aim of this research was to investigate the subclinical findings of dysthyroid optic neuropathy (DON) and to look for early indicators for optic nerve compression in patients with Graves’ orbitopathy.

Patients and Methods

In this observational, retrospective study, the medical charts of 24 patients (32 eyes) with a diagnosis of DON between 2008 and 2019 were included. Our goal was to identify potential pathological signs in patients with DON prior to the definitive diagnosis of DON.

Results

We discovered that the earliest pathological sign in the subclinical cases was tritan deficiency obtained with a standardised colour vision test by Arden. In all cases but one, regardless of the visual field (VF) defects, the tritan values were pathological (based on a threshold of ≥8%) in the subclinical phase. The mean tritan value was 19.12% (range 6.9–80.8%) at the time of the subclinical phase and 32.16% (range 6.3–100.0%) at the time of the diagnosis of DON. The sensitivity of the colour vision test was 20% for protan and 96.67% for tritan in the subclinical phase. At the time of the definitive diagnosis of DON, the sensitivity of protan was 48.15% compared to 96.30% for tritan.

Conclusion

We found that changes in vision affecting the blue-yellow (tritan) colours resulting from the compression of optic nerve, even in affected patients with normal VF tests, are a reliable early sign of DON.
Cost analysis of the flash monitoring system (FreeStyle Libre 2) in adults with type 1 diabetes mellitus
Authors: Oyagüez Itziar , Merino-Torres Juan Francisco , Brito Miguel , Bellido Virginia , Cardona-Hernandez Roque , Gomez-Peralta Fernando , Morales-Perez Francisco
Published: July 2020

Introduction

Compare cost of the interstitial liquid glucose flash monitoring (FM) system (FreeStyle Libre 2) versus self-monitoring of blood glucose (SMBG) in adults with type 1 diabetes mellitus (T1DM) in Spain.

Research design and methods

A model was developed to estimate, with the perspective of the Spanish health system, the annual costs associated with glucose monitoring and hypoglycemic events management in T1DM population, with multiple insulin daily doses (MDI). According to published evidence, rate of severe hypoglycemia (SHE) of 4.90 episodes per patient-year was applied. Reduction of SHE (58.6%) was modeled associated with FM use. Published rates of hospital care (20.2%) and subsequent admission (16%) were assumed for SHE. The daily consumption of strips and lancets was 9 in patients with SMBG (before and after 4 daily intakes and at bedtime) and 0.5 for FM users (according to IMPACT trial findings). Annual consumption of 26 FM sensors was considered (1 every 14 days). Unit costs (in € of 2019, excluding VAT) were obtained from literature and national databases. Sensitivity analyses (SA) were carried out to evaluate the model robustness.

Results

The total annual cost/patient was €4437 for SMBG and €2526 for FM. The use of FM would be associated with an annual savings in the costs of monitoring and managing hypoglycemic events of €1911 per patient-year. In a hypothetical cohort of 1000 patients with T1DM MDI, FM could avoid in 1 year 4900 SHE, 93 hospitalizations for SHE. In addition, the use of FM would generate total savings of up to €1 910 000 per year. In the SA with alternative hypoglycemia events rates and use of strips and lancets, and including non-SHE episodes, savings from €370 000 to €1 760 000 were observed with FM.

Conclusions

The use of the FM system to monitor glucose in adults with T1DM treated with MDI, would reduce hypoglycemic events and would result in cost savings for the health system.
Diversification in causes of death in low-mortality countries: emerging patterns and implications
Authors: Bergeron-Boucher Marie-Pier , Aburto José Manuel , van Raalte Alyson
Published: July 2020

Introduction

An important role of public health organisations is to monitor indicators of variation, so as to disclose underlying inequality in health improvement. In industrialised societies, more individuals than ever are reaching older ages and have become more homogeneous in their age at death. This has led to a decrease in lifespan variation, with substantial implications for the reduction of health inequalities. We focus on a new form of variation to shed further light on our understanding of population health and ageing: variation in causes of death.

Methods

Data from the WHO Mortality Database and the Human Mortality Database are used to estimate cause-of-death distributions and life tables in 15 low-mortality countries. Cause-of-death variation, using 19 groups of causes, is quantified using entropy measures and analysed from 1994 to 2017.

Results

The last two decades have seen increasing diversity in causes of death in low-mortality countries. There have been important reductions in the share of deaths from diseases of the circulatory system, while the share of a range of other causes, such as diseases of the genitourinary system, mental and behavioural disorders, and diseases of the nervous system, has been increasing, leading to a more complex cause-of-death distribution.

Conclusions

The diversification in causes of death witnessed in recent decades is most likely a result of the increase in life expectancy, together with better diagnoses and awareness of certain diseases. Such emerging patterns bring additional challenges to healthcare systems, such as the need to research, monitor and treat a wider range of diseases. It also raises new questions concerning the distribution of health resources.
Healthy living practices in families and child health: 5-year follow-up of Taiwan Birth Cohort Study
Authors: Lin Yi-Ching , Li Yi-Fan , Chiang Tung-liang
Published: July 2020

Objectives

We have previously developed the Child Healthy Living Practices in Family (CHLPF) Index and found that the CHLPF Index was concurrently associated with the health of children at age 3. In this follow-up study, we aimed to examine whether healthy living practices in family at age 3 predicted health of children at school age.

Design and setting

Data came from the Taiwan Birth Cohort Study designed to assess the development and health of 24 200 children born in 2005.

Participants

A total of 18 553 cohort members whose mothers or primary caregivers had completed 6-month, 3-year, 5-year and 8-year surveys were included for analysis, representing a response rate of 87.3%.

Outcome measures

A multiple logistic regression model was used to test the relationship between mother-rated children’s health at age 8 and the CHLPF Index level, after controlling for sex, birth outcomes, family structure, parental education, residential area, family income and mother-rated child’s health at age 3.

Results

The percentage of mother-rated good health at age 8 was 79.7%. Compared with the low CHLPF level, the adjusted OR of mother-rated good health was 1.38 (95% CI 1.19 to 1.60), 1.21 (95% CI 1.10 to 1.35) and 1.17 (95% CI 1.07 to 1.29), respectively, for high, high–low and mid-low CHLPF levels. Moreover, the prevalence of mother-rated good health at age 8 with high-level CHLPF Index in the low-income group was similar to that of the high-income group (83.72% vs 84.18%); the prevalence with low-level CHLPF Index in the low-income group was much lower than that of the high-income group (70.21% vs 78.98%).

Conclusions

Our study underscores that high level of healthy living practices in early childhood is positively associated with good health at school age, particularly for children from disadvantaged families.
Medical leadership: boon or barrier to organisational performance? A thematic synthesis of the literature
Authors: Savage Mairi , Savage Carl , Brommels Mats , Mazzocato Pamela
Published: July 2020

Objective

The influx of management ideas into healthcare has triggered considerable debate about if and how managerial and medical logics can coexist. Recent reviews suggest that clinician involvement in hospital management can lead to superior performance. We, therefore, sought to systematically explore conditions that can either facilitate or impede the influence of medical leadership on organisational performance.

Design

Systematic review using thematic synthesis guided by the Enhancing Transparency in Reporting the synthesis of Qualitative research statement.

Data sources

We searched PubMed, Web of Science and PsycINFO from 1 January 2006 to 21 January 2020.

Eligibility criteria

We included peer-reviewed, empirical, English language articles and literature reviews that focused on physicians in the leadership and management of healthcare.

Data extraction and synthesis

Data extraction and thematic synthesis followed an inductive approach. The results sections of the included studies were subjected to line-by-line coding to identify relevant meaning units. These were organised into descriptive themes and further synthesised into analytic themes presented as a model.

Results

The search yielded 2176 publications, of which 73 were included. The descriptive themes illustrated a movement from 1. medical protectionism to management through medicine; 2. command and control to participatory leadership practices; and 3. organisational practices that form either incidental or willing leaders. Based on the synthesis, the authors propose a model that describes a virtuous cycle of management through medicine or a vicious cycle of medical protectionism.

Conclusions

This review helps individuals, organisations, educators and trainers better understand how medical leadership can be both a boon and a barrier to organisational performance. In contrast to the conventional view of conflicting logics, medical leadership would benefit from a more integrative model of management and medicine. Nurturing medical engagement requires participatory leadership enabled through long-term investments at the individual, organisational and system levels.
Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE): protocol for a multisite prospective observational study of the causes of fever in Africa and Asia
Authors: Hopkins Heidi , Bassat Quique , Chandler Clare IR , Crump John A , Feasey Nicholas A , Ferrand Rashida A , Kranzer Katharina , Lalloo David G , Mayxay Mayfong , Newton Paul N , Mabey David
Published: July 2020

Introduction

Fever commonly leads to healthcare seeking and hospital admission in sub-Saharan Africa and Asia. There is only limited guidance for clinicians managing non-malarial fevers, which often results in inappropriate treatment for patients. Furthermore, there is little evidence for estimates of disease burden, or to guide empirical therapy, control measures, resource allocation, prioritisation of clinical diagnostics or antimicrobial stewardship. The Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE) study seeks to address these information gaps.

Methods and analysis

FIEBRE investigates febrile illness in paediatric and adult outpatients and inpatients using standardised clinical, laboratory and social science protocols over a minimum 12-month period at five sites in sub-Saharan Africa and Southeastern and Southern Asia. Patients presenting with fever are enrolled and provide clinical data, pharyngeal swabs and a venous blood sample; selected participants also provide a urine sample. Laboratory assessments target infections that are treatable and/or preventable. Selected point-of-care tests, as well as blood and urine cultures and antimicrobial susceptibility testing, are performed on site. On day 28, patients provide a second venous blood sample for serology and information on clinical outcome. Further diagnostic assays are performed at international reference laboratories. Blood and pharyngeal samples from matched community controls enable calculation of AFs, and surveys of treatment seeking allow estimation of the incidence of common infections. Additional assays detect markers that may differentiate bacterial from non-bacterial causes of illness and/or prognosticate illness severity. Social science research on antimicrobial use will inform future recommendations for fever case management. Residual samples from participants are stored for future use.

Ethics and dissemination

Ethics approval was obtained from all relevant institutional and national committees; written informed consent is obtained from all participants or parents/guardians. Final results will be shared with participating communities, and in open-access journals and other scientific fora. Study documents are available online (https://doi.org/10.17037/PUBS.04652739).
Development of a checklist for people communicating evidence-based information about the effects of healthcare interventions: a mixed methods study
Authors: Oxman Andrew D , Glenton Claire , Flottorp Signe , Lewin Simon , Rosenbaum Sarah , Fretheim Atle
Published: July 2020

Objectives

To make informed decisions about healthcare, patients and the public, health professionals and policymakers need information about the effects of interventions. People need information that is based on the best available evidence; that is presented in a complete and unbiased way; and that is relevant, trustworthy and easy to use and to understand. The aim of this paper is to provide guidance and a checklist to those producing and communicating evidence-based information about the effects of interventions intended to inform decisions about healthcare.

Design

To inform the development of this checklist, we identified research relevant to communicating evidence-based information about the effects of interventions. We used an iterative, informal consensus process to synthesise our recommendations. We began by discussing and agreeing on some initial recommendations, based on our own experience and research over the past 20–30 years. Subsequent revisions were informed by the literature we examined and feedback. We also compared our recommendations to those made by others. We sought structured feedback from people with relevant expertise, including people who prepare and use information about the effects of interventions for the public, health professionals or policymakers.

Results

We produced a checklist with 10 recommendations. Three recommendations focus on making it easy to quickly determine the relevance of the information and find the key messages. Five recommendations are about helping the reader understand the size of effects and how sure we are about those estimates. Two recommendations are about helping the reader put information about intervention effects in context and understand if and why the information is trustworthy.

Conclusions

These 10 recommendations summarise lessons we have learnt developing and evaluating ways of helping people to make well-informed decisions by making research evidence more understandable and useful for them. We welcome feedback for how to improve our advice.
Endoscopy and central reading in inflammatory bowel disease clinical trials: achievements, challenges and future developments
Authors: Gottlieb Klaus , Daperno Marco , Usiskin Keith , Sands Bruce E , Ahmad Harris , Howden Colin W , Karnes William , Oh Young S , Modesto Irene , Marano Colleen , Stidham Ryan William , Reinisch Walter
Published: July 2020

Central reading, that is, independent, off-site, blinded review or reading of imaging endpoints, has been identified as a crucial component in the conduct and analysis of inflammatory bowel disease clinical trials. Central reading is the final step in a workflow that has many parts, all of which can be improved. Furthermore, the best reading algorithm and the most intensive central reader training cannot make up for deficiencies in the acquisition stage (clinical trial endoscopy) or improve on the limitations of the underlying score (outcome instrument). In this review, academic and industry experts review scoring systems, and propose a theoretical framework for central reading that predicts when improvements in statistical power, affecting trial size and chances of success, can be expected: Multireader models can be conceptualised as statistical or non-statistical (social). Important organisational and operational factors, such as training and retraining of readers, optimal bowel preparation for colonoscopy, video quality, optimal or at least acceptable read duration times and other quality control matters, are addressed as well. The theory and practice of central reading and the conduct of endoscopy in clinical trials are interdisciplinary topics that should be of interest to many, regulators, clinical trial experts, gastroenterology societies and those in the academic community who endeavour to develop new scoring systems using traditional and machine learning approaches.
Alpha-1 antitrypsin governs alcohol-related liver disease in mice and
humans
Authors: Grander Christoph , Schaefer Benedikt , Schwärzler Julian , Grabherr Felix , de Graaf Dennis M , Enrich Barbara , Oberhuber Georg , Mayr Lisa , Sangineto Moris , Jaschke Nikolai , Adolph Timon E , Effenberger Maria , Moschen Alexander R , Dinarello Charles A , Zoller Heinz , Tilg Herbert
Published: July 2020

Objective

Alcohol-related liver disease (ALD) is a global healthcare problem with limited
treatment options. Alpha-1 antitrypsin (AAT, encoded by
SERPINA1) shows potent anti-inflammatory activities in
many preclinical and clinical trials. In our study, we aimed to explore the role of
AAT in ALD.

Design

An unselected cohort of 512 patients with cirrhosis was clinically
characterised. Survival, clinical and biochemical parameters including AAT serum
concentration were compared between patients with ALD and other aetiologies of liver
disease. The role of AAT was evaluated in experimental ALD models.

Results

Cirrhotic ALD patients with AAT serum concentrations less than 120 mg/dL had a
significantly higher risk for death/liver transplantation as compared with patients
with AAT serum concentrations higher than 120 mg/dL. Multivariate Cox regression
analysis showed that low AAT serum concentration was a NaMELD-independent predictor of
survival/transplantation. Ethanol-fed wild-type (wt) mice displayed a significant
decline in hepatic AAT compared with pair-fed mice. Therefore,
hAAT-Tg mice were ethanol-fed, and these mice displayed
protection from liver injury associated with decreased steatosis, hepatic neutrophil
infiltration and abated expression of proinflammatory cytokines. To test the
therapeutic capability of AAT, ethanol-fed wt mice were treated with human AAT.
Administration of AAT ameliorated hepatic injury, neutrophil infiltration and
steatosis.

Conclusion

Cirrhotic ALD patients with AAT concentrations less than 120 mg/dL displayed an
increased risk for death/liver transplantation. Both
hAAT-Tg mice and AAT-treated wt animals showed protection
from ethanol-induced liver injury. AAT could reflect a treatment option for human ALD,
especially for alcoholic hepatitis.
Xp11 translocation renal cell carcinoma with morphological features mimicking multilocular cystic renal neoplasm of low malignant potential: a series of six cases with molecular analysis
Authors: Song Yankun , Yin Xiaoxue , Xia Qiuyuan , Zheng Linmao , Yao Jin , Zeng Hao , Nie Ling , Gong Jing , Zhou Qiao , Chen Ni
Published: July 2020

Aims

Xp11 translocation renal cell carcinoma (RCC) is a distinctive subtype of RCC withTFE3(Transcription Factor Binding to IGHM Enhancer 3) gene rearrangement. The gross features in most Xp11 translocation RCCs closely resemble clear cell RCCs. In this study, we report six cases of Xp11 translocation RCCs with a unique multicystic architecture, reminiscent of multilocular cystic renal cell neoplasm of low malignant potential (MCRN-LMP).

Methods and results

Microscopically, the renal mass was well circumscribed with multilocular cystic architecture. The cyst walls and septa were mostly lined by a single layer of cells with clear cytoplasm and low-grade nuclei, reminiscent of MCRN-LMP. Psammoma bodies were detected in four cases. One particular patient was misdiagnosed with benign cysts in local hospitals and led to second operation. Tumour cells were settled according to the track of the first surgical procedure.TFE3fluorescence in situ hybridization (FISH) assay confirmed the diagnosis of Xp11 translocation RCCs. FISH and RNA sequencing analyses confirmedMED15-TFE3gene fusion in all six cases. Respective patients were alive, without any recent evidence of disease recurrence and/or metastasis.

Conclusions

Here, we introduce a relatively inertia-variant of Xp11 translocation RCC which mimics MCRN-LMP. The distinctive morphological condition is linked toMED15-TFE3gene fusion. In fact, renal neoplasms with morphological features of MCRN-LMP, especially those containing psammoma bodies, should be routinely evaluated for evidence ofTFE3gene rearrangements.