bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Efficacy of Rivaroxaban for Inferior Vena Cava Thrombosis after Successful Catheter-Directed Thrombolysis
Authors: Du Jun , Nie Menglin , Yan Zhitong , Fu Jian , Sun Jianming , Liu Fanyun
Published: October 2021

Rivaroxaban use for inferior vena cava (IVC) thrombosis after successful catheter-directed thrombolysis (CDT) is rarely reported. This study aimed at investigating the safety and efficacy of rivaroxaban for IVC thrombosis after CDT. The clinical data on 38 consecutive patients with IVC thrombosis (68% male; mean age, 51.5 ± 16.5), who received rivaroxaban after CDT between July 2017 and January 2020, were retrospectively analyzed in this study. Safety and efficacy of rivaroxaban (bleedings and recurrent venous thromboembolism), cumulative prevalence of post-thrombotic syndrome (PTS), primary patency, clinically driven target lesion revascularization rate, and other adverse events including all-cause mortality and vascular events (systemic embolism, acute coronary syndrome, ischemic stroke, and transient ischemic attack) were retrospectively analyzed. Of the 38 patients who received rivaroxaban for IVC thrombosis after CDT, 27 (71%) had an anticoagulant duration of 6 months and 11 patients (29%) of more than 6 months. Four patients (10%) suffered recurrent thrombosis. No patient suffered major bleeding, while clinically relevant nonmajor bleeding occurred in two (5%) patients. The cumulative prevalence of PTS was 18% (7/38) during the 12 months follow-up period. Primary patency at 1, 3, 6, and 12 months was 97, 92, 90, and 90%, respectively. According to follow-up data, the clinically driven target lesion revascularization of this study was 10%. Cardiovascular events and mortality did not occur in any patient during the study period. Rivaroxaban for IVC thrombosis after successful CDT can be safe and effective.
Platelet Behavior Contributes to Neuropathologies: A Focus on Alzheimer's and Parkinson's Disease
Authors: Page Martin J. , Pretorius Etheresia
Published: October 2021

The functions of platelets are broad. Platelets function in hemostasis and thrombosis, inflammation and immune responses, vascular regulation, and host defense against invading pathogens, among others. These actions are achieved through the release of a wide set of coagulative, vascular, inflammatory, and other factors as well as diverse cell surface receptors involved in the same activities. As active participants in these physiological processes, platelets become involved in signaling pathways and pathological reactions that contribute to diseases that are defined by inflammation (including by pathogen-derived stimuli), vascular dysfunction, and coagulation. These diseases include Alzheimer's and Parkinson's disease, the two most common neurodegenerative diseases. Despite their unique pathological and clinical features, significant shared pathological processes exist between these two conditions, particularly relating to a central inflammatory mechanism involving both neuroinflammation and inflammation in the systemic environment, but also neurovascular dysfunction and coagulopathy, processes which also share initiation factors and receptors. This triad of dysfunction—(neuro)inflammation, neurovascular dysfunction, and hypercoagulation—illustrates the important roles platelets play in neuropathology. Although some mechanisms are understudied in Alzheimer's and Parkinson's disease, a strong case can be made for the relevance of platelets in neurodegeneration-related processes.
Editorial
Authors: Kucera Martin
Published: October 2021

Die Pandemie verdeutlicht die Stärken der deutschen Kliniklandschaft – trotzdem bangen gerade kleinere Krankenhäuser zunehmend um ihre Existenz. Neben richtungsweisenden Neubauprojekten beleuchtet der aktuelle Report „Bauen, Planen, Technik“ die Vorteile des Konsortialkredites und die Frage, wie sich mit den Sanierungsinstrumenten des Insolvenzrechtes ein finanziell angeschlagenes Haus wieder in die schwarzen Zahlen bringen lässt. Lesen Sie auch, was Klinikbauer in Sachen Modulbauweise von Aldi und Lidl lernen können, wie ein Patientenzimmer aussehen kann, das Patientinnen und Patienten einen besseren Schutz vor einer Infektion mit multiresistenten Erregern bietet – und warum mit einem digitalisierten Zentrallager die Prozesse vom Wareneingang bis zur Warenausgabe erheblich beschleunigt werden.
Klinikbauten von der Stange: Was Klinikplaner von Aldi und Lidl lernen können
Authors: Thalmayr Maria
Published: October 2021

Der Kostendruck im Gesundheitswesen ist in aller Munde. Trotzdem leisten wir uns bei jedem Klinikneu- oder -umbau den Luxus eines Unikats. Dabei ließen sich mit Lösungen von der Stange eine Menge Geld sparen und bessere Ergebnisse erzielen. Nicht hip, aber zweifellos zweckmäßig.
Reprowebs: a conceptual approach to elasticity and change in the global assisted reproduction industry
Authors: König Anika , Jacobson Heather
Published: October 2021

In the last few decades, assisted reproductive technologies (ARTs) have become increasingly transregional and transnational, often involving travel within or between countries or even continents. Until recently, the global ART industry was marked by so-called ‘reprohubs’—places (such as southern California, Dubai, Anand, and Mumbai) specializing in the provision of reproductive services. While reprohubs continue to exist, in the last few years, many have splayed out, transforming into something more akin to webs that encompass, but go beyond these hubs. These webs show a unique dynamic capability to tighten, entangle, or extend in reaction to local and global changes, a characteristic which became particularly obvious during the global Covid-19 pandemic. In this paper, we propose conceptualizing this new dynamic capability as ‘reprowebs’—an approach that adds a new dimension to the existing conceptualization of reproductive travel and helps us to better understand current developments in the global ART industry.
Time domain optical imaging device based on a commercial time-to-digital converter
Authors: Pérez-Tirador P. , Papadimitriou K. I. , Powell S. , Hebden J. C.
Published: October 2021

Time-domain diffuse optical imaging is a noninvasive technique that uses pulsed near-infrared light as the interrogation source to produce quantitative images displaying the variation in blood volume and oxygenation in the human brain. Measuring the times of flights of photons provides information on the photon pathlengths in tissue, which enables absolute concentrations of the oxygenated and deoxygenated forms of hemoglobin to be estimated. Recent advances in silicon electronics have enabled the development of time-domain systems, which are lightweight and low cost, potentially enabling the imaging technique to be applied to a far greater cohort of subjects in a variety of environments. While such technology usually depends on customized circuits, in this article, we present a system assembled from commercially available components, including a low-cost time-to-digital converter and a silicon photomultiplier detector. The system is able to generate histograms of photon flight times at a rate of 81–90 kS/s and with a sampled bin width of 54 ps. The linearity and performance of the system are presented, and its potential as the basis for a modular multi-detector imaging system is explored.
Infrared erbium photoluminescence enhancement in silicon carbide nano-pillars
Authors: Parker R. A. , Dontschuk N. , Sato S.-I. , Lew C. T.-K. , Reineck P. , Nadarajah A. , Ohshima T. , Gibson B. C. , Castelletto S. , McCallum J. C. , Johnson B. C.
Published: October 2021

Color centers that emit light at telecommunication wavelengths are promising candidates for future quantum technologies. A pressing challenge for the broad use of these color centers is the typically low collection efficiency from bulk samples. Here, we demonstrate enhancements of the emission collection efficiency for Er3+ incorporated into 4H-SiC surface nano-pillars fabricated using a scalable top-down approach. Optimal Er ion implantation and annealing strategies are investigated in detail. The substitutional fraction of Er atoms in the SiC lattice is closely correlated with the peak photoluminescence intensity. This intensity is further enhanced via spatial wave-guiding once the surface is patterned with nano-pillars. These results have broad applicability for use with other color centers in SiC and also demonstrate a step toward a scalable protocol for fabricating photonic quantum devices with enhanced emission characteristics.
Relative calibration of a retarding field energy analyzer sensor array for spatially resolved measurements of the ion flux and ion energy in low temperature plasmas
Authors: Ries Stefan , Schroeder Manuel , Woestefeld Marc , Corbella Carles , Korolov Ihor , Awakowicz Peter , Schulze Julian
Published: October 2021

A calibration routine is presented for an array of retarding field energy analyzer (RFEA) sensors distributed across a planar electrode surface with a diameter of 450 mm that is exposed to a low temperature plasma. Such an array is used to measure the ion velocity distribution function at the electrode with radial and azimuthal resolutions as a basis for knowledge-based plasma process development. The presented calibration procedure is tested by exposing such an RFEA array to a large-area capacitively coupled argon plasma driven by two frequencies (13.56 and 27.12 MHz) at a gas pressure of 0.5 Pa. Up to 12 sensors are calibrated with respect to the 13th sensor, called the global reference sensor, by systematically varying the sensor positions across the array. The results show that the uncalibrated radial and azimuthal ion flux profiles are incorrect. The obtained profiles are different depending on the sensor arrangement and exhibit different radial and azimuthal behaviors. Based on the proposed calibration routine, the ion flux profiles can be corrected and a meaningful interpretation of the measured data is possible. The calibration factors are almost independent of the external process parameters, namely, input power, gas pressure, and gas mixture, investigated under large-area single-frequency capacitively coupled plasma conditions (27.12 MHz). Thus, mean calibration factors are determined based on 45 different process conditions and can be used independent of the plasma conditions. The temporal stability of the calibration factors is found to be limited, i.e., the calibration must be repeated periodically.
Gradient in refractive index reveals denser near free surface region in thin polymer films
Authors: Han Yixuan , Roth Connie B.
Published: October 2021

A gradient in refractive index that is linear in magnitude with depth into the film is used to fit ellipsometric data for thin polymer films of poly(methyl methacrylate) (PMMA), polystyrene (PS), and poly(2-vinyl pyridine) (P2VP). We find that the linear gradient model fits provide more physically realistic refractive index values for thin films compared with the commonly used homogeneous Cauchy layer model, addressing recent reports of physically unrealistic density increases. Counter to common expectations of a simple free volume correlation between density and dynamics, we find that the direction of refractive index (density) gradient indicates a higher density near the free surface, which we rationalize based on the observed faster free surface dynamics needed to create vapor deposited stable glasses with optimized denser molecular packings. The magnitude of refractive index gradient is observed to be three times larger for PMMA than for PS films, while P2VP films exhibit a more muted response possibly reflective of a decoupling in free surface and substrate dynamics in systems with strong interfacial interactions.
The role of secondary species emission in vacuum facility effects for electrospray thrusters
Authors: Uchizono N. M. , Collins A. L. , Marrese-Reading C. , Arestie S. M. , Ziemer J. K. , Wirz R. E.
Published: October 2021

Theoretical, analytical, and experimental investigations of electrospray operation in vacuum facilities show that secondary species emission (SSE) plays a significant role in the behavior of electrospray thrusters during ground testing. A review of SSE mechanisms, along with an analysis of onset thresholds for electrospray thruster conditions, indicates that secondary species (e.g., electrons, anions, cations, etc.) must be carefully considered for accurate measurements and determination of performance and life. Presented models and experiments show that SSE-induced thruster-to-facility coupling can lead to considerable measurement uncertainty but can be effectively mitigated with an appropriate beam target design. The Electrospray SSE Control-volume Analysis for Resolving Ground Operation of Thrusters model is applied to experimental data to analyze SSE behavior. A heat and mass flux analysis of the Air Force Electrospray Thruster Series 2 (AFET-2) shows that SSE-induced Ohmic dissipation can cause performance limitations in ionic liquid ion source thrusters. The presented analytical models show that backstreaming current density contributing to less than 0.1% of measured emitter current density can cause substantial variation in propellant properties. Additionally, backstreaming current density contributing to less than 3% of emitted current can cause the 0.86 μg s−1 neutral loss rate estimated during AFET-2 testing. Arguments are presented to support the notion that glow discharges observed in electrospray thrusters during vacuum operation are a consequence of secondary species backstreaming to the emission site, rather than a process intrinsically caused by ion evaporation. Recommendations for general best practices to minimize the effects of SSE on electrospray thruster operation are provided.
Rotational pumping revisited
Authors: O'Neil Thomas M.
Published: October 2021

This paper considers a pure electron plasma, with a small admixture of negative ions, confined in a Penning–Malmberg trap. When a diocotron mode is excited on the plasma, the end sheaths of the plasma are azimuthally distorted. During reflection at a distorted end sheath, an ion steps off of the surface characterizing the drift motion in the plasma interior, and this step produces transport. The diocotron mode transfers canonical angular momentum to the ions, and in response damps. These transport mechanism and associated damping are called rotational pumping. It is particularly strong when the axial bounce motion and the rotational drift motion, in the rotating frame of the mode, satisfy a resonance condition. This paper calculates the transport flux of ions and the associated damping rate of the mode in the resonant regime. Previous papers have discussed the theory and the experimental observation of rotational pumping for the special case of a diocotron mode with azimuthal wave number l = 1, and this paper extends the theory to modes with l≠1, which may sound like a trivial extension, but in fact is not.
Magnetocaloric properties of melt-spun MnFe-rich high-entropy alloy
Authors: Huang Shuo , Dong Zhihua , Mu Wangzhong , Ström Valter , Chai Guocai , Varga Lajos Károly , Eriksson Olle , Vitos Levente
Published: October 2021

High-entropy functional materials are of great interest in materials science and engineering community. In this work, ab initio electronic structure calculations of the phase stability and magnetic transition temperature of AlxCr0.25MnFeCo0.25−yNiy (x = 0–0.5, y = 0–0.25) alloys were performed to screen for compositions showing promising magnetocaloric properties in the vicinity of room temperature. The selected Al0.44Cr0.25MnFeCo0.05Ni0.2 alloy was synthesized via a rapid solidification technique and systematically characterized with respect to its structural and magnetocaloric properties. The results indicate that this alloy possesses a homogeneous microstructure based on an underlying body-centered cubic lattice and has a Curie temperature of ∼340 K. The temperature dependence of the adiabatic temperature change was evaluated using both direct and indirect methods. The ab initio-assisted design of 3d-metal-based high-entropy alloys, explored here, is intended to contribute to the development of magnetic refrigerators for room-temperature applications.
All-atom molecular dynamics study of hepatitis B virus containing pregenome RNA in solution
Authors: Fujimoto Kazushi , Yamaguchi Youhei , Urano Ryo , Shinoda Wataru , Ishikawa Tetsuya , Omagari Katsumi , Tanaka Yasuhito , Nakagawa Atsushi , Okazaki Susumu
Published: October 2021

Immature hepatitis B virus (HBV) captures nucleotides in its capsid for reverse transcription. The nucleotides and nucleotide analog drugs, which are triphosphorylated and negatively charged in the cell, approach the capsid via diffusion and are absorbed into it. In this study, we performed a long-time molecular dynamics calculation of the entire HBV capsid containing pregenome RNA to investigate the interactions between the capsid and negatively charged substances. Electric field analysis demonstrated that negatively charged substances can approach the HBV capsid by thermal motion, avoiding spikes. The substances then migrate all over the floor of the HBV capsid. Finally, they find pores through which they can pass through the HBV capsid shell. Free energy profiles were calculated along these pores for small ions to understand their permeability through the pores. Anions (Cl−) showed higher free energy barriers than cations (Na+ and K+) through all pores, and the permeation rate of Cl− was eight times slower than that of K+ or Na+. Furthermore, the ions were more stable in the capsid than in the bulk water. Thus, the HBV capsid exerts ion selectivity for uptake and provides an environment for ions, such as nucleotides and nucleotide analog drugs, to be stabilized within the capsid.
Multi-population analysis of the Cuban SARS-CoV-2 epidemic transmission before and during the vaccination process
Authors: Guinovart-Sanjuán D. , Guinovart-Díaz R. , Vajravelu K. , Morales-Lezca W. , Abelló-Ugalde I.
Published: October 2021

In this work, several mathematical models for the spread of viruses and diseases are presented. In particular, the work focuses on the coronavirus disease 2019 (COVID-19) pandemic. A multi-population model is presented for the study of the interaction of various populations and the contagion of the virus between them. A second model on vaccination is presented, which allows analyzing the behavior of the disease taking into account the effectiveness of the vaccine and the speed of COVID-19 after the vaccination process. Finally, both models are applied to analyze the epidemic in Cuba. For this study, the official data reported by the Cuban Ministry of Health from March 2020 to August 2021 is used.
Hydrodynamic instabilities of a viscous liquid film flowing down an inclined or vertical plane
Authors: Dholey S. , Gorai S.
Published: October 2021

In this paper, we have investigated theoretically linear as well as weakly nonlinear stability of a viscous liquid film flowing down an inclined or vertical plane under the action of gravity. The classical momentum-integral method, which is applicable for small as well as large values of Reynolds number Re, has been used to formulate the single nonlinear free surface equation in terms of the dimensionless perturbed film thickness η(x,t). Using sinusoidal perturbation in the linearized part of the surface evolution equation, we obtain the stability criterion and the critical value of the wave number kc which conceives the physical parameters Re, inclination angle θ and Weber number We. However, the linear stability analysis reveals the stabilizing influence of We as well as the destabilizing influence of Re and θ on this flow dynamics. The multiple-scale analysis has been used to derive the complex Ginzburg–Landau type nonlinear equation for investigating the weakly nonlinear stability analysis. We demarcate all the four states of the flow in the Re-k (or θ-k)-plane which are found after the critical value of Rec (or θc) depending upon the values of the other parameters. A novel result which emerges from the nonlinear stability analysis is a simple relationship among the parameters k, Re, We, and θ. This relationship essentially gives us the conditions needed for the existence of an explosive unstable zone when (3Re−3cot θ−4ReWek2)= 0; otherwise, the flow system will be free from this zone. Indeed, this zone decreases with the increase in We, whereas it increases with the increase in Re and θ confirming the stabilizing role of We and destabilizing role of Re and θ as found in linear stability analysis.
mmBCFA C17iso ensures endoplasmic reticulum integrity for lipid droplet growth
Authors: Zhang Jingjing , Hu Ying , Wang Yanli , Fu Lin , Xu Xiumei , Li Chunxia , Xu Jie , Li Chengbin , Zhang Linqiang , Yang Rendan , Jiang Xue , Wu Yingjie , Liu Pingsheng , Zou Xiaoju , Liang Bin
Published: October 2021

In eukaryote cells, lipid droplets (LDs) are key intracellular organelles that dynamically regulate cellular energy homeostasis. LDs originate from the ER and continuously contact the ER during their growth. How the ER affects LD growth is largely unknown. Here, we show that RNAi knockdown of acs-1, encoding an acyl-CoA synthetase required for the biosynthesis of monomethyl branched-chain fatty acids C15iso and C17iso, remarkably prevented LD growth in Caenorhabditis elegans. Dietary C17iso, or complex lipids with C17iso including phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol, could fully restore the LD growth in the acs-1RNAi worms. Mechanistically, C17iso may incorporate into phospholipids to ensure the membrane integrity of the ER so as to maintain the function of ER-resident enzymes such as SCD/stearoyl-CoA desaturase and DGAT2/diacylglycerol acyltransferase for appropriate lipid synthesis and LD growth. Collectively, our work uncovers a unique fatty acid, C17iso, as the side chain of phospholipids for determining the ER homeostasis for LD growth in an intact organism, C. elegans.
Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses
Authors: Shinnakasu Ryo , Sakakibara Shuhei , Yamamoto Hiromi , Wang Po-hung , Moriyama Saya , Sax Nicolas , Ono Chikako , Yamanaka Atsushi , Adachi Yu , Onodera Taishi , Sato Takashi , Shinkai Masaharu , Suzuki Ryosuke , Matsuura Yoshiharu , Hashii Noritaka , Takahashi Yoshimasa , Inoue Takeshi , Yamashita Kazuo , Kurosaki Tomohiro
Published: October 2021

Broadly protective vaccines against SARS-related coronaviruses that may cause future outbreaks are urgently needed. The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. We found that glycan addition elicited higher proportions of the core-RBD–specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. These results have implications for the design of SARS-like virus vaccines.
Reframing spatial policy through targeting diagnostic tools: potential and deprivation
Authors: Hooton Christopher A
Published: October 2021

Spatial policy targeting can differ greatly across programs due to myriad thematic goals, geographical unit systems, and conceptualisations. The current paper seeks to better understand how these differences may impact policy effectiveness by examining the theory of spatial targeting accuracy and the methodological tools for assessing it ex ante. It is the first comprehensive examination, to the extent of the author’s knowledge, of these concepts. The paper finds two clear families of diagnostic tools—concentration-based measures and characteristic-based measures—and two conceptual camps for improving ex ante accuracy—one based on economic potential and one based on deprivation.
Behçet’s disease: a case report about a rare cause of intra-cardiac mass
Authors: Briosa Alexandra , Gomes Ana Catarina , CastelBranco Ana , Cunha Margarida , Sousa Sandra , Almeida Ana Rita , Calhau Paulo , Pereira Hélder
Published: October 2021

Background

Intra-cardiac masses are always a challenging diagnosis, especially when it involves the right side of the heart. There are multiples aetiologies that can be responsible for these masses, namely thrombosis, neoplasm, or vegetations. Occasionally, these may be related to an autoimmune process not yet diagnosed. We present a case of a 17-year-old patient with an exuberant right ventricular mass due to a not yet diagnosed Behçet’s disease. The best approach and treatment for these patients remains uncertain.

Case summary

The authors present a case of a 17-year-old patient with a right ventricular mass who presented as an initial manifestation of Behçet’s disease. It was firstly assumed as a thrombotic mass and medicated with anticoagulation, with no resolution. After performing a cardiac magnetic resonance, the case was discussed in a multidisciplinary team, including cardiology, paediatrics, and rheumatology, and the diagnosis of Behçet’s disease with cardiac complication was established. The patient started immunosuppressive therapy with clinical and echocardiographic response.

Discussion

Behçet’s disease is a multi-systemic autoimmune vasculitis that usually manifests by recurrent oral and genital ulcers as well as ocular symptoms. Cardiac manifestations are rare but important aspects of the course of the disease, especially in what concerns morbidity burden. The treatment of these cardiovascular complications is generally empirical and involves the treatment of the underlying disease.
Income tax progressivity and inflation during the world wars
Authors: Torregrosa-Hetland Sara , Sabaté Oriol
Published: October 2021

This paper studies the impact of inflation on income taxes in Sweden, the UK, and the United States during the world wars. As tax reforms were rising top marginal rates and reducing exemption thresholds, extraordinary levels of inflation eroded the real value of exemptions, brackets, and deductions. The micro-simulation of actual and alternative scenarios shows that inflation made the tax less progressive, particularly in Sweden during World War I and the UK during World War II. Nevertheless, its redistributive effect increased due to the related growth in tax revenue. Inflation contributed to transform a “class tax’’ into a “mass tax”.
Egyptian Association of Vascular Biology and Atherosclerosis Consensus on The Usage of SGLT2 Inhibitors in Heart Failure
Authors: Reda Ashraf , Elserafy Ahmed Shawky , Farag Elsayed , Mostafa Tamer , Farag Nabil , Elbahary Atef , Sanad Osama , Tabl Mohamed Abdelshafy , Bendary Ahmed , Elkersh Ahmed , Ashraf Mohamed , Attia Ihab , Beshay Morad , Ragy Hany , Selim Mohammed , Khamis Hazem
Published: October 2021

Aims

Analysis of SGLT2i data from DAPA-HF and EMPEROR- reduced trials to put a simplified consensus statement on the use of these glucose lowering agents in patients with established heart failure.

Methods and Results

Sixty experts in the field of cardiology revised the literature of the SGLT2i in heart failure, their recommended indications, and their contraindications. Data from DAPA-HF and EMPEROR-reduced trials were tabulated and statistically analysed. SGLT2 inhibitors investigated initially for their glucose lowering capability, have shown a significant benefit in chronic heart failure eit reduced ejection fraction (HFrEF).

Conclusions

We recommend early use of dapagliflozin 10 mg, or empagliflozin 10 mg in patients suffering from symptomatic chronic HFrEF, whether the patient is diabetic or non, to improve heart failure hospitalization, death, symptoms, and decline of renal function.
Energetic Cost of Walking and Brain Atrophy in Mid-to-Late Life
Authors: Dougherty Ryan J , Liu Fangyu , An Yang , Wanigatunga Amal A , Tian Qu , Davatzikos Christos , Simonsick Eleanor M , Ferrucci Luigi , Resnick Susan M , Schrack Jennifer A
Published: October 2021

Background

Higher energetic costs for mobility are associated with declining gait speed, and slow gait is linked to cognitive decline and Alzheimer’s disease. However, the physiological underpinnings of gait and brain health have not been well explored. We examined the associations of the energetic cost of walking with brain volume in cognitively unimpaired adults from the Baltimore Longitudinal Study of Aging.

Methods

We used brain magnetic resonance imaging (MRI) data from 850 participants (mean baseline age 66.3 ± 14.5 years), of whom 451 had longitudinal MRI data (2.8 ± 1.0 MRI scans over 4.0 ± 2.0 years). The energetic cost of walking was assessed as the average energy expended (V̇O2) during 2.5 minutes of customary-paced overground walking. Multivariable linear mixed-effects models examined the associations between baseline energetic cost of walking and regional brain volumes adjusting for covariates.

Results

At baseline, higher energetic cost of walking was cross-sectionally associated with lower gray and white matter volumes within the frontal, parietal, and temporal lobes, as well as hippocampal, total brain, and larger ventricular volumes (all false-discovery rate [FDR] p < .05). A baseline energetic cost of walking × time interaction demonstrated that participants with higher energetic cost of walking had faster annual decline in hippocampal volume (FDR p = .02) and accelerated annual increase in ventricular volumes (FDR p = .02).

Conclusions

The energetic cost of walking is associated with gray and white matter volumes and subsequent hippocampal atrophy and ventricular enlargement. Collectively, these data suggest the energetic cost of walking may be an early marker of neurodegeneration that contributes to the gait brain connection.
Becoming a normative power? China's Mekong agenda in the era of Xi Jinping
Authors: Song Yao , Qiao-Franco Guangyu , Liu Tianyang
Published: October 2021

Maintaining robust diplomatic relationships with neighbouring countries in the Mekong region has become strategically critical to China. Since President Xi Jinping took office, China has been renovating normative power in the Mekong region, endeavouring to socialize the Mekong countries into accepting normative Chinese concepts, such as ‘community of shared destiny’, by mobilizing and reconfiguring their material and normative recourses. This article argues that China's normative power stems from two primary mechanisms: 1) an organized, top-down diffusion driven by political elites, involving inter-governmental dialogues, socialization via bilateral and multilateral cooperation mechanisms, and negotiations with countries co-opted into China-led connectivity and infrastructure initiatives; 2) a bottom-up diffusion of ideas from practices (i.e. exchange of goods, trade, aid) and the physical presence of China in the Mekong region, exemplified by the massive scale of infrastructure widely constructed in the region. Taken together, China's expanded normative engagement in the Mekong subregion is comprised of multiple, oscillating modes of normative production that have been ‘synchronized’ across riparian countries with varied geoeconomic and geopolitical circumstances. Our findings suggest that while normative Chinese discourses have been accepted by the ruling classes of certain Mekong countries, China's attempts to build normative power have been largely shunned by the civil societies in the region.
Interventions to Improve Adherence to Preventive Care in Inflammatory Bowel Disease: A Systematic Review
Authors: Yu Natalie , Basnayake Chamara , Connell William , Ding Nik Sheng , Wright Emily , Stanley Annalise , Fry Stephanie , Wilson-O’Brien Amy , Niewiadomski Ola , Lust Mark , Schulberg Julien , Kamm Michael A
Published: October 2021

Background

Preventive health measures reduce treatment and disease-related complications including infections, osteoporosis, and malignancies in patients with inflammatory bowel disease (IBD). Although guidelines and quality measures for IBD care highlight the importance of preventive care, their uptake remains variable. This systematic review evaluates interventions aimed at improving the rates of provision and uptake of preventive health measures, including vaccinations, bone density assessment, skin cancer screening, cervical cancer screening, and smoking cessation counseling.

Methods

We searched PubMed, MEDLINE, EMBASE, and CENTRAL for full text articles published until March 2021. Studies were included if they evaluated interventions to improve the provision or uptake of 1 or more preventive health measures in adult IBD patients and if they reported pre- and postintervention outcomes.

Results

In all, 4655 studies were screened, and a total of 17 studies were included, including 1 randomized controlled trial, 1 cluster-controlled trial, and 15 prospective interventional studies. A variety of interventions were effective in improving the rates of adherence to preventive health measures. The most common interventions targeted gastroenterologists, including education, electronic medical records tools, and audit feedback. Other interventions targeted patients, such as education, questionnaires, and offering vaccine administration at clinic visits. Few interventions involved IBD nurses or primary care physicians.

Conclusions

A range of interventions—targeted at gastroenterologists, patients, or both—were effective in improving the provision and uptake of preventive care. Future studies should involve randomized controlled trials evaluating multifaceted interventions that target barriers to adherence and involve IBD nurses and primary care physicians.
The Tropical Symplectic Grassmannian
Authors: Balla George , Olarte Jorge Alberto
Published: October 2021

We launch the study of the tropicalization of the symplectic Grassmannian, that is, the space of all linear subspaces isotropic with respect to a fixed symplectic form. We formulate tropical analogues of several equivalent characterizations of the symplectic Grassmannian and determine all implications between them. In the process, we show that the Plücker and symplectic relations form a tropical basis if and only if the rank is at most 2. We provide plenty of examples that show that several features of the symplectic Grassmannian do not hold after tropicalizing. We show exactly when do conormal fans of matroids satisfy these characterizations, as well as doing the same for a valuated generalization. Finally, we propose several directions to extend the study of the tropical symplectic Grassmannian.
The Expected Number of Roots over The Field of p-adic Numbers
Authors: Shmueli Roy
Published: October 2021

We study the roots of a random polynomial over the field of $p$-adic numbers. For a random monic polynomial with i.i.d. coefficients in ${\mathbb{Z}}_p$, we obtain an estimate for the expected number of roots of this polynomial. In particular, if the coefficients take the values $\pm 1$ with equal probability, the expected number of $p$-adic roots converges to $(p-1)/(p+1)$ as the degree of the polynomial tends to $\infty $.
Real Eigenvalues of Elliptic Random Matrices
Authors: Byun Sung-Soo , Kang Nam-Gyu , Lee Ji Oon , Lee Jinyeop
Published: October 2021

We consider the real eigenvalues of an $(N \times N)$ real elliptic Ginibre matrix whose entries are correlated through a non-Hermiticity parameter $\tau _N\in [0,1]$. In the almost-Hermitian regime where $1-\tau _N=\Theta (N^{-1})$, we obtain the large-$N$ expansion of the mean and the variance of the number of the real eigenvalues. Furthermore, we derive the limiting densities of the real eigenvalues, which interpolate the Wigner semicircle law and the uniform distribution, the restriction of the elliptic law on the real axis. Our proofs are based on the skew-orthogonal polynomial representation of the correlation kernel due to Forrester and Nagao.
UNMASC: tumor-only variant calling with unmatched normal controls
Authors: Little Paul , Jo Heejoon , Hoyle Alan , Mazul Angela , Zhao Xiaobei , Salazar Ashley H , Farquhar Douglas , Sheth Siddharth , Masood Maheer , Hayward Michele C , Parker Joel S , Hoadley Katherine A , Zevallos Jose , Hayes D Neil
Published: October 2021

Despite years of progress, mutation detection in cancer samples continues to require significant manual review as a final step. Expert review is particularly challenging in cases where tumors are sequenced without matched normal control DNA. Attempts have been made to call somatic point mutations without a matched normal sample by removing well-known germline variants, utilizing unmatched normal controls, and constructing decision rules to classify sequencing errors and private germline variants. With budgetary constraints related to computational and sequencing costs, finding the appropriate number of controls is a crucial step to identifying somatic variants. Our approach utilizes public databases for canonical somatic variants as well as germline variants and leverages information gathered about nearby positions in the normal controls. Drawing from our cohort of targeted capture panel sequencing of tumor and normal samples with varying tumortypes and demographics, these served as a benchmark for our tumor-only variant calling pipeline to observe the relationship between our ability to correctly classify variants against a number of unmatched normals. With our benchmarked samples, approximately ten normal controls were needed to maintain 94% sensitivity, 99% specificity and 76% positive predictive value, far outperforming comparable methods. Our approach, called UNMASC, also serves as a supplement to traditional tumor with matched normal variant calling workflows and can potentially extend to other concerns arising from analyzing next generation sequencing data.
O004 Obstructive sleep apnoea severity is associated with parasympathetic withdrawal in coronary artery disease
Authors: Ucak S , Dissanayake H , Sutherland K , Bin Y , Skilton M , Patel S , Yee B , Bhindi R , Allahwala U , de Chazal P , Cistulli P
Published: October 2021

Introduction

Patients with Coronary Artery Disease (CAD) are exposed to myocardial ischemia and hypoxia, resulting in altered autonomic function. Obstructive sleep apnoea (OSA) is highly prevalent in CAD and is associated with increased sympathetic activity which could further exacerbate cardiovascular risk. We aimed to determine whether OSA severity is associated with altered autonomic function in CAD patients.

Methods

Patients presenting to the coronary care unit with CAD underwent level 2 portable polysomnography to assess the presence and severity of OSA. Autonomic function was calculated from continuous blood pressure and 3-lead ECG 5 minute recordings while awake. Mean spontaneous baroreceptor sensitivity (sBRS msec/mmHg); vagally mediated heart rate variability (HRV) markers (pNN50%, RMSSD, HF-HRV); and, sympathetically mediated vascular autonomic function (LF-BPV) were measured. Autonomic function was assessed in relation to OSA severity (Apnoea Hypopnea Index, AHI; oxygen desaturation index, ODI).

Results

OSA was present in 49/51 (96%) participants with CAD (age 54±9 years; BMI 28.9±5.4 kg/m2; male 41(77%)). No association was found between sBRS and AHI. There was a modest inverse correlation between AHI and vagally mediated HRV (RMSSD, r= -0.28 p=0.04; HF, r= -0.31 p=0.03). AHI positively correlated with LF-SBP (r=0.29, p=0.04) suggesting upregulation of sympathetic modulation. Linear regression analyses, adjusted for age, sex, and BMI, showed AHI was a determinant of parasympathetically modulated HRV measures (pNN50% -0.25(0.12), p=0.05).

Conclusions

In patients with CAD, increased AHI was associated with parasympathetic withdrawal suggesting that OSA could increase poor cardiovascular prognosis in this population.
O015 Upper airway collapsibility measurement under anaesthesia in children: feasibility and utility in predicting perioperative respiratory adverse events
Authors: Ohn M , Julie J , Salerno S , Herbet H , Bumbak P , Hillman D , Khan N , Maddison K , Walsh J , von Ungern-Sternberg B , Eastwood P
Published: October 2021

Background

Perioperative respiratory adverse events (PRAE) pose significant risk in paediatric anaesthesia, and identifying risk is vital. Perioperative measurement of pharyngeal closing pressure (PCLOSE) is a quick, objective method of assessing upper airway collapsibility that may identify PRAE risk.

Aim

To investigate if PCLOSE measurement is feasible and predictive of PRAE in children.

Method

Fifty-six children (1-8years, 34 male, without significant co-morbidities) underwent PCLOSE measurements immediately preceding (pre-PCLOSE) and following (post-PCLOSE) adenotonsillectomy. Measurement was performed under anaesthesia while breathing spontaneously in supine posture with head/jaw neutral.

After application of a face mask, inspiratory flow was occluded with an associated decrease in mask/nasal pressure seen with each inspiratory effort. With airway collapse, a plateau developed in minimum pressure observed (= PCLOSE): less collapsible airways occluded at more negative pressures. PCLOSE was averaged over 5–6 sequential efforts, at least 3 times on each occasion.

Results

Both pre-and post-PCLOSE were successfully measured in 94.6% children without affecting procedure. Pre-PCLOSE and change in PCLOSE from pre- to post- were associated with an increased incidence of PRAE (Poisson regression coefficient 0.083(0.03) (mean, SE); p=0.0054 and 0.03(0.01); p=0.018, respectively). There was no significant association between post-PCLOSE and PRAE. The odd of PRAE occurrence during recovery was 1.5 times higher than in other phases.

Conclusion

This study demonstrated the feasibility of obtaining PCLOSE. A more collapsible airway before surgery and an increase in collapsibility with surgery were both associated with increased PRAE. PCLOSE measurement could be a valuable risk assessment tool for PRAE in children undergoing surgery.
Pharyngeal enlargement via tongue advancement differs with mandibular advancement therapy response and improves treatment prediction
Authors: Jugé L , Knapman F , Humburg P , Burke P , Lowth A , Brown E , Butler J , Eckert D , Ngiam J , Sutherland K , Cistulli P , Bilston L
Published: October 2021

Introduction

Mandibular advancement splint (MAS) treatment outcome prediction for obstructive sleep apnoea (OSA) is currently unreliable. Lower baseline AHI has been associated with better MAS response but is a poor predictor on its own. Imaging markers may enhance prediction. We investigate how the upper airway enlarges via posterior tongue advancement, using tagged MRI during mandibular advancement, as a potential predictor of MAS treatment response.

Methods

101 untreated OSA participants (AHI 10–102 events/hr) underwent an MRI scan wearing a MAS. Mid-sagittal tagged MRI images were collected to quantify tongue movement during passive jaw advancement. Upper airway cross-sectional areas were measured with the mandible in a neutral position and advanced to 70% of the maximum protrusion. Treatment outcome was determined after a minimum of 9 weeks of therapy.

Results

71 participants completed the study: 33 were responders (AHI<5 or AHI≤10 events/hr with >50% AHI reduction), 11 were partial responders (>50% AHI reduction but AHI>10 events/hr), and 27 non-responders (AHI reduction<50% and AHI≥10 events/hr). Responders had the greatest naso- and oropharyngeal tongue advancement (0.40±0.08 and 0.47±0.13mm, respectively) and oropharynx enlargement (6.41±2.12%) per millimetre of mandibular advancement. The inclusion of these imaging markers along with baseline AHI in a multivariate model classified more patients in the right MAS response group (69.2%) than a model based only on baseline AHI (50.0%) when the mandible was advanced by at least 4 mm.

Conclusions

Tongue advancement and upper airway enlargement with mandibular advancement in conjunction with baseline AHI improves MAS treatment response categorisation to a satisfactory level.
P001 Safety, tolerability, and efficacy of 1 month of atomoxetine plus oxybutynin in obstructive sleep apnoea
Authors: Aishah A , Loffler K , Tonson B , Mukherjee S , Adams R , Altree T , Ainge-Allen H , Yee B , Grunstein R , Taranto-Montemurro L , Carberry J , Eckert D
Published: October 2021

Introduction

Single-night studies with noradrenergic and anti-muscarinics have recently been shown to improve upper-airway function and reduce obstructive sleep apnoea (OSA) severity. This study aimed to determine the safety, tolerability, and efficacy profile of longer-term use of different doses of the noradrenergic agent atomoxetine combined with the anti-muscarinic oxybutynin (ato-oxy) in people with OSA.

Methods

Thirty-nine people with predominantly severe OSA received either 80/5mg ato-oxy, 40/5mg ato-oxy, 40/2.5mg ato-oxy or placebo nightly for 30 days according to a double-blind, randomised, parallel design. Safety and tolerability were assessed via weekly phone calls for adverse events, vital signs and objective measures of alertness and memory. Participants completed 3 in-laboratory sleep studies (baseline, night 1 and night 30) to assess efficacy.

Results

Side effects were generally mild and consistent with the known side-effect profile of each drug alone (e.g. dose-dependent increases in dry mouth with oxybutynin). Heart rate increased by night 30 in two of the drug arms versus placebo (e.g. 80/5mg ~9 beats/min, p=0.01). Blood pressure and measures of alertness and memory did not change between conditions. AHI4 and hypoxic burden decreased by ~50% in the 80/5mg arm on night 1 with similar magnitude reductions at night 30. ~50% of participants indicated willingness to continue taking the medication post-study.

Discussion

1 month of nightly noradrenergic and anti-muscarinic combination therapy is generally well-tolerated with a side effect profile consistent with each agent alone. These findings also further highlight the potential to target noradrenergic and anti-muscarinic mechanisms for OSA pharmacotherapy development.
P002 Targeted non-CPAP combination therapy resolves obstructive sleep apnoea
Authors: Aishah A , Tong B , Osman A , Donegan M , Pitcher G , Kwan B , Brown L , Altree T , Adam R , Mukherjee S , Eckert D
Published: October 2021

Introduction

Mandibular advancement splint (MAS) therapy is an effective alternative to CPAP for many people with obstructive sleep apnoea (OSA) but ~50% have residual OSA. This study aimed to resolve OSA in these individuals by combining MAS with other targeted therapies based on OSA endotype characterisation.

Methods

Eleven people with OSA (apnoea-hypopnoea index (AHI): 35±13 events/h), not fully resolved with MAS alone (AHI>10 events/h) were recruited. Initially, OSA endotypes were assessed via a detailed physiology night. Step one of combination therapy focused on anatomical interventions including MAS plus an oral expiratory positive airway pressure valve (EPAP) and a supine-avoidance device. Participants with residual OSA (AHI>10 events/h) following the anatomical combination therapy night, were then given one or more targeted non-anatomical therapies according to endotype characterisation. This included oxygen (4L/min) to reduce unstable respiratory control (high loop gain), 10mg zolpidem to increase arousal threshold, or 80/5mg atomoxetine-oxybutynin (ato-oxy) for poor pharyngeal muscle responsiveness.

Results

OSA was successfully treated (AHI<10 events/h) in all participants with combination therapy. MAS combined with EPAP and supine-avoidance therapy resolved OSA in ~65% of participants (MAS alone vs. combination therapy: 17±4 vs. 5±3, events/h, n=7). For the remaining participants, OSA resolved with the addition of oxygen (n=2), one with 80/5mg ato-oxy and another required both oxygen and 80/5mg ato-oxy.

Discussion

Targeted combination therapy may be a viable treatment alternative for people with OSA who cannot tolerate CPAP or for those who have an incomplete therapeutic response with monotherapy.